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pubmed_507_7975 | Strong evidence indicates that many or most adults in the United States and Europe would benefit from vitamin D supplements with respect to fracture and fall prevention, and possibly other public health targets, such as cardiovascular health, diabetes and cancer. This review discusses the amount of vitamin D supplementation needed and a desirable 25-hydroxyvitamin D level to be achieved for optimal musculoskeletal health. Vitamin D modulates fracture risk in two ways: by decreasing falls and increasing bone density. Two most recent meta-analyses of double-blind randomised controlled trials came to the conclusion that vitamin D reduces the risk of falls by 19%, the risk of hip fracture by 18% and the risk of any non-vertebral fracture by 20%; however, this benefit was dose dependent. Fall prevention was only observed in a trial of at least 700 IU vitamin D per day, and fracture prevention required a received dose (treatment dose*adherence) of more than 400 IU vitamin D per day. Anti-fall efficacy started with achieved 25-hydroxyvitamin D levels of at least 60 nmol l(-1) (24 ng ml(-1)) and anti-fracture efficacy started with achieved 25-hydroxyvitamin D levels of at least 75 nmol l(-1) (30 ng ml(-1)) and both endpoints improved further with higher achieved 25-hydroxyvitamin D levels. Founded on these evidence-based data derived from the general older population, vitamin D supplementation should be at least 700-1000 IU per day and taken with good adherence to cover the needs for both fall and fracture prevention. Ideally, the target range for 25-hydroxyvitamin D should be at least 75 nmol l(-1), which may need more than 700-1000 IU vitamin D in individuals with severe vitamin D deficiency or those overweight. | 10.1016/j.berh.2009.09.005 |
pubmed_544_203 | Because of certain analogies between the spread of tumors and different steps of pregnancy culminating in egg implantation and invasive growth, pregnant mice were treated at different intervals post coitum with two thrombocytopenic agents which can reduce metastases by interfering with vascular lodgement and growth of tumor cells. It was found that both neuraminidase and antiplatelet serum were active against pregnancy, the enzyme being by far the more effective of the two. The mechanism of this effect involves both egg implantation and egg development. The effect cannot be explained solely by the thrombocytopenia produced by both agents. | 10.1073/pnas.67.2.793 |
pubmed_351_19443 | The endpoint of fixed prosthesis design is an esthetic and functional pontic that is compatible with soft-tissue health. In the posterior segment, where esthetics is not as critical, a sanitary pontic form is most compatible with function and hygiene. In the maxillary anterior region, a properly contoured modified ridge-lap pontic design constructed of glazed porcelain most readily fulfills both the esthetic and physiologic requirements. Although the ovate pontic form may satisfy esthetic demands to a greater degree, this is often at the expense of underlying soft-tissue health. In maxillary edentulous regions, ridge deformities may preclude a good pontic fit and esthetic result and dictate the need for surgical augmentation of the collapsed ridge. Selection of the appropriate surgical procedure and graft material depends on the nature and extent of the defect and availability of donor tissue. The subepithelial graft employing the tunnel approach is appropriate when augmentation in only a labial dimension is necessary. When the employing the trapdoor approach or full thickness gingival onlay graft may be employed. In large defects, sequential grafting procedures may be necessary to achieve the desired result. An esthetic and functional result can be attained through proper execution of an appropriate surgical technique and adherence to the principles of proper pontic design. | pubmed_351_19443 |
pubmed_1041_20166 | OBJECTIVE
To determine the effect of intrauterine inflammation on fetal responses to umbilical cord occlusion (UCO).
STUDY DESIGN
In pregnant sheep, lipopolysaccharide (LPS) or saline (SAL) was infused intra-amniotically for 4 weeks from 80 days of gestation (d). At 110 d, fetuses were instrumented for UCOs (5 × 2-minutes, 30-minute intervals: LPS + UCO, n = 6; SAL + UCO, n = 8) or no UCO (sham, n = 6) on 117 and 118 d. Tissues were collected at 126 d.
RESULTS
Fetal physiological responses to UCO were similar between LPS + UCO and SAL + UCO. Histologic chorioamnionitis and increased amniotic fluid interleukin 8 (IL-8) were observed in LPS + UCO pregnancies (versus SAL + UCO, P < .05). CNPase-positive oligodendrocyte number in the cerebral white matter was lower in LPS + UCO and SAL + UCO than sham (P < .05); there was no effect on astrocytes or activated microglia/macrophages. Two of the SAL + UCO fetuses had white matter lesions; none were observed in LPS + UCO or sham.
CONCLUSION
Chronic pre-existing intrauterine inflammation did not exacerbate fetal brain injury induced by intermittent UCO. | 10.1177/1933719111399928 |
pubmed_817_15678 | Vibrio owensii is a widely distributed marine vibrio species that causes acute hepatopancreatic necrosis in the larvae of Panulirus ornatus and Penaeus vannamei, and is also associated with Montipora white syndrome in corals. We characterized V. owensii GRA50-12 as a potent pathogen using phenotypic, biochemical, and zebrafish models. A virulent phage, vB_VowP_phi50-12 (phi50-12), belonging to the N4-like Podoviridae, was isolated from the same habitat as that of V. owensii GRA50-12 and characterized. This phage possesses a unique sequence with no similar hits in the public databases and has a short latent time (30 min), a large burst size (106 PFU/infected cell), and a wide range of pH and temperature stabilities. Moreover, phi50-12 also demonstrated a strong lysis ability against V. owensii GRA50-12. SDS-PAGE revealed at least nine structural proteins, four of which were confirmed using LC-MS/MS analysis. The size of the phi50-12 genome was 68,059 bp, with 38.5% G + C content. A total of 101 ORFs were annotated, with 17 ORFs having closely related counterparts in the N4-like vibrio phage. Genomic sequencing confirmed the absence of antibiotic resistance genes or virulence factors. Comparative studies have shown that phi50-12 has a unique genomic arrangement, except for the well-conserved core regions of the N4-like phages. Phylogenetic analysis demonstrated that it belonged to a group of smaller genomes of N4-like vibrio phages. The therapeutic effect in the zebrafish model suggests that phi50-12 could be a potential candidate for application in the treatment of V. owensii infection or as a biocontrol agent. However, further research must be carried out to confirm the efficacy of phage50-12. | 10.1038/s41598-022-20831-2 |
pubmed_885_2523 | Septic shock is a critical clinical condition with a high mortality rate. A better understanding of the underlying mechanisms is important to develop effective therapies. Basic and clinical studies suggest that activation of complements in the common cascade, for example, complement component 3 (C3) and C5, is involved in the development of septic shock. The involvement of three upstream complement pathways in septic shock is more complicated. Both the classical and alternative pathways appear to be activated in septic shock, but the alternative pathway may be activated earlier than the classical pathway. Activation of these two pathways is essential to clear endotoxin. Recent investigations have shed light on the role of lectin complement pathway in septic shock. Published reports suggest a protective role of mannose-binding lectin (MBL) against sepsis. Our preliminary study of MBL-associated serine protease-2 (MASP-2) in septic shock patients indicated that acute decrease of MASP-2 in the early phase of septic shock might correlate with in-hospital mortality. It is unknown whether excessive activation of these three upstream complement pathways may contribute to the detrimental effects in septic shock. This paper also discusses additional complement-related pathogenic mechanisms and intervention strategies for septic shock. | 10.1155/2012/407324 |
pubmed_71_14676 | Walkers are commonly prescribed worldwide to individuals unable to walk independently. Walker usage leads to improved postural control and voluntary movement during step. In the present study, we aimed to provide a concept-proof on the feasibility of an event-related protocol integrating the analyses of biomechanical variables of step initiation and functional near-infrared spectroscopy (fNIRS) to measure activation of the supplementary motor area (SMA) while using a walker. Healthy young participants were tested while stepping with versus without the use of the walker. Behavioral analysis showed that anticipatory postural adjustments (APA) decreased when supporting the body weight on the walker. Delta (without-with) of activation magnitude of the muscle tibialis anterior was positively correlated to the delta of deoxyhemoglobin concentration changes in the SMA. The novelty of this study is the development of a protocol to assess brain function together with biomechanical analysis during the use of a walker. The method sheds light to the potential utility of combining fNIRS and biomechanical assessment during assistive step initiation, which can represent a new opportunity to study populations with mobility deficits. | 10.1016/j.gaitpost.2017.05.018 |
pubmed_386_10691 | BACKGROUND
Data on psychological distress (DIS), behavioral impact (BI) and health-related quality of life (HRQoL) are important yet lacking among Asian patients with Type 2 diabetes mellitus (T2DM). We aim to identify factors associated with DIS, BI and HRQoL among T2DM to better understand patient needs.
METHODS
DIS was measured with Diabetes Health Profile (DHP-18) Psychological Distress (DHP-PD) subscale, Problem Areas in Diabetes (PAID) and Kessler-10 (K10), BI with DHP-18 Barriers to Activity and Disinhibited Eating subscales and HRQoL with Audit of Diabetes-Dependent Quality of Life. Multiple linear regression analyses were performed to evaluate the associations between these outcomes and patient demographic, socioeconomic status, glycated hemoglobin (HbA1C) and comorbidities.
RESULTS
213 T2DM patients (mean (SD) age: 45.0 (12.1) years, mean (SD) HbA1C: 8.3% (1.9%) and 70.0% reported at least one comorbidity) were evaluated. Poorer glycemic control was significantly associated with higher DHP-PD, PAID and worse HRQoL. Taking oral hypoglycemic agents plus insulin was independently associated with Barrier to Activity and Disinhibited Eating.
CONCLUSION
Poorer glycemic control was only associated with diabetes-related distress (measured by DHP-PD and PAID) but not major depressive disorder (measured by K10). It may be more appropriate to screen for diabetes-related distress rather than major depressive disorder for patients with T2DM. | pubmed_386_10691 |
pubmed_980_1379 | BACKGROUND
Cancer stem cells (CSCs) are considered the main cause of cancer recurrence and metastasis, and DNA methylation is involved in the maintenance of CSCs. However, the methylation profile of esophageal CSCs remains unknown.
METHODS
Side population (SP) cells were isolated from esophageal squamous cell carcinoma (ESCC) cell lines KYSE150 and EC109. Sphere-forming cells were collected from human primary esophageal cancer cells. SP cells and sphere-forming cells were used as substitutes for cancer stem-like cells. We investigated the genome-wide DNA methylation profile in esophageal cancer stem-like cells using reduced representation bisulfite sequencing (RRBS).
RESULTS
Methylated cytosine (mC) was found mostly in CpG dinucleotides, located mostly in the intronic, intergenic, and exonic regions. Forty intersected differentially methylated regions (DMRs) were identified in these 3 groups of samples. Thirteen differentially methylated genes with the same alteration trend were detected; these included OTX1, SPACA1, CD163L1, ST8SIA2, TECR, CADM3, GRM1, LRRK1, CHSY1, PROKR2, LINC00658, LOC100506688, and NKD2. DMRs covering ST8SIA2 and GRM1 were located in exons. These differentially methylated genes were involved in 10 categories of biological processes and 3 cell signaling pathways.
CONCLUSIONS
When compared to non-CSCs, cancer stem-like cells have a differential methylation status, which provides an important biological base for understanding esophageal CSCs and developing therapeutic targets for esophageal cancer. | 10.1177/1533033820983793 |
pubmed_228_23729 | BACKGROUND
With 4 years until 2015, it is essential to monitor progress towards Millennium Development Goals (MDGs) 4 and 5. Although estimates of maternal and child mortality were published in 2010, an update of estimates is timely in view of additional data sources that have become available and new methods developed. Our aim was to update previous estimates of maternal and child mortality using better data and more robust methods to provide the best available evidence for tracking progress on MDGs 4 and 5.
METHODS
We update the analyses of the progress towards MDGs 4 and 5 from 2010 with additional surveys, censuses, vital registration, and verbal autopsy data. For children, we estimate early neonatal (0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (ages 1-4 years), and under-5 mortality. We use an improved model for estimating mortality by age under 5 years. For maternal mortality, our updated analysis includes greater than 1000 additional site-years of data. We tested a large set of alternative models for maternal mortality; we used an ensemble model based on the models with the best out-of-sample predictive validity to generate new estimates from 1990 to 2011.
FINDINGS
Under-5 deaths have continued to decline, reaching 7·2 million in 2011 of which 2·2 million were early neonatal, 0·7 million late neonatal, 2·1 million postneonatal, and 2·2 million during childhood (ages 1-4 years). Comparing rates of decline from 1990 to 2000 with 2000 to 2011 shows that 106 countries have accelerated declines in the child mortality rate in the past decade. Maternal mortality has also continued to decline from 409,100 (uncertainty interval 382,900-437,900) in 1990 to 273,500 (256,300-291,700) deaths in 2011. We estimate that 56,100 maternal deaths in 2011 were HIV-related deaths during pregnancy. Based on recent trends in developing countries, 31 countries will achieve MDG 4, 13 countries MDG 5, and nine countries will achieve both.
INTERPRETATION
Even though progress on reducing maternal and child mortality in most countries is accelerating, most developing countries will take many years past 2015 to achieve the targets of the MDGs 4 and 5. Similarly, although there continues to be progress on maternal mortality the pace is slow, without any overall evidence of acceleration. Immediate concerted action is needed for a large number of countries to achieve MDG 4 and MDG 5.
