title: An update and systematic review on the treatment of primary dysmenorrhea.

text: OBJECTIVES Primary dysmenorrhea is a painful uterine contraction caused by endometrial laceration. Drug therapies and complementary medicine have been used to treat dysmenorrhea. The aim of this study was to investigate and offer an updated perspective on the treatments for dysmenorrhea. METHODS The present study was conducted in accordance with the PRISMA checklist for systematic reviews and meta-analyses. The required information was collected based on searches for the following keywords: treatment, primary dysmenorrhea, medicinal plants, chemical drugs, and herbs. Searches were performed on databases Pubmed, Web of Sciences, Scopus, Iran medex, and SID by March 2018 to find literature in the English and Persian languages on this subject without a time limit. RESULTS This review included 17 papers, 10 of which on complementary medicine, three on drug therapies, and four on acupuncture and acupressure. The largest and smallest samples had 303 and 24 patients, respectively. Length of treatment ranged from one to six months and the measures most commonly used in the studies were the visual analogue scale and clinical efficacy. Reported complications included gastrointestinal events, nausea, vomiting, diarrhea, abdominal pain, and liver and kidney disorders. CONCLUSION Medicinal plants, drugs, and acupressure seem to suppress pain by reducing the level of prostaglandins, mediating nitric oxide, increasing beta-endorphin levels, blocking the calcium channel, and enhancing circulatory flow through the uterine pathway. Further trials are required to confirm the benefits of the procedures described and ensure the absence of complications.


Rural and Remote Communities: Unique Ethical Issues in the COVID-19 Pandemic.


title: Surveillance for Avibacterium paragallinarum in autopsy cases of birds from small chicken flocks using a real-time PCR assay.

text: Infectious coryza is a severe respiratory disease of chickens associated with large economic losses in affected commercial flocks. The fastidious causative pathogen, Avibacterium paragallinarum, is difficult to recover and identify, resulting in delayed diagnosis and enhanced spread of the agent. Small poultry flocks are increasingly common in rural and suburban environments. We assessed the frequency of A. paragallinarum using real-time PCR and clinical conditions present in samples from such flocks submitted to the California Animal Health and Food Safety Laboratory System (Davis, CA) in 2018. From the 294 samples collected for our study, 86 (30%) were PCR-positive for A. paragallinarum. Juvenile birds (≤1 y) were significantly more likely to be PCR-positive ( p = 0.017), and birds diagnosed with respiratory disease had lower Ct values ( p = 0.001) than those without. Concurrent infections were also identified, including with Mycoplasma gallisepticum (18.6%), M. synoviae (18.6%), infectious bronchitis virus (12.8%), and infectious laryngotracheitis virus (7.0%). Only 46.5% of PCR-positive chickens had antemortem respiratory signs, making endemic infections in these flocks highly likely. Our study demonstrates that A. paragallinarum is present in small-flock operations including those without respiratory disease and may present a risk for airborne pathogen transmission to commercial poultry operations.


Modern techniques of fixing of meshes in surgical repair of inguinal and abdominal hernias.


title: Prospective comparative cohort study evaluating incompetent great saphenous vein closure using radiofrequency-powered segmental ablation or 1470-nm endovenous laser ablation with radial-tip fibers (Varico 2 study).

text: BACKGROUND Endovenous laser ablation (EVLA) and radiofrequency-powered segmental ablation (RPSA) of the incompetent great saphenous vein (GSV) are both known for their excellent technical and clinical outcomes for the treatment of varicose veins. RPSA has reduced postprocedural pain and morbidity with shorter recovery time for the patient compared with EVLA using bare-tip fibers. However, new-generation EVLA devices with less traumatic radial-tip fibers (RTFs) operating at longer wavelengths up to 1470 nm also reduce postprocedural pain. The objective of this study was to compare long-term effectiveness of GSV thermal ablation and postprocedural recovery using RPSA or 1470-nm EVLA with RTF (EVLA-RTF). METHODS In a comparative prospective monthly altering-treatment cohort study of 311 patients (346 treated legs), each leg with incompetence of the GSV was treated with either RPSA (158 patients, 175 legs) or EVLA-RTF (153 patients, 171 legs). The primary outcome was anatomic occlusion of the GSV, assessed at 12, 24, 36, 48, and 60 months using Kaplan-Meier statistics and compared using the log-rank test. Secondary outcomes included freedom of varicose vein recurrence, clinical success measured by Venous Clinical Severity Score (VCSS), disease-specific quality of life determined using the Aberdeen Varicose Vein Questionnaire (AVVQ), postoperative pain scores, and time to return to work. RESULTS The total primary obliteration rate after 36 and 60 months was 96.2% with RPSA and 96.7% with EVLA-RTF (P = .81). Freedom of symptomatic anterior accessory vein recurrence after 5 years was 85% after RPSA and 87% after EVLA-RTF (P = .50). VCSS and AVVQ score presented similar and durable improvements in both groups between 6 weeks and 60 months. There was no difference in postoperative pain scores after both treatments during the first 14 days (mean visual analog scale score, 0.54-2.19). The median time for return to work was 1 day after both treatments. No severe adverse events were observed. CONCLUSIONS RPSA and EVLA-RTF have similarly high GSV obliteration rates in the long term, and the treatments are equally effective clinically. Both treatments are associated with similar minimal postprocedural pain scores and short recovery times.


title: Renovascular reactivity measured by near-infrared spectroscopy.

text: Hypotension and shock are risk factors for death, renal insufficiency, and stroke in preterm neonates. Goal-directed neonatal hemodynamic management lacks end-organ monitoring strategies to assess the adequacy of perfusion. Our aim is to develop a clinically viable, continuous metric of renovascular reactivity to gauge renal perfusion during shock. We present the renovascular reactivity index (RVx), which quantifies passivity of renal blood volume to spontaneous changes in arterial blood pressure. We tested the ability of the RVx to detect reductions in renal blood flow. Hemorrhagic shock was induced in 10 piglets. The RVx was monitored as a correlation between slow waves of arterial blood pressure and relative total hemoglobin (rTHb) obtained with reflectance near-infrared spectroscopy (NIRS) over the kidney. The RVx was compared with laser-Doppler measurements of red blood cell flux, and renal laser-Doppler measurements were compared with cerebral laser-Doppler measurements. Renal blood flow decreased to 75%, 50%, and 25% of baseline at perfusion pressures of 60, 45, and 40 mmHg, respectively, whereas in the brain these decrements occurred at pressures of 30, 25, and 15 mmHg, respectively. The RVx compared favorably to the renal laser-Doppler data. Areas under the receiver operator characteristic curves using renal blood flow thresholds of 50% and 25% of baseline were 0.85 (95% CI, 0.83-0.87) and 0.90 (95% CI, 0.88-0.92). Renovascular autoregulation can be monitored and is impaired in advance of cerebrovascular autoregulation during hemorrhagic shock.


title: Clinical Relevance and Role of Neuronal AT1 Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension.

text: RATIONALE Neurogenic hypertension is characterized by an increase in sympathetic activity and often resistance to drug treatments. We previously reported that it is also associated with a reduction of angiotensin-converting enzyme type 2 (ACE2) and an increase in a disintegrin and metalloprotease 17 (ADAM17) activity in experimental hypertension. In addition, while multiple cells within the central nervous system have been involved in the development of neurogenic hypertension, the contribution of ADAM17 has not been investigated. OBJECTIVE To assess the clinical relevance of this ADAM17-mediated ACE2 shedding in hypertensive patients and further identify the cell types and signaling pathways involved in this process. METHODS AND RESULTS Using a mass spectrometry-based assay, we identified ACE2 as the main enzyme converting angiotensin II into angiotensin-(1-7) in human cerebrospinal fluid. We also observed an increase in ACE2 activity in the cerebrospinal fluid of hypertensive patients, which was correlated with systolic blood pressure. Moreover, the increased level of tumor necrosis factor-α in those cerebrospinal fluid samples confirmed that ADAM17 was upregulated in the brain of hypertensive patients. To further assess the interaction between brain renin-angiotensin system and ADAM17, we generated mice lacking angiotensin II type 1 receptors specifically on neurons. Our data reveal that despite expression on astrocytes and other cells types in the brain, ADAM17 upregulation during deoxycorticosterone acetate-salt hypertension occurs selectively on neurons, and neuronal angiotensin II type 1 receptors are indispensable to this process. Mechanistically, reactive oxygen species and extracellular signal-regulated kinase were found to mediate ADAM17 activation. CONCLUSIONS Our data demonstrate that angiotensin II type 1 receptors promote ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a loss in compensatory activity during neurogenic hypertension.


