Pharmacokinetics of aditoprim and trimethoprim in buffalo calves

Pharmacokinetic parameters of two antifolates, trimethoprim and aditoprim, were studied in buffalo calves. The elimination half-life of aditoprim (6.14 h) was nearly twice as long as that of trimethoprim (3.08 h) and compares well with values observed in heifers. This longer half-life of aditoprim is a result of its much larger distribution volume (four to five times larger) because the clearance of aditoprim was about twice as high as that of trimethoprim. The longer half-life of aditoprim is expected to give a longer duration of in vivo bacteriostatic activity than that of trimethoprim.     

Pathogenic potential of environmental Vibrio cholerae strains carrying genetic variants of the toxin-coregulated pilus pathogenicity island

The major virulence factors of toxigenic Vibrio cholerae are cholera toxin (CT), which is encoded by a lysogenic bacteriophage (CTXPhi), and toxin-coregulated pilus (TCP), an essential colonization factor which is also the receptor for CTXPhi. The genes for the biosynthesis of TCP are part of a larger genetic element known as the TCP pathogenicity island. To assess their pathogenic potential, we analyzed environmental strains of V. cholerae carrying genetic variants of the TCP pathogenicity island for colonization of infant mice, susceptibility to CTXPhi, and diarrheagenicity in adult rabbits. Analysis of 14 environmental strains, including 3 strains carrying a new allele of the tcpA gene, 9 strains carrying a new allele of the toxT gene, and 2 strains carrying conventional tcpA and toxT genes, showed that all strains colonized infant mice with various efficiencies in competition with a control El Tor biotype strain of V. cholerae O1. Five of the 14 strains were susceptible to CTXPhi, and these transductants produced CT and caused diarrhea in adult rabbits. These results suggested that the new alleles of the tcpA and toxT genes found in environmental strains of V. cholerae encode biologically active gene products. Detection of functional homologs of the TCP island genes in environmental strains may have implications for understanding the origin and evolution of virulence genes of V. cholerae.     

An inventory-location optimization model for equitable influenza vaccine distribution in developing countries during the COVID-19 pandemic

The addition of other respiratory illnesses such as flu could cripple the healthcare system during the coronavirus disease 2019 (COVID-19) pandemic. An annual seasonal influenza vaccine is the best way to help protect against flu. Fears of coronavirus have intensified the shortage of influenza shots in developing countries that hope to vaccinate many populations to reduce stress on their health services. We present an inventory-location mixed-integer linear programming model for equitable influenza vaccine distribution in developing countries during the pandemic. The proposed model utilizes an equitable objective function to distribute vaccines to critical healthcare providers and first responders, elderly, pregnant women, and those with underlying health conditions. We present a case study in a developing country to exhibit efficacy and demonstrate the optimization model’s applicability.     

Telemedicine to deliver diabetes care in low- and middle-income countries: a systematic review and meta-analysis

ObjectiveTo determine the effectiveness of telemedicine in the delivery of diabetes care in low- and middle-income countries.MethodsWe searched seven databases up to July 2020 for randomized controlled trials investigating the effectiveness of telemedicine in the delivery of diabetes care in low- and middle-income countries. We extracted data on the study characteristics, primary end-points and effect sizes of outcomes. Using random effects analyses, we ran a series of meta-analyses for both biochemical outcomes and related patient properties.FindingsWe included 31 interventions in our meta-analysis. We observed significant standardized mean differences of −0.38 for glycated haemoglobin (95% confidence interval, CI: −0.52 to −0.23; I² = 86.70%), −0.20 for fasting blood sugar (95% CI: −0.32 to −0.08; I² = 64.28%), 0.81 for adherence to treatment (95% CI: 0.19 to 1.42; I² = 93.75%), 0.55 for diabetes knowledge (95% CI: −0.10 to 1.20; I² = 92.65%) and 1.68 for self-efficacy (95% CI: 1.06 to 2.30; I² = 97.15%). We observed no significant treatment effects for other outcomes, with standardized mean differences of −0.04 for body mass index (95% CI: −0.13 to 0.05; I² = 35.94%), −0.06 for total cholesterol (95% CI: −0.16 to 0.04; I² = 59.93%) and −0.02 for triglycerides (95% CI: −0.12 to 0.09; I² = 0%). Interventions via telephone and short message service yielded the highest treatment effects compared with services based on telemetry and smartphone applications.ConclusionAlthough we determined that telemedicine is effective in improving several diabetes-related outcomes, the certainty of evidence was very low due to substantial heterogeneity and risk of bias.     