FUNDING
Bill & Melinda Gates Foundation. | 10.1016/S0140-6736(11)61337-8 |
others_119_1861 | Characterization of creole sheep is essential for the conservation of their genes for breeding purposes as well as to meet future needs. The objective of the study was to determine the analysis of principal components for morphological characteristics in Creole sheep. A population of 380 sheep classified by age was used and body weight data and the following morphological measurements were recorded: Head length; Head width; Head depth; Ear length; Ear width; Neck length; Neck perimeter; Height at the withers; Longitudinal body diameter; Thoracic perimeter; Bicostal diameter; Sternal dorsal diameter; Rump width; Rump length; Height at the rump; Leg perimeter; Height at hock; Metacarpus perimeter and Metatarsus perimeter. Data were processed using R statistical software. The correlation of the main morphological characteristics were significant and high. Age significantly influences morphological characteristics, showing high correlations between characters. Two principal components were obtained for sheep morphological characteristics that were evaluated according to Kaiser’s criteria, PCA 1 and PCA 2 had high values for variables related to body size and body shape. The conclusion is that morphological characteristics can be useful for the selection of elite animals and the formulation of genetic improvement programs. © 2023 by the authors. Licensee ResearchersLinks Ltd, England, UK | 10.17582/journal.aavs/2023/11.6.903.909 |
others_46_622 | Sixteen multifarious cows were selected on the basis of average daily milk yield and stage of lactation; they were divided into four groups (four cows in each group) with parity within each group. These cows were fed 10gm, 15gm and 20gm probiotics just before evening milk. The multi-strain probiotic used were containing four strains consist of acteria and fungi namely Lactobacillus acidophilus, Saccharomyces cerevisiae, Saccharomyces boulardii and Propionibacterium frendenreichii. It was found that, the use of probiotics proved to be effective in increasing milk production of lactating cows. Milk fat, milk protein and SNF content tended to be higher in cows supplemented with probiotics preparations. The appropriate level of 20 gm probiotic per day per animal was found effective. The economic advantage of probiotics depends on its relative prices and on the levels of milk production of the cows | 10.5455/vetworld.2011.557-561 |
pubmed_153_1081 | Melanoma-associated leukoderma (MAL) is a relatively uncommon phenomenon in the literature that can present (1) before melanoma detection, (2) after detection and before treatment, and (3) after treatment with immunotherapeutic agents. We report a case of MAL in an 83-year-old man after treatment with high dose IL-2 for metastatic melanoma and further describe the literature of the underlying mechanisms behind it that involve the immune system. Cytotoxic CD8+ T cells are thought the mediate the process at a cellular level. Self-antigens (e.g. MART-1/2, gp100, tyrosinase) have been presented on the surface of both normal and malignant melanocytes and mediate the development of MAL after cytotoxic CD8+ T cells attack both cell types. Autoimmune manifestations have a positive effect on tumor immunity, with patients at stage III and stage IV melanoma showing a better prognosis after leukoderma development. In addition, immunotherapy induced leukoderma has been associated with a higher therapeutic response rate. Recently, newer immuno-therapeutic drugs, such as vemurafenib and ipilimumab, have been associated with leukoderma as a side effect. | 10.2340/00015555-1897 |
pubmed_471_15593 | Background
Treatment with immune checkpoint blockade (ICB) with agents such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can result in impressive response rates and durable disease remission but only in a subset of patients with cancer. Expression of PD-L1 has demonstrated utility in selecting patients for response to ICB and has proven to be an important biomarker for patient selection. Tumor mutation burden (TMB) is emerging as a potential biomarker. However, refinement of interpretation and contextualization is required.
Materials and methods
In this review, we outline the evolution of TMB as a biomarker in oncology, delineate how TMB can be applied in the clinic, discuss current limitations as a diagnostic test, and highlight mechanistic insights unveiled by the study of TMB. We review available data to date studying TMB as a biomarker for response to ICB by tumor type, focusing on studies proposing a threshold for TMB as a predictive biomarker for ICB activity.
Results
High TMB consistently selects for benefit with ICB therapy. In lung, bladder and head and neck cancers, the current predictive TMB thresholds proposed approximate 200 non-synonymous somatic mutations by whole exome sequencing (WES). PD-L1 expression influences response to ICB in high TMB tumors with single agent PD-(L)1 antibodies; however, response may not be dependent on PD-L1 expression in the setting of anti-CTLA4 or anti-PD-1/CTLA-4 combination therapy. Disease-specific TMB thresholds for effective prediction of response in various other malignancies are not well established.
Conclusions
TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required. TMB determination by selected targeted panels has been correlated with WES. Calibration and harmonization will be required for optimal utility and alignment across all platforms currently used internationally. Key challenges will need to be addressed before broader use in different tumor types. | 10.1093/annonc/mdy495 |
pubmed_201_10302 | Emotion recognition plays an important role in several applications, such as human computer interaction and understanding affective state of users in certain tasks, e.g., within a learning process, monitoring of elderly, interactive entertainment etc. It may be based upon several modalities, e.g., by analyzing facial expressions and/or speech, using electroencephalograms, electrocardiograms etc. In certain applications the only available modality is the user's (speaker's) voice. In this paper we aim to analyze speakers' emotions based solely on paralinguistic information, i.e., not depending on the linguistic aspect of speech. We compare two machine learning approaches, namely a Convolutional Neural Network and a Support Vector Machine. The former is trained using raw speech information, while the latter is trained on a set of extracted low-level features. Aiming to provide a multilingual approach, training and testing datasets contain speech from different languages. | 10.1007/978-3-319-57348-9_13 |
pubmed_598_2791 | BACKGROUND
The Griffiths Mental Development Scales (GMDS) are used in many countries to assess the development of children from birth to 8 years. There is a need for accurate and culturally appropriate developmental assessment tools for Chinese children. Here, we adapted the GMDS for use in Chinese children and compare the developmental trajectories between Chinese and British children.
METHODS
Children with typical development were recruited from 7 urban cities in China between 2009 and 2013. The Griffiths Mental Development Scales-Chinese (GDS-C) were adapted and used to assess the development of urban Chinese children. Developmental curves were computed for 6 subscales using learning management system methods and compare against the British curves from the Griffiths Mental Development Scales-Extended Revised (GMDS-ER).
RESULTS
The GDS-C were used to assess the developmental status of 815 Chinese children. Plots of the 1st, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 99th percentiles, and full percentile tables were obtained, which showed similar trends to data from the British GMDS-ER.
CONCLUSIONS
The Chinese developmental curves obtained from the GDS-C showed similarities and differences to the developmental curves from the British GMDS-ER. The development of urban Chinese children should be assessed with the culturally appropriate GDS-C. | 10.1111/cch.12548 |
pubmed_142_23403 | Phenotypic approach of the treatment of coronary artery disease and heart failure used in prospective randomized trials has contributed to significantly improve patieni prognosis. However, gene polymorphisms have been shown to be able to alter treatment efficacy with anti-platelets, beta-blockers or ACE-inhibitors in these settings. As suggested by several studies, therapeutic approaches based on genotype should contribute to personalize treatments with better efficacy and safety. | pubmed_142_23403 |
pubmed_649_4962 | In this study, density, specific heat, thermal conductivity, and thermal diffusivity were measured experimentally along the lengths of human cadaveric femora. Fresh and dry bone samples were selected from both male and female specimens, and for different age groups varying between 44 and 73 years old. Measured values for specific heat vary between 1.14 and 2.37 J/gm degrees C; for thermal conductivities the range is from 0.16 to 0.34 W/m degrees C; and for thermal diffusivities the range is from 0.10 to 0.23 cm2/sec, depending on whether the bone samples were fresh or dry, cancellous or cortical. The experimental results are presented in non-dimensional coordinates and are compared with the few other data available in the literature. | 10.1002/jbm.820200908 |
pubmed_999_11973 | The presence of wildlife in areas with a high concentration of farming activities can create a conflict between conservation objectives and productive purposes. Near Brindisi (Apulia, S-E Italy), a substantial amount of cash compensation claims for damages reported by local farmers and attributed to starlings (Sturnus vulgaris) has been registered. The aim of this study was to quantify the starling population wintering in the Apulia region, in order to assess the potential damage to crop production caused by this species. Our analysis was conducted over three years and included three main activities: a study of starling abundance and movements, the identification of areas and crops affected by damages, and a determination of the damage to the agricultural system in terms of quantity and concentration (heatmap). The study showed a loss of expected production that was coherent with the eating capacity of starlings wintering in the region. This means a loss, in terms of gross profitable production, of around 550,000 euros concentrated in a few narrow areas close to the roosts. Results on species behavior, damage quantification, and mapping are useful elements aimed to activate trade-off measures to preserve production and protection objectives, and to allow policymakers to address enforcement interventions and to establish parameters for financial compensation. | 10.3390/ani11041119 |
pubmed_80_8472 | BACKGROUND
To explore experiences of parents of children with disabilities using the WWW, roadmap, a tool to support them in exploring needs, finding information, and asking questions of professionals and to explore differences between parents who had used the WWW-roadmap to prepare for consultation with their rehabilitation physician and parents who had not.
METHODS
In a sequential cohort study, we included 128 parents; 54 used the WWW-roadmap prior to consultation and 74 received care-as-usual. Both groups completed questionnaires after consultation, assessing empowerment, self-efficacy, parent and physician satisfaction, family centredness of care, and experiences using the tool. Additionally, 13 parents were interviewed.
RESULTS
Parents who used the WWW-roadmap looked up more information on the Internet. No other differences between parents and physicians were found. In the interviews, parents said that the WWW-roadmap was a useful tool for looking up information, exploring and asking questions, and maintaining a comprehensive picture.
CONCLUSION
Using the WWW-roadmap prior to consultation did not improve self-efficacy, satisfaction, or family centredness of care. Findings suggest positive experiences regarding factors determining empowerment, creating conditions for a more equal parent-physician relationship. The WWW-roadmap is useful for parents to explore their needs and find information, but more is needed to support empowerment in consultations. | 10.1111/cch.12700 |
others_253_524 | Twenty male volleyball players were taken for this study and during an 8-week-period they did physical conditioning exercises by weight training 5 days a week. Physical fitness tests, auditory and visual reaction times were measured at the beginning and at the end of training period. When results statistically analysed, it was observed that physical conditioning exercises affected their physical fitness positively and moreover auditory and visual reaction times were shorten | others_253_524 |
pubmed_540_17922 | Transcription factors regulate gene expression by binding to regulatory DNA and recruiting regulatory protein complexes. The DNA-binding and protein-binding functions of transcription factors are traditionally described as independent functions performed by modular protein domains. Here, I argue that genome binding can be a 2-part process with both DNA-binding and protein-binding steps, enabling transcription factors to perform a 2-step search of the nucleus to find their appropriate binding sites in a eukaryotic genome. I support this hypothesis with new and old results in the literature, discuss how this hypothesis parsimoniously resolves outstanding problems, and present testable predictions. | 10.1093/genetics/iyac111 |
pubmed_796_11787 | Coughing in response to irritation of the airways is a fundamental protective reflex that is dependent on rapidly adapting bronchopulmonary receptors and their vagal afferent fibers; reflex airway constriction, which is effected by vagomotor efferent fibers, usually accompanies coughing. Although dysfunction of vagally mediated cardiovascular and gastrointestinal reflexes is a well-documented complication of autonomic neuropathy, to date there have been no studies of the effect of peripheral autonomic failure on the cough reflex. In the study reported here, we examined the effect of acrylamide-induced neuropathy, a distal axonopathy, on the ventilatory and tracheomotor components of the cough reflex in conscious dogs. There was a reduction in the cough reflex in response to mechanical irritation of the large airways in the preclinical phase of the neuropathy, and the cough reflex was virtually abolished when the dogs had moderate neuropathy. Following withdrawal of the neurotoxin, there was a substantial recovery of the cough reflex in surviving animals. It is possible that the cough reflex may be reduced in patients with vagal neuropathy and that this might compromise protection of the airway. | 10.1002/ana.410260609 |
pubmed_89_3056 | Removal of the monosynaptic corticospinal pathway (CSP) terminating within the forelimb segments severely impairs manual dexterity. Functional recovery from the monosynaptic CSP lesion can be achieved through the remaining multisynaptic CSP toward the forelimb segments. In the present study, we applied retrograde transsynaptic labeling with rabies virus to a monkey model of spinal cord injury. By injecting the virus into the spinal forelimb segments immediately after the monosynaptic CSP lesion, we showed that the contralateral primary motor cortex (M1), especially its caudal and bank region (so-called "new" M1), was the principal origin of the CSP linking the motor cortex to the spinal forelimb segments disynaptically (disynaptic CSP). This forms a striking contrast to the architecture of the monosynaptic CSP that involves extensively other motor-related areas, together with M1. Next, the rabies injections were made at the recovery period of 3 months after the monosynaptic CSP lesion. The second-order labeled neurons were located in the ipsilateral as well as in the contralateral "new" M1. This indicates that the disynaptic CSP input from the ipsilateral "new" M1 is recruited during the motor recovery from the monosynaptic CSP lesion. Our results suggest that the disynaptic CSP is reorganized to connect the ipsilateral "new" M1 to the forelimb motoneurons for functional compensation after the monosynaptic CSP lesion. | 10.3389/fncir.2022.847100 |
others_80_79 | This article summarizes recent advances in understanding of the epidemiology, pathogenesis, clinical and laboratory diagnosis, immunology, treatment, and control of Rhodococcus equi infections in foals. Our understanding of these aspects currently is sufficient to ensure control of this problem on affected farms and in infected foals. More information, however, is needed on factors predisposing foals to R. equi pneumonia, in particular, the nature of the naturally occurring cellular immunodeficiency in foals of 2 to 4 months of age, which also predisposes them to severe respiratory infection with certain other intracellular pathogens. In addition, the relative importance of R. equi pneumonia in the context of other causes of lower respiratory tract infection of foals needs to be defined. © 1993 W.B. Saunders Company | 10.1016/S0749-0739(17)30404-2 |
