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The present invention pertains to a system of collaborative modifiers that are assembled into a multi molecule complex in vivo within a cell using bioorthogonal chemical reactions. The system of the invention is composed of multiple binding molecules having a binding affinity to a biological target macromolecule. Each of the binding molecules individually can easily be delivered into a target cell and then, when they bind to their target in the cell, will assemble into a higher multi-molecule complex on the target to increase overall binding specificity, selectivity and strength. Using the invention allows to mimic complex protein-protein interactions, for example the binding of biological macromolecules such as antibodies or receptor ligands with a set of small binding molecules that can be irreversibly assembled during use. The invention is of particular use for therapeutic applications involving intracellular drug targets and/or for crossing the blood brain barrier for targets within the central nervous system and/or for improving therapeutics penetration in tumour tissue. Thus, invention further provides pharmaceutical compositions comprising the components of the system of the invention, and their use in therapy of various diseases. Also provided are methods for the manufacture and design of the collaborative system and system components of the invention.
Reproduction studies have been performed in mice, rats, and rabbits at doses up to ten (10) times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ampicillin and sulbactam. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. (see – PRECAUTIONS-Drug/Laboratory Test Interactionssection). Labor and Delivery: Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However, it is not known whether the use of ampicillin and sulbactam in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. Nursing Mothers: Low concentrations of ampicillin and sulbactam are excreted in the milk; therefore, caution should be exercised when ampicillin and sulbactam is administered to a nursing woman. Pediatric Use: The safety and effectiveness of ampicillin and sulbactam have been established for pediatric patients one year of age and older for skin and skin structure infections as approved in adults. Use of ampicillin and sulbactam in pediatric patients is supported by evidence from adequate and well-controlled studies in adults with additional data from pediatric pharmacokinetic studies, a controlled clinical trial conducted in pediatric patients and post-marketing adverse events surveillance. (see CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE, ADVERSE REACTIONS, DOSAGE AND ADMINISTRATION, and CLINICAL STUDIESsections). The safety and effectiveness of ampicillin and sulbactam have not been established for pediatric patients for intra-abdominal infections.
Bipolar I Disorder, manic or mixed episodes Adults The efficacy of SEROQUEL XR in the acute treatment of manic episodes was established in one 3-week, placebo-controlled trial (Study 1 in Table 27) in patients who met DSM-IV criteria for bipolar I disorder with manic or mixed episodes with or without psychotic features (N=316). Patients were hospitalized for a minimum of 4 days at randomization. Patients randomized to SEROQUEL XR received 300 mg on Day 1 and 600 mg on Day 2. Afterwards, the dose could be adjusted between 400 mg and 800 mg per day. The primary rating instrument used for assessing manic symptoms in these trials was the Young Mania Rating Scale (YMRS), an 11-item clinician-rated scale traditionally used to assess the degree of manic symptoms in a range from 0 (no manic features) to 60 (maximum score). SEROQUEL XR was superior to placebo in the reduction of the YMRS total score at week 3. The efficacy of SEROQUEL in the treatment of acute manic episodes was also established in 3 placebo-controlled trials in patients who met DSM-IV criteria for bipolar I disorder with manic episodes. These trials included patients with or without psychotic features and excluded patients with rapid cycling and mixed episodes. Of these trials, 2 were monotherapy (12 weeks) and 1 was adjunct therapy (3 weeks) to either lithium or divalproex. Key outcomes in these trials were change from baseline in the YMRS score at 3 and 12 weeks for monotherapy and at 3 weeks for adjunct therapy. Adjunct therapy is defined as the simultaneous initiation or subsequent administration of SEROQUEL with lithium or divalproex. The results of the trials follow: Monotherapy In two 12-week trials (n=300, n=299) comparing SEROQUEL to placebo, SEROQUEL was superior to placebo in the reduction of the YMRS total score at weeks 3 and 12. The majority of patients in these trials taking SEROQUEL were dosed in a range between 400 mg/day and 800 mg/ day (Studies 2 and 3 in Table 27). Adjunct Therapy In a 3-week placebo-controlled trial, 170 patients with bipolar mania (YMRS ≥20) were randomized to receive SEROQUEL or placebo as adjunct treatment to lithium or divalproex. Patients may or may not have received an adequate treatment course of lithium or divalproex prior to randomization. SEROQUEL was superior to placebo when added to lithium or divalproex alone in the reduction of YMRS total score. The majority of patients in this trial taking SEROQUEL were dosed in a range between 400 mg/day and 800 mg/day (Study 4 in Table 27). Children and Adolescents (ages 10-17) The efficacy of SEROQUEL XR in the acute treatment of manic episodes associated with bipolar I disorder in children and adolescents (10 - 17 years of age) was extrapolated from a 3-week, double-blind, placebo-controlled, multicenter trial. Patients who met DSM-IV diagnostic criteria for a manic episode were randomized into one of three treatment groups: SEROQUEL 400 mg/day (n=95), SEROQUEL 600 mg/day (n=98), or placebo (n=91). Study medication was initiated at 50 mg/day and on day 2 increased to 100 mg/day (divided doses given two or three times daily). Subsequently, the dose was titrated to a target dose of 400 mg/day or 600 mg/day using increments of 100 mg/day, given in divided doses two or three times daily. The primary efficacy variable was the mean change from baseline in total YMRS score. SEROQUEL 400 mg/day and 600 mg/day were superior to placebo in the reduction of YMRS total score (Study 5 in Table 27). Bipolar Disorder, Depressive Episodes Adults The efficacy of SEROQUEL XR for the acute treatment of depressive episodes associated with bipolar disorder in patients who met DSM-IV criteria for bipolar disorder was established in one 8-week, randomized, double-blind, placebo-controlled study (N=280 outpatients). This study included patients with bipolar I and II disorder, and those with and without a rapid cycling course. Patients randomized to SEROQUEL XR were administered 50 mg on Day 1, 100 mg on Day 2, 200 mg on Day 3, and 300 mg on Day 4 and after. The primary rating instrument used to assess depressive symptoms was the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated scale with scores ranging from 0 (no depressive features) to 60 (maximum score). The primary endpoint was the change from baseline in MADRS score at week 8. SEROQUEL XR was superior to placebo in reduction of MADRS score at week 8 (Study 6 in Table 28). The efficacy of SEROQUEL for the treatment of depressive episodes associated with bipolar disorder was established in 2 identical 8-week, randomized, double-blind, placebo-controlled studies (N=1045). These studies included patients with either bipolar I or II disorder and those with or without a rapid cycling course. Patients randomized to SEROQUEL were administered fixed doses of either 300 mg or 600 mg once daily. The primary rating instrument used to assess depressive symptoms in these studies was the MADRS. The primary endpoint in both studies was the change from baseline in MADRS score at week 8. In both studies, SEROQUEL was superior to placebo in reduction of MADRS score at week 8 (Studies 7 and 8 in Table 28). In these studies, no additional benefit was seen with the 600 mg dose. For the 300 mg dose group, statistically significant improvements over placebo were seen in overall quality of life and satisfaction related to various areas of functioning, as measured using the Q-LES-Q(SF). Maintenance Treatment as an Adjunct to Lithium or Divalproex The efficacy of SEROQUEL in the maintenance treatment of bipolar I disorder was established in 2 placebo-controlled trials in patients (n=1326) who met DSM-IV criteria for bipolar I disorder (studies 9 and 10). The trials included patients whose most recent episode was manic, depressed, or mixed, with or without psychotic features. In the open-label phase, patients were required to be stable on SEROQUEL plus lithium or divalproex for at least 12 weeks in order to be randomized. On average, patients were stabilized for 15 weeks. In the randomization phase, patients continued treatment with lithium or divalproex and were randomized to receive either SEROQUEL (administered twice-daily totaling 400 mg/day to 800 mg/day) or placebo. Approximately 50% of the patients had discontinued from the SEROQUEL group by day 280 and 50% of the placebo group had discontinued by day 117 of double-blind treatment. The primary endpoint in these studies was time to recurrence of a mood event (manic, mixed, or depressed episode). A mood event was defined as medication initiation or hospitalization for a mood episode; YMRS score ≥20 or MADRS score ≥20 at 2 consecutive assessments; or study discontinuation due to a mood event. In both studies, SEROQUEL was superior to placebo in increasing the time to recurrence of any mood event (Figure 2 and Figure 3). The treatment effect was present for increasing time to recurrence of both manic and depressed episodes. The effect of SEROQUEL was independent of any specific subgroup (assigned mood stabilizer, sex, age, race, most recent bipolar episode, or rapid cycling course). Figure 2: Kaplan-Meier Curves of Time to Recurrence of a Mood Event (Study 9) Figure 3: Kaplan-Meier Curves of Time to Recurrence of a Mood Event (Study 10)
Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects of SARS-CoV-2 virus by productively infecting healthy human lung tissue and using scRNA-seq to reconstruct the transcriptional program in "infection pseudotime" for individual lung cell types. SARS-CoV-2 predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands of viral RNA molecules, taking over 60% of the cell transcriptome and forming dense viral RNA bodies while inducing host profibrotic (TGFB1, SPP1) and inflammatory (early interferon response, CCL2/7/8/13, CXCL10, and IL6/10) programs and destroying host cell architecture. Infected alveolar macrophages (AMs) showed none of these extreme responses. Spike-dependent viral entry into AMs used ACE2 and Sialoadhesin/CD169, whereas IM entry used DC-SIGN/CD209. These results identify activated IMs as a prominent site of viral takeover, the focus of inflammation and fibrosis, and suggest targeting CD209 to prevent early pathology in COVID-19 pneumonia. This approach can be generalized to any human lung infection and to evaluate therapeutics.
Usual adult dose: Initial dose of 200 mg, then 100 mg administered over 60 minutes every 12 hours and should not exceed 400 mg in 24 hours. The lyophilized powder should be reconstituted with 5 mL Sterile Water for Injection USP and immediately further diluted in 100 mL to 1,000 mL with Sodium Chloride Injection USP, Dextrose Injection USP, or Dextrose and Sodium Chloride Injection USP, or in 250 mL to 1000 mL Lactated Ringer's Injection USP, but not with other solutions containing calcium because a precipitate may form especially in neutral and alkaline solutions. When diluted in compatible solutions, the pH usually ranges from 4.5 to 6.0. Once diluted into an intravenous bag, MINOCIN® for Injection may be stored either at room temperature for up to 4 hours or refrigerated at 2 to 8°C (36 to 46°F) for up to 24 hours. Any unused portions must be discarded after that period. The pharmacokinetics of minocycline in patients with renal impairment (CLCR <80 mL/min) have not been fully characterized. Current data are insufficient to determine if a dosage adjustment is warranted. The total daily dosage should not exceed 200 mg in 24 hours in patients with renal impairment. However, due to the anti-anabolic effect of tetracyclines, BUN and creatinine should be monitored (See WARNINGS). Because MINOCIN (minocycline) for Injection contains magnesium sulfate heptahydrate, serum levels of magnesium should be monitored in patients with renal impairment (See DESCRIPTION, PRECAUTIONS). Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
An oral care composition comprising a peroxide containing compound dispersed in an orally acceptable carrier, wherein the carrier comprises a humectant and a combination of bioadhesive agents consisting essentially of at least one natural gum and a carbomer. The Preferred peroxide sources include hydrogen peroxide, carbamide peroxide, calcium peroxide and percarbonates. Preferred humectants include glycerine, sorbitol, propylene glycol, glucose, sucrose and low molecular weight polyethylene glycols. Preferred gums include xanthan gum, carrageenan, alginates, gum karaya, guar gum, gum Arabic and pectins. Suitable carbomers homo- or copolymers are high molecular weight polymers of acrylic acid crosslinked with allylsucrose or allyl ethers of pentaerythritol. These carbomers may be partially or fully neutralised. Compositions comprising carabamide peroxide or hydrogen peroxide, glycerine, xanthan gum and a carbomer copolymer are exemplified. Such compositions show excellent substantivity to the teeth as a result of a synergistic interation between the gelling agents.