Sequencing Treatments for Cancer During the COVID-19 Pandemic.


title: Ivor Lewis minimally invasive esophagectomy for esophageal cancer: An excellent operation that improves with experience.

text: OBJECTIVE Esophagectomy is associated with major morbidity. In this study we sought to assess the learning curve of minimally invasive Ivor Lewis esophagectomy (MIILE) and to evaluate perioperative outcomes, including anastomotic leak and hospital readmission, as a function of graduated surgeon experience. METHODS Data were extracted from the electronic medical records of patients who underwent MIILE, performed by a single surgeon over an 8-year period (2009-2017). Primary outcomes were 5-year overall survival, postoperative complications, and 90-day readmission rates. Surgeon experience was divided into 4 quartiles, representing graduated experience. Statistical analysis was performed using univariate and multivariate logistic regression, whereas Kaplan-Meier estimators were used to assess survival outcomes. RESULTS A total of 170 patients underwent MIILE and were analyzed after exclusion criteria were applied. Five-year overall survival was 50.1% (95% confidence interval, 39.7%-63.2%). Mortality at 90 days was 3.9% (95% confidence interval, 0.8%-6.9%). Major complications occurred in 25.3% (n = 43) and 25.9% (n = 44) were readmitted to the hospital within 90 days after surgery. Conversion to open surgery, anastomotic leaks, and readmissions decreased over time. CONCLUSIONS MIILE can be performed safely and effectively with improving results as the surgeon's experience evolves.


title: Antagonism of type I interferon responses by new world hantaviruses.

text: Evasion of interferon (IFN)-mediated antiviral signaling is a common defense strategy for pathogenic RNA viruses. To date, research on IFN antagonism by hantaviruses is limited and has focused on only a subset of the numerous recognized hantavirus species. The host IFN response has two phases, an initiation phase, resulting in the induction of alpha/beta IFN (IFN-α/β), and an amplification phase, whereby IFN-α/β signals through the Jak/STAT pathway, resulting in the establishment of the cellular antiviral state. We examined interactions between these critical host responses and the New World hantaviruses. We observed delayed cellular responses in both Andes virus (ANDV)- and Sin Nombre virus (SNV)-infected A549 and Huh7-TLR3 cells. We found that IFN-β induction is inhibited by coexpression of ANDV nucleocapsid protein (NP) and glycoprotein precursor (GPC) and is robustly inhibited by SNV GPC alone. Downstream amplification by Jak/STAT signaling is also inhibited by SNV GPC and by either NP or GPC of ANDV. Therefore, ANDV- and SNV-encoded proteins have the potential for inhibiting both IFN-β induction and signaling, with SNV exhibiting the more potent antagonism ability. Herein we identify ANDV NP, a previously unrecognized inhibitor of Jak/STAT signaling, and show that IFN antagonism by ANDV relies on expression of both the glycoproteins and NP, whereas the glycoproteins appear to be sufficient for antagonism by SNV. These data suggest that IFN antagonism strategies by hantaviruses are quite variable, even between species with similar disease phenotypes, and may help to better elucidate species-specific pathogenesis.


title: RNase-resistant virus-like particles containing long chimeric RNA sequences produced by two-plasmid coexpression system.

text: RNase-resistant, noninfectious virus-like particles containing exogenous RNA sequences (armored RNA) are good candidates as RNA controls and standards in RNA virus detection. However, the length of RNA packaged in the virus-like particles with high efficiency is usually less than 500 bases. In this study, we describe a method for producing armored L-RNA. Armored L-RNA is a complex of MS2 bacteriophage coat protein and RNA produced in Escherichia coli by the induction of a two-plasmid coexpression system in which the coat protein and maturase are expressed from one plasmid and the target RNA sequence with modified MS2 stem-loop (pac site) is transcribed from another plasmid. A 3V armored L-RNA of 2,248 bases containing six gene fragments-hepatitis C virus, severe acute respiratory syndrome coronavirus (SARS-CoV1, SARS-CoV2, and SARS-CoV3), avian influenza virus matrix gene (M300), and H5N1 avian influenza virus (HA300)-was successfully expressed by the two-plasmid coexpression system and was demonstrated to have all of the characteristics of armored RNA. We evaluated the 3V armored L-RNA as a calibrator for multiple virus assays. We used the WHO International Standard for HCV RNA (NIBSC 96/790) to calibrate the chimeric armored L-RNA, which was diluted by 10-fold serial dilutions to obtain samples containing 10(6) to 10(2) copies. In conclusion, the approach we used for armored L-RNA preparation is practical and could reduce the labor and cost of quality control in multiplex RNA virus assays. Furthermore, we can assign the chimeric armored RNA with an international unit for quantitative detection.


title: A simple prediction rule for all-cause mortality in a cohort eligible for bariatric surgery.

text: IMPORTANCE Current eligibility criteria for bariatric surgery use arbitrarily chosen body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) thresholds, an approach that has been criticized as arbitrary and lacking evidence. OBJECTIVES To verify the importance of BMI as a mortality predictor, to identify other important mortality predictors, and to construct a mortality prediction rule in a population eligible for bariatric surgery. DESIGN We studied individuals from a population-representative register who met contemporary eligibility criteria for bariatric surgery (BMI, ≥35.0 alone or 30.0-34.9 with an obesity-related comorbidity) from January 1, 1988, through December 31, 1998. We used binary logistic regression to construct a parsimonious model and a clinical prediction rule for 10-year all-cause mortality. SETTING The United Kingdom General Practice Research Database, a population-representative primary care registry. PARTICIPANTS Fifteen thousand three hundred ninety-four patients aged 18 to 65 years. EXPOSURE Bariatric surgery. MAIN OUTCOME AND MEASURE Ten-year all-cause mortality. RESULTS Mean (SD) age was 46.9 (11.9) years, BMI was 36.2 (5.5), and 63.2% of the patients were women. All-cause mortality was 2.1%, and mean follow-up duration was 9.9 years. The final model, which included age (odds ratio, 1.09 per year [95% CI, 1.07-1.10]), type 2 diabetes mellitus (2.25 [1.76-2.87]), current smoking (1.62 [1.28-2.06]), and male sex (1.50 [1.20-1.87]), had a C statistic of 0.768. Although BMI significantly predicted mortality (odds ratio, 1.03 per unit [95% CI, 1.01-1.05]), it did not improve model discrimination or calibration. We divided clinical prediction rule scoring into 4 tiers. All-cause mortality was 0.2% in tier 1, 0.9% in tier 2, 2.0% in tier 3, and 5.2% in tier 4. CONCLUSIONS AND RELEVANCE All-cause 10-year mortality in obese individuals eligible for bariatric surgery can be estimated using a simple 4-variable prediction rule based on age, sex, smoking, and diabetes mellitus. Body mass index was not an important mortality predictor. Further work is needed to define low, moderate, and high absolute risk thresholds and to provide external validation.


title: "Top down no-touch" technique in robotic complete mesocolic excision for extended right hemicolectomy with intracorporeal anastomosis.

text: BACKGROUND Proper identification of the mesocolic vessels is essential for achieving complete mesocolic excision (CME) in cases of colon cancer requiring an extended right hemicolectomy. In robotic procedures, we employed a "top down technique" to allow early identification of the gastrocolic trunk and middle colic vessels. The aim of our study was to illustrate the details of this technique in a series of 12 patients. METHODS The top down technique consists of two steps. First, the omental bursa was entered to identify the right gastroepiploic vein. Tracing down this vein as a landmark, the gastrocolic trunk was exposed, branches of this trunk and the middle colic vessels were divided. Second, dissection was directed to the ileocolic region and proceeded in an inferior-to-superior direction along the superior mesenteric vein to divide the ileocolic and right colic vessels consecutively. The ileotranverse anastomosis was created intracorporeally. RESULTS There were 8 males and 4 females with a mean age of 64.8 ± 16.9 years and a mean body mass index of 25.6 ± 3.7 kg/m2. All the procedures were completed successfully. No conversions occurred. The mean operative time and blood loss were 312.1 ± 93.9 min and 110.0 ± 89.9 ml, respectively. The mean number of harvested lymph nodes was 45.2 ± 11.1. The mean length of hospital stay was 7.6 ± 4.7 days. Two patients had intraoperative complications and two had postoperative complications. There was no disease recurrence at a mean follow-up period of 10.4 ± 7.1 months. CONCLUSIONS The top down technique appears to be useful in robotic CME for an extended right hemicolectomy. Early identification of the gastrocolic trunk and middle colic vessels via this technique may prevent inadvertent vascular injury at the mesenteric root of the transverse colon.


title: [2019 Novel coronavirus, renin-angiotension system imbalance and coronavirus disease 2019].

text: 2019 Novel coronavirus (2019-nCoV) destroys angiotensin converting enzyme 2 (ACE2) and breaks the balance of renin-angiotension system (RAS) by interacting with ACE2. The imbalance of RAS takes part in the development of organ injury of different systems through pro-inflammation, oxidative stress, cell proliferation and so on. 2019-nCoV not only attacks the lung, but also influences many other systems. It is speculated that RAS imbalance plays an important role in the development of multi-organ dysfunction caused by 2019-nCoV, and the usage of angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) may become a new treatment of 2019-nCoV-related organ injury. Further studies are need to confirm the relationship between coronavirus infection, multi-organ injury and RAS imbalance.


title: Genetic and antigenic characterization of newly isolated bovine toroviruses from Japanese cattle.

text: Torovirus, a member of the Coronaviridae family, is a gastrointestinal infectious agent that has been identified in humans, cattle, pigs, and equines. Toroviruses, except equine torovirus, are difficult to propagate in cell culture; indeed, to date, only the Aichi/2004 strain of bovine torovirus (BToV) has been isolated among the human, bovine, and porcine toroviruses. In the present study, four cytopathogenic BToVs were isolated from diarrheal feces of the cattle using the HRT-18 cell line, and their genetic and antigenic properties were compared. The cytopathogenic features of BToV isolates in HRT-18 cells were similar to those of the Aichi/2004 strain. However, none of the isolates showed cytopathogenic effects in the HRT-18 cells of different origin, suggesting that one significant factor contributing to the cytopathogenicity of BToV depends on properties of the HRT-18 cells themselves. All BToVs isolated were able to agglutinate mouse, but not chicken, erythrocytes, while they lacked receptor-destroying enzyme activity. Analysis of the N terminus of the spike gene showed that three isolates, but not the Gifu-2007TI/E strain, were phylogenetically located in cluster 1 and its analogs and revealed high cross-reactivity with each other, as demonstrated by neutralization (NT) and hemagglutination inhibition (HI) assays. The Gifu-2007TI/E strain was classified close to cluster 2 and exhibited relatively low cross-reactivity with these viruses; however, the difference was not sufficient to classify BToVs into serotypes, suggesting that at least two subtypes distinguishable by the structure of the N terminus of the spike gene and that both NT and HI tests may be exist.


title: Autophagy and SARS-CoV-2 infection: Apossible smart targeting of the autophagy pathway.

