CFTR mutation is associated with bone differentiation abnormalities in cystic fibrosis.

Background: Cystic Fibrosis-related Bone Disease is an emerging challenge faced by 50 % of adult people with cystic fibrosis (CF). The multifactorial causes of this comorbidity remain elusive. However, congenital bone defects have been observed in animal models with CFTR mutations, suggesting its importance.

Highly parallel simulation tool for the design of isotachophoresis experiments.

Background: Isotachophoresis (ITP) is a well-established electrokinetic method for separation and preconcentration of analytes. Several simulation tools for ITP have been published, but their use for experimental design is limited by the computational time for a single run and/or by the number of conditions that can be investigated per simulation run. A large fraction of the existing solvers also do not account for ionic strength effects, which can influence whether an analyte focuses in ITP.

Motor abilities and cognitive performance in Latinos with autosomal dominant Alzheimer's disease.

Background: Declining motor abilities might be a noninvasive biomarker for Alzheimer's disease (AD). Studying motor ability and AD progression in younger Latinos with autosomal dominant Alzheimer's disease (ADAD) can provide insights into the interplay between motor ability and cognition in individuals with minimal confounding from age-normative changes and comorbid medical conditions.

Objectives: This study aimed to (1) examine motor abilities as a function of years to dementia diagnosis and (2) examine associations between motor ability and cognitive performance.

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Systematic review of health and social outcomes among Indigenous People exposed to the child welfare system: a protocol.

Introduction: The link between parent-child separation through child welfare systems and negative health and social outcomes is well documented. In contrast, despite the over-representation of Indigenous children and youth in child welfare systems, the relationship between child welfare system involvement and health and social outcomes among Indigenous populations has not been systematically reviewed. Our objective is to assess whether Indigenous People who have been exposed to a child welfare system personally or intergenerationally (ie, parents and/or grandparents) within Canada, Australia, New Zealand and the USA (CANZUS countries) and the circumpolar region are at an increased risk for negative health and social outcomes compared with other exposed and non-exposed groups.

What role did serious mental illness play in Jackson Pollock's drip paintings? Abstract expressionism and possible links to serious mental illness and encrypted images (polloglyphs).

The link between creativity and serious mental illness (SMI) is widely discussed. Jackson Pollock is one example of a giant in the field of art who was both highly creative and experiencing an SMI. Pollock created a new genre of art known as abstract expressionism ("action painting") defined as showing the frenetic actions of painting.

Developmental exposure to legacy environmental contaminants, medial temporal lobe volumes and spatial navigation memory in late adolescents.

Exposure to lead, mercury, and polychlorinated biphenyls (PCBs) has been causally linked to spatial memory deficits and hippocampal changes in animal models. The Inuit community in Northern Canada is exposed to higher concentrations of these contaminants compared to the general population. This study aimed to 1) investigate associations between prenatal and current contaminant exposures and medial temporal brain volumes in Inuit late adolescents; 2) examine the relationship between these brain structures and spatial memory; and 3) assess the mediating role of brain structures in the association between contaminant exposure and spatial memory.

Validation of the Contraception-Focused Preference-Aligned Fertility Management Index in Uganda and Nigeria.

Objective: To evaluate construct validity of the contraception-focused "Preference-aligned Fertility Management" (PFM) Index, a new person-centered and rights-based outcome measure, in Nigeria and Uganda.

Study Design: We analyzed survey data from convenience samples of new users of contraception and non-users of contraception in Uganda and users of contraception in Nigeria. PFM Index scores were calculated by combining two indicators: Indicator 1 assessing alignment between desire to use contraception and actual use; Indicator 2 evaluating whether users' current methods are desired.

Safety and efficacy of valoctocogene roxaparvovec with prophylactic glucocorticoids: 1-year results from the phase 3b, single-arm, open-label GENEr8-3 study.