A 26-week, randomized, open-label, active-controlled, non-inferiority study was conducted in children and adolescents older than 4 years of age with type 1 diabetes mellitus to assess the safety and efficacy of APIDRA (n=277) compared to insulin lispro (n=295) when administered subcutaneously within 15 minutes before a meal. Patients also received insulin glargine (administered once daily in the evening) or NPH insulin (administered once in the morning and once in the evening). There was a 4-week run-in period with insulin lispro and insulin glargine or NPH prior to randomization. Most patients were Caucasian (91%). Fifty percent of the patients were male. The mean age was 12.5 years (range 4 to 17 years). Mean BMI was 20.6 kg/m2. Glycemic control (see Table 10) was comparable for the two treatment regimens.
Infiltration of local anaesthetic into the surgical site by the surgeon using a combination of 0.5% L-bupivicaine prior to incision and 1% lignocaine topically after the wound is opened. Maximum dose limits of 2mg/kg for bupivicaine, and 3mg/kg for lignocaine will be observed, recognising that these are additive.
Preoxygenation anesthesia induction is an important part of airway management to reduce the risk of hypoxemia when the patient is apneic. The effectivity of preoxygenation is influenced by several things such as patient's head position. This study aimed to compare preoxygenation with head elevation 20°, 30° and 45° and conventional position to the time of desaturation before endotracheal intubation in patients undergoing general anesthesia. This was a randomized clinical trial of 56 patients, divided into four groups (conventional or 0° head elevation group, 20° head elevation group, 30° head elevation and 45° head elevation group). All subject was preoxygenated for 3 minutes with 100% oxygen. Induction of anesthesia was started with fentanyl, propofol, followed by rocuronium after the patient lost consciousness. Time was recorded from the start of induction until the oxygen saturation showed 93% or a time limit of 5 minutes. There was a significant difference in mean desaturation time among the four groups (p = 0.011). The most significant different was in 45o head elevation group (p \< 0.05). . In patients undergoing general anesthesia, pre-oxygenation with head elevation 20°, 30° and 45° slows down the time for desaturation before endotracheal intubation compared to the conventional position. The 45° head elevation has the best result.
In Kenya, up to 46% of women report childhood sexual assault. In an implementation research project, a team at Stanford University will be pairing with three Kenyan NGO's to research the effectiveness of an intervention to prevent sexual assault among adolescent girls in the informal settlements around Nairobi, Kenya. The study design will be a cluster-randomized controlled trial with two arms comparing the intervention to a standard of care group. The intervention consists of two side-by-side behavioral and skills-based interventions, one for girls and one for boys, taught in schools. The interventions include identifying and avoiding risky situations, verbal techniques to diffuse situations, as well as bystander intervention techniques for boys and self-defense techniques for girls. Settlements with schools participating in the project include Kibera, Dandora, Huruma, and Mukuru. This grant is part of the larger "What Works to Prevent Violence: A global program to prevent violence against women and girls" initiative, which is a large international initiative aimed at the prevention of gender-based violence. The initiative includes 18 projects from around the globe, and is supported by the Medical Research Council of South Africa, the London School of Hygiene and Tropical Medicine, and the UK Department for International Development (DFID). The primary contact people at Stanford University for this project are Clea Sarnquist, DrPH, MPH ([email protected]) and Michael Baiocchi, PhD ([email protected]).
Surgery and endovascular therapy are the primary treatment options for spinal dural arteriovenous fistula (SDAVF). Due to the absence of a consensus regarding which therapy yields a superior outcome, we conducted a comparative analysis of the surgical and endovascular treatment of SDAVF through a multicenter case series and a systematic literature review. Patients with SDAVF, surgically or endovascularly treated at four neurosurgical centers from January 2001 to December 2021, were included in this study. Level of SDAVF, primary treatment modality, baseline and post-procedural neurological status were collected. The primary outcomes were failure, complication rates, and a newly introduced parameter named as therapeutic delay. A systematic review of the literature was performed according to PRISMA-P guidelines. The systematic review identified 511 papers, of which 18 were eligible for analysis, for a total of 814 patients, predominantly male (72%) with a median age of 61 and mainly thoracic SDAVFs (65%). The failure rate was significantly higher for endovascular therapy (20%) compared to surgery (4%) (p < 0.01). Neurological complications were generally rare, with similar rates among the two groups (endovascular 2.9%; surgery 2.6%). Endovascular treatment showed a statistically significantly higher rate of persistent neurological complications than surgical treatment (2.9% versus 0.2%; p < 0.01). Both treatments showed similar rates of clinical improvement based on Aminoff Logue scale score. The multicenter, retrospective study involved 131 patients. The thoracic region was the most frequent location (58%), followed by lumbar (37%). Paraparesis (45%) and back pain (41%) were the most common presenting symptoms, followed by bladder dysfunction (34%) and sensory disturbances (21%). The mean clinical follow-up was 21 months, with all patients followed for at least 12 months. No statistically significant differences were found in demographic and clinical data, lesion characteristics, or outcomes between the two treatment groups. Median pre-treatment Aminoff-Logue score was 2.6, decreasing to 1.4 post-treatment with both treatments. The mean therapeutic delay for surgery and endovascular treatment showed no statistically significant difference. Surgical treatment demonstrated significantly lower failure rates (5% vs. 46%, p < 0.01). In the surgical group, 2 transient neurological (1 epidural hematoma, 1 CSF leak) and 3 non-neurological (3 wound infections) complications were recorded; while 2 permanent neurological (spinal infarcts), and 5 non-neurological (inguinal hematomas) were reported in the endovascular group. According to the literature review and this multicenter clinical series, surgical treatment has a significantly lower failure rate than endovascular treatment. Although the two treatments have similar complication rates, endovascular treatment seems to have a higher rate of persistent neurological complications.
After meeting the full eligibility requirement, participants will be randomized. Approximately 26 of the 51 participants will assigned to this arm of the study.
Prostate cancer (PCa) is the most common non-skin cancer effecting American males. Several reports suggest that physical activity after cancer diagnosis is associated with better cancer- specific and overall survival in individuals diagnosed with PCa. There is a growing body of evidence for lifestyle interventions that aim to promote physical activity as having the potential to counter some of the adverse effects of cancer treatments, disease progression and other health outcomes. Exercise performed 2-3 times a week has been shown to improve physical fitness, functional performance, and quality of life in men with PCa; however, few men with PCa exercise regularly and do not meet national physical activity guidelines. A potential explanation on the lack of exercise in men with PCa is the absence of a structured, home-based, exercise program. While studies have shown positive effects of exercise in men with PCa, little is known about how physical activity effects tumor physiology in men with PCa. The primary objective of this pilot study is to gather preliminary data regarding the impact of a novel, home-based exercise program on PCa biomarkers associated with recurrence and metastasis of PCa in men under active surveillance.
The recommended starting dose of testosterone gel 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet) applied topically once daily in the morning to the shoulders and upper arms. The dose can be adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation) and a maximum of 81 mg of testosterone (4 pump actuations). To ensure proper dosing, the dose should be titrated based on the pre-dose morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step. The application site and dose of testosterone gel 1.62% are not interchangeable with other topical testosterone products.
Patients receive rituximab IV over 4-8 hours on days 1, 8, 15, and 22. Patients also receive pembrolizumab IV over 1 hour on day 2 every 3 weeks for up to 16 cycles (1 year) in the absence of disease progression or unacceptable toxicity.
This is an open label randomized controlled trial. Women who present to the MEU with headache will be assessed by trained nurse practitioners and/or OB/GYN residents. If the woman meets criteria for the study she will be enrolled by an MEU provider doing the primary assessment. See Figure 1 for the flow diagram depicting the patient's course through MEU. If eligible for inclusion, women will be randomly assigned to ONB or headache cocktail. Randomization will occur at time of enrollment. Prior to headache treatment 10-point visual/verbal rating scale (VRS) will be obtained. Treatment time is defined as time the patient takes the medication or the time that the needle is inserted into the greater occipital notch. At 60 min after treatment VRS will again be obtained by nursing staff or primary provider. If headache pain is resolved, defined as a VRS 0, the patient will be discharged to home (at the discretion of the managing team providing there are no other indications for further observation or admission). If pain continues to be present VRS will again be assessed at 120 min after treatment. If pain is not improved to mild range, defined as a VRS ≤ 3, or resolved, crossover treatment will be given. VRS will be obtained at 60 min after cross over treatment; if pain is resolved patient will be discharge to home. If pain continues to be present VRS will be obtained at 120 min after cross over treatment. If pain is not improved to mild pain or resolved; second line treatment of Promethazine 25mg/Benadryl 25mg will be given. VRS will again be obtained 60 min after second line treatment. If pain is not improved to mild pain (VRS ≤3) or resolved neurology consult will be considered. If at any point during treatment the patient develops new neurological symptoms study protocol will be stopped and neurology will be consulted. Patients will be called 7 days after discharge to access short term outcomes (headache frequency since MEU visit, injection site complications, and satisfaction with treatment.) Patients will again be called at 28 days and a chart abstraction will be done to access for long term outcomes (recurrent presentation for headache to the MEU, maternal complications including preeclampsia, or fetal complications).
Pirmella 7/7/7 and Pirmella 1/35 Tablets are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptives are highly effective. Table 1 lists the typical accidental pregnancy rates for users of combined oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and the NORPLANT® System depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates. Pirmella 7/7/7 and Pirmella 1/35 have not been studied for and are not indicated for use in emergency contraception.
Compositions for preventing or treating inflammatory diseases such as inflammatory diseases of the joint, multiple sclerosis, leukemia, ischemic injury or reperfusion injury, are described. A fusion protein comprising an interleukin-1 receptor antagonist (IL-1ra) with all or part of a constant domain of a heavy or light chain of human immunoglobulin at the carboxy terminus is also described. Three useful forms of IL-1ra (IL-1raa, IL-1raß and IL-1rax) and variants thereof are disclosed and described in US Patent No. 5,075,222. Described herein are modified forms of IL-1ra. The modified forms of IL-1ra include polypeptides in which amino acids have been deleted from, inserted into and substituted for residues within the amino acid sequence of IL-1ra. For IL-1ra addition variants, each polypeptide may include an amino- and/or carboxyl-terminus fusion ranging in length from 1>100 residues.
Ultrasound guided TAP block will be performed in this group. Bupivicaine 0.25 % 20 ml will be administered in the block on either side.
OBJECTIVE: The first international consensus criteria for optic neuritis (ICON) were published in 2022. We applied these criteria to a prospective, global observational study of acute optic neuritis (ON). METHODS: We included 160 patients with a first-ever acute ON suggestive of a demyelinating CNS disease from the Acute Optic Neuritis Network (ACON). We applied the 2022 ICON to all participants and subsequently adjusted the ICON by replacing a missing relative afferent pupillary defect (RAPD) or dyschromatopsia if magnetic resonance imaging pathology of the optical nerve plus optical coherence tomography abnormalities or certain biomarkers are present. RESULTS: According to the 2022 ICON, 80 (50%) patients were classified as definite ON, 12 (7%) patients were classified as possible ON, and 68 (43%) as not ON (NON). The main reasons for classification as NON were absent RAPD (52 patients, 76%) or dyschromatopsia (49 patients, 72%). Distribution of underlying ON etiologies was as follows: 78 (49%) patients had a single isolated ON, 41 (26%) patients were diagnosed with multiple sclerosis, 25 (16%) patients with myelin oligodendrocyte glycoprotein antibody-associated disease, and 15 (9%) with neuromyelitis optica spectrum disorder. The application of the adjusted ON criteria yielded a higher proportion of patients classified as ON (126 patients, 79%). INTERPRETATION: According to the 2022 ICON, almost half of the included patients in ACON did not fulfill the requirements for classification of definite or possible ON, particularly due to missing RAPD and dyschromatopsia. Thorough RAPD examination and formal color vision testing are critical to the application of the 2022 ICON.
