Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1.

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (Cohort 1; N=11, enrolled in USA) and breastfed (Cohort 2; N=11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1.

Effect of occlusal appliances on the sleep of individuals with bruxism: A systematic review and meta-analyses.

Objective: This systematic review determined whether occlusal appliance use influences the sleep of individuals with sleep bruxism.

Material And Methods: Six databases and the gray literature were searched to identify randomized and non-randomized clinical trials comparing slow wave sleep and sleep quality of sleep bruxers before and after occlusal appliance use. The Risk of Bias was assessed using Cochrane tools and Meta-analyses were performed to compare data.

Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial.

Background: Multiple broadly neutralising monoclonal antibodies (mAbs) are in development for HIV-1 prevention. The aim of this trial was to test the PGT121.414.

HIV drug resistance, viral suppression, and survival in children living with HIV in Brazil.

Introduction: Mutations associated with HIV drug resistance (DR) affect clinical outcomes. Understanding the prevalence of HIV DR and its association with viral suppression and survival in the paediatric population is key to inform patient care and health policies.

Methods: We used Brazilian monitoring systems to identify genotyping tests performed in children living with HIV aged ≤18 months between 2009 and 2020.

Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial.

Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies. A combination of three bNAbs provides improved neutralization coverage of global viruses, which may more potently suppress viral escape and rebound. Here we performed an open-label, two-part study evaluating a single intravenous dose of HIV-1 bNAbs, PGT121, PGDM1400 and VRC07-523LS, in six adults without HIV in part 1 and a multicenter trial of up to six monthly infusions of these three bNAbs in 12 people living with HIV with an antiretroviral therapy (ART) interruption in part 2.

Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIV infection.

Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIV infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs.

Safety and pharmacokinetics of subcutaneous administration of broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs), given to HIV-1 exposed, uninfected neonates and infants: study protocol for a phase I trial.

Background: The ambitious goal to eliminate new pediatric HIV infections by 2030 requires accelerated prevention strategies in high-risk settings such as South Africa. One approach could be pre-exposure prophylaxis (PrEP) with broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs). The aim of our study is to define the optimal dose(s), the ideal combination(s) of bNAbs in terms of potency and breadth, and timing of subcutaneous (SC) administration(s) to prevent breast milk transmission of HIV.

Nandrolone decanoate impairs gastrointestinal motility and duodenal morphometry in moderately exercised rats.

The misuse of anabolic androgenic steroid associated or not with physical workouts disrupts gastrointestinal (GI) function homeostasis. Our goal was to investigate the effects of nandrolone decanoate (ND) and moderate swimming on the GI transit of solid meals, GI motor contractility, and intestinal histology in rats. Male Wistar rats were allocated to four groups that received intramuscular injections of ND (5.

Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial.

Background: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life.

Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV.

Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV.

Post-COVID-19 condition: systemic inflammation and low functional exercise capacity.

Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.

Tuberculosis: Cliché or Outsider?

Tuberculosis is an infectious disease with the potential for multisystemic dissemination, including the central nervous system (CNS). It is difficult to diagnose when the central nervous system is involved. Brain biopsy is the diagnostic method par excellence for diagnostic confirmation; however, as it is an invasive method and therefore not free from risks, before carrying it out, extra-CNS sites should be privileged, whenever available, through mycobacteriological culture.

Strategies to target the central nervous system HIV reservoir.

Purpose Of The Review: The central nervous system (CNS) is an hotspot for HIV persistence and may be a major obstacle to overcome for curative strategies. The peculiar anatomical, tissular and cellular characteristics of the HIV reservoir in the CNS may need to be specifically addressed to achieve a long-term HIV control without ART. In this review, we will discuss the critical challenges that currently explored curative strategies may face in crossing the blood-brain barrier (BBB), targeting latent HIV in brain-resident myeloid reservoirs, and eliminating the virus without eliciting dangerous neurological adverse events.

Influence of occlusal appliances on the masticatory muscle function in individuals with sleep bruxism: A systematic review and meta-analysis.

This systematic review answers the question: "Does occlusal appliance use influence masticatory muscle function of dentate individuals with sleep bruxism?". The literature search included six databases, grey literature, and manual search for articles. Randomized and non-randomized clinical trials were included comparing muscle function of sleep bruxers before and after receiving occlusal appliances.