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak resulted in 5,993,317 confirmed cases worldwide with 365,394 confirmed deaths (as of May 29th, 2020, WHO). The molecular mechanism of virus infection and spread in the body is not yet disclosed, but studies on other betacoronaviruses show that, upon cell infection, these viruses inhibit macroautophagy/autophagy flux and cause the accumulation of autophagosomes. No drug has yet been approved for the treatment of SARS-CoV-2 infection; however, preclinical investigations suggested repurposing of several FDA-approved drugs for clinical trials. Half of these drugs are modulators of the autophagy pathway. Unexpectedly, instead of acting by directly antagonizing the effects of viruses, these drugs appear to function by suppressing autophagy flux. Based on the established cross-talk between autophagy and apoptosis, we speculate that over-accumulation of autophagosomes activates an apoptotic pathway that results in apoptotic death of the infected cells and disrupts the virus replication cycle. However, administration of the suggested drugs are associated with severe adverse effects due to their off-target accumulation. Nanoparticle targeting of autophagy at the sites of interest could be a powerful tool to efficiently overcome SARS-CoV-2 infection while avoiding the common adverse effects of these drugs.


title: Rectovaginal fistula: a new technique and preliminary results using collagen matrix biomesh.

text: BACKGROUND A rectovaginal fistula (RVF) is a debilitating condition that is difficult to treat. Many available techniques are invasive and involve extensive surgery. A local procedure with good closure rates would be preferable as a first step in the treatment of RVF. The aim of this study was the development of a local technique for the closure of RVF with good closure rates to prevent the use of more invasive procedures. METHODS This was a pilot study. Patients with RVF who had undergone multiple operations in the pelvic area, local radiotherapy, chemotherapy or had been diagnosed with Crohn's disease were included in the study. All had a history of surgery for RVF. A cross-linked collagen matrix biomesh was placed in the rectovaginal septum using a transperineal or a transvaginal approach. The main outcome measure in this study was the closure rate reported as absence of the fistula at 1 year. RESULTS Twelve patients were included in the study. Absence of fistula at 1 year was 0.64 (95 % confidence interval 0.30-0.85). Three patients (25.0 %) developed a recurrence, two were reoperated on with a gracilis flap transposition, and one was treated with laparoscopic ligation. In one patient (8.3 %), the fistula failed to close within 3 months after the mesh placement. CONCLUSIONS Our technique shows promising results. A local and simple technique with acceptable closure and morbidity rates, like our local repair with biomesh, would be ideal as a first step in treating RVFs. Long-term results are needed.


title: Robotic Gastrotomy With Intracorporeal Suture for Patients With Gastric Gastrointestinal Stromal Tumors Located at Cardia and Subcardiac Region.

text: PURPOSE Few studies of robotic gastric gastrointestinal stromal tumors (GISTs) resection have been conducted. This study was aimed to evaluate the robotic gastrotomy with intracorporeal suture for patients with GISTs located at cardia and subcardiac region. MATERIALS AND METHODS From January 2014 to August 2016, 11 patients with GISTs located at cardia and subcardiac region underwent robotic gastrotomy with intracorporeal suture. Data of these patients were collected. RESULTS The mean operative time was 82.7 minutes and the mean blood loss was 30.0 mL. No complication was reported. The postoperative length of stay was 3.3 days. On postoperative day 14, inflammation recovered to preoperative level. On postoperative month 6, the nutritional status was similar to that before the surgery. After 25.5 months follow-up, all patients survived with no recurrence or metastasis. CONCLUSIONS Robotic gastrotomy with intracorporeal suture for patients with GISTs located at cardia and subcardiac region is safe and feasible.


title: Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.

text: SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.


title: Herbal medicines: challenges in the modern world. Part 3. China and Japan.

text: INTRODUCTION Medicinal plants, and formulations prepared from them, have been used in China and Japan for thousands of years. Nowadays, ancient formulations of Traditional Chinese and Kampo (Japanese) Medicines coexist with Western herbal medicines (HMs) and complement each other. HMs are used for the treatment of mild and chronic diseases, as an adjunct therapy, to improve wellbeing and delay aging, or as healthy (functional) foods. AREAS COVERED This article, a third part in a series of reviews, is focusing on history, use and regulation of the traditional and modern HMs in Japan and China. Materials available from legislative and governmental websites, PubMed and news media were used. Expert commentary: HMs are heavily regulated in both countries, often in a similar manner as conventional pharmaceutical drugs. The majority of herbal formulations are sold as over-the-counter medications supplied with leaflets describing indications and appropriate dosages for patients of different ages. Medical practitioners prescribe herbal formulations that are tailored to the needs of particular patients. Both countries had problems with adverse drug reactions and toxicity of single herbs and herbal formulations that have been investigated by authorities, and some drugs have been removed from the market.


title: Bispectral index to monitor propofol sedation in trauma patients.

text: BACKGROUND This study tested the hypothesis that the bispectral index (BIS) is reliable relative to clinical judgment for estimating sedation level during daily propofol spontaneous awakening trials (SATs) in trauma patients. METHODS This was a prospective observational trial with waiver of consent conducted in the intensive care unit of Level I trauma center in 94 mechanically ventilated trauma patients sedated with propofol alone or in combination with midazolam. BIS, Richmond Agitation Sedation Scale (RASS), electromyography, and heart rate variability, as a test of autonomic function, were measured for 45 minutes during daily SATs. Data were evaluated with analysis of variance, linear regression, and nonparametric tests. RESULTS The BIS wave form coincided almost exactly with propofol on/off. Steady-state BIS correlated with RASS (p < 0.0001) and with propofol dose (p < 0.0001), but the strengths of association were relatively low (all r(2) < 0.5). BIS wave form was not altered by age, heart rate, or heart rate variability and was similar with propofol alone or propofol plus midazolam, but the presence of brain injury or the use of paralytics shifted the curve downward (both p < 0.001). The overall test characteristics for BIS versus RASS without neuromuscular blockade were sensitivity: 90% versus 77% (p = 0.034); specificity: 90% versus 75% (p = 0.021); positive predictive value: 90% versus 76% (p = 0.021), and negative predictive value: 90% versus 76% (p = 0.021). CONCLUSIONS In the first trial in trauma patients and largest trial in any surgical population, the (1) BIS was reliable and has advantages over RASS of being continuous and objective, at least during a propofol SAT; (2) BIS interpretation remains somewhat subjective in patients receiving paralytic agents or with traumatic brain injury.


title: Mannitol and Outcome in Intracerebral Hemorrhage: Propensity Score and Multivariable Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 Results.

text: BACKGROUND AND PURPOSE Mannitol is often used to reduce cerebral edema in acute intracerebral hemorrhage but without strong supporting evidence of benefit. We aimed to determine the impact of mannitol on outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS INTERACT2 was an international, open, blinded end point, randomized controlled trial of 2839 patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure allocated to intensive (target systolic blood pressure, <140 mm Hg within 1 hour) or guideline-recommended (target systolic blood pressure, <180 mm Hg) blood pressure-lowering treatment. Propensity score and multivariable analyses were performed to investigate the relationship between mannitol treatment (within 7 days) and poor outcome, defined by death or major disability on the modified Rankin Scale score (3-6) at 90 days. RESULTS There was no significant difference in poor outcome between mannitol (n=1533) and nonmannitol (n=993) groups: propensity score-matched odds ratio of 0.90 (95% confidence interval, 0.75-1.09; P=0.30) and multivariable odds ratio of 0.87 (95% confidence interval, 0.71-1.07; P=0.18). Although a better outcome was suggested in patients with larger (≥15 mL) than those with smaller (<15 mL) baseline hematomas who received mannitol (odds ratio, 0.52 [95% confidence interval, 0.35-0.78] versus odds ratio, 0.91 [95% confidence interval, 0.72-1.15]; P homogeneity<0.03 in propensity score analyses), the association was not consistent in analyses across other cutoff points (≥10 and ≥20 mL) and for differing grades of neurological severity. Mannitol was not associated with excess serious adverse events. CONCLUSIONS Mannitol seems safe but might not improve outcome in patients with acute intracerebral hemorrhage. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.


Thoracoscopic basilar segmentectomy.


title: Thrombus remnant despite intra-arterial thrombolysis for thrombus formation during endovascular treatment of ruptured cerebral aneurysms: Does it harm?

text: BACKGROUND The fate and safety of thrombus remnant despite intra-arterial thrombolysis for unexpected thrombus formation has rarely been reported. METHODS From January 2010 to May 2015, 131 consecutive patients with ruptured intracranial aneurysms were treated by endovascular methods at our institution. Among the 21 patients (16%) treated by intra-arterial thrombolysis for the thrombus formation during the procedure, nine patients (nine aneurysms) suffered from thrombus remnant. We reviewed the clinical and radiologic outcomes of patients with thrombus remnant as well as intraoperative and postoperative management of thrombus formation. RESULTS Thrombus formation occurred near the coiled aneurysm in eight patients, and distal embolic occlusion was observed in one patient. All nine patients were initially managed by intra-arterial thrombolysis with tirofiban. One patient with persistent distal embolic occlusion and two patients with distal migration of the thrombus after intra-arterial thrombolysis were additionally treated with stent retriever. One patient with occlusion of the parent artery near the coiled aneurysm despite intra-arterial thrombolysis was partially recanalized by permanent deployment of a stent retriever. Delayed cerebral angiography showed no increase in size of thrombus remnant in any patients. After the procedure, thrombus remnant was managed by intravenous tirofiban. Follow-up CT angiography on the first postoperative day showed patent arterial flow, and ischemic complication related with thromboembolism did not occur in any patients. One patient suffered from hemorrhagic complication. CONCLUSION If the patency of parent artery is maintained and the size of the thrombus remnant does not increase on delayed angiography after intra-arterial thrombolysis, postoperative thromboembolic events rarely occur.