Ventricular Septal Rupture (VSR) is a rare complication of acute myocardial infarction and has a high mortality rate. Surgery is the definitive treatment. However, in hospitals with limited facilities, treating acute myocardial infarction patients with ventricular septal rupture, is challenging. A 74-year-old woman came to the emergency room of Dr. Koesma General Hospital, Tuban, East Java in December, 2019 with late-onset Acute Myocardial Infarction. On the following day, a new holosystolic murmur was heard in the left lower sternal border with palpable thrill. Transthoracic echocardiography showed VSR with severe pulmonary hypertension. This was followed by a drop in the blood pressure to 80/50 mmHg. The blood pressure was dependent on vasopressors until lisinopril and coenzyme Q10 were introduced. After 3 months, the haemodynamics of the patient were stable. This proved that the use of angiotensin-converting enzyme and coenzyme Q10 promotes more energy production, enables tissue healing and leads to balanced remodelling to increase the survival rate in cases of non-surgical treatment.
A randomized clinical trial was conducted in the Institute of Translational Nutrigenetics and Nutrigenomics, Department of Molecular Biology in Medicine, Health Sciences Center, at the University of Guadalajara, Guadalajara, Jalisco, Mexico, from February of 2018 to February of 2019. All participants were recruited through flyers and social media invitations. Sample size was determined according to the mean difference formula for clinical trials. To achieve a statistical power of 80% and an alpha of 5%, a sample size of 13 participants in each study group was required. However, 37 obese individuals who met the selection criteria were randomized in exercise-diet group or diet-group. Blood sample, height and weight were measured after 8-12 hour fast and wearing light clothes. The participants in the exercise-diet group were cited in the Respiratory Unit of the University of Guadalajara with the indication of not consuming caffeine, tobacco or energy drinks 24 hours before the test, and not having eaten food at least two hours before the Astrand-rhyming Test. This study was approved by the Ethics and Biosafety Committee of the Health Sciences Center, University of Guadalajara (registry number CUCS/CINV/0476/18). The procedures were in accordance with this institution's guidelines and all the participants signed a written consent-informed.
FIELD: biotechnology, vaccines. SUBSTANCE: vaccine has protective pneumococcus antigens and preserving agent. Protein components of pneumococcus were used as protective antigens (molecular mass - 50, 60, 74, 80 and 94 kDa). Protective effect of vaccine is based on the use of T-dependent protein antigens. Vaccine is used for control and prophylaxis of pneumococcal infection. EFFECT: enhanced effectiveness as compared with polysaccharide antigens, prolonged protective effect for control of any known pneumococcus serotype.
The intervention will last 3-months, a time frame that overlaps with the typical duration of a VA suicide high risk flag. Meetings will be 30-45 minutes and occur primarily in the community, home, or by telephone. Session content will be rooted in Peer Specialists (PSs) offering nonjudgmental empathic support, active listening, and constructive disclosure and role modeling. A primary focus will be helping patients with flags to identify and strengthen connections with informal supports and participation in activities in their community that will enable them to feel more worthwhile as individuals and hopeful about their future.
This study is to determine if a locally applied immune response modifier will eliminate high grade dysplasia in Barrett's esophagus. Barrett's esophagus is a premalignant condition caused by chronic reflux of gastric contents into the lower esophagus. Present practice is to do a periodic esophagoscopy on patients with Barrett's esophagus and take biopsies in search of dysplasia. If the pathologist reports low grade dysplasia, the patient usually receives more intensive surveillance. If the pathologist reports high grade dysplasia, the patient and his physician are faced with a dilema. High grade dysplasia is carcinoma in situ and there is a strong propensity for such patients to progess to frank carcinoma of the esophagus. Carcinoma of the esophagus is a miserable disease which is difficult to treat and leads to death in about 95% of the cases at 5 years. The present standard for patients with high grade dysplasia is to recommend esophagectomy. Esophagectomy is a major surgical procedure with significant associated morbidity and mortality. Porfimer sodium(Photofrin) photodynamic therapy is effective in eliminating high grade dysplasia in Barrett's esophagus. It has been approved by the FDA but it is not widely utilized because of its complexity and expense. Other modalities such as endoscopic mucosal resection and endoscopic thermal ablation techiques are being studied. Although endoscopic techniques are much safer than surgery, they all are uncomfortable and carry some risk. Many patients with Barrett's esophagus are elderly and most with high grade dysplasia do not live long enough to develop cancer. This fact has made some gastroenterolgists recommend intensive surveillance as an alternative to the above mentioned therapeutic modalities. Intensive surveillance in this setting means endoscopy with biopsies every 3 months with specific therapy recommended only if frank cancer is found. This study is based upon the fact that intensive surveillance is an acceptable way of following these patients. The only difference is an oral agent will be added in hopes of getting rid of high grade dysplasia. If high grade dysplasia could be eliminated by an oral medication it would be a quantum improvement over what we have. The present belief is if high grade dysplasia is eliminated there would be no progression to cancer. 852A is an immune response modifier being developed by 3M Pharmaceuticals. It is thought to exert its therapeutic effect by simulating alpha interferon. 852A is similar to the immune response modifier imiquimod(Aldara). Imiquimod is presently approved by the precancerous dermatological condition, actinic keratosis. It is very effective. Treatment is simply applying 5% imiquimod cream twice weekly to the skin lesion for 16 weeks. It seems reasonable that if an immune response modifier will eliminate precancerous lesions of the skin by local application, the same should be true for precancerous lesions of the esophagus. In this study 852A will be swallowed to see whether it can eliminate high grade dysplasia from the esophagus. Entrance into the present study would be predicated on the confirmation of high grade dysplasia in Barrett's esophagus. If the prospective subject meets all of the inclusion and exclusion criteria set out in the protocol, endoscopic ultrasound of the esophagus would be done. If endoscopic ultrasound shows no invasion into the submucosa the patient would be asked to sign an informed consent. Once entered into the sudy the subject would be given the study drug twice weekly, 3-4 days apart, for 8 weeks. 852A will be supplied in sterile vials by 3M Pharmaceuticals. Five mg of 852A will be mixed with sterile 5% dextrose in water to give a final volume of 30 ml. The patient will promply swallow the study drug after it is mixed. The subject will then assume a recumbent position for 30 minutes in hopes that the medication will stay in contact with the mucosa of the esophagus long enough to get an effect. All doses of the study medication will be given in the principal investigator's clinic. After the first dose is given that patient will stay in the clinic under observation for 4 hours. Observation includes taking the temperature, pulse, and blood pressure every hour. If there are no adverse effects after the first dose, the observation period after subsequent doses will reduced to one hour. Laboratory tests will be repeated 1,2,4 and 8 weeks after the first dose is given. As set out in the study protocol, if the patient has any significant adverse event or laboratory deviation, the subject would be dropped from the study. Throughout the study the subjects will be treated with a double dose of a proton pump inhibitor to control gastric acid reflux. After 8 weeks of therapy the study medication will be stopped. Four weeks thereafter and 12 weeks from the beginning, repeat endosocpy with biopsies will be done. If biopsies show no residual high grade dysplasia, the patient will be continued in an intensive surveillance program. Intensive surveillance means endoscopy with biopsies every 3 months for 1 year, then every 6 months for 1 year then yearly for 3 more years. If high grade dysplsia persists after 8 weeks of treatment or cancer is found, the patient would be referred for conventional therapy. Likewise, if high grade dysplsia recurs or cancer is found during the intensive surveillance program, the subject will be referred for conventional therapy.
Subject will dress in water-circulating trousers that are connected to a Heat Therapy (HT) pump. Warm water (42-43 degrees C) will be perfused through the pants for 90 minutes.
Chronic kidney disease (CKD) is a significant public health concern. Renal fibrosis is the final common pathway in the progression of kidney diseases, irrespective of the initial injury. Substantial evidence underscores the pivotal role of renal inflammation in the genesis of renal fibrosis. The presence of macrophages within normal renal tissue is significantly increased within diseased renal tissue, indicative of their crucial regulatory function in inflammation and fibrosis. Macrophages manifest a high degree of heterogeneity, exhibiting distinct phenotypic and functional traits in response to diverse stimuli within the local microenvironment in various types of kidney diseases. Broadly, macrophages are categorized into two principal groups: Classically activated, designated as M1 macrophages and alternatively activated, designated as M2 macrophages. A number of experimental models are widely used to study the underlying mechanisms driving renal inflammation and fibrosis progression. The present review delineated the phenotypic and functional attributes of macrophages present in diverse induced models, analyzing their disposition in relation to M1 and M2 polarization states.
The present invention relates to a medical equipment learning system and, particularly, to a medical artificial intelligence learning system in which medical data expressed in characters is converted into image data, and the image data is provided so as to be used for learning of a medical artificial intelligence. A medical equipment learning system according to the present invention comprises: a data extraction module (100) for collecting and then extracting character data (120) from medical data (110); a visualization module (200) for generating image data (210), which is visualization data, by using the character data (120) extracted by the data extraction module (100); a preprocessing module (300) for generating an input data set (310) for execution of machine learning on the basis of the visualization data; a learning module (400) for executing machine learning on the input data set (310) generated by the preprocessing module (300); a prediction module (500) for predicting a disease when new image data is input, on the basis of a result learned by the learning module (400); and a storage module (600) provided so as to store and check data of each module. The data extraction module (100) is a preconfigured two-dimensional or three-dimensional model. The visualization module (200) may change one or more among the color, brightness or transparency, pattern, and texture of the visualization data according to a name of a disease, severity of the disease, a degree of being acute/chronic and a degree of being malignant, various test results, function test results, and data results extracted from the equipment. The preprocessing module (300) adds a blood test result and a function test result to the image data (210) generated by the visualization module (200). Further, the preprocessing module (300) generates the input data set (310) by processing the visualization data.
The absence of speech is a clinical phenotype seen across neurodevelopmental syndromes, offering insights for neural language models. We present a case of bilateral perisylvian polymicrogyria (BPP) and complete absence of speech with considerable language comprehension and production difficulties. We extensively characterized the auditory speech perception and production circuitry by employing a multimodal neuroimaging approach. Results showed extensive cortical thickening in motor and auditory-language regions. The auditory cortex lacked sensitivity to speech stimuli despite relatively preserved thalamic projections yet had no intrinsic functional organization. Subcortical structures implicated in early stages of processing exhibited heightened sensitivity to speech. The arcuate fasciculus, a suggested marker of language in BPP, showed similar volume and integrity to a healthy control. The frontal aslant tract, linked to oromotor function, was partially reconstructed. These findings highlight the importance of assessing the auditory cortex beyond speech production structures to understand absent speech in BPP. Despite profound cortical alterations, the intrinsic motor network and motor-speech pathways remained largely intact. This case underscores the need for comprehensive phenotyping using multiple MRI modalities to uncover causes of severe disruption in language development.
Disclosed is a soap-gel preparation for the topical application of cosmetic and pharmaceutical substances, in particular a preparation in the form of a stick, the preparation being based on a soap gel consisting of 3-10 % by wt. of alkali soaps of a C16-C22 fatty-acid mixture, 30-90 % by wt. of polyols and 1-30 % by wt. of water. Preparations of this kind are particularly transparent, are dimensionally stable and have satisfactory release characteristics on contact with the skin when the fatty-acid mixture contains 60-95 % by wt. of saturated straight-chain fatty acids and 5-40 % by wt. of saturated branched-chain fatty acids.
Patients undergo surgical resection with standard intraoperative guidance using contrast-enhanced MRI. Patients also undergo post operative standard of care radiation therapy over 30 fractions and receive standard of care temozolomide PO for 6 weeks. Additionally, patients undergo MRI during follow up.
Pulmonary hypertension (PH) is a cardiovascular disorder characterized by substantial morbidity and mortality rates. It is a chronic condition characterized by intricate pathogenesis and uncontrollable factors. We summarized the pathological effects of estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification on PH. PH is not only a pulmonary vascular disease, but also a systemic disease. The findings emphasize that the onset of PH is not exclusively confined to the pulmonary vasculature, consequently necessitating treatment approaches that extend beyond targeting pulmonary blood vessels. Hence, the research on the pathological mechanism of PH is not limited to target organs such as pulmonary vessels, but also focuses on exploring other fields (such as estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification).