Background: Valoctocogene roxaparvovec, an adeno-associated virus vector that transfers a human factor VIII (FVIII) coding sequence to hepatocytes, provides bleeding protection for people with severe hemophilia A (HA).

Objective: Determine the efficacy and safety of valoctocogene roxaparvovec with concomitant prophylactic glucocorticoids in the open-label, single-arm, phase 3b GENEr8-3 trial.

Methods: Participants with severe HA who were using HA prophylaxis received one 6x10 vg/kg infusion of valoctocogene roxaparvovec concomitantly with daily prophylactic glucocorticoids (40 mg prednisolone equivalent/d weeks 0‒8; taper to 5 mg/d weeks 9‒19).

Evaluating student understanding of core pharmacokinetic concepts.

Both educators and graduates have expressed concern about a perceived pharmacology knowledge gap that includes difficulty applying fundamental principles to clinical and research problems. Consequently, we sought to determine the extent to which current students can explain the meaning of, and appropriately apply, a subset of core concepts, and to identify any misconceptions arising from the responses. Of the twenty-four pharmacology core concepts arising from the recent international collaboration, four pharmacokinetic concepts were chosen, namely drug bioavailability, drug clearance, volume of distribution, and steady-state concentration.

Peripherally administered TNF inhibitor is not protective against α-synuclein-induced dopaminergic neuronal death in rats.

The underlying cause of neuronal loss in Parkinson's disease (PD) remains unknown, but evidence implicates neuroinflammation in PD pathobiology. The pro-inflammatory cytokine soluble tumor necrosis factor (TNF) seems to play an important role and thus has been proposed as a therapeutic target for modulation of the neuroinflammatory processes in PD. In this regard, dominant-negative TNF (DN-TNF) agents are promising antagonists that selectively inhibit soluble TNF signaling, while preserving the beneficial effects of transmembrane TNF.

Prevalence and Patterns of Social Media Use in Early Adolescents.

Objective: To describe patterns of social media use, including underage (under 13 years) use and sex differences, in a diverse, national sample of early adolescents in the U.S.

Methods: We analyzed the social media use data in the Adolescent Brain Cognitive Development Study (2019-2021, Year 3), which includes a national sample of early adolescents in the U.

Personalized theta-burst stimulation enhances social skills in young minimally verbal children with autism: a double-blind randomized controlled trial.

Background: Minimally verbal children with autism are understudied and lack effective treatment options. Personalized continuous theta-burst stimulation (cTBS) targeting the amygdala and its circuitry may be a potential therapeutic approach for this population.

Methods: In a double-blind randomized controlled trial, minimally verbal children with autism (ages 2-8 years) received 4 weeks of cTBS.

Phase 3, Randomized, Comparison Study of Intracameral Bimatoprost Implant 10 µg and Selective Laser Trabeculoplasty.

Purpose: To evaluate the intraocular pressure (IOP)-lowering effect and safety of up to two bimatoprost implant administrations versus selective laser trabeculoplasty (SLT).

Design: Phase 3 (Stage 2), randomized, 24-month, multicenter, patient- and efficacy evaluator-masked, paired-eye clinical trial (NCT02507687).

Participants: Patients (n=183) with open-angle glaucoma or ocular hypertension inadequately managed with topical IOP-lowering medication for reasons other than efficacy.

A lipidated peptide derived from the C-terminal tail of the vasopressin 2 receptor shows promise as a new β-arrestin inhibitor.

β-arrestins play pivotal roles in seven transmembrane receptor (7TMR) signalling and trafficking. To study their functional role in regulating specific receptor systems, current research relies mainly on genetic tools, as few pharmacological options are available. To address this issue, we designed and synthesised a novel lipidated phosphomimetic peptide inhibitor targeting β-arrestins, called ARIP, which was developed based on the C-terminal tail (A343-S371) of the vasopressin V2 receptor.

Associations of prenatal maternal psychosocial stress and depression with neurodevelopmental outcomes in 7.5-month-old infants in the ECHO.CA.IL prospective birth cohorts.

Background: Exposure to maternal stress and depression during pregnancy can have a marked impact on birth outcomes and child development, escalating the likelihood of preterm birth, lower birth weight, and various domains of physical and neurodevelopment.

Methods: The joint ECHO.CA.

Statistical harmonization of versions of measures across studies using external data: self-rated health and self-rated memory.

Purpose: Harmonizing variables for constructs measured differently across studies is essential for comparing, combining, and generalizing results. We developed and fielded a brief survey to harmonize Likert and continuous versions of measures for two constructs, self-rated health and self-rated memory, for use in studies of French older adults.

Methods: We recruited 300 participants from a French memory clinic in 2023 to answer both the Likert and continuous versions of self-rated health and self-rated memory questions.

Prevalence and impact of parental co-morbid anxiety and depression during the first 2 years postpartum in China.

Background: Parental postpartum co-morbid anxiety and depression negatively impact personal well-being, family dynamics, and child developmental outcomes. This study investigates the prevalence of co-morbid anxiety and depression in both mothers and fathers during the first 2 years postpartum in China, and to explore its associations with parental family support, maternal health-related quality of life (HRQoL), and child development.

Methods: This cross-sectional study was conducted in China, involving families with children aged 0-2 years who participated in community child health care.

Design, optimization, and inference of biphasic decay of infectious virus particles.

Virus population dynamics are driven by counter-balancing forces of production and loss. Whereas viral production arises from complex interactions with susceptible hosts, the loss of infectious virus particles is often approximated as a first-order kinetic process. As such, experimental protocols to measure infectious virus loss are not typically designed to identify non-exponential decay processes.

Probing ligand-induced conformational changes in an MFS transporter in vivo using site-directed PEGylation.

So far, site-directed alkylation (SDA) studies on transporters in the Major Facilitator Superfamily (MFS) are mostly performed at conditions different from the native cellular environment. In this study, using GFP-based site-directed PEGylation, ligand-induced conformational changes in the lactose permease of Escherichia coli (LacY), were examined in vivo for the first time. Accessibility/reactivity of single-Cys replacements in a Cys-less LacY-eGFP fusion background was tested using methoxy polyethylene glycol-maleimide-5K (mPEG-Mal-5K) in the absence or presence of a ligand, and the band-shift of the fusion upon PEGylation was detected by in-gel fluorescence.

Effect of mass drug administration on malaria incidence in southeast Senegal during 2020-22: a two-arm, open-label, cluster-randomised controlled trial.

Background: In Africa, the scale-up of malaria-control interventions has reduced malaria burden, but progress towards elimination has stalled. Mass drug administration (MDA) is promising as a transmission-reducing strategy, but evidence from low-to-moderate transmission settings is needed. We aimed to assess the safety, coverage, and effect of three cycles of MDA with dihydroartemisinin-piperaquine plus single, low-dose primaquine on Plasmodium falciparum incidence and prevalence in southeast Senegal.

Spotted fever group rickettsiae in black rats, pets, and humans in Zungarococha community, A rural area in the surroundings of Iquitos, Peru.

Rickettsiae are a family of ectoparasite-borne bacteria that can produce high morbidity and mortality among humans. There are scarce data on rickettsial ecology in rural areas of the Peruvian Amazon basin, where seroprevalence has not been determined, and the identities of animals acting as reservoirs of these bacteria are not known. We conducted a cross-sectional study in Zungarococha (between 2019 and 2021), a rural community located approximately 20 km away from Iquitos city.

The paradox of the self-studying brain.

The paradox of a brain trying to study itself presents a conundrum, raising questions about self-reference, consciousness, psychiatric disorders, and the boundaries of scientific inquiry. By which means can this complex organ shift the focus of study towards itself? We aim at unpacking the intricacies of this paradox. Historically, this question has been raised by philosophers under different frameworks.