Masticatory function and mortality among older adults living in long-term care facilities in Brazil.

Objective: To investigate the association between mortality and masticatory function in older adults living in long-term care facilities (LTCFs), controlling for demographic and health covariates.

Background: Poor oral health has been associated with mortality; however, no previous study investigated whether objective and self-reported poor masticatory function is a predictor of early mortality in LTCFs.

Materials And Methods: Baseline characteristics of 295 participants were collected, including age, sex, polypharmacy, mobility, activities of daily living, frailty, nutritional status, and objective (masticatory performance - chewing gum) and self-reported masticatory function.

Lofgren Syndrome: Achieving an Accurate Diagnosis for Improved Patient Care.

Lofgren syndrome is a clinically distinct phenotype of sarcoidosis. It is characterized by the triad of bilateral hilar lymphadenopathy, arthritis (usually the ankles), and fever. We present the case of a 31-year-old male patient who presented with fever and edema in both lower limbs, with palpation of subcutaneous nodules.

Does occlusal morphology of artificial teeth improve chewing of removable dentures wearers? A systematic review and meta-analysis.

Purpose: This systematic review aimed to verify whether anatomic, semi-anatomic, or nonanatomic occlusal morphology of artificial teeth improves the masticatory function of complete or removable partial denture wearers.

Materials And Methods: According to the PICO strategy, six databases and the grey literature were searched to identify randomized (RCT) and non-randomized clinical trials (N-RCT) comparing masticatory function, in terms of masticatory performance and efficiency, and muscle activity as primary outcomes; and patient-reported results (O) in individuals using removable dentures (P) with different occlusal morphologies of artificial teeth (I/C). Masticatory ability, satisfaction with the prosthetic treatment, and oral health-related quality of life (OHRQoL) were evaluated as secondary outcomes.

Membrane process and adsorption on pine nut shell for removal of dye from synthetic wastewater.

Purification methods such as membrane technology and adsorption have been studied for the purification of textile effluents. This article aimed to evaluate the membrane separation process and adsorption on pine nut shell, separately and sequentially, for reactive dye blue 5G removal from a synthetic effluent. The membrane separation process was carried out in a front filtration module using polymeric membranes.

Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01.

Broadly neutralizing monoclonal antibodies (mAbs) are being developed for HIV-1 prevention. Hence, these mAbs and licensed oral pre-exposure prophylaxis (PrEP) (tenofovir-emtricitabine) can be concomitantly administered in clinical trials. In 48 US participants (men and transgender persons who have sex with men) who received the HIV-1 mAb VRC01 and remained HIV-free in an antibody-mediated-prevention trial (ClinicalTrials.

Gastric plication surgery changes gastrointestinal and metabolic parameters in an obesity-induced high-fat diet model.

Background: Obesity treatment includes less invasive procedures such as gastric plication (GP) surgery; however, its effects on gastrointestinal (GI) motility parameters are underestimated. We aimed to verify the metabolic and gastrointestinal effects of GP surgery in the rat obesity model.

Methods: A high-fat diet-induced obesity was used.

Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial.

Background: Preclinical and clinical studies suggest that combinations of broadly neutralising antibodies (bnAbs) targeting different HIV envelope epitopes might be required for sufficient prevention of infection. We aimed to evaluate the dual and triple anti-HIV bnAb combinations of PGDM1400 (V2 Apex), PGT121 (V3 glycan), 10-1074 (V3 glycan), and VRC07-523LS (CD4 binding site).

Methods: In this phase 1 trial (HVTN 130/HPTN 089), adults without HIV were randomly assigned (1:1:1) to three dual-bnAb treatment groups simultaneously, or the triple-bnAb group, receiving 20 mg/kg of each antibody administered intravenously at four centres in the USA.

Extended safety and tolerability of subcutaneous CAP256V2LS and VRC07-523LS in HIV-negative women: study protocol for the randomised, placebo-controlled double-blinded, phase 2 CAPRISA 012C trial.

Introduction: Women-controlled HIV prevention technologies that overcome adherence challenges of available daily oral pre-exposure prophylaxis and give women a choice of options are urgently needed. Broadly neutralising monoclonal antibodies (bnAbs) administered passively may offer a valuable non-antiretroviral biological intervention for HIV prevention. Animal and human studies have demonstrated that bnAbs which neutralise HIV can prevent infection.