Structural development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage.

Broadly neutralizing antibodies (bNAbs) targeting the apex of the HIV-1-envelope (Env) trimer comprise the most potent category of HIV-1 bNAbs and have emerged as promising therapeutics. Here, we investigate the development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage and report cryo-EM structures at 3.4 Å resolution of PGDM1400 and of an improved PGT145 variant (PGT145-R100aS), each bound to the BG505 Env trimer.

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.

Edinburgh postpartum depression scores are associated with vaginal and gut microbiota in pregnancy.

Background: Prenatal and postpartum depression may be influenced by the composition of host associated microbiomes. As such, the objective of this study was to elucidate the relationship between the human gut or vaginal microbiomes in pregnancy with prenatal or postpartum depression.

Methods: 140 female participants were recruited at their first prenatal visit and completed the Edinburgh Postnatal Depression Scale (EPDS) to screen for depression and anxiety, in addition the EPDS was completed one month postpartum.

Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques.

An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID] ∼100) on a 208-strain panel.

Perceived Importance of Types and Characteristics of Support to Informal Caregivers among Spouse Caregivers of Persons with Dementia in Sweden: A Cross-Sectional Questionnaire-Based Study.

Informal caregivers play a crucial role in the care of individuals with dementia, and their caregiving may significantly impact their own health and well-being. This cross-sectional survey study focuses on the perceived importance of various types and characteristics of formal support in a convenience sample of caregivers aged 65 years or older (N = 175) caring for a spouse with dementia. Participants completed a questionnaire containing 17 items describing different types of support and 12 items describing different characteristics of support, rating their importance.

Cycling of labile and recalcitrant carboxyl-rich alicyclic molecules and carbohydrates in Baffin Bay.

Marine dissolved organic matter (DOM) is an important, actively cycling carbon reservoir (662 GtC). However, the chemical structure and cycling of DOM within rapidly warming, polar environments remains largely unconstrained. Previous studies have shown rapid surface cycling of carbohydrates as biologically-labile DOM (LDOM).

A Detailed Analysis of the Dynamic Behavior of a MEMS Vibrating Internal Ring Gyroscope.

This paper presents the development of an analytical model of an internal vibrating ring gyroscope in a Microelectromechanical System (MEMS). The internal ring structure consists of eight semicircular beams that are attached to the externally placed anchors. This research work analyzes the vibrating ring gyroscope's in-plane displacement behavior and the resulting elliptical vibrational modes.

Design and Modelling of MEMS Vibrating Internal Ring Gyroscopes for Harsh Environments.

This paper presents a design, model, and comparative analysis of two internal MEMS vibrating ring gyroscopes for harsh environmental conditions. The proposed design investigates the symmetric structure of the vibrating ring gyroscopes that operate at the identical shape of wine glass mode resonance frequencies for both driving and sensing purposes. This approach improves the gyroscope's sensitivity and precision in rotational motion.

Antenatal depression and drug use among deaf and hard-of-hearing birthing parents: results from a U.S. National Survey.

Purpose: This study aimed to investigate antenatal depression and drug use among deaf and hard-of-hearing (DHH) birthing parents who use American Sign Language (ASL), spoken English, or bilingually both ASL and English.

Methods: DHH participants in the United States responded to the Survey on Pregnancy Experiences of Deaf and Hard-of-Hearing Women. Respondents self-reported their antenatal depression diagnoses and drug use (i.

Advice to People with Parkinson's in My Clinic: Orthostatic Hypotension.

Orthostatic hypotension (OH) is the most common manifestation of cardiovascular autonomic dysfunction in Parkinson's disease. In this viewpoint, we discuss five practical questions regarding OH in Parkinson's disease: 1) How common is the problem? 2) Why should people with Parkinson's disease and providers care about OH? 3) What are the symptoms of OH? 4) How to confirm a diagnosis of OH? And 5) How to treat OH? OH is an important non-motor symptom of Parkinson's disease for which we have available treatments to significantly mitigate morbidity and possibly positively impact the disease course.

Physicochemical and structural insights into lyophilized mRNA-LNP from lyoprotectant and buffer screenings.

The surge in RNA therapeutics has revolutionized treatments for infectious diseases like COVID-19 and shows the potential to expand into other therapeutic areas. However, the typical requirement for ultra-cold storage of mRNA-LNP formulations poses significant logistical challenges for global distribution. Lyophilization serves as a potential strategy to extend mRNA-LNP stability while eliminating the need for ultra-cold supply chain logistics.

The effect of dietary sodium octanoate on Ghrelin concentration and feed intake in chickens and turkeys: a comparative study.

Active ghrelin (AG) is produced through the post-translational addition of n-octanoic acid to the amino residue Ser-3, making it the natural ligand for the ghrelin receptor. The synthesis of AG is contingent upon specific dietary fatty acids as substrates for the acylation process. Prior studies have demonstrated that AG infusion can lead to reduced feed intake (FI) in broiler chickens, suggesting that manipulating AG may serve as an alternative to quantitative feed restriction in broiler breeders.

Looking Ahead: Advancing Measurement and Analysis of the Block Design Test Using Technology and Artificial Intelligence.