pubmed_291_24546 | The Food, Math, and Science Teaching Enhancement Resource (FoodMASTER) Initiative is a compilation of programs aimed at using food as a tool to teach mathematics and science. In 2007-2008, a foods curriculum developed by professionals in nutrition and education was implemented in 10 3(rd)-grade classrooms in Appalachian Ohio; teachers in these classrooms implemented 45 hands-on foods activities that covered 10 food topics. Subjects included measurement; food safety; vegetables; fruits; milk and cheese; meat, poultry, and fish; eggs; fats; grains; and meal management. Students in four other classrooms served as the control group. Mainstream 3(rd)-grade students were targeted because of their receptiveness to the subject matter, science standards for upper elementary grades, and testing that the students would undergo in 4(th) grade. Teachers and students alike reported that the hands-on FoodMASTER curriculum experience was worthwhile and enjoyable. Our initial classroom observation indicated that the majority of students, girls and boys included, were very excited about the activities, became increasingly interested in the subject matter of food, and were able to conduct scientific observations. | 10.1111/j.1541-4329.2010.00090.x |
pubmed_781_20381 | Diverse cell types have unique transcriptional signatures that are best interrogated at single-cell resolution. Here we describe a novel RNA amplification approach that allows for high fidelity gene profiling of individual cells. This technique significantly diminishes the problem of 3' bias, enabling detection of all regions of transcripts, including the recognition of mRNA with short or completely absent poly(A) tails, identification of noncoding RNAs, and discovery of the full array of splice isoforms from any given gene product. We assess this technique using statistical and bioinformatics analyses of microarray data to establish the limitations of the method. To demonstrate applicability, we profiled individual cells isolated from the mouse subventricular zone (SVZ)-a well-characterized, discrete yet highly heterogeneous neural structure involved in persistent neurogenesis. Importantly, this method revealed multiple splice variants of key germinal zone gene products within individual cells, as well as an unexpected coexpression of several mRNAs considered markers of distinct and separate SVZ cell types. These findings were independently confirmed using RNA-fluorescence in situ hybridization (RNA-FISH), contributing to the utility of this new technology that offers genomic and transcriptomic analysis of small numbers of dynamic and clinically relevant cells. | 10.2144/000114331 |
pubmed_107_7458 | The susceptibilities of 37 penicillinase-producing strains of Neisseria gonorrhoeae (PPNG), isolated in Hawaii from December 1991 through January 1994, were determined to ciprofloxacin and ofloxacin, fluoroquinolone agents currently recommended by the Centers for Disease Control and Prevention as alternative regimens for the treatment of uncomplicated gonorrhea. Nine isolates (24.3%) exhibited decreased susceptibilities (MICs, > or = 0.06 microgram/ml) to ciprofloxacin and ofloxacin. Ciprofloxacin MICs for three isolates (8.1%) were 2.0 micrograms/ml; these isolates belonged to the auxotype/serovar class Pro/IB-7 and possessed the 3.2-MDa beta-lactamase and the 24.5-MDa conjugative plasmids. Six strains for which ciprofloxacin MICs were 0.06 to 0.125 microgram/ml belonged to a variety of gonococcal phenotypes. Strains for which ciprofloxacin MICs were 2.0 micrograms/ml were isolated from persons who had traveled to, or were sexual contacts of persons who had recently traveled to, Southeast Asia. Persons infected with these isolates had been treated with ceftriaxone (250 mg intramuscularly, single dose); therefore, none of these cases were associated with clinical failure following the use of fluoroquinolone therapy. Further studies are needed to confirm the clinical and public health significance of increased in vitro resistance to ciprofloxacin and ofloxacin in N. gonorrhoeae. | 10.1128/AAC.38.9.2200 |
pubmed_912_18622 | Parasympathetic tone is a dominant neural regulator for basal heart rate. Glutamate transporters (EAAT) via their glutamate uptake functions regulate glutamate neurotransmission in the central nervous system. We showed that EAAT type 3 (EAAT3) knockout mice had a slower heart rate than wild-type mice when they were anesthetized. We design this study to determine whether non-anesthetized EAAT3 knockout mice have a slower heart rate and, if so, what may be the mechanism for this effect. Young adult EAAT3 knockout mice had slower heart rates than those of their littermate wild-type mice no matter whether they were awake or anesthetized. This difference was abolished by atropine, a parasympatholytic drug. Carbamylcholine chloride, a parasympathomimetic drug, equally effectively reduced the heart rates of wild-type and EAAT3 knockout mice. Positive immunostaining for EAAT3 was found in the area of nuclei deriving fibers for vagus nerve. There was no positive staining for the EAATs in the sinoatrial node. These results suggest that EAAT3 knockout mice have a slower heart rate at rest. This effect may be caused by an increased parasympathetic tone possibly due to increased glutamate neurotransmission in the central nervous system. These findings indicate that regulation of heart rate, a vital sign, is one of the EAAT biological functions. | 10.1007/s11248-012-9680-5 |
pubmed_855_3165 | BACKGROUND
Bacterial adherence and biofilm formation are important factors in the blockage of biliary stents. Clinical studies with oral antibiotic prophylaxis to prevent stent blockage have produced conflicting results. The aim of this study was to evaluate the in vitro effect of single antibiotic (ciprofloxacin, ceftazidime, or ampicillin) treatment on adherence of Escherichia coli and Enterococcus to plastic stents.
METHODS
Selected clinical isolates of E coli and Enterococcus were perfused through a modified Robbins device containing segments of polyethylene stents. The stents were removed daily and the number of bacteria attached was measured. The effect of antibiotic treatment on bacterial adherence was tested by the perfusion of individual antibiotics into separate modified Robbins devices using a side-arm adaptor and the results were compared with saline controls.
RESULTS
Compared with the saline controls, ciprofloxacin and ceftazidime caused a 10- to 100-fold reduction in the number of E coli attached to the stents, whereas ampicillin had no effect on adherence of E coli. Ampicillin caused a 5- to 10-fold reduction in Enterococcus adherence but there was no change with ceftazidime. Sustained reduction in E coli adherence was observed with prolonged ciprofloxacin perfusion.
CONCLUSION
Timely treatment with appropriate antibiotics reduced bacterial adherence in vitro and may be potentially beneficial in the prevention of stent blockage. | 10.1016/s0016-5107(00)70358-0 |
pubmed_326_21778 | We investigated a possible relationship between the Kobe earthquake (January 17, 1995) and the quality of semen. We assessed sperm concentration and motility of 27 male patients who had a concentration of more than 30 million/ml and >40% sperm motility within 5 months before the earthquake. Twelve male patients from districts with a magnitude of <4 on the Richter scale showed no difference in sperm concentration and motility before and after the earthquake. Of 15 male patients from districts with a magnitude of >6, five patients whose houses received no damage showed no distinct changes in sperm concentration and motility. In contrast, 10 patients whose houses were partially or completely destroyed showed significantly (P < 0.001) lower sperm motility after the earthquake than before, although no significant difference of sperm concentration could be observed. Of these latter 10 patients, seven could be followed. In six patients, sperm motility was restored between 2 and 9 months after the earthquake; the sperm motility in one patient, whose father died a victim of the house crash, has not yet recovered. Thus, the acute stress resulting from such a catastrophic earthquake could be a possible cause of reduced sperm motility. | 10.1093/oxfordjournals.humrep.a019365 |
pubmed_651_10458 | The effect of combined insulin and growth hormone (GH) deficiency on compensatory renal growth (CRG) was studied in the dwarf mouse, "Little," after insulin suppression with streptozotocin (SZ). Nucleic acid and protein estimations were used to assess changes in cellular hyperplasia and hypertrophy. Mice aged 30 days received SZ while controls received buffers solution alone. Left nephrectomy was performed at 35 days of age with removal of the renoprival kidney 15 days later. In mice with normal GH, renoprival kidney weight was unaffected by SZ, but the total DNA (estimate of cell number) was higher than normal in both sham-operated and renoprival kidneys suggesting that insulin suppression may cause greater cell replication during both normal growth and CRG. The ratio of protein to DNA (estimate of cell size) in the renoprival kidney was not suppressed by SZ as reported in muscle. In GH-deficient mice (lit/lit) given SZ, CRG was significantly diminished (P less than 0.001). Total DNA in the renoprival kidney was slightly greater than the sham-operated control (P less than 0.005) but the protein:DNA ratio (cell size) was unchanged. These results suggest that when both GH and insulin are suppressed, adaptive cellular growth is inhibited. The proposal that GH and insulin are the two primary hormones controlling cellular growth is consistent with these results. | 10.1016/s0022-3468(84)80009-3 |
pubmed_1064_17396 | Framing effects occur when logically equivalent redescriptions of objects or outcomes lead to different behaviors, and, traditionally, such effects have been seen as irrational. However, recent evidence has shown that a speaker's choice among logically equivalent attribute frames can implicitly convey (or "leak") normatively relevant information about the speaker's reference point, among other things. In a reinterpretion of data published elsewhere, in this article it is shown that some common effects in inference tasks (covariation assessment and hypothesis testing) can also be seen as framing effects, thereby expanding the domain of framing. It is also shown that these framing effects are normatively defensible because normatively relevant information about event rarity is leaked through the description of data and through the phrasing of hypotheses, thereby broadening the information leakage approach to explaining framing effects. Information leakage can also explain why framing effects in such inference tasks disappear under certain conditions. | 10.3758/bf03196866 |
pubmed_299_5700 | Azeotropes famously impose fundamental restrictions on distillation processes, yet their special thermodynamic properties make them highly desirable for a diverse range of industrial and technological applications. Using neutron diffraction, we investigate the structures of two prototypical azeotropes, the negative acetone-chloroform and the positive benzene-methanol azeotrope. C-HO hydrogen bonding is the dominating interaction in the negative azeotrope but C-ClO halogen bonding contributes as well. Hydrogen-bonded chains of methanol molecules, which are on average longer than in pure methanol, are the defining structural feature of the positive azeotrope illustrating the fundamentally different local mixing in the two kinds of azeotropes. The emerging trend for both azeotropes is that the more volatile components experience the more pronounced structural changes in their local environments as the azeotropes form. The mixing of the acetone-chloroform azeotrope is essentially random above 20 Å, where the running Kirkwood-Buff integrals of our structural model converge closely to the ones expected from thermodynamic data. The benzene-methanol azeotrope on the other hand displays extended methanol-rich regions and consequently the running Kirkwood-Buff integrals oscillate up to at least 60 Å. Our study provides the first experimental insights into the microstructures of azeotropes and a direct link with their thermodynamic properties. Ultimately, this will provide a route for creating tailored molecular environments in azeotropes to improve and fine-tune their performances. | 10.1039/c6cp02450e |
pubmed_152_23161 | Enzymes belonging to the protein kinase C (PKC) family represent one of the major mediators of signal transduction in melanocytes. To identify PKC isoforms that may be associated with the process of malignant transformation and metastasis, we investigated the expression pattern of 11 different PKC isoforms (alpha, beta I, beta II, gamma, delta, epsilon, eta, theta, zeta, lambda, and iota) in melanoma lymph node metastases, in cell lines established from these metastases, in primary cell cultures from normal melanocytes, and in permanent cell lines established from spontaneously transformed melanocytes. PKC alpha, beta I, beta II, delta, epsilon, eta, zeta, lambda and iota were found to be expressed in total lysates from melanoma metastases. In permanent cell lines established from these metastases, the expression levels of PKC beta I, beta II, delta, epsilon, and eta were lower or undetectable when compared with initial expression in tumour lysates. In normal primary melanocyte cultures, the PKC isoforms beta II, delta, epsilon, eta and iota were undetectable. PKC gamma and theta isoforms were undetectable in all melanocytic cell types examined. PKC iota was the only isoform exclusively detected in tumour lysates, in spontaneously transformed melanoma cells and melanoma cell lines, but not in normal melanocytes, and may therefore be associated with the transformed phenotype in human melanoma in vitro and in vivo. | 10.1097/00008390-200206000-00003 |
pubmed_454_13015 | Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a major risk factor for ischemic stroke. Antithrombotic therapy using vitamin K antagonists (VKA) is currently prescribed for prevention of ischemic stroke in patients with AF. A narrow therapeutic range and frequent food and drug interactions underly the need for regular monitoring of anticoagulation intensity and impairs the utility and safety of VKA, stimulating a quest for alternative anticoagulant agents. Recently developed anticoagulants include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors rivaroxaban, apixaban, edoxaban, to name those in the most advanced stages of clinical development. This review focuses on advances in the development of novel antithrombotic agents to provide practical information to clinicians on the use of these new drugs in patients with AF. | 10.1111/j.1540-8167.2011.02104.x |
pubmed_445_14484 | To determine the character of the glucagon secretion and its modification by streptozotocin, were studied the plasma of a patient with recurrent pancreatic alpha-cell carcinoma. The plasma immunoreactive glucagon level before treatment of 4.80 ng per milliliter. Biogel column separation of the plasma immunoreactive glucagon revealed four components; the predominant component had a molecular weight of 9000 daltons and was designated as proglucagon-like. This fraction constituted 60 to 90 per cent of the total circulating immunoreactive glucagon, and had a biologic activity of 32 percent of that of an immunoequivalent amount of normal (porcine) pancreatic glucagon. After treatment with streptozocin (1.5 g per square meter) the plasma immunoreactive glucagon level decreased to 0.24 ng per milliliter. Treatment was accompanied by a marked reduction in the proglucagon-like component and the appearance of pancreatic glucagon (molecular weight of 3500 daltons) as the major post-therapy fraction. These findings support the use of streptozotocin in the management of unresectable glucagon-secreting tumors. | 10.1056/NEJM197607292950502 |
pubmed_529_25109 | BACKGROUND AND PURPOSE
The paradigm that GPCRs are able to prolong or initiate cellular signalling through intracellular receptors recently emerged. Melatonin binds to G protein-coupled MT1 and MT2 receptors. In contrast to most other hormones targeting GPCRs, melatonin and its synthetic analogues are amphiphilic molecules easily penetrating into cells, but the existence of intracellular receptors is still unclear mainly due to a lack of appropriate tools.
EXPERIMENTAL APPROACH
We therefore designed and synthesized a series of hydrophilic melatonin receptor ligands coupled to the Cy3 cyanin fluorophore to reliably monitor its inability to penetrate cells. Two compounds, one lipophilic and one hydrophilic, were then functionally characterized in terms of their affinity for human and murine melatonin receptors expressed in HEK293 cells and their signalling efficacy.
KEY RESULTS
Among the different ligands, ICOA-13 showed the desired properties as it was cell-impermeant and bound to human and mouse MT1 and MT2 receptors. ICOA-13 showed differential activities on melatonin receptors ranging from partial to full agonistic properties for the Gi /cAMP and ERK pathway and β-arrestin 2 recruitment. Notably, ICOA-13 enabled us to discriminate between Gi /cAMP signalling of the MT1 receptor initiated at the cell surface and neuronal mitochondria.
