Sex disparities in efficacy in covid-19 vaccines: A systematic review and meta-analysis

Sex differences in adaptive and innate immune responses have been shown to occur and anecdotal reports suggest that vaccine efficacy and safety may be sex-dependent. We investigated the influence of sex on the efficacy of COVID-19 vaccines through a systematic review and meta-analysis of clinical trials on COVID-19 vaccines. The safety profile of COVID-19 vaccines was also investigated. A systematic review included eligible articles published in three databases and three websites. A meta-analysis of available data, stratified by sex, was conducted. Statistical analysis was performed using the Hartung\u2013Knapp\u2013Sidik\u2013Jonkman method, as well as influence and heterogeneity analysis. Pooled analysis showed significantly higher efficacy, measured as the rate of new COVID-19 cases, in men compared to women in the vaccine group (OR = 0.67, 95% CI 0.48\u20130.94). No sex differences were found in the rate of new cases in the control group (OR = 0.92, 95% CI 0.78\u20131.09). Safety profiles derived from pharmacovigilance reports appear to indicate increased toxicity in women. In conclusion, evidence of a potential role of sex in COVID-19 vaccine efficacy was described. It strengthens the need to include sex as a core variable in the clinical trial design of COVID-19 vaccines

Molecular basis of autotrophic vs mixotrophic growth in Chlorella sorokiniana

In this work, we investigated the molecular basis of autotrophic vs. mixotrophic growth of Chlorella sorokiniana, one of the most productive microalgae species with high potential to produce biofuels, food and high value compounds. To increase biomass accumulation, photosynthetic microalgae are commonly cultivated in mixotrophic conditions, adding reduced carbon sources to the growth media. In the case of C. sorokiniana, the presence of acetate enhanced biomass, proteins, lipids and starch productivity when compared to autotrophic conditions. Despite decreased chlorophyll content, photosynthetic properties were essentially unaffected while differential gene expression profile revealed transcriptional regulation of several genes mainly involved in control of carbon flux. Interestingly, acetate assimilation caused upregulation of phosphoenolpyruvate carboxylase enzyme, enabling potential recovery of carbon atoms lost by acetate oxidation. The obtained results allowed to associate the increased productivity observed in mixotrophy in C. sorokiniana with a different gene regulation leading to a fine regulation of cell metabolism

Educating the Next Generation of Pharmacogenomics Experts: Global Educational Needs and Concepts

Personalised Therapeutic

[18F]FDG PET/MRI in rectal cancer

We conducted a systematic literature review on the use of [18F]FDG PET/MRI for staging/restaging rectal cancer patients with PubMed, Scopus, and Web of Science, based on the PRISMA criteria. Three authors screened all titles and abstracts and examined the full texts of all the identified\ua0relevant articles. Studies containing aggregated or duplicated data, review articles, case reports, editorials, and letters were excluded. Ten reports met the inclusion criteria. Four studies examined T staging and one focused on local recurrences after surgery; the reported sensitivity (94\u2013100%), specificity (73\u201394%), and accuracy (92\u2013100%) varied only slightly from one study to another. The sensitivity, specificity, and accuracy of [18F]FDG PET/MRI for N staging were 90\u201393%, 92\u201394%, and 42\u201392%. [18F]FDG PET/MRI detected malignant nodes better than MRI, resulting in treatment change. For M staging, [18F]FDG PET/MRI outperformed [18F]FDG PET/CT and CT in detecting liver metastases, whereas it performed worse for lung metastases. The results of this review suggest that [18F]FDG PET/MRI should be used for rectal cancer restaging after chemoradiotherapy and to select patients for rectum-sparing approaches thanks to its accuracy in T and N staging. For M staging, it should be associated at least with a chest CT scan to rule out lung metastases