The most frequent side effects of oral erythromycin preparations are gastrointestinal and are dose-related. They include nausea, vomiting, abdominal pain, diarrhea and anorexia. Symptoms of hepatitis, hepatic dysfunction and/or abnormal liver function test results may occur. (See WARNINGS.) Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. (See WARNINGS.) Erythromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes. (See WARNINGS.) Allergic reactions ranging from urticaria to anaphylaxis have occurred. Skin reactions ranging from mild eruptions to erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely. There have been reports of interstitial nephritis coincident with erythromycin use. There have been rare reports of pancreatitis and convulsions. There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency and in patients receiving high doses of erythromycin.
Eletriptan hydrobromide tablets are contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of eletriptan hydrobromide. Some of these reactions occurred in patients without known CAD. Eletriptan hydrobromide may cause coronary artery vasospasm (Prinzmetal's angina), even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naÏve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving eletriptan hydrobromide. Do not use eletriptan hydrobromide if there is evidence of CAD or coronary artery vasospasm [see Contraindications (4)]. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first eletriptan hydrobromide dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following administration of eletriptan hydrobromide. For such patients, consider periodic cardiovascular evaluation in intermittent long- term users of eletriptan hydrobromide.
This fixed combination drug is not indicated for the initial therapy of edema or hypertension except in individuals in whom the development of hypokalemia cannot be risked. Triamterene and hydrochlorothiazide capsules, USP are indicated for the treatment of hypertension or edema in patients who develop hypokalemia on hydrochlorothiazide alone. Triamterene and hydrochlorothiazide capsules, USP are also indicated for those patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked. Triamterene and hydrochlorothiazide capsules, USP may be used alone or as an adjunct to other antihypertensive drugs, such as beta-blockers. Since triamterene and hydrochlorothiazide capsules, USP may enhance the action of these agents, dosage adjustments may be necessary. Usage in Pregnancy: The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia. Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical consequences of pregnancy. Diuretics are indicated in pregnancy when edema is due to pathologic causes, just as they are in the absence of pregnancy. Dependent edema in pregnancy resulting from restriction of venous return by the expanded uterus is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances this edema may cause extreme discomfort which is not relieved by rest. In these cases a short course of diuretics may provide relief and may be appropriate.
Selective Serotonin Reuptake Inhibitors(SSRIs) are the first line pharmacotherapy for Obsessive-Compulsive Disorder (OCD) according to APA（American Psychological Association）guideline. Nevertheless, a large proportion (40% or more) of patients response only partially or not at all to treatment with a SSRI. On the basis of the existing sparse literature, several pharmacotherapy options for OCD patients who do not respond, or who respond but do not remit, have been outlined in current treatment guidelines. These include 1) treatment with higher than usual doses of an SSRI, 2) switch to a different SSRI, 3) switch to a different class of medication, 4) augmentation with a dopamine blocker, and 5) augmentation with a glutamatergic agent. There is a need for additional data, particularly real-world data, on how best to choose between these options. This proposed Randomized Controlled Trial (RCT) study is a multi-center clinical study with a total of 13 centers that specialize in OCD patients. A randomized block design will be used in this study and all eligible participants accepted into this study will undergo an initial course of pharmacotherapy (phase I), and non-remmitters will be randomly allocated to five treatment arms (phase II). In phase I all participants will be treated with sertraline for 12 weeks.In phase II,The 5 arms will comprise 1) treatment with higher than usual doses of sertraline, 2) switch to fluvoxamine, 3) switch to venlafaxine, 4) augmentation with memantine, and 5) augmentation with aripiprazole. Clinicians and patients will know which treatment arm is being employed, but raters will be kept blind to treatment group.
This study tests the powered hand orthosis device on a small number of participants (up to 6). Research participants with neuromusculoskeletal impairments were recruited for the study and consented with an approved protocol. The study was conducted during 1 visit to LTI in Holliston, MA . The study consists of several assessments. Participants are surveyed for cognitive limitations and self-assessment of difficulties in completing tasks of daily living by completing surveys such as the Quickdash Questionnaire \[1\], the Mini-Mental State test \[2\], and the McGann Feedback form \[3\]. Pinch strength without and with the powered orthosis is evaluated. A selection of functional outcome measures are performed such as the Southampton Hand Assessment Procedure (SHAP) \[4\], the Nine-Hole Peg Test (NHP) \[5\], and the Box and Blocks Test (BBT) \[6\].
Individuals in the first group to be included in the study group will be included in a virtual reality-based exercise program for half an hour a day, 5 days a week for a total of 4 weeks, in addition to routine electrotherapy programs for half an hour a day, 5 days a week for a total of 4 weeks. These individuals will be able to play the games saved in the Oculus Quest 2 SG system in the virtual environment, thanks to the three-dimensional glasses and handpiece that can be worn on the head.
PURPOSE: Arterial stiffness has gained recognition as a stand-alone risk factor for cardiovascular disease (CVD). Obesity is intricately linked to elevated arterial stiffness, the development of left ventricular (LV) hypertrophy, and the emergence of diastolic dysfunction, all of which collectively contribute substantially to an unfavorable prognosis. Weight loss has become a standard recommendation for all patients with CVD concurrent with morbid obesity; however, randomized evidence to support this recommendation was limited earlier. The latest scientific studies revealed dynamic changes in aortic stiffness after substantial weight loss by bariatric surgery, also known as metabolic surgery, in patients with obesity. There is also a favorable evolution in LV hypertrophy and a significant impact on arterial hypertension and other promising cardiovascular outcomes in obese people after bariatric surgery. METHODS/RESULTS: We aimed to examine the cardiovascular effects of various metabolic surgeries in morbidly obese individuals, especially their role in improving arterial health, the potential impact on surrogate markers of atherosclerotic vascular disease, and consequently reducing the likelihood of cardiovascular events. CONCLUSION: In conclusion, metabolic surgery is associated with a significant decrease in the occurrence of major adverse cardiovascular events (MACE) and all-cause mortality among obese individuals, alongside remarkable enhancement of arterial health. These findings underscore the critical importance of implementing strategies to combat obesity and reduce adiposity within the general population.
PURPOSE:To obtain the titled porcelain material resistant to yellowing phenomenon in the baking of the porcelain material on a porcelain-baking alloy composed mainly of a silver-containing palladium without considerably varying the physical properties of the porcelain material, by including a nitric acid compound into a baking porcelain for dental use. CONSTITUTION:Total or a part of a principal composition constituting a baking porcelain material for dental use, e.g. opaque, body, incisal or translucent is surface-treated with an aqueous solution of a nitric acid compound and dried. As an alternative method, said porcelain material is mixed with 0.2-2.0wt.% of an insoluble or scarcely soluble nitric acid compound to include the nitric acid compound into the porcelain material. An artificial dental crown having a color tone close to that of natural tooth can be produced with normal operation by the above process. The obtained artificial dental crown is resistant to the yellowing phenomenon (yellow discoloration) caused by silver and developed in the application and baking of the porcelain material on an inexpensive and easily solderable porcelain-baking alloy composed mainly of a silver-containing palladium without considerably varying the physical properties of the porcelain material.
A method and system for diagnosing a subject with respect to a pancreatic cancer disease state. Peptide structure data corresponding to a biological sample obtained from the subject is received. The peptide structure data is analyzed using a supervised machine learning model to generate a disease indicator that indicates whether biological sample evidences the PC disease state based on at least 3 peptide structures selected from a group of peptide structures of Group I identified in Table 1 or of Group II of Table 8. The group of peptide structures in Table 1 or Table 8 comprises a group of peptide structures associated with the PC disease state. The group of peptide structures is listed in Table 1 with respect to relative significance to the disease indicator. A diagnosis output is generated based on the disease indicator
This group will be follow up in Primary Care at 1, 3 and 6 month. At each visit patients receive advice on CPAP treatment, management of adverse effects associated with CPAP, making anthropometric and blood pressure measurements and also were asked to complete questionnaires.
AIM: To evaluate the impact of aldosterone excess on renal function in individuals with primary aldosteronism and to compare its evolution after surgery or mineralocorticoid receptor antagonist (MRA) treatment. METHODS: A multicentre, retrospective cohort study of primary aldosteronism patients in follow-up in 36 Spanish tertiary hospitals, who underwent specific treatment for primary aldosteronism (MRA or adrenalectomy). RESULTS: A total of 789 patients with primary aldosteronism were included, with a median age of 57.5 years and 41.8% being women. At primary aldosteronism diagnosis, the prevalence of chronic kidney disease (CKD) was 10.7% ( n = 84), with 75% of cases classified as state 3a ( n = 63). Primary aldosteronism patients with CKD had a longer duration of hypertension, a higher prevalence of type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. Unilateral adrenalectomy was performed in 41.8% of cases ( n = 330), and 459 patients were treated with MRA. After a median follow-up of 30.7 months (range 13.3-68.4), there was a significant decline in the estimated glomerular filtration rate (eGFR) in operated patients and those receiving MRA. During follow-up, 24.4% of patients with CKD at the time of primary aldosteronism diagnosis had normalized renal function, and 39% of those with albuminuria had albuminuria remission. There were no differences in renal function or albuminuria regression between the two therapy groups. However, development of albuminuria was less common in operated than in medically treated patients (0 vs. 6.0%, P = 0.009). CONCLUSION: CKD affects around 10% of the patients with primary aldosteronism, with a higher risk in individuals with long-term hypertension, type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. At short-term, both MRA and surgical treatment lead to a reduction of renal function, but adrenalectomy led to higher renal protection.
Limited data is available on the health-related quality of life (HRQoL) and symptoms of patients with chronic myeloid leukemia (CML) who are in treatment-free remission (TFR). We herein report HRQoL results from the EURO-SKI trial. Patients who had been on tyrosine kinase inhibitors (TKIs) therapy for at least 3 years and achieved MR4 for at least 1 year were enrolled from 11 European countries, and the EORTC QLQ-C30 and the FACIT-Fatigue questionnaires were used to assess HRQoL and fatigue respectively. Patients were categorized into the following age groups: 18-39, 40-59, 60-69 and ≥70 years. Of 728 patients evaluated at baseline, 686 (94%) completed HRQoL assessments. The median age at TKI discontinuation was 60 years. Our findings indicate that HRQoL and symptom trajectories may vary depending on specific age groups, with younger patients benefiting the most. Improvements in patients aged 60 years or older were marginal across several HRQoL and symptom domains. At the time of considering TKI discontinuation, physicians could inform younger patients that they may expect valuable HRQoL benefits. Considering the marginal improvements observed in patients aged 60 years or above, it may be important to further investigate the value of TFR compared to a lowest effective dose approach in this older group of patients.
On-site monitoring of pulse, blood pressure, weight, and surveys, at Months 0,1,3,6; Four educational sessions to address: 1) basics about blood pressure (BP); 2) training in home BP monitoring with personal Omron 10 device; 3) information about Dietary Intervention to lower Systemic Blood Pressure (DASH) eating plan, recipes and cooking demonstrations; 4) education about BP medication adherence. Interventions occur on the background of Carter Burden Network's implementation of a DASH-congruent menus for congregant meals for all seniors attending the sites, including those not enrolled in the protocol.