CONCLUSIONS AND IMPLICATIONS
We report here the first cell-impermeant melatonin receptor agonist, ICOA-13, which allows us to discriminate between signalling events initiated at the cell surface and intracellular compartments. Detection of mitochondrial MT1 receptors may have an important impact on the development of novel melatonin receptor ligands relevant for neurodegenerative diseases, such as Huntington disease. | 10.1111/bph.13856 |
pubmed_86_674 | Twenty-one castrated oestrogen-primed Wistar rats, which were 2-months-old, were injected via the jugular vein with 100 mu Ci/100 g body weight of [3H]RU 486 or [3H]progesterone. Some of these received unlabelled compounds for competition studies. Samples of reproductive tract, pituitary and hypothalamus were excised after 15 min. The 4-microns frozen sections were processed for thaw-mounted autoradiography. The exposure time of the autoradiogram was approximately 6 months. After the injection of [3H]RU 486 and [3H]progesterone, the nuclear concentration of radioactivity was most distinct in muscular and stromal cells of the uterus, and the epithelial nuclei of lumina and glands showed weak labelling. Nuclear localization was also observed in muscle cells of the vagina, cervix and oviduct. After injection of [3H]progesterone, the radioactivity was found in the nuclei and cytoplasm of anterior pituitary cells and some cells showed a preferential nuclear concentration of radioactivity. The distribution of [3H]RU 486 in the anterior pituitary was more extensive than that of [3H]progesterone. In the hypothalamus, specific localization of [3H]RU 486 and [3H]progesterone existed in neurones accumulated in the preoptic nucleus, preoptic suprachiasmatic nucleus and the periventricular nucleus. No localization was found in the diaphragm. Pretreatment with RU 486, but not with dexamethasone, reduced the nuclear concentration of radioactivity of [3H]progesterone in the vagina, uterus, oviduct, pituitary and hypothalamus. The nuclear concentration of radioactivity after injection of [3H]RU 486 was also decreased by preinjection with progesterone. The autoradiographic results suggest that RU 486 and progesterone competed for the specific binding site (possibly a progesterone receptor) in the target cells at the levels of the uterus, pituitary and hypothalamus in vivo. | pubmed_86_674 |
pubmed_4_15756 | Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B - Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI and FA in the genu and body of the corpus callosum. In addition, higher RHI and FA were each associated with better executive task performance. Tractography was used to localize the WM tracts associated with RHI to specific portions of cortex. Results indicated that the RHI-FA relationship observed in the corpus callosum primarily involved tracts interconnecting frontal regions, including the superior frontal gyrus (SFG) and frontopolar cortex, linked with executive function. These findings suggest that superior endothelial function may help to attenuate age-related declines in WM microstructure in portions of the corpus callosum that interconnect prefrontal brain regions involved in executive function. | 10.3389/fnagi.2017.00255 |
others_375_19764 | The object of the study was to investigate the clinical and endocrine patterns of progesterone, oestradiol-17β and LH during the peripubertal period in female pigs. Crossbred gilts were penned in groups at an age of 10-12 weeks and boars were kept in adjacent pens during the entire experimental period. Daily oestrous checks started at 4.5 months of age and the gilts were slaughtered after their third heat. At the age of 4.5-5 months a permanent catheter was inserted in the cephalic vein and blood samples were collected from the gilts once daily until either the first or second oestrus. In three gilts hourly blood samples were taken during their first and second oestrus, beginning at early pro-oestrus. The gilts showed their first oestrus at the average age of 183 days. No corpora lutea from earlier ovulations were observed in gilts laparoscoped after their first detected oestrus. During the 30-day period before first oestrus the mean daily progesterone levels varied between 32 and 329 pmol/l. The average levels of oestradiol-17β varied between 15.6 and 30.8 pmol/l. There was no tendency for the oestradiol-17β level to rise before onset of first pro-oestrus. The average levels of LH varied between 0.15 and 0.94 μg/l. The statistical analyses revealed no significant relationship between the level of the hormones studied and onset of first oestrus. The mean progesterone levels during the first and second oestrous cycles were almost identical, however. Oestradiol-17β increased gradually during pro-oestrus, reaching maximum levels before onset of oestrus and thereafter decreasing sharply to values around 30 pmol/l. The oestradiol-17β levels were higher at the second than at the first pro-oestrous period. The concentrations of plasma LH rose sharply with declining plasma levels of oestradiol-17β. The duration of elevated plasma LH levels (> 1 μg/l) was, on average, 26 h and the LH levels were higher during the first oestrus than during the second oestrus. The first rise in progesterone was observed 11-29 h after the LH levels had decreased to concentrations below 1 μg/l. © 1982 | 10.1016/0378-4320(82)90044-6 |
pubmed_311_5885 | Characterization of single cell metabolism is imperative for understanding subcellular functional and biochemical changes associated with healthy tissue development and the progression of numerous diseases. However, single-cell analysis often requires the use of fluorescent tags and cell lysis followed by genomic profiling to identify the cellular heterogeneity. Identifying individual cells in a noninvasive and label-free manner is crucial for the detection of energy metabolism which will discriminate cell types and most importantly critical for maintaining cell viability for further analysis. Here, we have developed a robust assay using the droplet microfluidic technology together with the phasor approach to fluorescence lifetime imaging microscopy to study cell heterogeneity within and among the leukemia cell lines (K-562 and Jurkat). We have extended these techniques to characterize metabolic differences between proliferating and quiescent cells-a critical step toward label-free single cancer cell dormancy research. The result suggests a droplet-based noninvasive and label-free method to distinguish individual cells based on their metabolic states, which could be used as an upstream phenotypic platform to correlate with genomic statistics. © 2018 International Society for Advancement of Cytometry. | 10.1002/cyto.a.23673 |
pubmed_291_19489 | BACKGROUND
Recurrent pleomorphic adenoma (RPA) is an uncommon and challenging disease. The aim of this study was to review the clinical information obtained by examining RPA patients, to determine its histomorphological features and to verify the expression of the Mcm-2 markers of cell proliferation and the expression of p-53 in pleomorphic adenoma (PA), RPA, and RPA with malignant transformation (TRPA).
METHODS
A total of 10 cases of PA and 29 cases of RPA were examined in detail for the presence of nodules and their histomorphological features. Cell proliferation and expression of p-53 were detected by the immunohistochemical technique using the antibodies against Mcm-2 and p-53.
RESULTS
Histopathologically, RPA is very similar to PA; the only difference found was that all the cases of RPA were multinodular. When comparing primary and recurrent tumor, no significant difference was found in terms of cell proliferation and the expression of p-53; however, in the RPA with areas of malignant transformation there was an increased expression of these proteins.
CONCLUSION
This study showed that recurrences were multinodular, with nodules varying in numbers and sizes. No significant difference in histological features was found between RPA and PA. Moreover, the immunohistochemical study showed a low expression of p-53 and Mcm-2 in PA and RPA and an increased expression of these proteins in the RPA with areas of malignant transformation. | 10.1111/j.1600-0714.2010.00956.x |
pubmed_814_7830 | Anthropogenic contamination of Cd, Cr, Cu, Ni, Pb and Zn in riverbed sediments of the Pampean area (Matanza-Riachuelo Basin, MRB), Argentina, was evaluated using various indices: Geo-accumulation Index (Igeo), Contamination Factor (Cf), Metal Pollution Index (MPI), Pollution Load Index (PLI) and Contamination Degree (Cdeg). A database based on previous samplings of heavy metal concentrations at different sites in the Upper, Middle and Lower MRB was used. The Igeo and Cf values are calculated using selected local background (Pristine Pampean loess, LZB), and global average shale values (ASTW). Paired Igeo and Cf results with LZB and ASTW fall in dissimilar classes, especially in respect of Cd. In turn, MPI, PLI and Cdeg show similar results, as they do not have the same degree of confidence as Igeo and Cf. The Upper Basin, mainly rural, shows the following profile of sediment contamination: Cd > Ni > Cu ≫ Pb > Zn > Cr. The Middle Basin, which is at the periphery of a very industrialised and urban area, displays the following contamination profile for both Igeo and Cf: Cu > Pb > Zn > Ni > Cd > Cr. Conversely, in the Lower Basin, where land-use is urban/industrial, the levels of metal contamination are higher and appear in this order: Cr > Pb > Cu > Zn > Ni > Cd. Cadmium, Cu, Ni and Zn have shown no significant oral and/or dermal HQ nor carcinogenic risk but the potential risk posed by Cr and Pb must be taken into account. Maximum and mean values of Cr total carcinogenic risk (TCR) as well as Ni TCR also point to a health risk to children in the Lower Basin Area. All the data analysed confirm that industrial and urban growth without land-use planning, and a poor environmental legislation until the beginning of the 21st century, have not provided the necessary framework for sustainable development in the MRB. | 10.1016/j.envres.2021.110979 |
pubmed_433_23997 | BACKGROUND
Infectious mononucleosis (IM) is a common adverse presentation of primary infection with Epstein-Barr virus (EBV) in adolescence and later, but is rarely recognized in early childhood where primary EBV infection commonly occurs. It is not known what triggers IM, and also not why IM risk upon primary EBV infection (IM attack rate) seemingly varies between children and adolescents. IM symptoms may be severe and persist for a long time. IM also markedly elevates the risk of Hodgkin lymphoma and multiple sclerosis for unknown reasons. The way IM occurrence depends on age and sex is incompletely described and hard to interpret etiologically, because it depends on three quantities that are not readily observable: the prevalence of EBV-naϊve persons, the hazard rate of seroconverting and the attack rate, i.e. the fraction of primary EBV infections that is accompanied by IM. We therefore aimed to provide these quantities indirectly, to obtain epidemiologically interpretable measures of the dynamics of IM occurrence to provide etiological clues.
METHODS AND FINDINGS
We used joint modeling of EBV prevalence and IM occurrence data to provide detailed sex- and age-specific EBV infection rates and IM attack rates and derivatives thereof for a target population of all Danes age 0-29 years in 2006-2011. We demonstrate for the first time that IM attack rates increase dramatically rather precisely in conjunction to typical ages of puberty onset. The shape of the seroconversion hazard rate for children and teenagers confirmed a priori expectations and underlined the importance of what happens at age 0-2 years. The cumulative risk of IM before age 30 years was 13.3% for males and 22.4% for females. IM is likely to become more common through delaying EBV infection in years to come.
CONCLUSIONS
The change in attack rate at typical ages of puberty onset suggests that the immunologic response to EBV drastically changes over a relatively short age-span. We speculate that these changes are an integrated part of normal sexual maturation. Our findings may inform further etiologic research into EBV-related diseases and vaccine design. Our methodology is applicable to the epidemiological study of any infectious agent that establishes a persistent infection in the host and the sequelae thereof. | 10.1371/journal.pone.0226436 |
pubmed_51_7183 | Abnormal decision-making has been described as a key-concept to understand some behavioral disturbances in schizophrenia. However, whether schizophrenia patients display impairments in profitable decision-making on experimental designs is still controversial (1) to assess performance on decision-making paradigms under ambiguity and under risk conditions in a large sample of schizophrenia patients and (2) to study the impact of clinical variables on decision-making performance in schizophrenia. The Iowa gambling task (IGT) and the game of dice task (GDT) were administered to assess, respectively, decision-making under ambiguity and under risk in 63 schizophrenia patients and 67 healthy controls. In addition, clinical variables (e.g., schizophrenic symptoms, self-reported depression, and impulsivity) were evaluated using appropriate questionnaires the same day. Pharmacological treatments were reported. Schizophrenia patients had impaired performances on both IGT and GDT tasks. No correlation between the decision-making tasks performance and clinical variables was found. Lower gains on the GDT were associated with executive dysfunctioning in schizophrenia. These findings give evidence that schizophrenia patients display impairments in both decision-making under ambiguity and under risk. | 10.1007/s00406-012-0330-y |
pubmed_427_1333 | Owing to the very low levels of adenine in the intracellular and extracellular compartments and its low excretion by the kidney, no method of estimation was, until now, sufficiently specific and sensitive to determine precisely quantities of the order of 1 nanomole. The method of "isotopic enzymatic kinetic dilution" proposed by Newsholme et Taylor, has been used. The kinetic conditions of the reaction catalysed by adenine-phosphoribosyltransferase are favourable, [in particular KM (adenine) is very low, about 2.1(-6) M] and are not very sensitive to the action of other effectors. The technique proposed permits one to determine quantities of adenine between 0.05 and 1.2 nmole, i.e. 0.007 to 0.16 mug, with a precision of about 5 p. cent. Easy to carry out, it is useful in large series. Normal values in man of adenine thus measured (15 adult subjects) were as follows: Plasma: 1.13 +/- 0.41 nmoles.ml(-1), i.e. 0.152 +/-0 0.055 mug.ml(-1). Red cells: 3.65 +/- 0.87 nmoles.ml(-1), i.e. 0.493 +/- 0.117 mug.ml(-1). Urine (24 hour excretion): 11.41 +/- 1.24 mumoles, i.e. 1.54 +/- 0.17 mg. | pubmed_427_1333 |
pubmed_1136_20994 | BACKGROUND
Previous epidemiological, animal and human data report that lycopene has a protective effect against ultraviolet radiation (UVR)-induced erythema.
OBJECTIVES
We examined whether tomato paste--rich in lycopene, a powerful antioxidant--can protect human skin against UVR-induced effects partially mediated by oxidative stress, i.e. erythema, matrix changes and mitochondrial DNA (mtDNA) damage.
METHODS
In a randomized controlled study, 20 healthy women (median age 33 years, range 21-47; phototype I/II) ingested 55 g tomato paste (16 mg lycopene) in olive oil, or olive oil alone, daily for 12 weeks. Pre- and postsupplementation, UVR erythemal sensitivity was assessed visually as the minimal erythema dose (MED) and quantified with a reflectance instrument. Biopsies were taken from unexposed and UVR-exposed (3 × MED 24 h earlier) buttock skin pre- and postsupplementation, and analysed immunohistochemically for procollagen (pC) I, fibrillin-1 and matrix metalloproteinase (MMP)-1, and by quantitative polymerase chain reaction for mtDNA 3895-bp deletion.