CDK4/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions

Palbociclib, ribociclib, and abemaciclib belong to the third generation of cyclin-dependent kinases inhibitors (CDKis), an established therapeutic class for advanced and metastatic breast cancer. Interindividual variability in the therapeutic response of CDKis has been reported and some individuals may experience increased and unexpected toxicity. This narrative review aims at identifying the factors potentially concurring at this variability for driving the most appropriate and tailored use of CDKis in the clinic. Specifically, concomitant medications, pharmacogenetic profile, and pathophysiological conditions could influence absorption, distribution, metabolism, and elimination pharmacokinetics. A personalized therapeutic approach taking into consideration all factors potentially contributing to an altered pharmacokinetic/pharmacodynamic profile could better drive safe and effective clinical use

Azathioprine Biotransformation in Young Patients with Inflammatory Bowel Disease: Contribution of Glutathione-S Transferase M1 and A1 Variants

The contribution of candidate genetic variants involved in azathioprine biotransformation on azathioprine efficacy and pharmacokinetics in 111 young patients with inflammatory bowel disease was evaluated. Azathioprine doses, metabolites thioguanine-nucleotides (TGN) and methylmercaptopurine-nucleotides (MMPN) and clinical effects were assessed after at least 3 months of therapy. Clinical efficacy was defined as disease activity score below 10. Candidate genetic variants (TPMT rs1142345, rs1800460, rs1800462, GSTA1 rs3957357, GSTM1, and GSTT1 deletion) were determined by polymerase chain reaction (PCR) assays and pyrosequencing. Statistical analysis was performed using linear mixed effects models for the association between the candidate variants and the pharmacological variables (azathioprine doses and metabolites). Azathioprine metabolites were measured in 257 samples (median 2 per patient, inter-quartile range IQR 1-3). Clinical efficacy at the first evaluation available resulted better in ulcerative colitis than in Crohn's disease patients (88.0% versus 52.5% responders, p = 0.0003, linear mixed effect model, LME). TGN concentration and the ratio TGN/dose at the first evaluation were significantly higher in responder. TPMT rs1142345 variant (4.8% of patients) was associated with increased TGN (LME p = 0.0042), TGN/dose ratio (LME p < 0.0001), decreased azathioprine dose (LME p = 0.0087), and MMPN (LME p = 0.0011). GSTM1 deletion (58.1% of patients) was associated with a 18.5% decrease in TGN/dose ratio and 30% decrease in clinical efficacy. GSTA1 variant (12.8% of patients) showed a trend (p = 0.049, LME) for an association with decreased clinical efficacy; however, no significant effect on azathioprine pharmacokinetics could be detected. In conclusion, GSTs variants are associated with azathioprine efficacy and pharmacokinetics

Behavioural and physiological responses of rabbits

ArticleThe profitability of a rabbit farming system must consider the thermal environment that the animal will be exposed during the productive period. The goal of this study was to evaluate the physiological responses and behaviours of 26 New Zealand rabbits during seven days of their lives at three times a day. The experiment was carried out in rabbit house in the Federal University of Lavras at Lavras, Brazil. To characterize the thermal environment sensors were used to measure the dry bulb temperature and relative humidity at 48 points inside the rabbit house, at 6:00 a.m., 12:00 a.m. and 6:00 p.m. In addition, the temperature and humidity index (THI) was calculated. The respiratory rate and the superficial temperature of the rabbits' ears were measured. Behaviour evaluations were monitored in punctual record, with duration of two min/cage. Later an ethogram was made with the main behaviours identified. Similar data of behaviour and data of physiological responses were identified by using Ward’s method of cluster analysis. It was observed the period of 6 a.m. showed more comfortable conditions of THI values than the others analysed. Besides, physiological responses presented better values at 6:00 a.m. in comparison to 12:00 and 6:00 p.m. Furthermore, in general, a similar behaviour was observed in the rabbits at 12:00 and 6:00 p.m., while at 6:00 a.m. was different. But rabbits demonstrated to be more comfortable at 6 a.m. maybe because at this time environment conditions were better than the rest of the day. Besides, it can be observed that rabbits were more active in sunrise and sunset than in the rest of the day

Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing

In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano- or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro- and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor–related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems