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The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, consistency, and validity, and the safety of the clinical research or trial participants and laboratory staff, as well as ensures adherence to regulatory requirements. This article describes the application of the DAIDS GCLP Guidelines, the DAIDS Integrated Laboratory Oversight Framework, and the coordinated efforts of the collaborative oversight team of laboratory experts to support and monitor the performance of over 175 participating laboratories worldwide. Data from two self-administered online surveys conducted in 2017 and 2023 assessed the laboratory staff's experience implementing the GCLP Guidelines. The results of the 2017 survey were instrumental in informing changes to GCLP audit activities and promoting harmonization in the approach to laboratory oversight. A key finding from the 2023 survey results is the preference for hybrid GCLP training, encompassing face-to-face and online modules. Overall, both surveys acknowledged satisfaction with applying and implementing GCLP Guidelines. The need to effectively disseminate information about DAIDS laboratory oversight requirements to support the improved implementation of GCLP Guidelines was notable from both survey results. The collaborative team of laboratory experts and the integrated oversight approach promote knowledge-sharing and accountability to support the application of the GCLP Guidelines and compliance monitoring. The systematic implementation of the integrated laboratory oversight activities helped identify valuable lessons for improving laboratory performance and opportunities to strengthen quality oversight for laboratories participating in clinical research or trials. [ABSTRACT FROM AUTHOR]

This talk will describe the fabrication of periodically poled lithium niobate non-linear waveguides for the emerging quantum technology industry. It will address the challenges of optical engineering high-efficiency frequency conversion devices for the field and their application.

Obesity is a recognized factor influencing immune function and infectious disease outcomes. Characterization of the influence of obesity on SARS-CoV-2 humoral vaccine immunogenicity is required to properly tailor vaccine type (mRNA, viral-vector, protein subunit vaccines) and dosing schedule. Data from a prospective cohort study collected over 34 months was used to evaluate the slope of antibody production and decay and neutralizing capacity following SARS-CoV-2 vaccination in individuals with and without obesity at baseline. Most participants were female (65.4%), white (92.4%), and received mRNA vaccines. 210 were obese and 697 non-obese. Sex and infection-acquired immunity were identified as effect modifiers for the relationship between obesity and COVID-19 vaccine humoral immunogenicity. No consistent influence of obesity on peak titres, titre retention, antibody isotype (IgG, IgM, IgA), or neutralization was identified when controlling for other key variables. It may not be necessary to consider this variable when developing SARS-CoV-2 vaccine dosing strategies., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events., Methods: A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores., Results: Elevated sGFAP levels (Z score >1) at 1 year were associated with a higher hazard for PIRA (hazard ratio [HR]: 1.80 [95% CI: 1.17-2.78]; p = 0.0079) than elevated sNfL levels (HR, 1.45 [0.95-2.24], p = 0.0886) in a combined model. Independent of PIRA events, sGFAP levels longitudinally increased by 0.49 Z score units per 10 years follow-up (estimate, 0.49 [0.29, 0.69], p < 0.0001). In patients experiencing PIRA, sGFAP Z scores were 0.52 Z score units higher versus stable patients (0.52 [0.22, 0.83], p = 0.0009). Different sNfL Z score trajectories were found in pwMS with versus without PIRA (interaction p = 0.0028), with an average decrease of 0.92 Z score units per 10 years observed without PIRA (-0.92 [-1.23, -0.60], p < 0.0001), whereas levels in patients with PIRA remained high., Interpretation: Elevated sGFAP and lack of drop in sNfL after BCDT start are associated with increased risk of future PIRA. These findings provide a rationale for combined monitoring of sNfL and sGFAP in pwMS starting BCDT to predict the risk of PIRA, and to use sGFAP as an outcome in clinical trials aiming to impact on MS progressive disease biology. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Reproductive counseling is crucial for women's health, especially for those with inflammatory bowel disease (IBD), which often affects younger patients during their childbearing years. Patients with IBD need special considerations when planning for pregnancy. Preconception counseling is important as it helps patients make informed decisions about pregnancy and allows for optimal management of IBD before, during, and after pregnancy. In this review, we aim to provide guidance for managing and treating patients with IBD throughout the preconception, pregnancy, and postpartum period., Competing Interests: None declared., (Thieme. All rights reserved.)