The block design test (BDT) has been used for over a century in research and clinical contexts as a measure of spatial cognition, both as a singular ability and as part of more comprehensive intelligence assessment. Traditionally, the BDT has been scored using methods that do not reflect the full potential of individual differences that could be measured by the test. Recent advancements in technology, including eye-tracking, embedded sensor systems, and artificial intelligence, have provided new opportunities to measure and analyze data from the BDT.

Cesarean birth and adverse birth outcomes among sub-populations of deaf and hard-of-hearing people.

Background: Deaf and hard-of-hearing (DHH) people are at higher risk than their non-DHH counterparts of experiencing adverse birth outcomes. There is a lack of research focusing on social, linguistic, and medical factors related to being DHH which may identify groups of DHH people who experience more inequity.

Objective: Examine difference in prevalence of cesarean and adverse birth outcomes among diverse sub-groups of DHH people.

Host factors are associated with vaginal microbiome structure in pregnancy in the ECHO Cohort Consortium.

Using pooled vaginal microbiota data from pregnancy cohorts (N = 683 participants) in the Environmental influences on Child Health Outcomes (ECHO) Program, we analyzed 16S rRNA gene amplicon sequences to identify clinical and demographic host factors that associate with vaginal microbiota structure in pregnancy both within and across diverse cohorts. Using PERMANOVA models, we assessed factors associated with vaginal community structure in pregnancy, examined whether host factors were conserved across populations, and tested the independent and combined effects of host factors on vaginal community state types (CSTs) using multinomial logistic regression models. Demographic and social factors explained a larger amount of variation in the vaginal microbiome in pregnancy than clinical factors.

Micro-elimination of chronic hepatitis C virus in mental health settings: A prospective multicentre pragmatic trial.

Introduction: Hepatitis C virus (HCV) prevalence is high in the mental health population. We sought to evaluate testing and treatment uptake for HCV following the implementation of a universal nurse led study in inpatient and outpatient mental health populations.

Methods: From January 2018 to December 2020, we screened mental health inpatients (n = 322) and community mental health patients (n = 615) for HCV with either specialist hepatology nurses or mental health nurses (mental health nurse).

Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion-stabilized HIV-1 envelope (Env) trimer, BG505 DS-SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4-binding site (CD4bs) of vulnerability. Two of the vaccine-elicited CD4bs-targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a-hinge region and human IgG1-constant region (G36×3-IgG2a and R27×3-IgG2a), neutralized 96% of a multiclade 208-strain panel at geometric mean ICs of 0.

Sterol O-Acyltransferase 1 (): A Genetic Modifier of Niemann-Pick Disease, Type C1.

Niemann-Pick disease type C1 (NPC1) is a lysosomal disorder due to impaired intracellular cholesterol transport out of the endolysosomal compartment.. Marked heterogeneity has been observed in individuals with the same genotype, thus suggesting a significant effect of modifier genes.

Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported.

Impact of Local Tailoring on Acute Stroke Care in 21 Disparate Emergency Departments: A Prospective Stepped Wedge Type III Hybrid Effectiveness-Implementation Study.

Background: Faster delivery of tPA (tissue-type plasminogen activator) results in better health outcomes for eligible patients with stroke. Standardization of stroke protocols in emergency departments (EDs) has been difficult, especially in nonstroke centers. We measured the effectiveness of a centrally led implementation strategy with local site tailoring to sustain adherence to an acute stroke protocol to improve door-to-needle (DTN) times across disparate EDs in a multihospital health system.

Defining acceptable data collection and reuse standards for queer artificial intelligence research in mental health: protocol for the online PARQAIR-MH Delphi study.

Introduction: For artificial intelligence (AI) to help improve mental healthcare, the design of data-driven technologies needs to be fair, safe, and inclusive. Participatory design can play a critical role in empowering marginalised communities to take an active role in constructing research agendas and outputs. Given the unmet needs of the LGBTQI+ (Lesbian, Gay, Bisexual, Transgender, Queer and Intersex) community in mental healthcare, there is a pressing need for participatory research to include a range of diverse queer perspectives on issues of data collection and use (in routine clinical care as well as for research) as well as AI design.

Effect of levodopa on postural blood pressure changes in Parkinson disease: a randomized crossover study.

Purpose: We investigated the effect of levodopa on postural blood pressure changes in individuals with Parkinson disease (PD) with (PD) and without neurogenic OH (PD).

Methods: We performed a prospective randomized crossover study with autonomic testing performed ON and OFF levodopa. The primary outcome was the change in systolic blood pressure (SBP) from supine to 70° tilt at 3 min (ΔSBP-3').

Dissociation and other trauma symptomatology are linked to imbalance in the competing neurobehavioral decision systems.

Objective: Dissociation is a conscious state characterized by alterations in sensation and perception and is thought to arise from traumatic life experiences. Previous research has demonstrated that individuals with high levels of dissociation show impairments in cognitive-emotional processes. Therefore, using the Competing Neurobehavioral Decisions System (CNDS) theory, we used statistical modeling to examine whether dissociative experience and trauma symptoms are independently predicted by impulsivity, risk-seeking, affective state (i.