A novel mutation in FNIP1 associated with a syndromic immunodeficiency and cardiomyopathy.

Genetic variants in Folliculin interacting protein 1 (FNIP1) were recently discovered as monogenic causes for immunodeficiency and cardiomyopathy, with only a few patients diagnosed thus far. In this study, we describe a patient harboring a novel genetic variant in FNIP1 causing immunodeficiency with cardiac involvement. Clinical and immunological workups were performed.

Excellence in Antibiotic Stewardship: A Mixed-Methods Study Comparing High-, Medium-, and Low-Performing Hospitals.

Background: Despite antibiotic stewardship programs existing in most acute care hospitals, there continues to be variation in appropriate antibiotic use. While existing research examines individual prescriber behavior, contextual reasons for variation are poorly understood.

Methods: We conducted an explanatory, sequential mixed-methods study of a purposeful sample of 7 hospitals with varying discharge antibiotic overuse.

The STOP COVID 2 Study: Fluvoxamine vs Placebo for Outpatients With Symptomatic COVID-19, a Fully Remote Randomized Controlled Trial.

Background: Prior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days.

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial.

Background: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients.

Methods: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk.

Synchrotron single-crystal XRD, IR-, Raman spectroscopy and high pressure study of synthetic krieselite.

Spontaneous crystals of krieselite (Ge analogue of topaz) with the chemical formula Al[(GeSi)O](FOH) were synthesized using a thermo-gradient hydrothermal method at a temperature of 600/650 °C and pressure of 100 MPa. The unit cell parameters are: a = 8.9732(8) Å, b = 8.

BIOMARKER AND ECHOCARDIOGRAPHIC CHARACTERISTICS OF HEART FAILURE IN PATIENTS HAVING ACUTE MYOCARDIAL INFARCTION COMBINED WITH DIABETES MELLITUS OF TYPE 2.

Objective: The aim: To investigate the level of B-type natriuretic peptide (BNP) and to establish its relationship with structural and functional indicators of the myocardium in patients having acute myocardial infarction (AMI), which is complicated by heart failure (HF) with concomitant type 2 diabetes mellitus (DM2).

Patients And Methods: Materials and methods: The study included 120 patients who were grouped by clinical diagnosis. Every patient underwent transthoracic echocardiography of the heart: left ventricular (LV) ejection fraction (EF), left ventricular myocardial mass index (LVMI), LV relative wall thickness (LVWT), BNP, HbA1c.

Early Outpatient Treatment for Covid-19 with Convalescent Plasma.

Background: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain.

Methods: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status.

SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection.

In-depth analysis of SARS-CoV-2 quasispecies is pivotal for a thorough understating of its evolution during infection. The recent deployment of COVID-19 vaccines, which elicit protective anti-spike neutralizing antibodies, has stressed the importance of uncovering and characterizing SARS-CoV-2 variants with mutated spike proteins. Sequencing databases have allowed to follow the spread of SARS-CoV-2 variants that are circulating in the human population, and several experimental platforms were developed to study these variants.

Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma.

Background: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain.

Methods: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day.

Activation of the Anti-Oxidative Stress Response Reactivates Latent HIV-1 Through the Mitochondrial Antiviral Signaling Protein Isoform MiniMAVS.

The mitochondrial antiviral signaling protein (MAVS) is part of the cell's innate immune mechanism of defense. MAVS mRNA is bicistronic and can give rise to a full length-MAVS and a shorter isoform termed miniMAVS. In response to viral infections, viral RNA can be sensed by the cytosolic RNA sensors retinoic acid-inducible gene I (RIG-I) and/or melanoma differentiation-associated protein 5 (MDA5) and activate NF-κB through interaction with MAVS.

Mitochondria-targeted prooxidant effects of betulinic acid conjugated with delocalized lipophilic cation F16.

The paper examines the molecular mechanisms of the cytotoxicity of conjugates of betulinic acid with the penetrating cation F16. The in vitro experiments on rat thymocytes revealed that all the obtained F16-betulinic acid derivatives showed more than 10-fold higher cytotoxicity as compared to betulinic acid and F16. In this case, 0.

Pharmacological Activation of Non-canonical NF-κB Signaling Activates Latent HIV-1 Reservoirs .

"Shock and kill" strategies focus on purging the latent HIV-1 reservoir by treating infected individuals with therapeutics that activate the latent virus and subsequently eliminating infected cells. We have previously reported that induction of non-canonical nuclear factor κB (NF-κB) signaling through a class of small-molecule antagonists known as Smac mimetics can reverse HIV-1 latency. Here, we describe the development of Ciapavir (SBI-0953294), a molecule specifically optimized for HIV-1 latency reversal that was found to be more efficacious as a latency-reversing agent than other Smac mimetics under clinical development for cancer.

Decoding Odor Mixtures in the Dog Brain: An Awake fMRI Study.