RESULTS
Mean ± SD erythemal D(30) was significantly higher following tomato paste vs. control (baseline, 26·5 ± 7·5 mJ cm(-2); control, 23 ± 6·6 mJ cm(-2); tomato paste, 36·6 ± 14·7 mJ cm(-2); P = 0·03), while the MED was not significantly different between groups (baseline, 35·1 ± 9·9 mJ cm(-2); control, 32·6 ± 9·6 mJ cm(-2); tomato paste, 42·2 ± 11·3 mJ cm(-2)). Presupplementation, UVR induced an increase in MMP-1 (P = 0·01) and a reduction in fibrillin-1 (P = 0·03). Postsupplementation, UVR-induced MMP-1 was reduced in the tomato paste vs. control group (P = 0·04), while the UVR-induced reduction in fibrillin-1 was similarly abrogated in both groups, and an increase in pCI deposition was seen following tomato paste (P = 0·05). mtDNA 3895-bp deletion following 3 × MED UVR was significantly reduced postsupplementation with tomato paste (P = 0·01).
CONCLUSIONS
Tomato paste containing lycopene provides protection against acute and potentially longer-term aspects of photodamage. | 10.1111/j.1365-2133.2010.10057.x |
pubmed_996_10371 | Embryo transfer results after a 2 to 4 day period of embryo culture were compared. Two thousand two hundred ninety-seven ETs, performed in 1991 and 1992, were analyzed. Ongoing pregnancy rates after 2, 3, or 4 days of embryo culture were 23.3%, 21.9%, and 26.4%, respectively. Multiple pregnancy rates were 36.2%, 38.8%, and 32.6% per ongoing pregnancy for the three groups, respectively. The implantation rate of 73 cavitating morulae on day 4 was surprisingly high (41%) compared with that of other developmental stages. Transfer after 4 days of culture gives the ability to recognize embryos with a very high implantation potential. | 10.1016/s0015-0282(16)56715-6 |
pubmed_49_3656 | Relationship existing between enamel resistance (by developed colorimetric technique) and previous experience of caries and with further incidence, at a term of a year, was studied in schoolchildren aged 6, 8, 10 and 12 years. The study comprised 336 children in 1985-1986 period and 385 children in 1985-1987 period. Non significant positive correlation was found between values of colorimetric test and previous experience of caries; but, certainly, positive correlation was found with further incidence on permanent dentition. It is concluded that colorimetric test is useful for the selection of children with a very susceptible enamel, as well as for the prognosis of cariogenic activity valued together with other parameters. | pubmed_49_3656 |
pubmed_978_5963 | The research described here is part of a larger risk assessment project to aid the U.S. Environmental Protection Agency (EPA) in its review of the primary National Ambient Air Quality Standard for lead. The methodology can be applied to many situations in which a policy decision about a toxic substance is required in the face of incomplete data. Numerical results are presented for three potentially adverse lead-induced effects of interest to EPA: elevated erythrocyte protoporphyrin (EP), hemoglobin (Hb) decrement, and intelligence quotient (IQ) decrement. | 10.1111/j.1539-6924.1989.tb01240.x |
pubmed_154_12218 | An inflammatory response occurs during cardiac surgery involving cardiopulmonary bypass. Matrix metalloproteinase-9 is an enzyme involved in cytokine processing and leucocyte extravasation. It is secreted as a pro-enzyme in response to several inflammatory mediators and is inhibited by endogenous tissue inhibitor of metalloproteinase-1. The interaction between matrix metalloproteinase-9 and its inhibitor during cardiopulmonary bypass is not known. We measured tumour necrosis factor alpha, and matrix metalloproteinase-9 and its inhibitor using enzyme immunoassay at three time points in 20 patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass. Tumour necrosis factor and matrix metalloproteinase concentrations increased in all patients during bypass (both p < 0.0001), whereas the inhibitor in contrast, decreased (p < 0.0001). We conclude that matrix metalloproteinase-9 is released as part of the inflammatory response during cardiac surgery. Levels of the endogenous inhibitor of metalloproteinase, however, show a different pattern of release, suggesting independent regulation. | 10.1046/j.1365-2044.2002.02625.x |
pubmed_198_6704 | One hundred and one pregnant girls aged under 18 years were interviewed to collect information about the development of their sexual awareness, attitudes towards relationships, and about their social context. The data show that the girls were likely to come from homes where the parents were divorced, where the mother married when she was under 21 years of age, and where her first child was conceived out of wedlock. Altogether 76 of these pregnant girls first had intercourse before they were 16 years old. The younger the girl at first intercourse the sooner it occurred in the relationship and for almost half of the girls first intercourse was unplanned. Although almost half used contraception on the first occasion, only one third of the girls used contraceptives regularly. Most expressed the wish that they had delayed intercourse until they were older. | 10.1136/adc.63.4.373 |
pubmed_952_8864 | Childhood accidents in Dar es Salaam are among the ten top causes of morbidity. After eradication of protein energy malnutrition and infectious disease, accidents will be the leading cause of morbidity and mortality as it has occurred in developed countries. Accidents were the fifth cause of admission into paediatric wards totalling 589 cases out of 12,375 admissions. Of the accident cases, 37% were due to poisoning; 27% to trauma; 24% to burns; 7% to foreign bodies and 6% to other causes. Lack of parental care, low socio-economic status and large families were among important causal factors. There is need to create awareness of hazards of accidents to prevent these unnecessary accidents of childhood. | pubmed_952_8864 |
pubmed_18_8557 | Phase-vanishing reactions are triphasic reactions, which involve a reagent, a liquid perfluoroalkane, and a substrate. In a phase-vanishing reaction with PTFE tape as the phase screen instead of a liquid perfluoroalkane, there is no limitation related to the density of a phase and the denser phase can be in the top layer. The reactions were faster compared to traditional PV reactions, and it was possible to carry out sequential and tandem reactions and reactions under a reflux. | 10.1021/ol901450h |
pubmed_1097_21169 | BACKGROUND
Gender-based violence is an important risk factor for adverse reproductive health (RH). Community-level violence may inhibit young women's ability to engage in safer sexual behaviors due to a lack of control over sexual encounters. Few studies examine violence as a contextual risk factor.
METHODS
Using nationally representative data from five African countries, the association between community-level physical or sexual intimate partner violence (IPV) and the circumstances of first sex (premarital or marital) among young women (ages 20-29) was examined.
RESULTS
In Mali, and Kenya bivariate analyses showed that young women who had premarital first sex were from communities where a significantly higher percentage of women reported IPV experience compared to young women who had marital first sex. Multivariate analyses confirmed the findings for these two countries; young women from communities with higher IPV were significantly more likely to have had premarital first sex compared to first sex in union. In Liberia, community-level IPV was associated with a lower risk of premarital sex as compared to first sex in union at a marginal significance level. There was no significant relationship between community-level IPV and the circumstances of first sex in the Democratic Republic of Congo or Zimbabwe.
CONCLUSION
These findings indicate that context matters for RH. Individualized efforts to improve RH may be limited in their effectiveness if they do not acknowledge the context of young women's lives. Programs should target prevention of violence to improve RH outcomes of youth. | 10.1186/1742-4755-7-11 |
pubmed_265_10257 | Urinary exertional incontinence is a very common condition which requires a broad range of therapeutic options being available. Besides, the creation of specialised units in urology is now evident, one of the areas involved being Urogynaecology. To focus the issue of female urinary incontinence, the following should be considered: to begin with, treatment is not imperative, patients must be evaluated on a case-by-case basis, the least invasive principle must prevail, diagnosis must be early, and it should be taken into account that primary and secondary prevention is both possible and necessary. A working pattern was designed accordingly, to sustain therapeutic decisions, which consisted in a detailed anamnesis, complete examination and application of an established diagnostic-therapeutic algorithm. Even so, a therapeutic, medical or surgical decision will be chosen and patients will be monitored at one, four and sixteen months after completion of treatment. To achieve good results in the management of female urinary exertional incontinence it is essential to include a large number of patients. In fact, the key is to establish a close collaboration with the gynaecologists. | pubmed_265_10257 |
pubmed_293_20549 | BACKGROUND
Many young children in developing countries do not reach their developmental potential. Traditional methods for assessing developmental outcome are time consuming, thus, physiological measures that can contribute to the prediction of developmental outcomes in high risk groups have been suggested. Vagally mediated heart rate variability (vmHRV) is considered a neurophysiological or peripheral proxy for prefrontal and executive functioning and might serve as a supplement for traditional measurements of developmental status and as a potential useful risk indicator.
AIM
In the present study, we wanted to describe the vmHRV in Nepalese infants and relate it to the Bayley Scales of infant and toddler development, 3. edition (Bayley-III) subscales.
METHODS
600 Nepalese infants were included in the study. At 6-11 and 17-24 months, we measured neurodevelopmental and socio-emotional outcomes by the Bayley-III. Inter-beat intervals were recorded at two measurement points when the children were 17-24 months.
RESULTS
There was a high intraclass correlation between HRV indices generated from the two measurement points. No significant associations between vmHRV and Bayley-III sub scales were found at any time.
CONCLUSION
This study is the first to describe vmHRV in healthy infants and the relationship between Bayley-III scores. Our results suggest that vmHRV is not associated with measures of general development in infancy. | 10.3389/fnins.2019.00411 |
pubmed_158_21810 | Acidic and basic fibroblast growth factors (FGF-1 and FGF-2) are mitogenic polypeptides that may play a role in autocrine and paracrine growth control of malignant tumours. We have examined the expression of FGF-1 and FGF-2 in a series of 41 colorectal tumours (24 adenomas, 17 adenocarcinomas) and 50 gastric adenocarcinomas (23 intestinal, 27 diffuse), using immunohistochemistry. Whereas the FGF-1 distribution was cytoplasmic, FGF-2 was restricted to the nuclei of the epithelial cells. FGF-1 immunoreactivity was detected in all samples (100 per cent), whereas FGF-2 immunoreactivity was seen in 17 adenomas (71 per cent), 13 colorectal carcinomas (76 per cent), and 29 gastric carcinomas (58 per cent). Compared with the normal mucosa, FGF-1 was overexpressed in 42 per cent of colorectal adenomas, 76 per cent of colorectal cancers, and 54 per cent of gastric cancers. Conversely, FGF-2 expression was reduced in 16 (66 per cent), 8 (47 per cent), and 40 (80 per cent) adenomas and colorectal and gastric samples, respectively. We found a significant correlation only between reduced FGF-2 and gastric tumour grade. These data indicate that FGF-1 overexpression occurs in a large proportion of human colorectal and gastric cancers. This may play a role in the progression of these tumours. The topographic variation in FGF-2 expression between normal (nuclear) and tumour (cytoplasmic) cells implies a corresponding functional change that may in turn facilitate tumour growth. | 10.1002/(SICI)1096-9896(199701)181:1<39::AID-PATH711>3.0.CO;2-C |
pubmed_642_15435 | This work reports a multifunctional nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for targeting tumor therapy. Doxorubicin (DOX) was loaded into HMSNs and blocked with cytochrome C conjugated lactobionic acid (CytC-LA) via redox-cleavable disulfide bonds and pH-disassociation boronate ester bonds as intermediate linkers. The CytC-LA was used both as sealing agent and targeting motif. A series of characterizations demonstrated the successful construction of the drug delivery system. The system demonstrated pH and redox dual-responsive drug release behavior in vitro. The DOX loading HMSNs system displayed a good biocompatibility, which could be specifically endocytosed by HepG2 cells and led to high cytotoxicity against tumor cells by inducing cell apoptosis. In vivo data (tumor volume, tumor weight, terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining) proved that the system could deliver DOX to tumor site with high efficiency and inhibit tumor growth with minimal toxic side effect. | 10.1093/rb/rbw045 |
pubmed_151_12285 | BACKGROUND
Oral lacerations represent a unique challenge for anesthesia in the emergency department. Many options exist for local anesthesia, but these options are often associated with pain from injections or anxiety from anticipated needle injection.
CASE SERIES
We introduce a novel and needleless approach to achieving local anesthesia for oral mucosa repair by dripping injectable lidocaine directly onto mucosal wounds prior to repair. This method is well tolerated and achieves appropriate anesthesia without undesirable side effects. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Dripped injectable lidocaine may be an alternative method for mucosal anesthesia in the pediatric population. | 10.1016/j.jemermed.2018.05.025 |
pubmed_908_25869 | BACKGROUND
Adjustable-loop cortical buttons for femoral fixation of bone-tendon-bone grafts have potential advantages over interference screw fixation; however, these devices have not been benchmarked biomechanically against interference screws. Purpose/Hypothesis: The purpose was to compare the time zero biomechanical properties of commercially available, adjustable-loop cortical button and metallic interference screws for femoral fixation of bone-tendon-bone grafts. It was hypothesized that no significant differences would be found in biomechanical properties between fixation techniques.
STUDY DESIGN
Controlled laboratory study.
METHODS
Adjustable-loop cortical buttons (n = 8) and metallic interference screws (n = 8) were used to fix matched pairs of human bone-tendon-bone allografts in porcine distal femurs. These constructs were preconditioned (10 N to 50 N at 1 Hz, 10 cycles), subjected to cyclic loading (50 N to 250 N at 1 Hz, 500 cycles), and then pulled to failure at 20 mm/min.
RESULTS
The loads to failure (mean ± SD, 700 ± 256 N vs 688 ± 215 N, P = .92) and linear stiffnesses (219 ± 48 N/mm vs 218 ± 49 N/mm, P = .97) for the adjustable-loop cortical button and metallic interference screws, respectively, were not significantly different. Cyclic displacement was higher in the adjustable-loop cortical button group (2.1 ± 0.6 mm vs 1.3 ± 0.4 mm, P = .01). The mechanism of failure was different between groups, with bone block slippage occurring most commonly in the interference screw group (n = 5) and fracture of the bone block through the suture hole occurring most commonly in the adjustable-loop cortical button group (n = 6).
CONCLUSION
Adjustable-loop cortical buttons and interference screws have similar time zero failure loads, although cyclic displacement was higher with the adjustable-loop cortical buttons. The mean difference in displacement was less than 1 mm compared with the interference screw.