Public Health Approach of Ayurveda and Yoga for COVID-19 Prophylaxis.


title: [Facing the pandemic of 2019 novel coronavirus infections: the pediatric perspectives].

text: 自2019年12月中旬以来，武汉市暴发新型冠状病毒感染的肺炎流行，疫情很快扩散到全国各地以及境外国家，形势严峻。在本次重大突发疫情中，儿童确诊病例数占比很小，但随着疫情高峰及更多地区开展病原检测，儿童感染例数有较明显增多趋势，应予以高度重视。本文将从儿科医生的角度，重点就儿童病例的流行病学特征与防控措施、临床疾病特点与转归、诊断标准及治疗等方面进行讨论，并提出相应建议。.


COVID-19 lockdown in India triggers a rapid rise in suicides due to the alcohol withdrawal symptoms: Evidence from media reports.


COVID-19: children on the front line.


title: Combined lysis of thrombus with ultrasound and systemic tissue plasminogen activator for emergent revascularization in acute ischemic stroke (CLOTBUST-ER): design and methodology of a multinational phase 3 trial.

text: BACKGROUND We designed a Phase 3 clinical trial to determine the safety and efficacy of adding transcranial ultrasound using an operator-independent headframe to recombinant tissue-plasminogen-activator for the treatment of acute ischemic stroke. METHODS Combined lysis of thrombus with ultrasound and systemic tissue-plasminogen-activator for emergent revascularization in acute ischemic stroke is a randomized, double-blind, placebo-controlled clinical trial that will enroll subjects with the following main inclusion criteria: less than 4·5 hours from symptom onset (three-hours in US and Canada), age 18-80 years, baseline National Institutes of Health Stroke Scale score ≥ 10, and premorbid modified-Rankin-score of 0-1, eligibility for full dose recombinant tissue-plasminogen-activator. Subjects will receive two-hours of 2-MHz pulsed wave transcranial ultrasound (target group) or sham ultrasound (control group). The projected sample size is approximately 824 subjects. RESULTS The primary endpoint, based on intention-to-treat criteria of patients enrolled within three-hours of symptom onset is the comparison between target and control groups of modified-Rankin-score scores at day 90 poststroke assessed using the proportional odds method. The study will have two planned interim analyses after approximately one-third and two-thirds of subjects have reached the 90-day modified-Rankin-score evaluation. Safety outcomes are symptomatic intracranial hemorrhage within 24 h and an overall analysis of adverse events. CONCLUSIONS Since intravenous recombinant tissue-plasminogen-activator remains the only medical therapy to reverse ischemic stroke applicable in the emergency department, our trial will determine if the additional use of transcranial ultrasound improves functional outcomes in patients with severe acute ischemic stroke (NCT#01098981).


title: Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives.

text: Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity.


title: Intragastric Balloons: An Emerging Therapy for Nonalcoholic Steatohepatitis and Fibrosis?

text: Weight loss through lifestyle intervention remains the mainstay treatment for nonalcoholic steatohepatitis (NASH). Nevertheless, only a minority of patients undergoing lifestyle intervention are able to achieve the weight loss threshold that reverses NASH histologic features. This case report demonstrates a minimally invasive method of treating NASH using an intragastric balloon. With endoscopic ultrasound-guided liver biopsy at the time of intragastric balloon removal, we demonstrate a significant improvement in NASH histologic features including steatosis, ballooning, lobular inflammation, and fibrosis. This endoscopic method may offer an alternative solution to patients with NASH who fail lifestyle intervention.


Covid-19: face masks could foster distrust and blame.


title: Therapeutic occlusion of the vertebral artery using a new penumbra occlusion device system and ruby coils (penumbra): A technical note.

text: There are several methods to achieve the therapeutic sacrifice of the vessel, coiling brings the most commonly used. Penumbra occlusion device (POD) system is a newer modality for therapeutic large vessel occlusion, and it is the Food and Drug Administration approved only for peripheral vessels. We report a case where therapeutic vertebral artery (VA) occlusion was achieved with the POD system and Ruby coils for the first time. A patient was diagnosed with a new malignant-appearing tumor of the cervical spine. A conventional angiogram showed multiple tiny arterial feeders from the VA beyond scope of coil/onyx embolization, so we performed a balloon occlusion test followed by therapeutic sacrifice of the VA. A successful VA occlusion was achieved with significant reduction in the tumor blush, followed by open resection of the tumor. The patient had favorable postoperative course and without any neurological symptoms attributed to the VA occlusion.


title: The effect of ice slurry ingestion on body temperature and cycling performance in competitive athletes.

text: The effects of pre cooling on endurance performance are widely known. In contrast, the approach of cooling during endurance exercise in combination with pre-exercise cooling has been poorly understood. The purpose of the present study was to determine whether the effects of precooling and cooling during exercise enhance exercise performance compared to the ingestion of a thermo-neutral beverage (20 °C) or precooling alone in cycling performance. This was an experimental study using a randomised crossover design in which 7 cyclists underwent three trials comprising of 45 min steady state cycling (SS) at 70% VO2 max and a subsequent 10 km time trial (TT) in hot conditions (32 °C, 50% relative humidity). Rectal temperature (Tre), heat storage (HS), heart rate (HR), blood lactate concentration (BLA) and thermal sensation (TS) were measured. The intervention consisted of: (1) ingestion of thermo-neutral beverage before and during SS cycling (TN), (2) ingestion of ice slurry beverage and application of iced towels (precooling) prior to exercise, and then ingestion of thermo-neutral beverage during SS (PRE) and (3) precooling strategy as above plus ice slurry ingestion during SS cycling (PRE + MID). The intake of thermo-neutral or ice slurry beverage (14 g/kg) occurred over 30 min before and every 15 min during SS cycling. There was no significant difference in TT performance between all the conditions (P =0.72). However, PRE and PRE + MID caused a significant decrease in Tre (P < 0.05) from TN during exercise. Accordingly, both precooling and a combination of precooling and mid-cooling during exercise in hot conditions may be a practical and effective way of reducing core temperature. Future studies should investigate longer distance events and timing of ice slurry ingestion.


title: Endoscopic therapy for Barrett's oesophagus.

text: Barrett's oesophagus (BO) is thought to progress through the development of dysplasia (low grade and high grade) to oesophageal adenocarcinoma, a lethal cancer with poor survival. The overall goal of endoscopic therapy of BO is to eliminate metaplastic and dysplastic epithelium, to prevent and/or reduce the risk of progression to OAC. Endoscopic therapy techniques can be divided into two broad complementary techniques: tissue acquiring (endoscopic mucosal resection and endoscopic submucosal dissection) and ablative. Endoscopic therapy has been established as safe and effective for the subjects with intra-mucosal cancer (IMC), high-grade dysplasia (HGD) and more recently in treating low-grade dysplasia (LGD). Challenges to endoscopic therapy are being recognized, such as incomplete response and recurrence. While eradication of intestinal metaplasia is the immediate goal of endoscopic therapy, surveillance must continue after complete elimination of intestinal metaplasia, to detect and treat recurrences.


title: The EEG signal: a window on the cortical brain activity.

text: The accurate assessment of the depth of anesthesia, allowing a more accurate adaptation of the doses of hypnotics, is an important end point for the anesthesiologist. It is a particularly crucial issue in pediatric anesthesia, in the context of the recent controversies about the potential neurological consequences of the main anesthetic drugs on the developing brain. The electroencephalogram signal reflects the electrical activity of the neurons in the cerebral cortex. It is thus the key to assessment of the level of hypnosis. Beyond visual analysis, several monitoring devices allow an automated treatment of the electroencephalographic (EEG) signal, combining time and frequency domain analysis. Each of these monitors focuses on a specific combination of characteristics of the signal and provides the clinician with useful information that remains, however, partial. For a comprehensive approach of the EEG-derived indices, the main features of the normal EEG, in adults and children, will be presented in the awake state and during sleep. Age-related modifications accompanying cerebral maturation during infancy and childhood will be detailed. Then, this review will provide an update on how anesthetic drugs, particularly hypnotics, influence the EEG signal, and how the main available monitors analyze these drug-induced modifications. The relationships between pain, memory, and the EEG will be discussed. Finally, this review will focus on some specific EEG features such as the electrical epileptoid activity observed under sevoflurane anesthesia. The EEG signal is the best window we have on cortical brain activity and provides a fair pharmacodynamic feedback of the effects of hypnotics. However, the cortex is only one of several targets of anesthesia. Hypnotics and opiates, have also subcortical primary targets, and the EEG performances in the evaluation or prediction of nociception are poor. Monitoring subcortical structures in combination with the EEG might in the future allow a better evaluation and a more precise adaptation of balanced anesthesia.


title: A point prevalence cross-sectional study of healthcare-associated urinary tract infections in six Australian hospitals.