Quetiapine augmentation of prolonged exposure therapy in veterans with PTSD and a history of mild traumatic brain injury:design and methodology of a pilot study

Background:Selective serotonergic reuptake inhibitors(SSRIs)are first-line pharmacologic treatments for patients with posttraumatic stress disorder(PTSD),but must be given over extended period of time before the onset of action.The use of SSRIs in PTSD patients with mild traumatic brain injury(mTBI)is problematic since SSRIs could exacerbate post-concussion syndrome(PCS)symptoms.VA/DOD guidelines identify trauma-focused psychotherapy as the best evidence-based treatment for PTSD,but overall effectiveness is limited by reduced levels of patient engagement and retention.A previous study from this research group suggested that quetiapine monotherapy,but not risperidone or valproate,could increase engagement in trauma-focused psychotherapy.Methods:We report the study protocol of a pilot study funded under the South-Central Mental Illness Research,Education,and Clinical Center pilot study program from the U.S.Department of Veterans Affairs.This randomized,open-label study was designed to evaluate the feasibility of completing a randomized trial of quetiapine vs.treatment as usual to promote patient engagement in PTSD patients with a history of mTBI.Discussion:We expect that the success of this ongoing study should provide us with the preliminary data necessary to design a full-scale randomized trial.Positive efficacy results in a full-scale trial should inform new VA guidelines for clinical practice by showing that quetiapine-related improvements in patient engagement and retention may be the most effective approach to assure that VA resources achieve the best possible outcome for veterans.     

Evaluation of Mast Cell Density using CD117 antibody and Microvessel Density Using CD34 Antibody in Different Grades of Oral Squamous Cell Carcinoma

Objective: To compare mast cell and microvessel densities among histologic grades of oral squamous cell carcinoma. Setting: Armed Forces Institute of Pathology. Materials and Methods: A total of 60 specimens of OSCC comprising 20 each of well, moderately and poorly differentiated were evaluated. Immunohistochemical analysis was performed to measure MCD and MVD by applying monoclonal CD117 antibody and monoclonal CD34 antibody, on formalin fixed and paraffin embedded sections. ANOVA and Post Hoc Tukey test was employed to assess the densities and to compare the differences between different grades of OSCC. A p-value     

Right-sided diaphragmatic hernia in an adult after living donor liver transplant: a rare cause of post-transplant recurrent abdominal pain

Right-sided diaphragmatic hernia (DH) after living donor liver transplant in adult recipients has not been described previously. There have been a few reports of right-side DH in paediatric living donor liver transplant recipients and following right lobe donor hepatectomy. We herein describe the first instance of right-sided DH in a 44-year-old man who underwent left lobe live donor liver transplant. Twenty-eight months later, he presented with recurrent right upper abdominal pain. Radiographic workup revealed a right-sided DH. He underwent laparotomy and primary repair of the diaphragmatic defect. Seven months after the repair, the patient remains well and free from symptoms, with a normal chest X-ray. Right-sided DH is rare but may occur after living donor liver transplant. Successful outcome can be achieved by an early diagnosis and prompt management.     

Biliary,fecal and plasma deoxycholic acid in rabbit,hamster, guinea pig,and rat: comparative study and implication in colon cancer

Bile acids are believed to play a role in the etiology of colorectal cancer, and high fecal excretion of secondary bile acids was correlated with increased incidence of colon cancer. Recently, it was also reported that there is an increase in plasma of the secondary bile acid, deoxycholic acid in men with colorectal adenomas. Since deoxycholic acid is formed in the colon and absorbed into the portal systemic circulation, it was suggested that the blood concentration of this bile acid reflects the level of exposure of colonic cells to deoxycholic acid. The objective of this study was to investigate whether plasma deoxycholic acid level represents the fecal content of this bile acid in several animal species with different bile acid composition and deoxycholic acid contribution to the bile acid pool. Eight rabbits, hamsters, guinea pigs, and rats were used in this study. Blood samples and feces were collected on days 1, 3, 5 and 7. Bile samples were obtained only on day 7. The plasma, fecal and biliary bile acids were analyzed by gas chromatography-mass spectrometry. Bile acid composition and deoxycholic acid content varied greatly between the animal species studied. There was a variation in the concentration of total bile acids in the plasma and feces obtained at different times during the experiments, however, the bile acids profile remained constant throughout the study. The data obtained shows that although plasma bile acid profile was not similar to fecal bile acids profile, however, there was a significant correlation between the level of plasma and fecal deoxycholic acid. Plasma deoxycholic acid concentration might be a reliable biomarker for the degree of exposure of colon cells to this bile acid, and may be useful in further studies on the role of secondary bile acids in colon carcinogenesis.     

Evaluation of the antimycobacterium activity of the constituents from Ocimum basilicum against Mycobacterium tuberculosis

Ethnopharmacological relevance: Ocimum basilicum belongs to the genus Ocimum (Lamiaceae). Many species of this genus including O. basilicum have been traditionally used for the treatment of a variety of diseases including respiratory diseases and symptoms of tuberculosis.