CLINICAL RELEVANCE
Adjustable-loop cortical buttons may be an acceptable alternative to an interference screw for femoral fixation of bone-tendon-bone grafts in anterior cruciate ligament reconstruction. The clinical relevance of the observed differences in cyclic displacement is unknown and should be evaluated in future studies. | 10.1177/0363546518771365 |
pubmed_492_1564 | We present two experiments investigating the role of emotions concerning technological and natural hazards. In the first experiment, technological hazards aroused stronger emotions, and were considered to be riskier than natural hazards. No differences were found between the texts versus audio presentations. However, the presence of pictures aroused stronger emotions and increased the perceived risk. Emotions play a mediating role between hazard types and perceived risk, as well as between pictures and perceived risk. The second experiment adopted real-world materials from webpages and TV. Emotions again play a mediating role between pictorial information and risk perception. Moreover, specific emotions were found to be associated with different types of action tendencies. For example, loss-based emotions (e.g., fear, regret) tend to lead to prevention strategies, whereas ethical emotions (e.g., anger) lead to aggressive behavior. We also find that loss-based emotions in the technical hazard scenario trigger more coping strategies (from prevention to retaliation) than in the natural hazard scenario. | 10.1111/j.1539-6924.2010.01530.x |
pubmed_24_6930 | Monoblock appliances were used in combination with intermaxillary elastics for treatment of adult skeletal Class III patients. The patients showed predisposing upper incisors problems, significant mobility in patient 1 and root resorption in patient 2, which contraindicated direct intrusion of the incisors. Using the monoblock with selective extrusion of the molars, a clockwise rotation was induced to reduce overbite and to achieve a better profile. It was also possible to reduce the excessive force to the upper incisors during and after treatment, which improved incisor mobility to a physiologic extent (patient 1) and prevented further progression of root resorption (patient 2). Stability was high after the 2-year follow-up, which suggests a stable vertical control approach by using the monoblock appliance in combination with a fixed appliance in adults. | 10.1043/0003-3219(2006)076[0226:VCBCAM]2.0.CO;2 |
pubmed_846_9197 | The tremor produced by muscarinic cholinomimetics is believed to originate in the neostriatum but the efferent pathways are unknown. The intensity and frequency of tremor induced by tremorine was measured in the hindlegs of rats with unilateral basal ganglia lesions. A kainic acid lesion of one neostriatum reduced tremor intensity in the contralateral leg (CL). Unilateral electrolesions of the globus pallidus and nucleus accumbens had no effects on tremor. Both entopeduncular and subthalamic nuclei lesions reduced the frequency and intensity of tremorine tremor in the CL leg. The subthalamic lesion also increased tremor intensity and frequency in the ipsilateral leg. Lesions were made in some brain areas that receive basal ganglia efferent projections. Peak tremor intensity and frequency in both legs was greatly reduced by unilateral decortication. Unilateral lesions of the habenula, red nucleus and pedunculopontine nucleus had no effects on tremor intensity but reduced peak tremor frequency. Lesions of the substantia nigra and periaqueductal gray area had no effects on tremor. Unilateral removal of the superior colliculus reduced tremor intensity in both legs. The findings suggest that intensity and frequency of tremor are influenced by different basal ganglia efferent pathways; intensity involves strio-entopeduncular-cortical projections and frequency is determined by projections to midbrain and brainstem. The superior colliculus, with many muscarinic receptors, may be a direct target area for tremorine. | 10.1016/0022-510x(82)90030-2 |
pubmed_890_5437 | Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). We report the baseline cardiovascular characteristics of 2,238 participants by using the data of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) study. The cohort comprises 5 subcohorts according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), polycystic kidney disease (PKD), and unclassified. The average estimated glomerular filtration rate (eGFR) was 50.5 ± 30.3 mL/min⁻¹/1.73 m⁻² and lowest in the DN subcohort. The overall prevalence of previous CVD was 14.4% in all patients, and was highest in the DN followed by that in the HTN subcohort. The DN subcohort had more adverse cardiovascular risk profiles (higher systolic blood pressure [SBP], and higher levels of cardiac troponin T, left ventricular mass index [LVMI], coronary calcium score, and brachial-ankle pulse wave velocity [baPWV]) than the other subcohorts. The HTN subcohort exhibited less severe cardiovascular risk profiles than the DN subcohort, but had more severe cardiovascular risk features than the GN and PKD subcohorts. All these cardiovascular risk profiles were inversely correlated with eGFR. In conclusion, this study shows that the KNOW-CKD cohort exhibits high cardiovascular burden, as other CKD cohorts in previous studies. Among the subcohorts, the DN subcohort had the highest risk for CVD. The ongoing long-term follow-up study up to 10 years will further delineate cardiovascular characteristics and outcomes of each subcohort exposed to different risk profiles. | 10.3346/jkms.2017.32.2.231 |
pubmed_637_22317 | Regulation of sucrose-starch interconversion in plants is important to maintain energy supplies necessary for viability and growth. Arabidopsis mutants were screened for aberrant responses to sucrose to identify candidates with a defect in the regulation of starch biosynthesis. One such mutant, fpgs1-4, accumulated substantial amounts of starch in non-photosynthetic cells. Dark-grown mutant seedlings exhibited shortened hypocotyls and accumulated starch in etioplasts when supplied with exogenous sucrose/glucose. Similar starch accumulation from exogenous sucrose was observed in mutant chloroplasts, when photosynthesis was prevented by organ culture in darkness. Molecular genetic analyses revealed that the mutant was defective in plastidial folylpolyglutamate synthetase, one of the enzymes engaged in folate biosynthesis. Active folate derivatives are important biomolecules that function as cofactors for a variety of enzymes. Exogenously supplied 5-formyl-tetrahydrofolate abrogated the mutant phenotypes, indicating that the fpgs1-4 mutant produced insufficient folate derivative levels. In addition, the antifolate agents methotrexate and 5-fluorouracil induced starch accumulation from exogenously supplied sucrose in dark-grown seedlings of wild-type Arabidopsis. These results indicate that plastidial folate suppresses starch biosynthesis triggered by sugar influx into non-photosynthetic cells, demonstrating a hitherto unsuspected link between plastidial folate and starch metabolism. | 10.1093/pcp/pcx076 |
pubmed_484_117 | A 59-year-old woman with chronic renal failure due to type 2 diabetes mellitus (DM) is presented. Her father and a brother had a history of brain tumor. Her blood urea nitrogen and serum creatinine levels were 102 mg/dl and 4.5 mg/dl, respectively. Her serum Ca(2+) and Pi were within the normal range (9.4 mg/dl and 5.4 mg/dl, respectively). Her intact parathyroid hormone (PTH) level was 1 730 000 pg/ml. A (99m)Tc-methoxy-isobutylisonitrile scintigraphy showed high uptake in three parathyroid glands. A magnetic resonance image showed microadenoma in the pituitary gland. The serum gastrin level was high. Genetic examination revealed a mutation of the MEN1 gene (894-9 G --> A). From these findings, she was diagnosed with multiple endocrine neoplasia (MEN) type 1. Subsequently, a parathyroidectomy was performed successfully, a parathyroid gland was transplanted to her right forearm, and her serum Ca(2+) level was controlled at 8.5-9.0 mg/dl. It is very important to identify MEN1 if an end-stage renal disease (ESRD) patient has hyperparathyroidism with multigland involvement. Examination of the MEN1 gene may be valuable to make an accurate diagnosis and choose the appropriate therapy in some ESRD patients with hyperparathyroidism. | 10.1007/s10157-004-0318-7 |
pubmed_240_4393 | The process of new blood vessel formation, or angiogenesis, has become an important target for therapeutic intervention in many cancers, including metastatic colorectal cancer (mCRC). The growth and metastasis of primary tumors is dependent upon their ability to acquire and maintain an adequate blood supply; however, angiogenesis in tumors is an irregular process leading to chaotic and hyperpermeable vessels that may result in increased intratumoral pressure and poor exchange of macromolecules and oxygen. It has been hypothesized that inhibition of angiogenesis in tumors can both impair the formation of new tumor blood vessels and possibly 'normalize' the existing tumor vasculature, causing a more efficient delivery of cytotoxic chemotherapies (CTs). Over the last decade, therapies that target vascular endothelial growth factor (VEGF) have become a component of treatment for several cancers. In particular, the combination of bevacizumab with established chemotherapeutic regimens for mCRC has been shown to improve overall and progression-free survival, as well as response rates, over CT alone. Agents that target various members of the VEGF family, as well as signaling by the VEGF receptors and their tyrosine kinase components, are currently under development and evaluation in clinical trials. Integration of these new therapies into the treatment of mCRC will ultimately increase the available therapeutic options for patients. Still, many challenges remain, including identifying and validating relevant biomarkers to guide the optimal use of antiangiogenesis agents. | 10.1177/1758834012454464 |
pubmed_1122_12646 | RATIONALE AND OBJECTIVES
Three models of experimentally induced liver cirrhosis were evaluated for MRI research on chronic liver disease. The influence of different histopathologic changes in liver fibrosis and cirrhosis on relaxation times and signal intensities was studied in vitro and in vivo.
METHODS
Liver fibrosis and cirrhosis in rats was induced by oral or subcutaneous administration of carbon tetrachloride (CCl4) or by thioacetamide (TAA) in drinking water. On histology, the degree of liver fibrosis and cirrhosis, fatty infiltration, iron accumulation, and inflammatory changes were measured semiquantitatively. The amount of connective tissue was quantitatively determined by morphometry. The results were correlated with T1 and T2 relaxation times and signal intensities of the liver studied in vitro by relaxometry and in vivo by MRI.
RESULTS
In both groups with CCl4 administration, histology revealed different degrees of liver fibrosis and cirrhosis. Subcutaneous injection of CCl4 also resulted in increased fatty infiltration. On the contrary, TAA produced complete liver cirrhosis in all animals. Overall, there was a good correlation between the liver T2 relaxation time and the amount of connective tissue in liver fibrosis and cirrhosis. However, the degree of liver fibrosis and cirrhosis was also strongly correlated with the degree of inflammatory changes. In the group with CCl4 administration, there was a good correlation between the fatty infiltration and the T1 relaxation time, as well as with the liver signal intensity on the T1-weighted gradient echo sequence. An increased iron accumulation was also correlated with the degree of liver fibrosis/cirrhosis; however, there was no significant influence of the iron on relaxation times or signal intensities.