text: OBJECTIVES Urinary tract infections (UTIs) account for over 30% of healthcare-associated infections. The aim of this study was to determine healthcare-associated UTI (HAUTI) and catheter-associated UTI (CAUTI) point prevalence in six Australian hospitals to inform a national point prevalence process and compare two internationally accepted HAUTI definitions. We also described the level and comprehensiveness of clinical record documentation, microbiology laboratory and coding data at identifying HAUTIs and CAUTIs. SETTING Data were collected from three public and three private Australian hospitals over the first 6 months of 2013. PARTICIPANTS A total of 1109 patients were surveyed. Records of patients of all ages, hospitalised on the day of the point prevalence at the study sites, were eligible for inclusion. Outpatients, patients in adult mental health units, patients categorised as maintenance care type (ie, patients waiting to be transferred to a long-term care facility) and those in the emergency department during the duration of the survey were excluded. OUTCOME MEASURES The primary outcome measures were the HAUTI and CAUTI point prevalence. RESULTS Overall HAUTI and CAUTI prevalence was 1.4% (15/1109) and 0.9% (10/1109), respectively. Staphylococcus aureus and Candida species were the most common pathogens. One-quarter (26.3%) of patients had a urinary catheter and fewer than half had appropriate documentation. Eight of the 15 patients ascertained to have a HAUTI based on clinical records (6 being CAUTI) were coded by the medical records department with an International Classification of Diseases (ICD)-10 code for UTI diagnosis. The Health Protection Agency Surveillance definition had a positive predictive value of 91.67% (CI 64.61 to 98.51) compared against the Centers for Disease Control and Prevention definition. CONCLUSIONS These study results provide a foundation for a national Australian point prevalence study and inform the development and implementation of targeted healthcare-associated infection surveillance more broadly.


title: Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.

text: BACKGROUND Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. METHODS In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). FINDINGS Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. INTERPRETATION Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. FUNDING Netherlands Organisation for Health Research and Development.


title: Heat transfer within hydrodissection fluids: An analysis of thermal conduction and convection using liquid and gel materials.

text: Interventional oncology procedures such as thermal ablation are becoming widely used for many tumours in the liver, kidney and lung. Thermal ablation refers to the focal destruction of tissue by generating cytotoxic temperatures in the treatment zone. Hydrodissection - separating tissues with fluids - protects healthy tissues adjacent to the ablation treatment zone to improve procedural safety, and facilitate more aggressive power application or applicator placement. However, fluids such as normal saline and 5% dextrose in water (D5W) can migrate into the peritoneum, reducing their protective efficacy. As an alternative, a thermo-gelable poloxamer 407 (P407) solution has been recently developed to facilitate hydrodissection procedures. We hypothesise that the P407 gel material does not provide convective heat dissipation from the ablation site, and therefore may alter the heat transfer dynamics compared to liquid materials during hydrodissection-assisted thermal ablation. The purpose of this study was to investigate the heat dissipation mechanics within D5W, liquid P407 and gel P407 hydrodissection barriers. Overall it was shown that the gel P407 dissipated heat primarily through conduction, whereas the liquid P407 and D5W dissipated heat through convection. Furthermore, the rate of temperature change within the gel P407 was greater than liquid P407 and D5W. Testing to evaluate the in vivo efficacy of the fluids with different modes of heat dissipation seems warranted for further study.


title: A new approach to determine the results of minimally invasive pulmonary vein isolation using a continuous loop monitor: preliminary results.

text: OBJECTIVES Surgical ablation is a well-known treatment for atrial fibrillation (AF); however, little is known about the absolute success rate. The aim of this study is to compare the absolute pre- and postoperative incidence of AF after minimally invasive surgical ablation for paroxysmal AF. METHODS Twenty consecutive patients (mean age 55 ± 8; 55% male) received a continuous loop monitor (CLM) 4 weeks prior to a minimally invasive pulmonary vein isolation (MIPVI). The mean preoperative AF burden was compared with the mean AF burden during follow-up. Follow-up was achieved for a period of 12 months. RESULTS Seventeen patients underwent an MIPVI successfully. Two patients did not reach the threshold for surgery. In 1 patient, surgery was discontinued because of a perioperative bleeding due to adhesions after a previous percutaneous AF ablation. Mean AF burden preoperatively was 66%. After 12 months, there was an absolute reduction in AF burden of 65% (95% CI 42-88, P < 0.001) and 12 of 15 patients in follow-up (80%) were free of AF without antiarrhythmic drugs (AADs). CONCLUSIONS The use of a CLM in the follow-up of surgical ablation is a very accurate way to confirm absolute surgical results. Furthermore, with the use of a CLM, preoperative evaluation can be done more accurately, and the surgical procedure can be adjusted to the patients' needs.


title: Prioritizing "psychological" consequences for disaster preparedness and response: a framework for addressing the emotional, behavioral, and cognitive effects of patient surge in large-scale disasters.

text: While information for the medical aspects of disaster surge is increasingly available, there is little guidance for health care facilities on how to manage the psychological aspects of large-scale disasters that might involve a surge of psychological casualties. In addition, no models are available to guide the development of training curricula to address these needs. This article describes 2 conceptual frameworks to guide hospitals and clinics in managing such consequences. One framework was developed to understand the antecedents of psychological effects or "psychological triggers" (restricted movement, limited resources, limited information, trauma exposure, and perceived personal or family risk) that cause the emotional, behavioral, and cognitive reactions following large-scale disasters. Another framework, adapted from the Donabedian quality of care model, was developed to guide appropriate disaster response by health care facilities in addressing the consequences of reactions to psychological triggers. This framework specifies structural components (internal organizational structure and chain of command, resources and infrastructure, and knowledge and skills) that should be in place before an event to minimize consequences. The framework also specifies process components (coordination with external organizations, risk assessment and monitoring, psychological support, and communication and information sharing) to support evidence-informed interventions.


title: Detection of COVID-19 in a Vulvar Lesion.

text: As new information about coronavirus disease 2019 (COVID-19) is rapidly discovered, clinicians are better equipped to make informed decisions for their patients. While current research suggests COVID-19 viral antigen is not found in vaginal secretions, its detectability in the female lower genital tract may have clinical implications for obstetric and gynecologic care for women. We present a case of a woman at 31 weeks' gestation with simultaneous upper respiratory symptoms and vulvovaginitis. She was found to have a vulvar lesion positive for severe acute respiratory syndrome-COVID by viral swab. This case shows that COVID-19 is detectable in the vulva. This may have implications for health care workers' exposure and personal protective equipment needs. While vertical transmission has largely not been reported, the presence of detectable virus in the female lower genital tract makes this a continued possibility and area of study. KEY POINTS: · COVID-19 is detectable in the female lower genital tract.. · The detection of COVID-19 in the vulva may have implications for personal protective equipment use.. · The detection of COVID-19 in vulvovaginal lesions makes vertical transmission a continued possibility..


title: Protective effects of purple grape juice on carbon tetrachloride-induced oxidative stress in brains of adult Wistar rats.

text: The antioxidant properties of purple grape juice, organic and conventional, in brain tissues are not well known. In this study our objective was to evaluate the antioxidant activity in substantia nigra and striatum of rats chronically treated with organic or conventional purple grape juice and to correlate the results obtained with the polyphenol content (total polyphenolic content, resveratrol, and anthocyanins [malvidin, delphinidin, peonidin, and cyanidin]). We observed that CCl(4) damage decreased significantly in the grape juice-treated groups when compared with the control group. In the grape juice-treated groups we further observed a decrease of lipid (thiobarbituric acid-reactive substances assay) and protein (carbonyl) peroxidation, as well as a significant antioxidant protection through the increase of enzyme activity. Antioxidant activities were significantly correlated with polyphenol content. These findings demonstrated that both grape juices have potent antioxidant properties and these activities could be at least attributed to the high phenolic content present in these juices.


title: Viruses and non-allergen environmental triggers in asthma.

text: Asthma is a complex inflammatory disease with many triggers. The best understood asthma inflammatory pathways involve signals characterized by peripheral eosinophilia and elevated immunoglobulin E levels (called T2-high or allergic asthma), though other asthma phenotypes exist (eg, T2-low or non-allergic asthma, eosinophilic or neutrophilic-predominant). Common triggers that lead to poor asthma control and exacerbations include respiratory viruses, aeroallergens, house dust, molds, and other organic and inorganic substances. Increasingly recognized non-allergen triggers include tobacco smoke, small particulate matter (eg, PM2.5), and volatile organic compounds. The interaction between respiratory viruses and non-allergen asthma triggers is not well understood, though it is likely a connection exists which may lead to asthma development and/or exacerbations. In this paper we describe common respiratory viruses and non-allergen triggers associated with asthma. In addition, we aim to show the possible interactions, and potential synergy, between viruses and non-allergen triggers. Finally, we introduce a new clinical approach that collects exhaled breath condensates to identify metabolomics associated with viruses and non-allergen triggers that may promote the early management of asthma symptoms.


title: Detection of respiratory viruses and the associated chemokine responses in serious acute respiratory illness.

text: BACKGROUND A specific diagnosis of a lower respiratory viral infection is often difficult despite frequent clinical suspicion. This low diagnostic yield may be improved by use of sensitive detection methods and biomarkers. METHODS The prevalence, clinical predictors and inflammatory mediator profile of respiratory viral infection in serious acute respiratory illness were investigated. Sequential bronchoalveolar lavage (BAL) fluids from all patients hospitalised with acute respiratory illness over 12 months (n=283) were tested for the presence of 17 respiratory viruses by multiplex PCR assay and for newly discovered respiratory viruses (bocavirus, WU and KI polyomaviruses) by single-target PCR. BAL samples also underwent conventional testing (direct immunoflorescence and viral culture) for respiratory virus at the clinician's discretion. 27 inflammatory mediators were measured in a subset of the patients (n=64) using a multiplex immunoassay. RESULTS 39 respiratory viruses were detected in 37 (13.1% of total) patients by molecular testing, including rhinovirus (n=13), influenza virus (n=8), respiratory syncytial virus (n=6), human metapneumovirus (n=3), coronavirus NL63 (n=2), parainfluenza virus (n=2), adenovirus (n=1) and newly discovered viruses (n=4). Molecular methods were 3.8-fold more sensitive than conventional methods. Clinical characteristics alone were insufficient to separate patients with and without respiratory virus. The presence of respiratory virus was associated with increased levels of interferon gamma-inducible protein 10 (IP-10) (p<0.001) and eotaxin-1 (p=0.017) in BAL. CONCLUSIONS Respiratory viruses can be found in patients with serious acute respiratory illness by use of PCR assays more frequently than previously appreciated. IP-10 may be a useful biomarker for respiratory viral infection.


