A27V). This mutation was associated with lower serum T4 levels (p  less then  0.0001) when compared to the groups that did not carry the mutation. The previously reported p.L283F mutation was also found in the proband. The hemizygous p.L283F individuals presenting with lower T4 serum and TBG levels (p  less then  0.001) when compared to wildtype males and females. Both mutations were deleterious upon SIFT and PolyPhen-2 evaluation. CONCLUSION Associated with partial thyroxine-binding globulin deficiency, this study reports a novel p.A27V mutation in the TBG gene.BACKGROUND AND OBJECTIVE ∆9-Tetrahydrocannabinol (THC) exhibits several therapeutic effects, such as analgesics, anti-emetic, antispastic, and muscle relaxation properties. Knowledge concerning THC disposition in target organs is crucial for THC therapy. The objective of this study was to develop a physiologically-based pharmacokinetic (PBPK) model of THC in humans to characterize tissue-specific pharmacokinetics of THC in organs of interest. METHODS The model was extrapolated from the previously developed PBPK model conducted in mice, rats, and pigs. The model consisted of seven compartments brain, lungs, liver, kidneys, fat, and rapidly perfused and slowly perfused tissues. P-glycoprotein was included in the brain compartment to characterize an efflux of THC from the brain. Physiologic, biochemical, and physicochemical parameters were determined and acquired from the literature. Model validation was performed by comparisons of the predicted and observed THC concentrations acquired from published studies. RESULTS The developed PBPK model resulted in good agreement between the predicted and observed THC concentrations across several studies conducted following IV bolus, IV infusion, oral, and smoking and inhalation, with the coefficient of determination (R2) ranging from 0.54 to 0.95. CONCLUSIONS A PBPK model of THC in humans was developed. The model could describe THC concentration-time profiles in several dosing scenarios (i.e., IV bolus, IV infusion, oral administration and inhalation).BACKGROUND Various antibiotic regimens are used for primary and secondary prevention of spontaneous bacterial peritonitis (SBP). A systematic review and network meta-analysis to compare various antibiotics regimens for primary and secondary prevention of SBP were done. METHODS We did a comprehensive literature search using various databases (i.e. MEDLINE via Ovid and PubMed, Embase, Cochrane Central Register of Controlled Trials and others) from inception to 26th October 2019 using various keywords. Only randomised studies which evaluated the role of antibiotics in adult cirrhotic patients with ascites for primary or secondary prophylaxis of SBP were included. The primary outcome was occurrence/recurrence of SBP episode and other outcomes assessed were extra-peritoneal infections and reduction in mortality. We did random-effects network meta-analysis using a Bayesian approach, and calculated odds ratios (ORs) and 95% credible intervals (CrI); agents were ranked using rank probabilities. RESULTS We found total 1701 records in our systematic database search and out of these 17 randomised trials were found eligible for network meta-analysis. For primary prevention of SBP, the odds ratio (95% CrI) for norfloxacin daily was 0.061 (0.0060, 0.33) and for rifaximin daily was 0.037 (0.00085, 0.87) and norfloxacin and rifaximin alternate month was 0.027 (0.00061, 0.61) when compared to placebo or no comparator. For the secondary prevention of SBP, rifaximin daily had odds of 0.022 (0.00011, 0.73). CONCLUSION Rifaximin is useful for both primary and secondary prevention of SBP whereas norfloxacin daily and alternate norfloxacin and rifaximin are useful for primary prophylaxis.Cancer immunotherapy has opened a new chapter in Medical Oncology. Many novel therapies are under clinical testing and some have already been approved and implemented in cancer treatment protocols. In particular, cellular immunotherapies take advantage of the antitumor capabilities of the immune system. From dendritic cell-based vaccines to treatments centered on genetically engineered T cells, this form of personalized cancer therapy has taken the field by storm. They commonly share the ex vivo genetic modification of the patient's immune cells to generate or induce tumor antigen-specific immune responses. The latest clinical trials and translational research have shed light on its clinical effectiveness as well as on the mechanisms behind targeting specific antigens or unique tumor alterations.  https://www.selleckchem.com/products/bpv-hopic.html  This review gives an overview of the clinical developments in immune cell-based technologies predominantly for solid tumors and on how the latest discoveries are being incorporated within the standard of care.Exploration and characterisation of the human proteome is a key objective enabling a heightened understanding of biological function, malfunction and pharmaceutical design. Since proteins typically exhibit their behaviour by binding to other proteins, the challenge of probing protein-protein interactions has been the focus of new and improved experimental approaches. Here, we review recently developed microfluidic techniques for the study and quantification of protein-protein interactions. We focus on methodologies that utilise the inherent strength of microfluidics for the control of mass transport on the micron scale, to facilitate surface and membrane-free interrogation and quantification of interacting proteins. Thus, the microfluidic tools described here provide the capability to yield insights on protein-protein interactions under physiological conditions. We first discuss the defining principles of microfluidics, and methods for the analysis of protein-protein interactions that utilise the diffusion-controlled mixing characteristic of fluids at the microscale. We then describe techniques that employ electrophoretic forces to manipulate and fractionate interacting protein systems for their biophysical characterisation, before discussing strategies that use microdroplet compartmentalisation for the analysis of protein interactions. We conclude by highlighting future directions for the field, such as the integration of microfluidic experiments into high-throughput workflows for the investigation of protein interaction networks.