CONCLUSIONS
The TAA model is easier to perform and more reliable in liver cirrhosis induction than the CCl4 models. Although there is a positive correlation between the T2 relaxation times and the degree of liver fibrosis/cirrhosis, this probably results from the associated inflammatory changes and is not caused by the increased amount of connective tissue. | 10.1097/00004424-199905000-00006 |
pubmed_1142_2548 | The emergence of the novel SARS-CoV-2 and COVID-19 has brought into sharp focus the need for a vaccine to prevent this disease. Vaccines have saved millions of lives since their introduction to the public over 200 years ago. The potential for vaccination reached new heights in the mid-20th century with the development of technologies that expanded the ability to create novel vaccines. Since then, there has been continued technological advancement in vaccine development. The resulting platforms provide the promise for solutions for many infectious diseases, including those that have been with us for decades as well as those just now emerging. Each vaccine platform represents a different technology with a unique set of advantages and challenges, especially when considering manufacturing. Therefore, it is essential to understand each platform as a separate product and process with its specific quality considerations. This review outlines the relevant platforms for developing a vaccine for SARS-CoV-2 and discusses the advantages and disadvantages of each. | 10.1080/21645515.2021.1911204 |
pubmed_120_22717 | Increased brain natriuretic peptide (BNP) expression in the ventricles antedates elevated blood pressure (BP) in experimental studies. We hypothesized that higher plasma BNP levels in nonhypertensive individuals may be associated with a greater likelihood of future BP increase and/or hypertension. We evaluated the relations of plasma BNP to longitudinal BP tracking and incidence of hypertension in 1801 nonhypertensive Framingham Heart Study participants (mean age, 56 years; 57% women) by using gender-specific multivariable logistic regression. Progression of BP stage was defined as an increment of one or more BP categories, as classified by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Hypertension was defined as a systolic BP > or =140 or diastolic BP > or =90 mm Hg or use of antihypertensive medications. On follow-up 4 years from baseline, progression of BP category was observed in 36.2% of men and 33.1% of women; hypertension developed in 16.4% of men and 15.5% of women. In multivariable models adjusting for known risk factors, elevated plasma BNP level was associated with increased risk of BP progression in men (odds ratio of 1.15 for trend across categories, P=0.046) but not in women (P=0.82). There were no significant trends of increasing incidence of hypertension across BNP categories in men or women. In our community-based sample, higher plasma BNP levels were associated with increased risk of BP progression in men but not women. Additional investigations are warranted to confirm these findings and elucidate the basis for these gender-related differences. | 10.1161/01.HYP.0000061116.20490.8D |
pubmed_457_24499 | The function of metformin in colorectal cancer (CRC) patients with diabetes mellitus (DM) remains a controversial topic because studies are increasingly focusing on epidemiologic features. We examined Notch1/Hes1 signaling in CRC with DM (DM-CRC) and investigated alterations in signaling caused by metformin treatment. For this purpose, information on pathological characteristics was collected from each patient. The proliferation of epithelium labeled with proliferating cell nuclear antigen and the differentiation of goblet cells were investigated using immunohistochemistry and periodic acid-Schiff staining, respectively. The factors involved in Notch1/Hes1 signaling were detected using qRT-PCR and western blot. In our study, we found that lymphatic metastasis, pTNM staging, and the carcinoembryonic antigen level were significantly different between groups. The depth of crypts and the rate of proliferating cell nuclear antigen-positive cells were distinctly higher in DM-CRC and patients who were managed with insulin. Moreover, the goblet cell differentiation rate was decreased in DM-CRC. The expression of Dll1, Notch1, Math1, and RBP-Jκ was increased in DM-CRC, whereas the expression of Dll4 and Hes1 was decreased in this group in normal tissue. In CRC tissue, the expression of Dll1 and Notch1 was clearly higher than that in DM-CRC. Furthermore, the trend in these changes was aggravated with insulin management and alleviated with metformin treatment. In conclusion, the abnormal cell proliferation and differentiation observed in DM-CRC are correlated with overactivated Notch1/Hes1 signaling, which is potentially relieved by metformin treatment. | 10.1097/CAD.0000000000000483 |
others_403_4493 | The effects of β-blockade on muscle utilization of glycogen and triglycerides, as well as potassium metabolism, were studied in eight healthy male subjects performing long-duration exercise to exhaustion. Subjects were studied after treatment with either placebo (PLAC), β1-selective (atenolol, 100 mg/day, AT), or nonselective β-blockade (nadolol, 80 mg/day, NAD) each for 1 wk according to a randomized, double-blind, cross-over design. NAD and AT caused identical decreases in exercise heart rates, but endurance (71 ± 8 min with PLAC) decreased significantly more with NAD (-33 ± 4%) than with AT (-14 ± 6%). Muscle glycogen breakdown, taking exercise time into account, was unaffected by treatment. In contrast, muscle triglyceride utilization was completely blocked by NAD whereas it was unchanged with AT as compared to PLAC. Adipose tissue lipolysis was inhibited to a similar extent by the two β-blockers. Serum potassium increased to higher levels at exhaustion and muscle potassium decreased to lower levels with NAD than with AT or PLAC. These results suggest that decreased utilization of muscle triglycerides combined with lack of an enhanced glycogenolysis to compensate as well as alterations in potassium metabolism contribute to the decreased exercise capacity with nonselective β-blockade compared with β1-selective blockad | others_403_4493 |
pubmed_99_8217 | Mouse kidney histidine decarboxylase (HDC) provides a model system to study genetic control of a hormone-regulated enzyme (inducible by estrogen and thyroxine; repressible by testosterone). Five major HDC phenotypes scored on the basis of (i) enzyme activity and (ii) the difference in activity between the sexes (females usually higher than males) have been discovered by screening 38 strains of mice. One genetic difference between high-activity strains (DBA/2 and C3H/He) and low-activity strains (C57BL/6 and C57BL/10) has been examined in detail. The phenotypic difference segregates as a single gene in both conventional crosses and between recombinant inbred (RI) strains. Immunoprecipitation has shown that the activity difference is due to an alteration in the number of enzyme molecules. The phenotypic difference between high and low strains can therefore be attributed to different alleles of a single regulatory locus, Hdc; the allele Hdcb determines low HDC concentration, and the allele Hdcd high concentration. Hdc has been mapped to chromosome 2 using data from both comparisons of strain distribution patterns of previously mapped loci within RI strains and a conventional three-point cross. The probable gene order is B2m-pa-Hdc, with map distances of 3.1 +/- 1.7 and 2.0 +/- 1.4 cM, respectively. | 10.1007/BF00484230 |
pubmed_391_8329 | The effects of lithium on the beta-adrenoceptor-adenylate cyclase system in cerebral cortical membranes of rats were investigated. Lithium chloride inhibited adenylate cyclase activity in a concentration-dependent manner in vitro. However, relatively high concentrations of lithium were needed for this inhibition; and at 1 mM, no significant reduction in adenylate cyclase activity was seen under any condition. Administration of lithium carbonate for 21 days decreased the maximum number of [3H]dihydroalprenolol binding sites without changing the apparent dissociation constant. Activation of adenylate cyclase by (-)-isoproterenol in the presence of 1 microM guanyl-5'-ylimidodiphosphate (Gpp(NH)p) was significantly attenuated in lithium-treated rats compared with the controls. Lithium treatment reduced the Gpp(NH)p-stimulated adenylate cyclase activity in the presence of 10 microM (-)-isoproterenol, but not in the absence of this beta-adrenergic receptor agonist. Basal activity or adenylate cyclase activity stimulated by forskolin or manganese was not affected, whereas the activity stimulated by sodium fluoride was significantly attenuated by long-term lithium treatment. These results indicate that chronic lithium treatment induces subsensitivity in the beta-adrenoceptor-adenylate cyclase system, for which down-regulation of beta-adrenergic receptors is chiefly responsible. | 10.1254/jjp.55.407 |
pubmed_939_13988 | Carrots contain a significant content of phenolic compounds, mainly phenolic acids. Technological processing of carrots inflicts wounding stress and induces accumulation of these compounds, especially caffeic acid derivatives, in the periderm tissue. In this study, the effect of minimal processing (polishing, washing, peeling, and grating) on the retention of soluble phenolic acids in carrots was monitored during cold storage. Storage for up to 4 weeks and 24 h was used for whole and grated carrot samples, respectively. Total phenolic acid levels found in differently processed carrots varied greatly at the beginning of the storage period and on dry weight basis they ranged from 228 ± 67.9 mg/kg (grated carrot) to 996 ± 177 mg/kg (machine washed). In each case, processing followed by storage induced phenolic acid accumulation in the carrots. At the end of the experiment (4 weeks at +8 °C), untreated and machine-washed carrots contained ca. 4-fold more phenolic acids than at day 0. Similarly, polished carrots contained 9-fold and peeled carrots 31-fold more phenolic acids than at day 0. The phenolic acid content in grated carrot doubled after 24 h storage at +4 °C. Individual phenolic acids were characterized by high resolution mass spectrometry. MS data strongly suggest the presence of daucic acid conjugates of phenolic acids in carrot. Storage time did not have statistically similar effect on all compounds and generally in a way that dicaffeoyldaucic acid had the highest increase. This research provides important information for primary production, packaging, catering, the fresh-cut industry and consumers regarding the selection of healthier minimally processed carrots. | 10.3390/foods9101515 |
pubmed_551_777 | Methanol and ethanol have been identified as oil-soluble by-products generated by the aging of oil-impregnated cellulosic insulation materials of power transformers. Their presence provides useful information for diagnostics and end-of-life transformer estimation. Despite their value as cellulose degradation indicators, their sensitive and accurate determination is challenged by the complex oil matrix. To overcome this constraint, we present a simple, fast and direct procedure for their simultaneous determination in mineral insulating oil samples. The procedure uses a static headspace sampler coupled with a gas chromatograph equipped with a mass spectrometer. The selected method parameters permitted adequate separation of these two compounds from the complex oil matrix and quantification at ng g(-1) concentrations. An original internal standard procedure was developed, in which ethanol-d6 was added to all studied samples and blanks, with adequate resolution between the internal standard and its isotopomer ethanol. The method was validated in terms of accuracy and reproducibility for both analytes. The method detection limit, 4 ng g(-1) for methanol and ethanol, is well below the value (μg g(-1)) achieved by a standardized method for methanol determination in crude oil. During method validation studies, a relative error of approximately 6% was obtained for both methanol and ethanol with excellent reproducibility, average %RSD, below 2%. An experiment control chart, constructed to evaluate long-term reproducibility, indicate an overall good reproducibility (%RSD<3%) for 1000 ng g(-1) control solutions. The applicability of the method to the direct analysis of trace methanol and ethanol in oil from field transformer samples was successfully demonstrated. This analytical method is of high relevance to the electrical utilities as it allows indirectly assessment of the level of deterioration of the critical cellulose, an inaccessible part of a power transformer. | 10.1016/j.chroma.2012.07.069 |
pubmed_962_6903 | Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system. | 10.1161/CIRCULATIONAHA.106.171016 |
pubmed_1018_20464 | Effect of Hirudo therapy on the level of lipid peroxidation (LPO) products and catalase activity in the retina and pigmented epithelium (PE) after exposure to intensive illumination is assessed. Light injury to the eye (100,000 lux in 90 min) leads to accumulation of LPO products and suppression of catalase activity. Hirudo therapy after potent light exposure of the eye decreased the level of hydroperoxide and malonic dialdehyde and normalized retinal and PE catalase activity, thus exerting a therapeutic antioxidant effect. Hirudo therapy before illumination did not notably protect the eye as regards the content of LPO products and catalase activity. | pubmed_1018_20464 |
pubmed_644_3356 | To determine if patterns of predominant asthma disease activity are more closely related than baseline asthma severity to measures of morbidity (acute asthma attack, emergency room visit/hospitalization, missed school days, and/or steroid burst). Retrospective analysis was performed for inner-city Los Angeles asthmatic children (3 to 18 years of age) during their first year of enrollment in an asthma-specific disease management program. All measures of morbidity were more closely related to patterns of predominant disease activity than baseline severity. We conclude that patterns of predominant disease activity are a more significant predictor of asthma morbidity than is baseline severity. | 10.1080/02770900802085477 |
pubmed_1009_4540 | Cutaneous ureterostomy with application of an introverted skin flap was performed in 9 cases over a 2-year period. The method has been developed by the authors in view of the prevalence of strictures involving the terminal ureter and the stoma after unintubated cutaneous ureterostomy in case of a normal ureteral lumen. Ureteral drainage had to be resorted to in 2 cases (necrosis of the flap in one, and allergic skin reaction in the other). The intervention was carried out with success not only when the ureteral lumen was normal, but also when it was wide, short, or relatively short. | 10.1007/BF02082601 |
pubmed_972_19081 | Leptospirosis is a zoonosis with multisystem involvement caused by pathogenic strains of the genus Leptospira. OmpL1 is an outer membrane protein of Leptospira spp. that is expressed during infection. In this work, we investigated novel features of this protein. We describe that OmpL1 is a novel leptospiral extracellular matrix (ECM)-binding protein and a plasminogen (PLG) receptor. The recombinant protein was expressed in Escherichia coli BL21(DE3) Star/pLysS as inclusion bodies, refolded, and purified by metal-chelating chromatography. The protein presented a typical β-strand secondary structure, as evaluated by circular dichroism spectroscopy. The recombinant protein reacted with antibodies in serum samples from convalescent leptospirosis patients with a high specificity compared to serum samples from individuals with unrelated diseases. These data strengthen the usefulness of OmpL1 as a diagnostic marker of leptospirosis. The characterization of the immunogenicity of recombinant OmpL1 in inoculated BALB/c mice showed that the protein has the capacity to elicit humoral and cellular immune responses, as denoted by high antibody titers and the proliferation of lymphocytes. We demonstrate that OmpL1 has the ability to mediate attachment to laminin and plasma fibronectin, with K(D) (equilibrium dissociation constant) values of 2,099.93 ± 871.03 nM and 1,239.23 ± 506.85 nM, respectively. OmpL1 is also a PLG receptor, with a K(D) of 368.63 ± 121.23 nM, capable of generating enzymatically active plasmin. This is the first report that shows and characterizes OmpL1 as an ECM-interacting and a PLG-binding protein of Leptospira spp. that may play a role in bacterial pathogenesis when expressed during infection. | 10.1128/IAI.00474-12 |
pubmed_367_22937 | The reported uptake of the intrauterine device (IUD) as emergency contraception is very low despite its superior efficacy when compared with levonorgestrel emergency contraception. A prospective study was conducted to investigate the methods of emergency contraception offered to and accepted by women attending South Staffordshire Sexual Health Clinics. A total of 240 women attended the clinic for emergency contraception during the 2-month study period. The IUD as a method of emergency contraception was not offered to the majority of women presenting within 72 h of an episode of unprotected intercourse. Nulliparous women presenting before 72 h were significantly less likely to be offered an IUD compared with parous women, p < 0.01. This study shows that the IUD is not offered to the majority of patients, in particular nulliparous women, attending for emergency contraception. Also, the low rate of the uptake of the emergency IUD is related, at least in part, to the counselling patients receive from clinicians. | 10.1080/01443610902862712 |
pubmed_373_11061 | H19 is a paternally imprinted gene with unknown function. It is located in close proximity to the maternally imprinted IGF-2 gene on chromosome 11p15.5. In this study no consistent relationship between the expression of these two genes in clones derived from JEG-3 and JAr cell lines could be detected. Nor could a consistent relationship be detected between the expression levels of these two genes and between certain characteristic tumorigenic properties of these clones. We included in this study clones, expressing low H19 levels, which after transfection with an H19 expression construct highly expressed the H19 gene. In tumors, formed by the injection of cells of JAr or JEG-3 clones into nude mice, the H19 expression was high and irrelevant to the expression level in the cells before the injection. The same phenomenon was found for IGF-2 expression during tumorigenesis caused by cells of different JEG-3 clones and in some but not all JAr derived clones. Both H19 and IGF-2 are biallelicly expressed in all the JAr and JEG-3 clones. In summary, our observations point to the conclusion that H19 is not a tumor suppressor gene. However, its high expression in all the tumors formed after injection of cells of the JAr and JEG-3 clones, leaves its role, if any, in choriocarcinogenesis an open question. | 10.1038/sj.onc.1201175 |
pubmed_663_961 | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which preferentially induces apoptosis in cells that have undergone malignant transformation. In humans, non-neoplastic cells are normally protected from the effects of TRAIL by expressing decoy receptors, lacking death domains. In contrast, neoplastic cells tend to downregulate their decoy receptor expression, increasing their susceptibility to the pro-apoptotic effects of TRAIL, via the functional TRAIL receptors. The aim of the current study was to investigate the effect of TRAIL on the canine C2 mastocytoma cell line to determine whether this agent might be a suitable treatment for mast cell tumors in dogs. C2 and MDCK cells were cultured with recombinant human TRAIL. Apoptosis was assessed using a Caspase 3 and 7 chemiluminescence assay and flow cytometry following Annexin V:FITC labelling. Cell metabolism was assessed using a colorimetric MTT-based assay. C2 cells demonstrated greater sensitivity to TRAIL-induced apoptosis compared to MDCK cells by all assessment methods. The dog genome assembly was searched for orthologs of TRAIL and its receptors using published sequences from other species for reference. Although a canine ortholog for TRAIL was identified, only one TRAIL receptor ortholog (TNFRSF11B) could be found. C2, but not MDCK, cells expressed mRNA for TNFRSF11B, detected by RT-PCR. In other species, TNFRSF11B is a decoy receptor, as even though it has a death domain it is secreted due to its lack of a transmembrane domain. The effect of TRAIL on the C2 cell line suggests that this cytokine might be suitable for treatment of mast cell tumors in dogs. | 10.1016/j.vetimm.2008.12.023 |
pubmed_134_8305 | This within-family, longitudinal study including biological and stepfamilies investigated mutual influences between marital conflict and children's behavior problems. Children (4 to 17 years; N=296) residing in 127 families drawn from a general population study were investigated at Time 1 and again 2 years later. These nested data were analyzed using multilevel modeling, controlling for previous child behavior or marital conflict. Marital conflict about children predicted change in children's behavior. Children's behavior also predicted an increase in marital conflict, particularly in stepfamilies. Differences between siblings in exposure to conflict and the extent to which siblings were a source of argument increased more in stepfamilies than in biological families. Boys were exposed to more conflict over time than were girls. | 10.1111/j.1467-8624.2005.00827.x |
pubmed_1014_10136 | The homeobox gene Msx1 encodes a transcription factor that is highly expressed during embryogenesis and postnatal development in bone. Mutations of the MSX1 gene in humans are associated with cleft palate and (or) tooth agenesis. A similar phenotype is observed in newborn mice invalidated for the Msx1 gene. However, little is known about Msx1 function in osteoblast differentiation and bone mineralization in vivo. In the present study, we aimed to explore the variations of individualized bone shape in a subtle way avoiding the often severe consequences associated with gene mutations. We established transgenic mice that specifically express Msx1 in mineral-matrix-secreting cells under the control of the mouse 2.3kb collagen 1 alpha 1 (Col1α1) promoter, which enabled us to investigate Msx1 function in bone in vivo. Adult transgenic mice (Msx1-Tg) presented altered skull shape and mineralization resulting from increased Msx1 expression during bone development. Serial section analysis of the mandibles showed a high amount of bone matrix in these mice. In addition, osteoblast number, cell proliferation and apoptosis were higher in Msx1-Tg mice than in controls with regional differences that could account for alterations of bone shape. However, Von Kossa staining and μCT analysis showed that bone mineralization was lower in Msx1-Tg mice than in controls due to alteration of osteoblastic differentiation. Msx1 appears to act as a modeling factor for membranous bone; it stimulates trabecular bone metabolism but limits cortical bone growth by promoting apoptosis, and concomitantly controls the collagen-based mineralization process. | pubmed_1014_10136 |
pubmed_463_18327 | BACKGROUND
Helicobacter pylori (Hp) infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells that contribute to sustain and expand the local inflammation. Different clinical expressions of the infection may reflect distinctive patterns of cytokine expression. IL-1β, TNF-α, IL-17 and IL-23 have been reported to be involved in Hp-induced gastric mucosal inflammation, but the details and association to different patterns of inflammation and virulence factors remain unclear.