The patients will be divided into two groups. In group 1, the multimodal anesthetic cocktail consisted of 100 mg Levobupivacaine (0.5%, 20 mL) and 30 mg ketorolac (1 ml). In group 2, the multimodal anesthetic cocktail consisted of 100 mg Levobupivacaine (0.5%, 20 mL), 30 mg ketorolac (1 ml) and 0.6 mg 1:1000 epinephrine (0.6 ml). Both groups were mixed with a 0.9% normal saline solution to a total volume of 100 ml. The outcome research assistant who collects data was blinded to the treatment groups. Patients will be treated with the routine standard regimen for total knee arthroplasty. Surgeons will use same surgical techniques through a standard medial parapatellar approach. In addition, standardized posterior-stabilized TKA (Zimmer Nexgen LPS flex) was used in all patients. After bone cutting before inserting the actual implant, the assistant scrub nurse in the operating room will open the envelope that the patient was classified in group 1 or group 2 and perform mixing according to the prescribed medication. The doctor who undergoes surgery was blinded. The anesthetic cocktail was divided into 4 parts 25 ml each and it was injected into 4 areas. First 25 ml cocktail was injected into the posterior capsule (P), posteromedial (PM) and posterolateral capsule (PL). The second part was injected into the medial gutter (M). The third part was injected into the lateral gutter and the forth part was injected into quadriceps muscle, retinacula tissues, pes anserinus, suprapatellar and infrapatellar fat pads (A). During the first 48 hours, all patients received intravenous morphine prn for pain, as well as dynastat, Tylenol with codeine, as required, for control of pain. After 48 hours, the pain was controlled by oral intravenous morphine and medication as requires until the patient was discharged from the hospital. The primary outcome measure was the severity of postoperative pain during the first 48 hours after surgery. The pain was assessed by a Visual Analogue Scale (VAS) ranging from 0 (no pain) to 10 (extreme pain) every 6 hours postoperatively. Secondary outcome measures compared the consumption of intravenous morphine, which was measured every six hours in 48 hours after surgery. Additionally, blood loss in the drain at 24, 48 hours was recorded. Any complications following surgery were recorded.
Perception has long been envisioned to use an internal model of the world to explain the causes of sensory signals. However, such accounts have historically not been testable, typically requiring intractable search through the space of possible explanations. Using auditory scenes as a case study, we leveraged contemporary computational tools to infer explanations of sounds in a candidate internal generative model of the auditory world (ecologically inspired audio synthesizers). Model inferences accounted for many classic illusions. Unlike traditional accounts of auditory illusions, the model is applicable to any sound, and exhibited human-like perceptual organization for real-world sound mixtures. The combination of stimulus-computability and interpretable model structure enabled 'rich falsification', revealing additional assumptions about sound generation needed to account for perception. The results show how generative models can account for the perception of both classic illusions and everyday sensory signals, and illustrate the opportunities and challenges involved in incorporating them into theories of perception.
Exercise has been shown to be of fundamental importance in managing chronic diseases and improving health-related quality of life (HRQL) as well as psychological health. However, whether intradialyic exercise is safe and has positive impact on HRQL and depression status in hemodialysis patients requires further researches with diverse racial and cultural groups to clarify. This study aimed to evaluate the effects of intradialyic exercise on dialytic parameters, HRQL, and depression status in hemodialysis patients. A randomized controlled trial was conducted at a medical center in Northern Taiwan. Sixty-four participants from 112 eligible hemodialysis patients were recruited using stratified random sampling and allocated with a 1:1 randomization ratio to either experimental group (EG, treated in odd weekdays, n = 32) or comparison group (CG, treated in even weekdays, n = 32). The EG received a 12-week intradialytic exercise (supine lower-limb ergometer, 30 minutes/session, 3 sessions/week), while the CG maintained usual lifestyles. Dialytic parameters (serum chemistries, serum electrolytes, and estimated glomerular filtration rate), HRQL, and depression status were collected at baseline and at 12 weeks. The results indicated that there were no differences in changes of dialytic parameters from baseline between EG and CG. However, the EG had increased HRQL (ß = 22.6, p\<.001) and reduced depression status (ß = -7.5, p = .02) at 12 weeks compared with the CG. A 12-week intradialytic exercise is safe, feasible and effective in improved HRQL and reduced depression status for hemodialysis patients.
The invention discloses an application of NADH and NMN in preparation of a drug or a health caring product for Parkinson's disease, namely, [beta]-NADH and [beta]-NMN are applied for preparing the drug or the health caring product for the Parkinson's disease, wherein the [beta]-NADH and [beta]-NMN are prepared through enzyme catalysis. The invention provides the new drug or health caring product, which is prepared from the [beta]-NADH and [beta]-NMN which is prepared in an in-vitro enzyme catalysis manner, has cost advantage and is high in purity. The drug or health caring product is used for treating the Parkinson's disease. The [beta]-NADH and the [beta]-NMN, as active components, are used for preparing the drug or the health caring product for the Parkinson's disease, wherein the particular dosage can be decided according to the severity degree of the diseases, drug application approach and relative factors. The [beta]-NADH and the [beta]-NMN themselves exist in body cells, so that the [beta]-NADH and the [beta]-NMN are high in safety as the drug or the health caring product. In addition, the NMN is a monomer molecule so that the drug or the health is significant in function and is easy to stabilize.
PURPOSE: To obtain the proper antibacterial action required for cosmetics by soaking a nonwoven sheet substrate in solution containing an acid selected from a group composed of phosphatide, a sorbic acid, a benzoic acid and a mixture of these. CONSTITUTION: A quantity of solution passing through a sheet substrate is about 300 wt.% to about 500 wt.% on the basis of weight of the sheet substrate. Phosphatide is a triglyceride fatty acid substituted with a quaternary amine compound, and has a chemical formula I. Here, to put it more properly, R is a 16-26C aliphatic oil group, and (x+y) is 3. A desirable R group is cocamide propyl or linolic amide propyl. A quantity of phosphatide in a wet wipe solution is set for about 1 wt.% to about 3 wt.% on the basis of weight of the solution. A quantity of a sorbic acid or a benzoic acid is set for a sufficient quantity capable of offereing solution having pH of about 3.5 to about 7. A quantity of a sorbic acid is set for about 0.07 wt.% to about 0.3 wt.%.
PURPOSE:To provide a skin external agent containing an adrenocortical hormone and hyaluronic acid. CONSTITUTION:The external agent contains an adrenocortical hormone (e.g. hydrocortisone hydrochloride) and hyaluronic acid as active ingredients. The addition of the hyaluronic acid to the skin external agent in a concentration of 0.005-0.1wt.% permits to reduce the amount of the adrenocortical hormone to <= the usually used amount, such as approximately 1/2 to 1/10 of the amount. The adrenocortical hormone is useful for skin diseases such as eczema, contact dermatitis, atopic dermatitis, strophulus, urticaria, and psoriasis, but causes the adverse actions such as pituitary.adrenocortical function depression, skin infectious diseases and acne, when used as the external agent in a wide range over a long period. The addition of the hyaluronic acid enables to prepare the external agent having the excellent therapeutic effects and good in the safety and usability.
Minimally invasive non-surgical technique (MINST) with application of Enamel Matrix Derivative (EMD): Root instrumentation under local anesthesia using micro- curettes and delicate piezon ultrasonic instruments in the area of intraosseous defect. Experimental intervention by application of EDTA gel for 2 minutes on the root surface of the involved tooth, followed by rinsing with saline, drying and application of Enamel Matrix Derivative gel, to fill the defect.
Methods and systems for monitoring compliance of a patient with a prescribed treatment regimen are described. Patient speech is detected during use of a communication system such as a mobile telephone and analyzed to determine compliance with a treatment for a brain-related disorder, for example. Speech data representing one or more patient speech pattern and an identity signal containing information used to determine presence/identity of the patient are transmitted from a circuitry-based system at the patient location to a monitoring location. Identity of the patient as user of the communication system is determined through, e.g., biometric or authentication techniques. Speech data is analyzed to determine whether a patient speech pattern matches one or more characteristic speech patterns. Outcome of the analysis is reported to a medical caregiver or other party, for example.
Anemia is sometimes seen in patients receiving NSAIDs, including oxaprozin tablets. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythrogenesis. Patients on long-term treatment with oxaprozin should have their hemoglobin or hematocrit values determined if they exhibit any signs or symptoms of anemia. NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving oxaprozin tablets who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
Thiazides should be discontinued before carrying out tests for parathyroid function (see PRECAUTIONS: General). Carcinogenesis, Mutagenesis, Impairment of Fertility: Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 mcg/mL, and in the Aspergillus nidulans non-disjunction assay at an unspecified concentration. Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to conception and throughout gestation.
PURPOSE:To provide the subject new compound having an aldose reductase inhibitory effect and a lipoxygenase inhibitory effect and useful as a therapeutic agent for, e.g. cataract, retinopathy and neuropathy which are respectively diabetic complications or an intermediate of other medicines. CONSTITUTION:A dibenzocyclooctane derivative of formula I [R is a hydroxyl group, a lower alkyloxy, a (substituted) benzyloxy, etc.; R1 and R4 are each hydroxyl group; R2 and R3 are each methyl or methane-sulfonyloxymethyl], e.g. (6S,7R,R-biar)-5,6,7,8-tetrahydro-2,3,6,7-tetrahydroxy-6,7-dimethyl-1, 10,11,12- tetramethoxydibenzo[a,c]-cyclooctene. Among the compounds of formula I, the case in which R2 and R3 are each methanesulfonyloxymethyl can be synthesized by reacting a reducing agent with a compound of formula II to obtain a compound of formula III, subsequently reacting osmium tetraoxide therewith and conducting dihydroxylation and then methanesulfonylation.
The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects modulating Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.
Take an appropriate amount of Vaseline and mix thoroughly with 1% of the original ingredient, starch, and pigment. Take an appropriate amount of medication and place it in the center of the acupoint patch (8cm x 8cm). Press the medication evenly into a circular hole with a diameter of about 4cm and a depth of about 3mm, and align the patch.
This study was a single-arm study of the efficacy and safety of oral sonidegib in patients with Hh-pathway activated relapsed medulloblastoma. It was initially designed as a randomized, controlled, open-label phase III study of adults and children with Hh-pathway activated MB whose disease had failed standard of care therapy, including radiation therapy (RT). The original study consisted of a randomized controlled part and a non-randomized uncontrolled part. Approximately 69 patients were to be randomized in a 2:1 ratio to receive sonidegib oral suspension or the active control, temozolomide (TMZ) capsules. Randomization was to be stratified according to age, \<18 years versus ≥ 18 years. Approximately 40 patients were to receive sonidegib in the non-randomized uncontrolled part of the study. Following the enrollment of 11 patients, the study was amended to become a phase II single-arm study with only sonidegib, and the target enrollment was changed to 20 patients. Prior to the study amendment, TMZ participants whose disease progressed while on TMZ were permitted to crossover to sonidegib. After the amendment, participants receiving TMZ were crossed over to sonidegib.
The purpose of this study is to determine how daily activities, home, neighborhood and school environments affect Arkansas children's health. Children from Central Arkansas ages 7-10 years will be recruited to participate in a variety of physical activity tests including strength, flexibility, balance and endurance. During these tests, participants will perform tasks such as cycling on a stationary bike and extending and flexing their knees on a special type of chair. Body composition will be measured and blood, saliva, urine and stool samples collected. Participants and parents will be asked to complete questionnaires on physical activity, home and neighborhood environment as well as sleeping habits. Finally, participants will wear an accelerometer based monitor that will track their physical activity and sleeping patterns. One in person visit will take place at Arkansas Children's Nutrition Center (Little Rock, AR) and will last up to 8 hours. Reimbursement will be provided.
The control-test group (CTG) will initiate the task-oriented training protocol. The task-oriented training protocol will include functional exercise drills, such as sit-up and workout, obstacle course workout, speed-and-direction workout, balance workout, work-up and downhill workout, each tasks performed for eight minutes, with two minutes of rest between them. The difficulty in carrying out the tasks will be progressively adjusted. At all times, individuals will be instructed to contract the pelvic floor musculature. After 20 sessions, the patients will be reassessed and will remain for a period of one month without any intervention, and at the end of this period will be reevaluated again. Next, the CTG group will perform 20 sessions of Pilates exercises.
Participants randomized to the Cue Reactivity PFI condition will receive personalized feedback at the end of completing 17 days of ecological momentary assessments (EMAs) four times a day. The personalized feedback will be delivered online and contains information summarizing participants' desire to drink as it varied as a function of several real-world factors across the 17-day EMA period.
