Heterogeneity of aerobic fitness changes with exercise training in progressive multiple sclerosis: Secondary, exploratory analysis of data from the CogEx trial.

Background: There is heterogeneity of aerobic fitness (VO) changes with a standardized exercise training stimulus in the general population (i.e. some participants demonstrate improvements, others no change, and some a reduction in VO).

Inhibition of p38-MK2 pathway enhances the efficacy of microtubule inhibitors in breast cancer cells.

Microtubule-targeting agents (MTAs) have been successfully translated from basic research into clinical therapies and have been widely used as first- and second-line chemotherapy drugs for various cancers. However, current MTAs exhibit positive responses only in subsets of patients and are often accompanied by side effects due to their impact on normal cells. This underscores an urgent need to develop novel therapeutic strategies that enhance MTA efficacy while minimizing toxicity to normal tissues.

Tambjamines as Fast-Acting Multistage Antimalarials.

Well-tolerated and novel antimalarials that can combat multiple stages of the parasite life cycle are desirable but challenging to discover and develop. Herein, we report results for natural product-inspired novel tambjamine antimalarials. We show that they are potent against liver, asexual erythrocytic, and sexual erythrocytic parasite life cycle stages.

Obstacle Avoidance in Healthy Adults and People With Multiple Sclerosis: Preliminary fNIRS Study.

This study examined how gait adaptation during predictable and non-predictable obstacle avoidance affects the sensorimotor network in both healthy controls (HC) and persons with multiple sclerosis (pwMS). We utilized fNIRS measurements of HbO2 and HHb to estimate cortical activations and connectivity networks, which were then analyzed using power spectral density (PSD) and partial directed coherence (PDC). The findings revealed distinct patterns of cortical activation and connectivity for each task condition in both groups.

Optimization of B-Ring-Functionalized Antimalarial Tambjamines and Prodiginines.

Malaria has been a deadly enemy of mankind throughout history, affecting over 200 million people annually, along with approximately half a million deaths. Resistance to current therapies is of great concern, and there is a dire need for novel and well-tolerated antimalarials that operate by clinically unexploited mechanisms. We have previously reported that both tambjamines and prodiginines are highly potent novel antiplasmodial agents, but they required rigor optimizations to enhance the oral efficacy, safety, and physicochemical properties.

Speed of processing training to improve cognition in moderate to severe TBI: a randomized clinical trial.

Background: Moderate to severe traumatic brain injury (TBI) often results in cognitive deficits. Processing speed (PS) deficits are common, exerting a significant impact on daily life. Few studies have examined the efficacy of cognitive rehabilitation specifically for PS deficits in moderate to severe TBI.

Hemodynamics of the Frontopolar and Dorsolateral Pre-Frontal Cortex in People with Multiple Sclerosis During Walking, Cognitive Subtraction, and Cognitive-Motor Dual-Task.

Introduction: Higher cortical activity has been observed in people with multiple sclerosis (pwMS) during walking and dual-tasking. However, further studies in overground walking and considering pre-frontal cortex (PFC) sub-areas are necessary.

Objectives: To investigate PFC activity during a cognitive-motor dual-task (DT) and its single component tasks, in combination with behavioral outcomes in pwMS.

Associations between fatigue impact and physical and neurobehavioural factors: An exploration in people with progressive multiple sclerosis.

Background: Fatigue is common in people with multiple sclerosis (MS). Understanding the relationship between fatigue, physical and neurobehavioural factors is important to inform future research and practice. Few studies explore this explicitly in people with progressive MS (pwPMS).

The Effects of Slow Breathing during Inter-Set Recovery on Power Performance in the Barbell Back Squat.

Slow breathing (SB) reduces sympathetic nervous system activity, the heart rate (HR), and blood pressure (BP) and increases parasympathetic nervous system activity, HR variability, and oxygen saturation which may lead to quicker recovery between bouts of exercise. Therefore, the purpose of this study was to examine whether a SB technique using the 4-7-8 method between sets of barbell back squats (SQs) would attenuate drops in power and bar velocity. In a randomized, crossover design, 18 healthy resistance-trained college-aged males (age: 20.

A pilot study investigating the effect of the BEGIN psychoeducation intervention for people at clinical high risk for psychosis on emotional and stigma-related experiences.

Aim: There is concern that the provision of the clinical high risk for psychosis (CHR) label is stigmatizing. Prior research suggests people have nuanced reactions to feedback involving the CHR label, including a positive experience receiving feedback and improvement in negative emotions (e.g.