title: Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques.

text: The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.


title: Morphological changes and clinical impact of unstable plaques within untreated segments of acute myocardial infarction patients during a 3-year follow-up: an analysis from the HORIZONS-AMI trial.

text: OBJECTIVES Plaque ruptures and attenuated plaques are considered to be unstable and have been identified in both culprit and nonculprit lesions of patients with ST-segment elevation myocardial infarction (STEMI). However, there are limited data available on the natural evolution of these plaques and their long-term clinical outcome. We investigated the natural evolution and long-term impact of plaque ruptures and attenuated plaques in untreated segments of infarct-related arteries in patients with STEMI. METHODS In the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial, 389 patients with 429 lesions underwent intravascular ultrasound (IVUS) at baseline. Follow-up IVUS at 13 months was conducted in 245 patients. Three-year follow-up data were available for all patients. RESULTS Segments not treated between baseline and follow-up were compared. Baseline IVUS identified 29 plaque ruptures in 27 patients (7%). Of 11 plaque ruptures with follow-up IVUS, four healed and seven persisted. Conversely, through follow-up IVUS, nine new plaque ruptures in nine patients (4%) were identified. Attenuated plaques were identified in 31 of 38 plaque ruptures (81.5%), of which 24 were in the same circumferential segment as the ruptured cavity and seven were within 5 mm proximal or distal to the plaque rupture. Morphologic changes during follow-up, including new plaque ruptures and changes in the attenuated plaque frequency and distribution, were not accompanied by either serious lumen compromise or clinical events. CONCLUSION Serial IVUS analysis demonstrated that the morphology of unstable plaques within untreated segments in STEMI patients treated with optimal systemic therapies markedly changed during the 13-month follow-up period, without lumen compromise or clinical events at the 3-year follow-up.


title: Risk of bias and methodological appraisal practices in systematic reviews published in anaesthetic journals: a meta-epidemiological study.

text: The validity of primary study results included in systematic reviews plays an important role in drawing conclusions about intervention effectiveness and carries implications for clinical decision-making. We evaluated the prevalence of methodological quality and risk of bias assessments in systematic reviews published in the five highest-ranked anaesthesia journals since 2007. The initial PubMed search yielded 315 citations, and our final sample after screening consisted of 207 systematic reviews. One hundred and seventy-four reviews conducted methodological quality/risk of bias analyses. The Jadad scale was most frequently used. Forty-four of the 83 reviews that included high risk of bias studies re-analysed their data omitting these trials: 20 showed differences in pooled effect estimates. Reviews containing a greater number of primary studies evaluated quality less frequently than smaller reviews. Overall, the majority of reviews evaluated bias; however, many applied questionable methods. Given the potential effects of bias on summary outcomes, greater attention is warranted.


title: TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting TAB2 and TAB3 for degradation.

text: Toll-like receptor (TLR) signaling is pivotal to innate and adaptive immune responses and must be tightly controlled. The mechanisms of TLR signaling have been the focus of extensive studies. Here we report that the tripartite-motif protein TRIM30alpha, a RING protein, was induced by TLR agonists and interacted with the TAB2-TAB3-TAK1 adaptor-kinase complex involved in the activation of transcription factor NF-kappaB. TRIM30alpha promoted the degradation of TAB2 and TAB3 and inhibited NF-kappaB activation induced by TLR signaling. In vivo studies showed that transfected or transgenic mice overexpressing TRIM30alpha were more resistant to endotoxic shock. Consistent with that, in vivo 'knockdown' of TRIM30alpha mRNA by small interfering RNA impaired lipopolysaccharide-induced tolerance. Finally, expression of TRIM30alpha depended on NF-kappaB activation. Our results collectively indicate that TRIM30alpha negatively regulates TLR-mediated NF-kappaB activation by targeting degradation of TAB2 and TAB3 by a 'feedback' mechanism.


title: Chronic pain after laparoscopic transabdominal preperitoneal hernia repair: a randomized comparison of light and extralight titanized polypropylene mesh.

text: BACKGROUND The aim of this prospective, randomized, single-blinded clinical trial was to compare the incidence of chronic pain after laparoscopic transabdominal preperitoneal hernia repair (TAPP) using a 35-g/m2 titanized polypropylene mesh and a 16-g/m2 titanized polypropylene mesh. The reported incidence of chronic pain in patients who underwent laparoscopic hernia repair is a serious problem. The techniques of dissection, mesh fixation, and the mesh material used have all been identified as being part of the problem. Excellent biocompatibility through a unique combination of a lightweight open porous polypropylene mesh covered with a covalent-bonded titanium layer has been claimed. The aim of this study was to find out whether the titanium surface alone or the difference in material load between the two available meshes influences clinical outcomes. METHODS Three hundred eighty patients with 466 inguinal hernias were operated on between 2002 and 2006 with the laparoscopic transabdominal preperitoneal (TAPP) technique. Mesh fixation with staples was carried out routinely. After the dissection was completed just prior to the implantation of the mesh, patients were randomized into two groups. In Group A, 250 (53.6%) inguinal hernias were repaired with a 35-g/m2 titanized polypropylene mesh, and in Group B, 216 (46.4%) inguinal hernias were repaired with a 16-g/m2 titanized polypropylene mesh. The primary outcome was chronic pain 3 years after surgery. The degree of pain was determined using a visual analog scale (VAS) with a range from 0 to 10. The secondary outcome was the rate of recurrence. RESULTS The postoperative period of observation was at least 3 years for every patient. In both groups, 90% of the patients could be questioned and examined clinically: in Group A (Light), 5.3% of the patients and in Group B (Extralight), 1.5% of the patients suffered from chronic pain. Chronic pain was significantly more common in Group A than in Group B (p=0.037). There was no difference with respect to the rate of recurrence: for Group A it was 3.1% and for Group B it was 2.6% (p=0.724). CONCLUSIONS Chronic pain is not very common in patients who have had their inguinal hernias repaired with titanium-covered polypropylene mesh. Reducing the material load from 35 to 16 g/m2 seems to further improve the biocompatibility of these meshes, thus improving the clinical outcome by reducing chronic pain to a rare event. The role of staples in causing chronic pain following inguinal hernia repair may be overestimated. There was no evidence supporting the notion that the use of the 16-g/m2 titanized meshes is associated with increased recurrence rates.


title: Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists.

text: Considerable success has been made with many peptide antigen formulations, and peptide-based vaccines are emerging as the next generation of prophylactic and remedial immunotherapy. However, finding an optimal platform balancing all of the requirements for an effective, specific and safe immune response remains a major challenge for many infectious and chronic diseases. This review outlines how peptide immunogenicity is influenced by the way in which peptides are presented to the immune system, underscoring the need for multifunctional delivery systems that couple antigen and adjuvant into a single construct. Particular attention is given to the ability of Toll-like receptor agonists to act as adjuvants. A survey of recent approaches to developing peptide antigen delivery systems is given, many of which incorporate Toll-like receptor agonists into the design.


title: Differential diagnosis of alterations in arterial flow and tissue oxygenation on venoarterial extracorporeal membrane oxygenation.

text: BACKGROUND Venoarterial extracorporeal membrane oxygenation (VA-ECMO) may be life-saving in several clinical situations, but it is also one of the most invasive therapeutic procedures, with significant potential for life-threatening complications. Pulse pressure waves are typically very small or even absent at the onset of ECMO therapy, and will reappear with the improvement of cardiac function. A low pulse pressure may indicate low cardiac output due to heart failure during sustained ECMO support. A sudden loss of pulse pressure during ECMO therapy, however, may reveal complications like pericardial tamponade, hemothorax or pneumothorax. Near infrared spectroscopy (NIRS) has been shown to be useful in detecting cerebral and lower limb ischemic events during ECMO therapy and could furthermore improve differential diagnosis in the event pulsatility of the arterial pressure trace is lost. METHODS We are reporting on 3 different complications of ECMO and their impact on arterial pulse pressure, arterial oxygen tension and regional tissue oxygenation measured by NIRS. RESULTS Pericardial hematoma, overinflation of the lung, and tension pneumothorax may impede cardiac output during VA-ECMO and cause a loss of pulse pressure. Monitoring of regional tissue oxygenation using NIRS, in addition to arterial and mixed venous oxygen tension, may allow early recognition and treatment of ECMO complications. CONCLUSIONS Together with the appearance of a flat, non pulsatile arterial pressure trace as well as a reduction in mixed venous oxygen saturation the improvement of upper body rSO2 measured by NIRS enables timely recognition of complications that interfere with natural cardiac output during VA-ECMO.


title: Traumatic laryngotracheal stenosis treated by hyoid-sternohyoid osseomuscular flap combined with xenogenic acellular dermal matrix: A case report and literature review.

text: Objective The treatment of laryngotracheal stenosis is a major therapeutic challenge. Various treatments include observation, medical management, and surgical management. The most effective surgical management is resection and reconstruction. To the authors' knowledge, no reports have described the use of xenogenic acellular dermal matrix (ADM) for laryngotracheal stenosis. Methods A 27-year-old man presented with hemoptysis of the neck due to a traffic accident. Emergency orotracheal intubation was performed. Tracheostomy was then performed under local anesthesia. Computed tomography revealed fractures of the right thyroid cartilage and posterior arc of the cricoid cartilage and stenosis of the subglottis and first and second tracheal rings. We used a composite hyoid-sternohyoid osseomuscular flap with xenogenic ADM and a straight silicone tube as a lumen stent to reconstruct the laryngotracheal stenosis. Results Surgical recovery was uneventful. The tracheotomy opening was changed to a metal tube 5 days postoperatively. Four months postoperatively, the silicone tube was endoscopically removed under local anesthesia. The patient was decannulated 20 days later. The patient satisfied with his voice, respiration, and deglutition at the 16-month postoperative follow-up. Conclusion The use of ADM for laryngotracheal stenosis may reduce the growth of granulation tissues and promote the repair process.