METHODS
Total RNA was extracted from gastric biopsies of 51 Hp-infected patients and 44 Hp-negative patients. Mucosal IL-18 mRNA expression in gastric biopsies was determined by Real-Time PCR. Presence of virulence factors was evaluated using PCR.
RESULTS
IL-18 mRNA expression was significantly increased in biopsies of Hp-infected patients compared to Hp-uninfected individuals. There was no association between virulence factors and IL-18 mRNA expression. Also severity of mononuclear infiltration was significantly higher in gastritis patients with vacA (m1)-positive compare patients with vacA (m2)-positive.
CONCLUSIONS
IL-18 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the stomach. This may ultimately influence the outcome of Hp-associated diseases that arise within the context of gastritis. | pubmed_463_18327 |
pubmed_975_9264 | Measurement of P-glycoprotein and the gene that encodes it, mdr-1, is an important tool for assessing the impact of multidrug resistance in clinical cancer. We evaluated mdr-1 expression by a quantitative polymerase chain reaction (PCR) assay in 78 biopsy samples from 48 patients with refractory lymphoma enrolled on a trial of infusional chemotherapy (EPOCH) in which R-verapamil was added as an antagonist of P-glycoprotein in a subset of patients whose tumors were unresponsive to treatment. Expression of mdr-1 was detectable in all biopsies at the time of enrollment on study, and a fourfold or greater increase in mdr-1 expression was noted in 42% of patients at the time of treatment failure. Expression of mdr-1 was also detectable in biopsies from patients at the time of diagnosis of lymphoma. An endogenous control gene, beta 2-microglobulin, was quantitated for normalization of the mdr-1 values. The use of beta 2-microglobulin expression for normalization was validated in a subset of samples by comparing Northern blots detecting beta 2-microglobulin, beta actin, and GAPDH gene expression. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein level. Immunophenotyping of lymphomatous lymph nodes showed that infiltration of tumor cells ranged from 8% to 95% and of normal T cells from 1% to 83%. Expression of mdr-1 in normal T cells and monocytes was also shown to be low. The mdr-1 levels in patient samples were independent of T-cell contamination, suggesting that the presence of normal cells has at best a small impact on mdr-1 measurements. Expression of mdr-1 in lymphoma can be quantitated by PCR, and wide variations in expression can be observed. Increased expression in patients with refractory disease supports an important role for Pgp in drug resistance in lymphoma. These studies will aid in the design and interpretation of clinical trials in lymphoma. | pubmed_975_9264 |
pubmed_438_3903 | Dr. R.K. Gherardi presented two papers at the symposium, detailing his researches into a proposed new clinical entity which he has entitled Macrophagic Myofasciitis (MMF). In his first paper he described the histopathologic and immunologic characteristics of the condition, and in the second, the clinical and serologic features. Dr. Gherardi believes that MMF, a syndrome of ascending myalgias, fatigue and diffuse musculoskeletal pain, may be related to a chronic immune response to aluminum granulomas persisting at the sites of prior immunization with aluminum adjuvated vaccines. | 10.1016/s0264-410x(02)00167-6 |
pubmed_1141_16679 | A Symptom Checklist (SCL-90-R) is a potentially useful measure of psychological distress; it is frequently used in psychotherapy research and clinical practice. The purpose of this study was to illustrate the use of the SCL-90-R for determining statistically reliable change and clinical significance outlined by Jacobson and Truax in 1991. This paper describes the concepts of statistical and clinical significance of change. A proposal for obtaining and characterizing samples is made. Then a clinician's perspective is taken. Reliable change estimates and cut-off scores are chosen based on outcome data. Selected data from a single psychotherapeutic process and outcome study then were used to test the estimates of change and cut-off scores. | 10.2466/pr0.2000.86.1.263 |
pubmed_455_2059 | ExoU, a protein transported by the type III secretion system of Pseudomonas aeruginosa, is an important cytotoxin, though its mechanism of action is unclear. Here we show that the intracellular expression of ExoU is cytotoxic to Saccharomyces cerevisiae. Furthermore, internal amino- and carboxyl-terminal deletions confirmed that regions of ExoU previously shown to be essential for killing mammalian cells were also required for killing yeast cells. These findings indicate that S. cerevisiae is a useful model organism for the study of ExoU. | 10.1128/IAI.71.7.4144-4150.2003 |
pubmed_822_7718 | BACKGROUND
Advances have been made in the management of pregnancies in women receiving dialysis; however, single-centre studies and small numbers of cases have so far precluded a clear definition of the relationship between dialysis schedules and pregnancy outcomes. The aim of the present systematic review was to analyse the relationship between dialysis schedule and pregnancy outcomes in pregnancies in chronic dialysis in the new millennium.
METHODS
Medline-PubMed, Embase and the Cochrane library were searched (1 January 2000-31 December 2014: MESH, Emtree, free terms on pregnancy and dialysis). A separate analysis was performed for case series (more than five cases) and case reports. Meta-regression was performed in case series dealing with the larger subset of haemodialysis (HD) patients; case reports were analysed separately [according to peritoneal dialysis (PD) versus HD; conception before or during dialysis].
RESULTS
We obtained 190 full texts and 25 congress abstracts from 2048 references. We selected 101 full papers and 25 abstracts (36 series; 90 case reports), for a total of 681 pregnancies in 647 patients. In the case series (574 pregnancies in 543 patients), preterm delivery was extremely frequent (83%). Meta-regression analysis showed a relationship between hours of dialysis per week in HD and preterm delivery, and was significant for preterm deliveries (<37 gestational weeks: P = 0.044; r2 = 0.22) and for small for gestational age (SGA) (P = 0.017; r2 = 0.54). SGA was closely associated with the number of dialysis sessions per week (P = 0.003; r2 = 0.84). Case report analysis suggests a lower incidence of SGA on HD versus PD (31 versus 66.7%; P = 0.015). No evidence of an increased risk of congenital abnormality was found in the retrieved papers.
CONCLUSIONS
Data on pregnancy on dialysis are heterogeneous but rapidly accumulating; the main determinant of outcomes on HD is the dialysis schedule. The differences between PD and HD should be further analysed. | 10.1093/ndt/gfv395 |
pubmed_4_12721 | Cronin, J, Lawton, T, Harris, N, Kilding, A, and McMaster, DT. A brief review of handgrip strength and sport performance. J Strength Cond Res 31(11): 3187-3217, 2017-Tests of handgrip strength (HGS) and handgrip force (HGF) are commonly used across a number of sporting populations. Measures of HGS and HGF have also been used by practitioners and researchers to evaluate links with sports performance. This article first evaluates the validity and reliability of various handgrip dynamometers (HGD) and HGF sensors, providing recommendations for procedures to ensure that precise and reliable data are collected as part of an athlete's testing battery. Second, the differences in HGS between elite and subelite athletes and the relationships between HGS, HGF, and sports performance are discussed. | 10.1519/JSC.0000000000002149 |
pubmed_526_7959 | A 40-year-old man with dry cough for 5 years, no history of smoking, and a right lung mass, underwent a radiologically-guided core needle biopsy. The initial histopathological diagnosis was adenocarcinoma of the lung. After lobectomy, the final pathology was mucoepidermoid carcinoma. The initial biopsies sampled only a mucinous component of the tumor, leading to a diagnosis of adenocarcinoma. The possibility of mucoepidermoid carcinoma could be suspected on the basis of clinical history and radiologic evidence. This unusual case highlights the importance of adequate multidisciplinary review of patients who increasingly receive pathologic diagnoses based on ever smaller tissue samples. | 10.1177/0218492315577214 |
pubmed_386_17231 | Antimicrobial peptides are small proteins that exhibit a broad spectrum of antimicrobial activity. Their chemical structure allows them to interact (attach and insert) with membranes. The fine details about this interaction and their mode of action are not fully clarified yet. In order to better understand this mechanism, we have performed in situ atomic force microscopy studies using two types of nodule specific cysteine-rich NCR peptides on Escherichia coli bacteria and on natural purple membrane. On intact bacteria, both NCR247 and NCR335 caused increase in the surface roughness, indicating the damage of the bacterial cell envelope. In case of the tightly packed purple membrane, it is clear that the peptides prefer to disrupt the border of the disks indicating a strong lipid preference of the interaction. These results verify the concept that the first target of NCR peptides is probably the bacterial cell envelope, especially the lipid matrix. | 10.4149/gpb_2015002 |
pubmed_495_13127 | The mammalian small intestine is extensively innervated by cholinergic nerve fibers, including projections to the muscular and submucosal layers. This study tested the hypothesis that cholinergic agents modulate ileal transport independent of alterations in intestinal vascular resistance and motility. Ten-centimeter segments of rabbit ileum (n = 32) were vascularly perfused ex vivo with a physiologic electrolyte solution containing red cells. The lumen was perfused with an electrolyte solution containing [14C]polyethylene glycol. Net fluxes of water, sodium, and chloride were calculated during three 20-min periods: basal, drug infusion, and recovery. Agents infused at a final arterial concentration of 10(-5) mole/liter included acetylcholine, atropine, and hexamethonium. Measured perfusion pressure reflected changes in vascular resistance. Recovery calculations controlled for motility effects. Acetylcholine caused significant secretion of water, sodium, and chloride (P < 0.05). The infusion of atropine or hexamethonium alone had no effect. Atropine but not hexamethonium prevented the prosecretory effect of acetylcholine. There were no significant changes in perfusion pressure or 14C recovery for any infused agent. Acetylcholine-induced ileal secretion is (1) mediated via atropine-sensitive muscarinic cholinergic receptors, (2) independent of extraintestinal neural pathways, and (3) independent of changes in vascular resistance or motility. These data support the hypothesis that acetylcholine influences ileal transport directly, independent of alterations in vascular resistance and motility. | 10.1006/jsre.1995.1223 |
pubmed_33_4574 | We report the regio- and enantioselective allylation of an ester enolate, trimethylsiloxyfuran. This enolate reacts at the 3-position with linear aromatic allylic carbonates or aliphatic allylic benzoates to form the branched substitution products in the presence of a metallacyclic iridium catalyst. This process provides access to synthetically important 3-substituted butenolides in enantioenriched form. Stoichiometric reactions of the allyliridium intermediate suggest that the trimethylsiloxyfuran is activated by the carboxylate leaving group. | 10.1021/ja306850b |
pubmed_228_19641 | The major goal of this study is to gain a perspective on the prevalence of DNA enteric virus genomes in mesophilic anaerobic-digested (MAD) sewage sludge and manure by comparing their quantitative PCR (qPCR) concentrations and removals with traditional fecal indicators (Escherichia coli, enterococci, and Bacteroidetes). In addition, relationships between qPCR and culture measurements of fecal indicators (FIs) were determined. There was no significant difference between the qPCR concentrations of human adenovirus and E. coli/enterococci in MAD sewage sludge; however, the qPCR concentrations of bovine adenovirus were significantly lower than FIs and bovine polyomavirus (BPyV) in MAD manure. The qPCR concentrations of human polyomavirus were slightly lower than E. coli and enterococci (p ≤ 0.05), but no significant difference was observed between the qPCR concentrations of BPyV and FIs. The digestion treatment achieved higher genome removal of bovine DNA enteric viruses than FIs (p ≤ 0.05). Significant correlations were observed between qPCR and culture measurements of FIs, but the concentrations and removals of FIs determined by qPCR assays were still significantly different than those determined by culture assays. Overall, we determined that the prevalence of DNA enteric virus genomes in MAD biological wastes was high due to their comparable in qPCR concentrations to FIs, indicating that mesophilic anaerobic digestion treatment alone may not be effective enough to remove DNA viral pathogens in biological wastes. | 10.1007/s10661-011-2316-z |
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