In working and practical contexts, dogs rely upon their ability to discriminate a target odor from distracting odors and other sensory stimuli. Using awake functional magnetic resonance imaging (fMRI) in 18 dogs, we examined the neural mechanisms underlying odor discrimination between 2 odors and a mixture of the odors. Neural activation was measured during the presentation of a target odor (A) associated with a food reward, a distractor odor (B) associated with nothing, and a mixture of the two odors (A+B).

Serum Transferrin Is an Independent Predictor of Mortality in Severe Alcoholic Hepatitis.

Objectives: Severe alcoholic hepatitis (sAH) confers substantial mortality, but the disease course is difficult to predict. As iron parameters are attractive outcome predictors in other liver diseases, we tested their prognostic ability in sAH.

Methods: Serum ferritin, transferrin, iron, transferrin saturation, nontransferrin-bound iron, soluble transferrin receptor, and hepcidin were measured in 828 patients with sAH recruited prospectively through the STOPAH trial.

Canine sense of quantity: evidence for numerical ratio-dependent activation in parietotemporal cortex.

The approximate number system (ANS), which supports the rapid estimation of quantity, emerges early in human development and is widespread across species. Neural evidence from both human and non-human primates suggests the parietal cortex as a primary locus of numerical estimation, but it is unclear whether the numerical competencies observed across non-primate species are subserved by similar neural mechanisms. Moreover, because studies with non-human animals typically involve extensive training, little is known about the spontaneous numerical capacities of non-human animals.

Can tailored nanoceria act as a prebiotic? Report on improved lipid profile and gut microbiota in obese mice.

Background: Microbiome modulation is a pillar intervention to treat metabolic syndrome, prestages, and cascade of related pathologies such as atherosclerosis, among others. and probiotic strains demonstrate efficacy to reduce obesity, dyslipidemia, and improve metabolic health. Novel prebiotic substances composed with known probiotics may strongly synergize health benefits to the host.

Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction in Diabetic Patients.

Introduction: The cause of erectile dysfunction (ED) in diabetic patients is complex and involves both neurogenic and vasculogenic components and is often hard to treat.

Aim: To study the effect of low-intensity extracorporeal shock wave therapy (Li-ESWT) therapy on a subgroup of diabetic patients with ED who are responders (PDE5I-R) and non-responders (PDE5I-NR) to phosphodiesterase 5 inhibitors (PDE5I).

Methods: Analysis of pooled data from 5 double-blind, sham-controlled trials was performed.

Fast neural learning in dogs: A multimodal sensory fMRI study.

Dogs may follow their nose, but they learn associations to many types of sensory stimuli. Are some modalities learned better than others? We used awake fMRI in 19 dogs over a series of three experiments to measure reward-related learning of visual, olfactory, and verbal stimuli. Neurobiological learning curves were generated for individual dogs by measuring activation over time within three regions of interest: the caudate nucleus, amygdala, and parietotemporal cortex.

Comparison of the Drug-Drug Interaction Potential of Daptomycin in Combination with Rifampin in Healthy Adult Volunteers.

We evaluated the effects of rifampin coadministration and single nucleotide polymorphisms on the disposition of daptomycin in twelve healthy adults. There were no significant changes from baseline in the clearance (0.53 versus 0.

Specific properties of probiotic strains: relevance and benefits for the host.

Background: Probiotics have tremendous potential to develop healthy diets, treatment, and prevention. Investigation of in vitro cultural properties of health-promoting microorganisms like lactic acid bacteria (LAB) and bifidobacteria is crucial to select probiotic strains for treatments based on gut microbiota modulation to justify individualized and personalized approach for nutrition and prevention of variety of diseases. The was to study the biological properties of LAB and bifidobacteria probiotic strains, namely adhesive properties; resistance to antibiotics; and biological fluids (gastric juice, bile, pancreatic enzymes), and to overview the literature in the field.

Effects of neonicotinoid imidacloprid exposure on bumble bee (Hymenoptera: Apidae) queen survival and nest initiation.

Neonicotinoids are highly toxic to insects and may systemically translocate to nectar and pollen of plants where foraging bees may become exposed. Exposure to neonicotinoids can induce detrimental sublethal effects on individual and colonies of bees and may have long-term impacts, such as impaired foraging, reduced longevity, and reduced brood care or production. Less well-studied are the potential effects on queen bumble bees that may become exposed while foraging in the spring during colony initiation.

Comparative study of probiotic effects of and strains on cholesterol levels, liver morphology and the gut microbiota in obese mice.

Background: Microbiome-modulating interventions are promising for treatment and prevention of metabolic syndrome. The number of probiotic strains demonstrated ability to decrease cholesterol level in vivo, however, it was poorly confirmed in a clinical setting. The aim was to study the effects of IMV B-7279, IMV B-7280, VKL and VKB separately and in various compositions on the level of serum cholesterol, gut microbiota contents and liver morphology on a high-calorie-induced obesity model in BALB/c mice.

Probiotics for experimental obesity prevention: focus on strain dependence and viability of composition.

Introduction: a comparative animal study of the efficacy of intermittent short-course administration of lyophilised single-, three-, and live multistrain probiotic on obesity.

Methods: We included 70 rats divided into seven groups (n = 10 in each). Rats of group I were intact.