PURPOSE: To obtain a remedying agent capable of dramatically curing persistent pruritus through extremely effectively acting on various kinds of dermal pruritus, by incorporating a water-swollen body of sodium montmorillonite as the chief agent With a humectant, oil or crude drug. CONSTITUTION: This remedying agent is obtained by incorporating (A) a water- swollen body of sodium montmorillonite as the chief agent with (B) a humectant (pref. sodium lactate or sorbitol), oil (pref. squalene or rice germ oil) or crude drug (pref. an extract of mugwort or field horsetail). It is preferable in terms of dermal infiltrativity that the water contained in the component A be water small in cluster. It is recommended that this remedying agent be coated in the creamy form or sprayed as a spray.
We will undertake a cluster randomised trial of the efficacy of medical drone use by randomization of health facilities and their associated landing sites in Kalangala District. There are 64 landing sites and 18 health facilities. The unit of radomisation will be the landing site, so that all persons at one landing site will receive the drone delivery or boat delivery, facility pick-up. This will avoid contamination of drone delivery by sharing of ART between people getting drone and boat or other modes of deliveries. Bias in this situation will be managed by stratifying the landing sites by distance from drone operations base (a proxy of delivery cost), and number of decentralised service delivery (DSD) groups. Bias in gender and age will be managed at selection of members in DSD groups. We will also undertake a cost effectiveness analysis, carbon analysis and process evaluation. A qualitative study will assess acceptability and additional use cases
BACKGROUND: Orthopedic injuries are commonly managed in the emergency department (ED) setting. Fractures and dislocations may require reduction for proper management. There are a variety of analgesic and sedative strategies to provide patient comfort during reduction. OBJECTIVE: This narrative review evaluates hematoma block, intra-articular injection, intravenous regional analgesia (IVRA) (also known as the Bier block), and periosteal block for orthopedic analgesia in the ED setting. DISCUSSION: Analgesia is an essential component of management of orthopedic injuries, particularly when reduction is necessary. Options in the ED setting include hematoma blocks, intra-articular injections, IVRA, and periosteal blocks, which provide adequate analgesia without procedural sedation or opioid administration. When used in isolation, these analgesic techniques decrease complications from sedation and the need for other medications, such as opioids, while decreasing ED length of stay. Emergency clinicians can also use these techniques as analgesic adjuncts. However, training in these techniques is recommended prior to routine use, particularly with IVRA. CONCLUSIONS: Knowledge of analgesic techniques for orthopedic procedures can assist clinicians in optimizing patient care.
Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and venetoclax when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
For topical use only. Not for oral, ophthalmic, or intravaginal use. After the skin is gently washed and patted dry, apply approximately a pea-sized amount of ACZONE Gel, 7.5%, in a thin layer to the entire face once daily. In addition, a thin layer may be applied to other affected areas once daily. Rub in ACZONE Gel, 7.5%, gently and completely. If there is no improvement after 12 weeks, treatment with ACZONE Gel, 7.5% should be reassessed.
There is an urgent need for innovative approaches to pediatric obesity prevention and treatment. There is also a demand for targeted strategies that reduce attrition and improve compliance with obesity treatment. Intervening exclusively with parents of overweight children is a novel treatment approach, with demonstrated efficacy in reducing child body mass index (BMI) percentile. Motivational interviewing (MI), a brief communication style for exploring and resolving ambivalence about change, may enhance treatment engagement when implemented as part of obesity interventions. Further research investigating MI within pediatric obesity treatments is needed. In the current application, the investigators are examining whether MI implemented with parents for the treatment of their children's overweight can improve treatment effects. NOURISH+, a recently funded R01 (Nourishing Our Understanding of Role modeling to Improve Support and Health; PI, Mazzeo), is a culturally tailored parent intervention for overweight children ages 5-11. NOURISH+ targets lower-income, African American participants, a group at increased risk for pediatric overweight and associated complications, and builds on pilot work which yielded significant reductions in child BMI percentile. The investigators are adding an MI treatment into NOURISH+. Specifically, we will randomly select 60 parents at enrollment and investigate if adding two brief MI sessions prior to the NOURISH+ group intervention will enhance treatment effects. The investigators will be able to compare NOURISH+MI with participants from the two R01 treatment conditions (NOURISH+ and Control), matched on child ethnicity and gender. The investigators hypothesize that children whose parents participate in NOURISH+ MI will demonstrate lower attrition and greater compliance with NOURISH+, ultimately leading to greater treatment effects, compared with children whose parents are randomized to NOURISH+ or a control group.
Study procedure In each period, the subjects arrived at the clinical/unit site on the day before the commencement of the study and were randomized using Excel® 2007 to receive the test formulation followed by the reference formulation, or viceversa. No food was allowed from 10 h before until at least 4 h after drug administration. On the subsequent morning, a peripheral venous 21G catheter was inserted in the antecubital vein of the subjects and blood samples were collected (zero time). The subjects then received a single 75 mg tablet of either the test or the reference formulation, given with 250 mL water. Blood samples were collected at 0.16, 0.33, 0.5, 0.66, 0.83, 1, 1.5, 1.75, 2, 2.5, 3, 6, 8, 12, 16 and 24 h after drug administration. The blood samples were collected in coded EDTA tubes and plasma was obtained by centrifugation (2,053 g for 10 min at 5 C), after which the plasma was immediately transferred to prelabeled vials and stored at or below -70 After a week of washout, the alternative formulation was administered to the subjects and samples were drawn and analyzed as before.
Dosage for Hepatically Impaired Patients The use of sertraline in patients with liver disease should be approached with caution. The effects of sertraline in patients with moderate and severe hepatic impairment have not been studied. If sertraline is administered to patients with liver impairment, a lower or less frequent dose should be used (see CLINICAL PHARMACOLOGY and PRECAUTIONS). Treatment of Pregnant Women During the Third Trimester Neonates exposed to sertraline and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with sertraline during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. Discontinuation of Treatment with Sertraline Symptoms associated with discontinuation of sertraline and other SSRIs and SNRIs, have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.
[ 18F]FDG uptake may be changed by fasting or by blood sugar changes associated with diabetic mellitus. Blood glucose levels should be stabilized in non-diabetic patients by fasting before [ 18F]FDG injection. Diabetic patients may need stabilization of blood glucose on the day preceding, and on the day of the [ 18F]FDG scan. Patients should be monitored for arrhythmias and other manifestations of ischemia. [ 18F]FDG, CIDG and their metabolites theoretically could inhibit glucose metabolism. Their ability to potentiate the arrhythmogenic effects of ischemia has not been studied. The contents of each vial are sterile and non-pyrogenic. To maintain sterility, aseptic technique must be used during all operations involved in the manipulation and administration of [ 18F]FDG. [ 18F]FDG should be used within 12 hours of the end of synthesis (EOS). As with any other radioactive material, appropriate shielding should be used to avoid unnecessary radiation exposure to the patient, occupational workers, and other persons. Radiopharmaceuticals should be used only by physicians who are qualified by specific training in the safe use and handling of radionuclides.
A non-randomized, prospective study of up to 150 subjects with asthma. Patients will perform eNO testing with the Apieron INSIGHT(tm) eNO system and the NIOX eNO system at the physician's office/clinic after a short demonstration and training by a healthcare professional trained in the use of the devices. Exhaled NO testing involves inhaling to lung capacity, and then performing a controlled exhalation into a mouthpiece connected to each of the Apieron INSIGHT(tm) and NIOX systems. Patients will perform an eNO measurement with the Apieron INSIGHT(tm) system and with the FDA cleared NIOX system for the accuracy portion of the study. Patients will perform 2 sequential eNO measurements on each system for the precision part of the study. Subjects that measure eNO values over 100 ppb will be asked to repeat 2 sequential eNO measurements on each system.
Glutamate has been implicated in the aetiology of mood disorders and there is current interest in developing novel agents targeting this system. However, the role of glutamate in human emotional function is relatively unknown. Lamotrigine's pharmacological profile involves a blockade of voltage-gated sodium channels, leading to an inhibition in the release of glutamate and resulting in a general inhibitory effect on cortical neuronal function. The current study plans to investigate the effects of modifying glutamate on emotional processing, cognitive function and neural activity. For this, 36 healthy volunteers will be recruited to the study and randomised to receive a single dose of lamotrigine (300 mg) or placebo. Two hours after drug administration, the effects of emotional processing via the use of cognitive tasks will be assessed using fMRI. This will be followed by an emotional test battery that will measure aspects of cognitive function as well.
N= 42 For baseline day 1-7: Actiwatch Spectrum worn at the wrist of dominant hand, day 8-14 continued wearing of Actiwatch spectrum + blue-blocking goggles from 6 p.m. to 08 a.m. In addition to selfreport forms described in the outcome section self report forms Horne-Ostberg Morningness-Eveningness Questionaire (HOMEQ)and Seasonal Pattern Assessment Questionaire (SPAQ).
Caesarean-section was done in the usual manner. The transverse suprapubic skin incision was made and abdominal layers opened as usual. After delivering the baby, uterine muscle is closed in two layers with braided absorbable suture, polyglactin 910 (Vicryl no 1). After hemostasis secure, 1 mL Protescal gel was applied at the uterine suture site in Protescal group. Peritoneal layer closed using braided absorbable suture, polyglactin 910 (Vicryl no 1). Rectus sheath was sutured using braided absorbable suture, polyglactin 910 (Vicryl no 1). Subcutaneous tissue closed interruptedly using braided absorbable suture, polyglactin 910 (Vicryl no 1). Protescal gel (0.5 mL) was applied over the subcutaneous tissue prior to skin closure in Protescal group. The skin was then closed with the subcuticular method using braided absorbable suture, polyglactin 910 (Vicryl 3-0).
PROBLEM TO BE SOLVED: To obtain the subject absorbing barrier membrane, excellent in thermal stability, processability, reproducibility, storage stability, bioabsorptivity and agenesis, useful for reconstruction of tissues of animals including humans and usable for an anagenetic induction method. SOLUTION: This absorbing barrier membrane comprises a lactic acid-based polyester prepared by carrying out the inactivation treatment of a polymerization catalyst (e.g. tin octanoate, zinc chloride or an alkoxytitanium) with a chelating agent (e.g. ethylenediaminetetraacetic acid, oxalic acid or phosphoric acid) and/or acid phosphoric esters (e.g. an acid phosphoric ester or a phoshonic ester) as an essential ingredient and further a calcium phosphate (e.g. tricalcium phosphate or hydroxyapatite) and contains pores, having 0.1-200 μm diameter and present therein. The lactic acid-based pplyester contains a structural unit derived from lactic acid and a polyester structural unit with 2-60 wt.% content thereof derived from a dicarboxylic acid and a diol and has preferably 30,000-300,000 molecular weight.
Female patients with no known uterine pathologies and good general health undergoing treatment for unexplained infertility will be identified and invited to participate in the study. Endometrial biopsy will be obtained seven days after luteinizing hormone (LH) surge during a natural cycle. The following month, 5 days after LH surge, peripheral blood mononuclear cells (PBMC) will be isolated from patients' peripheral blood by density gradient (1.077g/ml) centrifugation and suspended in culture medium. The obtained PBMC will be incubated with 500 IU IFNt at 37˚C for 24 hours. This cell suspension will be carefully introduced in the uterine cavity by catheter on day 6 post LH surge. A second biopsy will be obtained the following day (LH+7). Immunohistochemistry evaluation of endometrial tissue will be performed in terms of quantities and spatial distribution of various cell types.
Background: Primary open angle glaucoma (OAG) is a chronic progressive neurodegenerative disease where intraocular pressure (IOP) is the main and successfully treatable risk factor. Although the treatment effect is quite large, a significant proportion of patients show disease progression with apparently well controlled IOP. Given the similarities with other neurodegenerative diseases - particularly in the mechanisms of cell death - neuroprotective treatments have been tested also in glaucoma. Interesting results from experimental studies and first evidence from human glaucoma trials have been published in recent years. Citicoline is one of the promising molecules with a putative neuroprotective action and has been evaluated in patients with various neurodegenerative diseases with encouraging results. The mechanism of action of citicoline is multifarious and includes preservation of cardiolipin and sphingomyelin, restoration of phosphatidylcholine, stimulation of glutathione synthesis, lowering of glutamate concentration, rescuing mitochondrial function, and others. Pilot studies on glaucomatous patients showed a possible effect of citicoline as additive therapy in the treatment of glaucoma, in reducing progression of visual field changes, in protecting retinal nerve fiber layers and in improving vision related Quality of Life (QoL), though these findings are yet to be confirmed by a large randomized clinical trial.
Aim 1 is to test the hypothesis that in patients prone to IDH, blockade of bradykinin B2 receptor with icatibant prevents the drop of blood pressure and maintains hemodynamic stability. For this purpose, heart rate and blood pressure during hemodialysis are monitored. Importantly, the study will be conducted in an outpatient clinic, using the patients' usual hemodialysis dose and settings as for a regular hemodialysis session. Aim 2 is to test the hypothesis that in patients prone to IDH, inhibition of the plasma kallikrein system with icatibant prevents symptoms associated with IDH such as cramps, dizziness, and nausea, and improves the quality of life (QoL) and recovery time after hemodialysis. Hemodialysis is associated with many complications, including IDH, that negatively affect the QoL of patients and their families. Any intervention that prevents the occurrence of IDH will result in a faster recovery from hemodialysis. The present study will evaluate the impact of icatibant on preventing symptoms associated with IDH and reducing recovery time after hemodialysis.
The pivotal role of myofibroblast contractility in the pathophysiology of fibrosis is widely recognized, yet HTS approaches are not available to quantify this critically important function in drug discovery. We developed, validated, and scaled-up a HTS platform that quantifies contractile function of primary human lung myofibroblasts upon treatment with pro-fibrotic TGF-β1. With the fully automated assay we screened a library of 40,000 novel small molecules in under 80 h of total assay run-time. We identified 42 hit compounds that inhibited the TGF-β1-induced contractile phenotype of myofibroblasts, and enriched for 19 that specifically target myofibroblasts but not phenotypically related smooth muscle cells. Selected hits were validated in an ex vivo lung tissue models for their inhibitory effects on fibrotic gene upregulation by TGF-β1. Our results demonstrate that integrating a functional contraction test into the drug screening process is key to identify compounds with targeted and diverse activity as potential anti-fibrotic agents.
INTRODUCTION: People should have access to healthcare services that are effective, safe and secure, patient-centred, and coordinated and continuous. One group that has consistently reported negative experiences and feels dissatisfied with services are patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). The objective of this study was to develop a deeper understanding of the experiences of dissatisfaction among ME/CFS patients and explore the reasons for such dissatisfaction. METHODS: We conducted in-depth interviews with 48 people from 24 households (comprising patients and family members), providing insight into the experiences of 37 ME/CFS sufferers in Norway. The participants were purposively sampled and included persons of different ages, genders, time since having the condition (3-30 years), and severity. RESULTS: Four main themes were developed: (1) 'Nonexistent services' cover patients' experience that healthcare services had nothing to offer them after receiving their ME/CFS-diagnosis. (2) 'Nonpersonalised services' documents experiences where patients did receive services, which in theory was appropriate for relieving a specific health problem, but in practice were experienced as inappropriate because they were not adapted to the patient's need. (3) 'Slow services' address patients' experience of getting services too late (or too little) to be useful. (4) 'Wrong services' comprise patients' experiences of being offered and/or 'forced' to accept services that they felt were inappropriate for their health problems. CONCLUSIONS: Providers' lacking knowledge of the condition and lack of precise recommendations for follow up may partly explain unsatisfactory experiences. Providers' belief (or disbelief) in the condition could furthermore influence caregiving. Also, systemic issues in the healthcare sector, like high workloads and bureaucracy, can negatively affect care provision. Finally, users' unsatisfactory experiences may also be due to a lack of patient involvement in the design of such services. Further research should investigate how patients can be involved in service design, and also providers' perspectives on caregiving and the barriers they experience for providing high-quality care. PATIENT OR PUBLIC CONTRIBUTION: The ME-patient organisation suggested research topics to the call from which this study got funding. Patients and caregivers provided feedback during analysis and interpretation of data.
The invention provides a lignin-verteporfin self-assembled nano-composite and preparation and application thereof. The nano-composite is composed of amphiphilic high polymer lignin and hydrophobic drug micromolecular verteporfin. Lignin and verteporfin spontaneously assemble to form micelle nano-composites, and then ionic liquid with permeability is prepared through salt decomposition reaction, so that the novel percutaneous delivery system ILs-LVNs is finally formed. LVNs not only has the function of scavenging active oxygen, but also can activate Wnt channel by up-regulating Trps1 transcription factor signal, accelerate wound regeneration, and block abnormal proliferation of fibroblast by inhibiting YAP gene expression, thereby reducing scar formation. The percutaneous delivery system ILs-LVNs provided by the invention has double functions, and can promote wound healing and inhibit scar formation. The innovative delivery strategy of the present invention provides a highly effective, low side effect method for chronic wound and hypertrophic scar treatment.
This study seeks to examine parent-offspring reproductive conflicts between Bofi forager mothers and children in the Republic of Congo. One of the most prominent theories in evolutionary studies of human behavior is Trivers' (1974) parent-offspring conflict theory, which predicts that offspring contrive to maximize investment from their parents, whereas parents try to balance the interests of their offspring with the interests of their future reproduction. Fouts (2002) and Fouts, Hewlett \& Lamb's (2001) research with the Bofi foragers indicated that weaning was not a time that elicited overt conflict between mothers and their offspring. Instead, transitions in investment appeared to have occurred prior to weaning, perhaps when the mothers became pregnant. This study proposes to document mother-child interactions when forager mothers are at different stages of pregnancy through naturalistic observations of public behavior, as well as measures including: the approximate week of pregnancy, maternal beliefs about child-care, and demographic features of families. The data will be analyzed statistically and used to evaluate Trivers' parent-offspring theory, as well as to evaluate the validity of claims by Western scholars about universal features of parent-child relationships. The foragers provide an excellent opportunity to examine child developmental theories that have been well studied among industrialized Euro-American cultures, but neglected cross-culturally. Furthermore, studies among contemporary hunter-gatherer groups, such as the foragers in Congo, provide insight into the evolutionary past of humans, as humans have lived as hunter-gatherers for approximately 99% of prehistory, and the few remaining groups are disappearing rapidly (Phillipson 1993).
The study discussed here is part of a broader research project (IOF project) that is aimed at the development and implementation of a point-of-care devices, in which Fiber-Optic Surface Plasmon Resonance (FO-SPR) is used as a detection system. This project includes the development and implementation of the (FUNGDETECT) sensor for fast and accurate detection of fungal pathogens in human blood samples. In first instance, the sensor will be tested in buffer solutions spiked with a known amount of Candida albicans cells. Further validation of the prototype includes detection of these cells in human blood samples. In a first experiment, detection of yeast cells will be performed in blood samples from 5 healthy volunteers each spiked with yeast cells from different Candida spp.. A second experiment includes the detection in blood samples from 15 patients who suffer from a candidemia. The blood samples will be collected from patients of University Hospitals (UZ) Leuven.
This study will evaluate the 2-5 year outcome of a cohort of 250 patients with early synovitis, who were recruited into protocol 94-AR-0194 (The Pathogenesis of Inflammatory Synovitis: A Study of Early Arthritis). Clinical, radiographic, and functional outcome parameters, particularly those relating to articular damage and functional loss, will be evaluated and related back to clinical, serologic, immunogenetic, and pathologic variables identified at the onset of the arthropathy. A model will be generated which incorporates and weighs the variables in order to determine diagnostic and prognostic markers in the early stages of arthritis. Synovial tissue samples have been obtained from the entire cohort at the initial visit of protocol 94-AR-0194. Studies of these biopsies have so far demonstrated evidence for the presence of infectious agents in a proportion of the samples, and have generated information regarding the cytokine profiles in the early stages of synovitis. In an attempt to further define the pathogenetic mechanisms of synovitis longitudinally, biopsies will be repeated on selected subsets of the cohort. Specific questions to be answered relate to the persistence of microbial agents in the synovium, and to the evolution of cellular and molecular mechanisms which mediate the invasive, destructive potential of the synovial lesion. It is anticipated that these studies should prove valuable to clinicians who are attempting to stratify patients for therapeutic strategies, early in their disease course. They should also prove valuable in enhancing the understanding of the pathogenetic mechanisms of synovitis.
Behavioral, PeACE, PeACE consists of 3 streamlined 30-minute psychosocial telephone counseling sessions delivered by a well-trained peer coach. Coaches are lay YARs from HBOC families demonstrating good knowledge, communication skills, and protocol mastery.
NEW MATERIAL:The monoclonal antibody reacting specifically with human gastric cancer cells, and produced by the hybridoma obtained by the fusion of myeloma cell and immunized cell of mammal immunized with human gastric cancer cell. USE:Diagnotic for human gastric cancer. PROCESS:Cultured human carcinoma cells MKN74 are suspended in physiological saline water, and the suspension is infused into the peritoneal cavity of a Balb/c mouse three times with intervals of 2 weeks. 3 days after the final immunization, the spleen is extracted, and the spleen cells are washed, mixed with mouse myeloma cell strain NS/1, and subjected to cell fusion in the presence of polyethylene glycol. The obtained cell is inoculated in a medium containing hypoxanthine, aminopterin and thymidine (HAT medium) and cultured in a CO2 incubator to obtain hybridoma. The hybridoma is cloned by critical dilution method to obtain a monoclonal antibody-producing hybridoma, by which the antibody for human gastric cancer is produced.
PURPOSE: A method for improving treatment effect of cancer cells is provided to suppress T cell activation and to enhance sensitivity of cancer cell on conventional anticancer drug. CONSTITUTION: A method for enhancing cancer treatment effect by knock-down of B7-H4 gene in cancer cells comprises: a step of preparing a vector expressing RNAi which is homologous with B7-H4 nucleic acid or B7-H4 gene sequence (Gene bank access No NM 024626) nucleic acid; and a step of transforming cancer cells with the vector. The RNAi is siRNA(small intefering RNA), shRNA(short hairpin RNA), or antisense nucleic acid. The vector is plamid, phage, or virus. The vector is lentivirus. The cancer cells are breast cancer(SK-BR3, KCLB No 30030), uterine cancer cells (HeLa, KCLB No 10002), liver cancer SNU 475 (KCLB No 00475), SNU 423 (KCLB No 00423), SNU 398 (KCLB No 00398), or Hur 7(KCLB 60104).
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reaction observed in controlled clinical trials with TRAVATAN and TRAVATAN Z was ocular hyperemia, which was reported in 30% to 50% of patients. Up to 3% of patients discontinued therapy due to conjunctival hyperemia. Ocular adverse reactions, reported at an incidence of 5% to 10% in these clinical trials, included decreased visual acuity, eye discomfort, foreign body sensation, pain, and pruritus. Ocular adverse reactions, reported at an incidence of 1% to 4% in clinical trials with TRAVATAN or TRAVATAN Z, included abnormal vision, blepharitis, blurred vision, cataract, conjunctivitis, corneal staining, dry eye, iris discoloration, keratitis, lid margin crusting, ocular inflammation, photophobia, subconjunctival hemorrhage, and tearing. Non-ocular adverse reactions, reported at an incidence of 1% to 5% in these clinical studies, were allergy, angina pectoris, anxiety, arthritis, back pain, bradycardia, bronchitis, chest pain, cold/flu syndrome, depression, dyspepsia, gastrointestinal disorder, headache, hypercholesterolemia, hypertension, hypotension, infection, pain, prostate disorder, sinusitis, urinary incontinence, and urinary tract infections.
Based on the 'AT(N)' system, individuals with normal amyloid biomarkers but abnormal tauopathy or neurodegeneration biomarkers are classified as non-Alzheimer's disease (AD) pathologic change. This study aimed to assess the long-term clinical and cognitive trajectories of individuals with non-AD pathologic change among older adults without dementia, comparing them to those with normal AD biomarkers and AD pathophysiology. Analyzing Alzheimer's Disease Neuroimaging Initiative data, we evaluated clinical outcomes and conversion risk longitudinally using mixed effects models and multivariate Cox proportional hazard models. We found that compared to individuals with A-T-N-, those with abnormal tauopathy or neurodegeneration biomarkers (A-T + N-, A-T-N + , and A-T + N + ) had a faster rate of cognitive decline and disease progression. Individuals with A-T + N + had a faster rate of decline than those with A-T + N-. Additionally, in individuals with the same baseline tauopathy and neurodegeneration biomarker status, the presence of baseline amyloid could accelerate cognitive decline and clinical progression. These findings provide a foundation for future studies on non-AD pathologic change and its comparison with AD pathophysiology.
In the Proof-of-Concept study (CAIN457A2102/ NCT00669916), AIN457 was proven to be efficacious in the treatment of moderate to severe chronic plaque-type psoriasis. As a result, a phase IIb regimen finding study had been started (CAIN457A2211/NCT00941031). The data gathered in this extension study of the core study (CAIN457A2211)was used to expand the safety database of the compound for the treatment of moderate to severe chronic plaque-type psoriasis. The participants in the extension study continued to stay on the exact same treatment regimen they were taking when completing the core study. The extension trial was first designed to provide long-term safety data of up to 100 weeks of treatment (32 weeks in the core study plus 68 weeks in the extension study (part 1)), and an additional 12 weeks of treatment-free follow-up for participants who did not continue in the extension study. Amendment 2 provided an additional 156 weeks of treatment (32 weeks in the core study plus 224 weeks in the extension study, equaling 256 weeks of total treatment (part 2)), before participants entered the 12 weeks of treatment-free follow-up. Protocol Amendment 3 extended the prolongation part of the study by up to 104 additional weeks of treatment (part 3) or until the drug was commercially available in the market of the country of participation, whichever occurred first.
This is a Phase 1, open-label, prospective, dose-finding and cohort expansion study to assess the safety, tolerability, pharmacodynamics and preliminary antitumor activity of the combination of NAP/pembrolizumab following pretreatment with Obi in patients with urothelial cancers who are candidates for pembrolizumab treatment. and will not be used to determine eligibility for enrollment. The study will test two doses of NAP 5 µg/kg/day (Dose Level 1) and 10 µg/kg/day (Dose Level 2), in combination with a fixed dose of pembrolizumab (200mg every 3 weeks). It is expected that full dose of both drugs can be safely combined. The purpose of this study is to define the recommended dose for phase 2 trials of the combination of NAP/pembrolizumab by employing a BOIN design for phase 1 trials. The BOIN design will find the highest dose for which the probability of a dose-limiting toxicity is less than 0.25. No dose level will have more than 12 patients. An initial cohort of 3 patients will be enrolled on Dose Level 1. After these patients have been observed for a DLT, the decision to escalate, de-escalate or remain at the current dose will be made according to the table in the statistical section of the protocol. The maximum tolerated dose (MTD) will be selected using isotonic regression that pools the information across doses. No intra-patient dose escalation is permitted. Patients who discontinue the study during the 21-day dose-limiting toxicity (DLT) observation period for reasons other than a DLT, or who do not receive a full cycle of NAP/pembrolizumab, will be replaced. Each patient will participate in 3 stages of the trial: a 21-day screening stage, followed by a treatment stage that may continue until evidence of progressive neoplastic disease, intolerance to treatment of fulfillment of any of the other criteria for treatment discontinuation as listed in Section 8.1 of the protocol, and a follow-up phase to determine the effect of protocol treatment on cancer progression. All patients will be seen at the end of treatment (EOT) visit 30 (+ 7) days after the last dose of protocol therapy.
The following will be the phototherapeutic parameters: total spot area: 1.44 cm²; continuous emission mode; output power: 10 mW; infrared wavelength (880 to 904 nm); fluence: 4 J/cm²; and application time: 10 minutes/session. Sessions will be held three times a week on alternating days for six consecutive weeks, totaling 18 sessions.
Alzheimer's disease and related dementias (ADRD) affect 47 million people worldwide with an annual global cost of $818 billion. The risk of developing ADRD is disproportionately borne by older adults with multiple chronic conditions from underrepresented racial and ethnic groups (URGs). One such high risk group is older survivors of critical illness who were admitted to the intensive care units (ICUs). Nearly half of ICU survivors experience subjective cognitive decline(SCD), i.e., perceived decline in memory and thinking even with normal objective cognitive data. With over 5 million adult ICU admissions in the US each year, an intervention reducing SCD in older ICU survivors could significantly prevent or lower the incidence of ADRD. Thus, there is an urgent need for an inclusive randomized controlled trial (RCT) to rigorously test whether a novel, accessible, and scalable intervention can reduce SCD in a diverse cohort of older ICU survivors. One potential target for such interventions is post-ICU depression, which affects about one-third of ICU survivors. To date, there are no large scale RCTs which have rigorously tested whether depression focused psychotherapies, such as cognitive behavioral therapy (CBT), reduce SCD in a diverse cohort of older ICU survivors with depression. We propose a two-arm, randomized, parallel-group, assessor-blinded clinical trial to evaluate the efficacy of internet CBT for depression compared to an active control in reducing SCD and slowing cognitive decline in older ICU survivors with post-ICU depression. The total duration of the intervention will be 6 months from randomization.
A single blind prospective randomized superiority study is conducted. Our hypothesis is that there is difference in the incidence of aortic valve replacement between the standard aortic valve reimplantation procedure and aortic root reimplantation procedure more than 21.1%. If there is truly difference between groups (Aortic Root Reimplantation Procedure and Aortic Valve Reimplantation Procedure), then total 64 patients for both groups are required to be 80% sure that the upper limit of a one-sided 95% confidence interval would reveal a difference in favour of the Aortic Root Reimplantation Procedure of 21.1%. The blinding process is applied to a patient, who is informed about received valve-sparing operation, but don't know the type of the last. The study was approved by Institutional Review Board. Depending on a type of the procedure, the patients are divided into two groups: Aortic Root Reimplantation Procedure group includes 32 patients and Aortic Valve Reimplantation Procedure group consists of 32 patients. Randomization is conducted intraoperatively by using accidental sampling after examining the aortic valve and making a decision on the possibility of a valve-sparing operation.
ETHNOPHARMACOLOGICAL RELEVANCE: Baoyuan Decoction (BYD) was initially recorded in the classic of "Bo Ai Xin Jian" in the Ming dynasty. It is traditionally used for treating weakness and cowardice, and deficiency of vital energy. In researches related to anti-fatigue effects, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in anti-fatigue mechanism, while it has not yet been revealed. Therefore, we elucidated the anti-fatigue mechanism of BYD through AMPK/CRY2/PER1 pathway. AIM OF THE STUDY: To investigate the effect and mechanism of BYD in reducing fatigue, using pharmacodynamics, network pharmacology and transcriptomics through the AMPK/CRY2/PER1 signaling pathway. MATERIALS AND METHODS: Firstly, the chemical constituents of BYD were qualitatively identified by UHPLC-Q-Exactive Orbitrap/MS, establishing a comprehensive strategy with an in-house library, Xcalibur software and Pubchem combined. Secondly, a Na2SO3-induced fatigue model and 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress model were developed to evaluate the anti-fatigue and anti-oxidant activities of BYD using AB zebrafish. The anti-inflammatory activity of BYD was evaluated using CuSO4-induced and tail cutting-induced Tg (lyz: dsRed) transgenic zebrafish inflammation models. Then, target screening was performed by Swiss ADME, GeneCards, OMIM and DrugBank databases, the network was constructed using Cytoscape 3.9.0. Transcriptome and network pharmacology technology were used to investigate the related signaling pathways and potential mechanisms after treatment with BYD, which were verified by real-time quantitative PCR (RT-qPCR). RESULTS: In total, 114 compounds from the water extract of BYD were identified as major compounds. Na₂SO₃-induced fatigue model and AAPH-induced oxidative stress model indicated that BYD has significant anti-fatigue and antioxidant effects. Meanwhile, BYD showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. The KEGG result of network pharmacology showed that the anti-fatigue function of BYD was mainly effected through AMPK signaling pathway. Besides, transcriptome analysis indicated that the circadian rhythm, AMPK and IL-17 signaling pathways were recommended as the main pathways related to the anti-fatigue effect of BYD. The RT-qPCR results showed that compared with a model control group, the treatment of BYD significantly elevated the expression mRNA of AMPK, CRY2 and PER1. CONCLUSION: Herein, we identified 114 chemical constituents of BYD, performed zebrafish activity validation, while demonstrated that BYD can relieve fatigue by AMPK/CRY2/PER1 signaling pathway through network pharmacology and transcriptome.
Subjects aged between 30 and 60 years old (male and female) with Type 2 diabetes mellitus (T2DM) will be recruited for this study. A randomized, crossover, double-blind study design will be carried out to investigate the acute effects of high fat meals prepared using palm olein (PO), chemically interesterified palm olein (IPO) and high oleic sunflower oil (HOS) (control) on study subjects with T2DM. Study subjects will have to undergo three postprandial challenges, separated by at least one week interval. Fasting blood sample and duplicate baseline blood samples will be taken in the morning of postprandial day. After that, subjects will be asked to consume a test meal consisting a high fat muffin baked using the aforementioned oils and a milkshake within 10 minutes. After meal, venous blood samples will be taken at time-points 15, 30, 60, 90, 120 min, 3 h, 4 h, 5 h, 6 h and post-heparin plasma 5 min and 15 min for analysis. Pulse wave analysis will be conducted to evaluate central blood pressure and arterial stiffness. Meal appreciation will be assessed by utilising visual analogue scale (VAS) before eating, after eating and at each time-point.
PURPOSE: This study aims to compare the functional and radiological outcomes following both guided growth surgery (GGS) and acute corrective osteotomy (ACO) correction of angular deformities in children with rickets. METHODS: A total of 8 and 7 children who had gradual GGS and ACO correction, respectively, for angular deformities due to rickets from 2002 to 2022 were recalled for follow-up. Demographic data, types of rickets, data on pharmacological treatment, biochemical parameters, recurrence of angular deformity and postoperative complications were obtained from the medical records. A radiographic evaluation of the leg was performed to determine the tibiofemoral angle. For functional evaluation, the Active Scale for Kids (ASK) and Lower Extremity Functional Scale (LEFS) instruments were used for children below and above 15 years old, respectively. RESULTS: In terms of the tibiofemoral angle, the GGS group documented greater angle changes compared to the ACO group, but the difference was not significant. In terms of functional outcomes, the overall score percentage of both groups was comparable with the GGS group showing a trend of higher score percentage compared to the ACO group. The GGS group presented no complication while 2 neurovascular injuries and 1 implant failure were recorded in the ACO group. CONCLUSION: Both GGS and ACO procedures resulted in similar radiographic and functional outcomes for the treatment of rickets in children. GGS may be advantageous in terms of reducing complications of surgery. Nevertheless, the choice of surgical intervention should be made based on the patient's circumstances and the surgeon's preference.
PURPOSE:To provide a composition reactive with the sugar chain developed on cell surface due to HIV infection, thus useful as a diagnostic or medicine for AIDS, containing, as active ingredient, the antibody capable of recognizing specific mucin-type glycolipids. CONSTITUTION:BALB/c mice are immunized with a mucin-type glycolipid of formula I (Cer is ceramide), II, III, or IV, and the splenocytes are taken from the resulting mice and fused with mouse myeloma cells followed by selecting a clone capable of producing the antibody reactive with the above mucintype glycolipids, and the resulting hybridoma is then cloned using e.g. limiting dilution method to provide it with monoclonality. The resultant hybridoma is then implanted into e.g. mice to produce monoclonal antibody in the ascites. The monoclonal antibody is then separated and purified to obtain the monoclonal antibody capable of recognizing the above mucin-type glycolipids. This monoclonal antibody is made, as active ingredient, into a pharmaceutical to obtain the objective medicine composition for AIDS.
Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur in uncomplicated influenza as well. There have been postmarketing reports of delirium and abnormal behavior leading to injury in patients with influenza who were receiving neuraminidase inhibitors, including RAPIVAB. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made, but they appear to be uncommon. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of RAPIVAB to these events has not been established. Patients with influenza should be closely monitored for signs of abnormal behavior.

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