Central Pancreatectomy with Double Pancreaticojejunostomy.


title: Disease avoidance as a functional basis for stigmatization.

text: Stigmatization is characterized by chronic social and physical avoidance of a person(s) by other people. Infectious disease may produce an apparently similar form of isolation-disease avoidance-but on symptom remission this often abates. We propose that many forms of stigmatization reflect the activation of this disease-avoidance system, which is prone to respond to visible signs and labels that connote disease, irrespective of their accuracy. A model of this system is presented, which includes an emotional component, whereby visible disease cues directly activate disgust and contamination, motivating avoidance, and a cognitive component, whereby disease labels bring to mind disease cues, indirectly activating disgust and contamination. The unique predictions of this model are then examined, notably that people who are stigmatized evoke disgust and are contaminating. That animals too show avoidance of diseased conspecifics, and that disease-related stigma targets are avoided in most cultures, also supports this evolutionary account. The more general implications of this approach are then examined, notably how it can be used to good (e.g. improving hygiene) or bad (e.g. racial vilification) ends, by yoking particular labels with cues that connote disease and disgust. This broadening of the model allows for stigmatization of groups with little apparent connection to disease.


title: A Simple Diagnostic Test to Confirm Correct Placement of Dysfunctional Central Venous Catheters Before Chemotherapy in Children.

text: BACKGROUND In children undergoing intravenous chemotherapy, partial dysfunction of the central venous catheter (CVC) is common. Fluids can be infused into the catheter; however, blood cannot be aspirated. In those situations, chemotherapy is withheld and a catheter investigation is performed. Usually, a radiographic study with contrast media or therapy with thrombolytic drugs followed by rechecking for blood return is undertaken. AIM To evaluate if a previously described method using dilute sodium bicarbonate injection and the resultant rise in measured end-tidal carbon dioxide tracing can confirm correct intravascular placement of a dysfunctional CVC in children at the bedside. PATIENTS Cohort group of 22 children scheduled for chemotherapy with partial dysfunction of a CVC in a tertiary hematology-oncology care facility. RESULTS All children with a partial dysfunctional CVC that was proven to be intravascular after venogram or thrombolytic therapy had a distinct and predictable increase in end-tidal carbon dioxide response to injected bicarbonate. CONCLUSION Injection of 1 mL/kg (maximum 20 mL) of 4.2% dilute sodium bicarbonate is a quick, simple, bedside test allowing confirmation of intravascular location of dysfunctional CVC.


title: Non-restraining EEG Radiotelemetry: Epidural and Deep Intracerebral Stereotaxic EEG Electrode Placement.

text: Implantable EEG radiotelemetry is of central relevance in the neurological characterization of transgenic mouse models of neuropsychiatric and neurodegenerative diseases as well as epilepsies. This powerful technique does not only provide valuable insights into the underlying pathophysiological mechanisms, i.e., the etiopathogenesis of CNS related diseases, it also facilitates the development of new translational, i.e., therapeutic approaches. Whereas competing techniques that make use of recorder systems used in jackets or tethered systems suffer from their unphysiological restraining to semi-restraining character, radiotelemetric EEG recordings overcome these disadvantages. Technically, implantable EEG radiotelemetry allows for precise and highly sensitive measurement of epidural and deep, intracerebral EEGs under various physiological and pathophysiological conditions. First, we present a detailed protocol of a straight forward, successful, quick and efficient technique for epidural (surface) EEG recordings resulting in high-quality electrocorticograms. Second, we demonstrate how to implant deep, intracerebral EEG electrodes, e.g., in the hippocampus (electrohippocampogram). For both approaches, a computerized 3D stereotaxic electrode implantation system is used. The radiofrequency transmitter itself is implanted into a subcutaneous pouch in both mice and rats. Special attention also has to be paid to pre-, peri- and postoperative treatment of the experimental animals. Preoperative preparation of mice and rats, suitable anesthesia as well as postoperative treatment and pain management are described in detail.


title: The Impact of Frailty on Short-Term Outcomes After Elective Hip and Knee Arthroplasty in Older Adults: A Systematic Review.

text: Introduction This systematic literature review evaluates (1) frailty in older adults as a risk factor for short-term adverse events and suboptimal clinical outcomes after total joint arthroplasty and (2) interventions to improve arthroplasty outcomes in these frail patients. Methods PubMed, EMBASE, Cochrane Register of Controlled Trials, SCOPUS, AgeLine, and Web of Science were searched from database inception to November 22, 2017; gray literature and references were also searched. Studies including adults ≥65 years of age undergoing hip or knee arthroplasty and measuring preoperative frailty and postoperative adverse events or clinical outcomes within 90 days of surgery were included. Two investigators independently screened all abstracts and extracted data; disagreements were adjudicated by a third reviewer. Risk of bias was assessed using the Newcastle-Ottawa scale for cohort studies and the Cochrane Risk of Bias tool for randomized controlled trials. Study quality was assessed using a 5-point scale modified from the Oxford Centre for Evidence-Based Medicine tool. Results Of 1913 abstracts identified, 82 full texts were reviewed, and 13 met inclusion criteria: 5 prospective cohort studies, 6 retrospective cohort studies, and 2 randomized controlled trials covering 382 763 total patients. These studies used 13 frailty instruments and assessed 32 distinct outcomes. Substantial heterogeneity precluded valid meta-analysis; results were qualitatively summarized by study design, frailty instrument, and outcome type. Of the 11 cohort studies, 10 found significant associations between frailty and poor postoperative outcomes. Trials of preoperative frailty-modifying interventions found no association between interventions and improved outcomes. Discussion Standardizing frailty measurement would improve generalizability, permitting the assessment of associations with patient-reported and functional outcome measures, as well as the efficacy of interventions to improve outcomes, in frail patients undergoing arthroplasty. Conclusions Frailty is associated with higher rates of short-term adverse events and worse clinical outcomes after elective hip and knee arthroplasty.


title: Single-incision laparoscopic colectomy for colon cancer: early experience with 31 cases.

text: BACKGROUND Transumbilical single-port surgery has been developed with the aim to further reduce the invasiveness of conventional laparoscopy. OBJECTIVE This study aimed to report our experience with 31 patients who were treated with transumbilical single-incision laparoscopic colectomy for colon cancer. DESIGN This is a retrospective review of prospectively gathered data. SETTINGS This study was conducted at the Department of Surgery of Juntendo University Urayasu Hospital between April 2009 and April 2010. Data were obtained from a prospectively maintained single-institution laparoscopic colon cancer database. PATIENTS Thirty-one consecutively selected patients (mean BMI, 22.5 ± 2.3) were evaluated. INTERVENTIONS All patients underwent single-incision laparoscopic colectomy for colon cancer. Two different approaches were used for single-incision laparoscopic colectomy: the trocar insertion method and the SILS port method. The trocar insertion method was adopted in 22 of 31 patients, and the SILS port method was used in 9 patients. MAIN OUTCOME MEASURES The main measures of outcomes were intraoperative findings, postoperative course, and oncological outcomes. RESULTS The most common procedure was sigmoid colon resection performed in 12 of 31 (39%) patients. The mean skin incision was 2.72 ± 0.79 (range, 3-5) cm. The operating time ranged from 101 to 263 (mean, 156 ± 45) minutes. The volume of bleeding ranged from 5 to 60 (mean, 27 ± 19) mL. No intraoperative complications were observed in this series. Postoperatively, there was no mortality. Wound infection was observed in 1 patient. The number of harvested lymph nodes was 18 ± 2.1, and the mean tumor-free resection margin was 11 ± 4.8 cm. CONCLUSION Our experience indicates that single-incision laparoscopic colectomy is feasible for selected patients with colon cancer.


title: Methamphetamine Use Associated with Non-adherence to Antiretroviral Treatment in Men Who Have Sex with Men.

text: Methamphetamine is a prevalent recreational drug among men who have sex with men (MSM) living with HIV and could cause the cognitive impairment and memory loss. However, studies on the association between methamphetamine use and adherence to antiretroviral treatment (ART) are limited and had inconsistent findings. This study aimed to determine the impact of methamphetamine use on adherence to ART among MSM living with HIV. From December 2018 to October 2019, MSM living with HIV were recruited (N = 351) and non-adherence to ART was defined as a Medication Adherence Report Scale score of <23. Overall, 16.0% of the participants reported methamphetamine use in the prior three months and 13.4% of the participants had non-adherence to ART. The proportion of non-adherence to ART among HIV-positive MSM were 28.6% and 10.5% with and without methamphetamine use, respectively. After controlling for demographics, illicit drug use, and co-morbidities, methamphetamine use during the prior three months was associated with a higher risk of non-adherence to ART (adjusted odds ratio = 3.08; 95% confidence intervals: 1.24-7.69). Compared with HIV-positive MSM with non-adherence to ART, HIV-positive MSM with good adherence to ART had a higher CD4 counts and were more likely to achieve an undetectable viral load. Since poor adherence to ART is associated with an increased HIV viral load and the risk of HIV transmission to others, our study suggests that it is imperative to screen HIV-positive patients for methamphetamine use and to provide effective therapy to reduce methamphetamine use and the associated non-adherence to ART.


title: What happens to people's lungs when they get coronavirus disease 2019?