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals.

Fatigue in multiple sclerosis: can we measure it and can we treat it?

Fatigue is a common and debilitating symptom in multiple sclerosis (MS). However, after over 100 years of inquiry its definition, measurement and understanding remains elusive. This paper describes the challenges clinicians and researchers face when assessing and treating MS patients, as well as our understanding of neural mechanisms involved in fatigue.

Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.

Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen-agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator-led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling.

Effect of methylphenidate on oculomotor function in individuals with multiple sclerosis: a pilot randomized placebo-controlled trial.

Introduction: Individuals with multiple sclerosis (MS) frequently experience visual and oculomotor symptoms that may impact and confound neuropsychological assessments of information processing speed (IPS). In this study, we examined the effect of the psychostimulant methylphenidate on oculomotor function and the association between change in oculomotor speed and change in information processing speed.

Methods: We used a repeated measures crossover design in which a sample of 11 participants with MS were randomly assigned to one of two treatment arms: one that received methylphenidate for 4 weeks and another that received a placebo for 4 weeks.

Exploring the Efficacy of a Remote Strategy-Based Intervention for People With Multiple Sclerosis With Everyday Memory Impairments: A Pilot Study.

Importance: This pilot study evaluates a remote strategy-based intervention for individuals with multiple sclerosis who experience everyday memory impairments. The intervention can potentially inform cognitive rehabilitation for this population.

Objective: To investigate the feasibility and efficacy of an intervention (TELE-Self-GEN) to determine whether it can alleviate everyday memory impairments of individuals with multiple sclerosis.

Improving HIV preexposure prophylaxis uptake with artificial intelligence and automation: a systematic review.

Objectives: To identify studies promoting the use of artificial intelligence (AI) or automation with HIV preexposure prophylaxis (PrEP) care and explore ways for AI to be used in PrEP interventions.

Design: Systematic review.

Methods: We searched in the US Centers for Disease Control and Prevention Research Synthesis database through November 2023; PROSPERO (CRD42023458870).

Training guidelines and competencies for serious mental illness (SMI) psychology.

Individuals with serious mental illness (SMI) face unique and significant challenges that require evidence-based practices and clinicians who have advanced, comprehensive training to provide them. SMI affects about 5.5% of the U.

Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial.

Background: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings.

Methods: Participants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention.

Discovery and Optimization of Tambjamines as a Novel Class of Antileishmanial Agents.

Leishmaniasis is a neglected tropical disease that is estimated to afflict over 12 million people. Current drugs for leishmaniasis suffer from serious deficiencies, including toxicity, high cost, modest efficacy, primarily parenteral delivery, and emergence of widespread resistance. We have discovered and developed a natural product-inspired tambjamine chemotype, known to be effective against spp, as a novel class of antileishmanial agents.

Confinement in fibrous environments positions and orients mitotic spindles.

Accurate positioning of the mitotic spindle within the rounded cell body is critical to physiological maintenance. Adherent mitotic cells encounter confinement from neighboring cells or the extracellular matrix (ECM), which can cause rotation of mitotic spindles and, consequently, titling of the metaphase plate (MP). To understand the positioning and orientation of mitotic spindles under confinement by fibers (ECM-confinement), we use flexible ECM-mimicking nanofibers that allow natural rounding of the cell body while confining it to differing levels.

B cell immunofocusing and repriming in two HIV-1 Env immunization regimens.

Diverse and rapidly mutating viruses pose challenges to immunogen and vaccine design. In this study, we evaluated the ability of memory B-cells obtained from two independent NHP trials to cross-react with individual HIV-1 vaccine components of two different multivalent immunization strategies. We demonstrated that while an HIV-1 Env multiclade, multivalent immunization regimen resulted in a dominant memory B-cell response that converged toward shared epitopes, in a sequential immunization with clonally-related non-stabilized gp140 HIV-1 Envs followed by SOSIP-stabilized gp140 trimers, the change in immunogen format resulted in repriming of the B-cell response.

Personal Recovery Among People at Risk for Developing Serious Mental Health Problems: A Qualitative Systematic Review.

Objective: Personal recovery refers to a person's pursuit of a full, meaningful life despite the potentially debilitating impact of a mental illness. An evidence base describing personal recovery among people at risk for developing a mental illness is lacking, limiting the potential for mental health services to support personal recovery. To address this gap, the authors synthesized the extant research describing personal recovery among people at risk for developing a mental illness.