text: The novel coronavirus SARS-CoV-2 was first identified in Wuhan in December 2019 as cause of the consequent novel coronavirus disease 2019 (COVID-19). The virus has since spread worldwide. The clinical presentation following human infection ranges from a mild upper respiratory tract infection to severe acute respiratory distress syndrome and sepsis. We reviewed literature using Pubmed to identify relevant English-language articles published until April 15, 2020. Search terms include novel coronavirus pneumonia, severe acute respiratory syndrome coronavirus 2, coronavirus and ventilation. We summarized what SARS-CoV-2 infection means for the lungs.


title: NOTES rectosigmoid resection using transanal endoscopic microsurgery (TEM) with transgastric endoscopic assistance: a pilot study in swine.

text: INTRODUCTION Transanal endoscopic microsurgery (TEM) provides direct endoscopic access to the rectum and peritoneal cavity. The feasibility of natural orifice translumenal endoscopic surgery (NOTES) rectosigmoid resection using TEM was evaluated in swine. Transgastric endoscopic assistance to extend transanal colon mobilization was also investigated. Full-thickness circumferential rectal dissection was performed and extended proximally. After maximal sigmoid mobilization, the specimen was exteriorized and transected, and the proximal colon was stapled to the distal rectum. In a subset of animals, transgastric endoscopic access was used to mobilize the colon further. RESULTS Rectosigmoid resection using TEM was performed in two non-survival and seven swine cadavers (n = 9). The mean procedure time was 3 h (2.5-4 h), and mean length of resected colon was 16.7 cm (10-25 cm). Transgastric endoscopic assistance was used in three cadavers and two non-survival swine (n = 5) with a mean operative time of 3.5 h (3.5-3.75 h). The mean length of colon mobilized with transgastric and transanal endoscopic access was 24.4 cm (20-27 cm) vs. 16.7 cm which mobilized the transanal approach alone (p = 0.016). A posterior anastomotic defect was noted in two animals. CONCLUSION Transanal rectosigmoid resection with TEM is feasible in swine. Combined transgastric and TEM access is a promising new technique for NOTES colorectal resection.


title: Mutations across murine hepatitis virus nsp4 alter virus fitness and membrane modifications.

text: UNLABELLED A common feature of infection by positive-sense RNA virus is the modification of host cell cytoplasmic membranes that serve as sites of viral RNA synthesis. Coronaviruses induce double-membrane vesicles (DMVs), but the role of DMVs in replication and virus fitness remains unclear. Coronaviruses encode 16 nonstructural proteins (nsps), three of which, nsp3, nsp4, and nsp6, are necessary and sufficient for DMV formation. It has been shown previously that mutations in murine hepatitis virus (MHV) nsp4 loop 1 that alter nsp4 glycosylation are associated with disrupted DMV formation and result in changes in virus replication and RNA synthesis. However, it is not known whether DMV morphology or another function of nsp4 glycosylation is responsible for effects on virus replication. In this study, we tested whether mutations across nsp4, both alone and in combination with mutations that abolish nsp4 glycosylation, affected DMV formation, replication, and fitness. Residues in nsp4 distinct from glycosylation sites, particularly in the endoplasmic reticulum (ER) luminal loop 1, independently disrupted both the number and morphology of DMVs and exacerbated DMV changes associated with loss of glycosylation. Mutations that altered DMV morphology but not glycosylation did not affect virus fitness while viruses lacking nsp4 glycosylation exhibited a loss in fitness. The results support the hypothesis that DMV morphology and numbers are not key determinants of virus fitness. The results also suggest that nsp4 glycosylation serves roles in replication in addition to the organization and stability of MHV-induced double-membrane vesicles. IMPORTANCE All positive-sense RNA viruses modify host cytoplasmic membranes for viral replication complex formation. Thus, defining the mechanisms of virus-induced membrane modifications is essential for both understanding virus replication and development of novel approaches to virus inhibition. Coronavirus-induced membrane changes include double-membrane vesicles (DMVs) and convoluted membranes. Three viral nonstructural proteins (nsps), nsp3, nsp4, and nsp6, are known to be required for DMV formation. It is unknown how these proteins induce membrane modification or which regions of the proteins are involved in DMV formation and stability. In this study, we show that mutations across nsp4 delay virus replication and disrupt DMV formation and that loss of nsp4 glycosylation is associated with a substantial fitness cost. These results support a critical role for nsp4 in DMV formation and virus fitness.


title: When chaos is the norm: How some veterans with PTSD are continuing to engage in trauma-focused treatments during the COVID-19 pandemic.

text: The COVID-19 pandemic has caused many Veterans Healthcare Administration providers working with veterans diagnosed with posttraumatic stress disorder to question the feasibility and appropriateness of continuing to provide trauma-focused treatment during this crisis. The Veterans Healthcare Administration is in a unique position to continue to provide trauma-informed care because of its capacity to offer telemental health services. Data from a Veterans Affairs medical center's posttraumatic stress disorder clinical team suggest that not only are veterans interested in continuing with treatment but also that the treatments can be modified to accommodate the current climate. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus nonabsorbable mesh: a randomized controlled trial.

text: OBJECTIVE Determine whether absorbable or nonabsorbable mesh in repair of large hiatus hernias reduces the risk of recurrence, compared with suture repair. BACKGROUND Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%, and to improve outcomes mesh repair has been recommended. Previous trials have shown less short-term recurrence with mesh, but adverse outcomes limit mesh use. METHODS Multicentre prospective double blind randomized controlled trial of 3 methods of repair: sutures versus absorbable mesh versus nonabsorbable mesh. Primary outcome-hernia recurrence assessed by barium meal radiology and endoscopy at 6 months. Secondary outcomes-clinical symptom scores at 1, 3, 6, and 12 months. RESULTS A total of 126 patients enrolled: 43 sutures, 41 absorbable mesh, and 42 nonabsorbable mesh. Among them, 96.0% were followed up to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any size) was identified in 23.1% after suture repair, 30.8% after absorbable mesh, and 12.8% after nonabsorbable mesh (P = 0.161). Clinical outcomes were similar, except less heartburn at 3 and 6 months and less bloating at 12 months with nonabsorbable mesh; more heartburn at 3 months, odynophagia at 1 month, nausea at 3 and 12 months, wheezing at 6 months; and inability to belch at 12 months after absorbable mesh. The magnitudes of the clinical differences were small. CONCLUSIONS No significant differences were seen for recurrent hiatus hernia, and the clinical differences were unlikely to be clinically significant. Overall outcomes after sutured repair were similar to mesh repair.


title: Total extraperitoneal approach for incarcerated obturator hernia repair.

text: PURPOSE To compare the feasibilities and efficacies of the total extraperitoneal (TEP) technique and laparotomy for incarcerated obturator hernia repair. METHODS All study subjects were diagnosed with incarcerated obturator hernia, preoperatively and TEP was performed as for TEP groin hernia repair. The incarcerated intestine was retracted into the peritoneal cavity with the hernia sac. The obturator foramen was then covered with a rectangular mesh (9 × 13 cm), which also covered the internal inguinal ring, Hesselbach's triangle, and the femoral ring. Non-ischemia of the incarcerated bowel was confirmed laparoscopically. In patients undergoing laparotomy, the obturator foramen was closed by continuous sutures, and no prosthesis was used. We recorded the length of hospital stay, operative time, amount of intraoperative bleeding, and postoperative complications. RESULTS Twenty-two patients underwent obturator hernia repair in our hospital between January 2000 and December 2012, of whom 10 were treated with laparotomy and the remaining 12 via TEP. Three patients undergoing TEP were converted to laparotomy. The operation time was significantly longer in the conversion group compared with either the laparotomy or the TEP groups. There was no difference between the laparotomy and TEP groups regarding intraoperative bleeding. Patients who underwent TEP without conversion had a significantly shorter hospital stay than those who underwent laparotomy or required conversion. CONCLUSIONS TEP provides a suitable approach for incarcerated obturator hernia repair, with favorable results regarding hospital stay. TEP is a feasible, minimally invasive technique for the repair of incarcerated obturator hernias.


title: Independent Predictors of the Duration and Overall Burden of Postoperative Delirium After Cardiac Surgery in Adults: An Observational Cohort Study.

text: OBJECTIVE Postoperative delirium (POD) is a common complication after cardiac surgery and is associated with increased patient morbidity and mortality. The objective of this study was to identify risk factors for long duration and overall burden of POD after cardiac surgery. DESIGN One-year, single-center, retrospective, observational cohort study. SETTING University hospital. PARTICIPANTS Adult patients undergoing cardiac surgery with cardiopulmonary bypass in 2013. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patients were screened for POD using the Intensive Care Delirium Screening Checklist. The primary outcome measure was the incidence of POD. Secondary outcome measures were the duration of POD and the area under the curve determined using the Intensive Care Delirium Screening Checklist score over time. Independent predictors of POD were estimated in multivariable logistic regression models. Hospital length of stay, medications, and outcome data also were analyzed. Among the 656 patients included in the cohort, 618 were analyzed. The overall incidence of POD was 39%. Older patient age (odds ratio [95% confidence interval]) 1.06 [1.04-1.09] for an increase of 1 year, p < 0.001); low preoperative serum albumin (1.08 [1.03-1.13] for a decrease of 1 g/L, p < 0.001); a history of atrial fibrillation (2.30 [1.30-4.09], p = 0.004); perioperative stroke (6.27 [1.54-43.64], p = 0.008); ascending aortic replacement surgery (2.99 [1.50-6.05], p = 0.002); longer duration of procedure (1.37 [1.16-1.63] for an increase of 1 hour, p < 0.001); and increased postoperative C-reactive protein concentration (2.16 [1.49-3.16] for a 2-fold increase, p < 0.001) were associated with higher odds of POD. Among patients affected by POD, older age, perioperative stroke, longer procedure time, and increased postoperative C-reactive protein were consistently predictive of longer duration of POD and greater area under the curve. CONCLUSIONS Known risk factors for the development of POD after cardiac surgery also are predictive of prolonged duration and high overall burden of POD.