Study Background: The experience of discrimination through stereotyping, profiling, and bias-informed care not only leads to poor access to healthcare services, but low retention rates of Indigenous health professionals (IHP). As health systems transformation evolves, a significant gap remains in supporting IHP to safely address racism, to be supported culturally to bring their authentic selves and voices to work, and to attend to one's own intellectual, physical, relational, cultural and spiritual wellness within a westernized model of care., Purpose: The aim of the study was to investigate the experiences of IHP working in mainstream healthcare in order to understand how their work environment impacts the delivery of cultural safe practices. What is reported in this manuscript, as an exercise in truth-telling, is findings about lived experiences of IHP working in one mainstream provincial healthcare region, and not the whole context and outcomes of the study., Methods: Using Indigenous research methodologies, we embodied our Indigeneity into every facet of the research process. We facilitated three talking circles with participants grounded in a distinct cultural and ceremonial context following Secwepemc protocols., Results: The collective voices of IHP revealed the following common experiences: confronting genocide; addressing Indigenous-specific racism; uprooting toxicity and inequities; and upholding Indigenous human rights while enhancing accountability of systems transformation., Conclusions: The experience of IHP working in health systems goes beyond mere individual employment obligations, its often about a families and communities advocacy for Indigenous rights, culturally safe working environments and access to dignified and respectful healthcare service. This study highlights the need for IHP to be actively involved in health system transformation to ensure the redesigning and restructuring of healthcare service delivery by and for Indigenous Peoples remains centered on Indigenous health and human rights., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Heparin-induced thrombocytopenia (HIT) is a life- and limb-threatening immune-mediated emergency classically associated with heparin therapy. This review focuses on type II HIT, characterized by the development of antibodies against platelet-factor 4 (PF4) bound to heparin after exposure, causing life-threatening thrombocytopenia, arterial thrombosis, and/or venous thrombosis. The high morbidity and mortality rates emphasize the need for early recognition and urgent intervention with discontinuation of heparin and initiation of non-heparin anticoagulation. We discuss the management of HIT with an emphasis on recent developments: (i) incorporating the phases of HIT (i.e., suspected, acute, subacute A and B, and remote) into its management, categorized according to platelet count, immunoassay, and functional assay results and (ii) direct-acting oral anticoagulants (DOACs), which are increasingly used in appropriate cases of acute HIT (off-label). In comparison to parenteral options (e.g., bivalirudin and danaparoid), they are easier to administer, are more cost-effective, and obviate the need for transition to an oral anticoagulant after platelet recovery. We also identify the knowledge gaps and suggest areas for future research.

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain-Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases.

In the 21 st century, impact of social media, particularly Social Networking Sites (SNSs) has been linked to a wide range of human beliefs and expectations. Growing body of research has indicated that body image concerns along with exercise motivation and social comparison are on the rise among young adults. The present study aimed to examine the sex difference in body image, exercise motivation and social comparison among people who use Instagram in the age group 20-30. A total of 212 participants (men=106, women=106) aged 20-30 years, who are users of Instagram completed Body Self Image Questionnaire Short Form as a measure of Body image, Exercise Motivation Inventory - 2 as a measure of Exercise Motivation and Instagram as a Tool for Social Comparison as a measure of Social Comparison. Results showed that a significant difference in body image exist across gender with body image issues higher among females and significant difference in exercise motivation across gender with exercise motivation higher among males. No sex differences were seen in social comparison. It was concluded that body image concerns are higher among females and the drive for exercise is higher among males who used Instagram. It was found that body image concerns were higher among people who exercised regularly as well as among those who followed fitness related pages on Instagram as compared to those who did not. These results provide an insight into the sex differences between the variables and future directions can be aimed at conducting an in-depth analysis using body image, exercise motivation and social comparison., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Nimiya A et al.)

Finite element studies of the tibiofemoral joint have increased use in research, with attention often placed on the material models. Few studies assess the effect of meniscus modelling assumptions in image-based models on contact mechanics outcomes. This work aimed to assess the effect of modelling assumptions of the meniscus on knee contact mechanics and meniscus kinematics. A sensitivity analysis was performed using three specimen-specific tibiofemoral models and one generic knee model. The assumptions in representing the meniscus attachment on the tibia (shape of the roots and position of the attachment), the material properties of the meniscus, the shape of the meniscus and the alignment of the joint were evaluated, creating 40 model instances. The values of material parameters for the meniscus and the position of the root attachment had a small influence on the total contact area but not on the meniscus displacement or the force balance between condyles. Using 3D shapes to represent the roots instead of springs had a large influence in meniscus displacement but not in knee contact area. Changes in meniscus shape and in knee alignment had a significantly larger influence on all outcomes of interest, with differences two to six times larger than those due to material properties. The sensitivity study demonstrated the importance of meniscus shape and knee alignment on meniscus kinematics and knee contact mechanics, both being more important than the material properties or the position of the roots. It also showed that differences between knees were large, suggesting that clinical interpretations of modelling studies using single geometries should be avoided., (© 2024. The Author(s).)

Objective: To explore associations of the main component (P100) of visual evoked potentials (VEP) to pre- and postchiasmatic damage in multiple sclerosis (MS)., Methods: 31 patients (median EDSS: 2.5), 13 with previous optic neuritis (ON), and 31 healthy controls had VEP, optical coherence tomography and magnetic resonance imaging. We tested associations of P100-latency to the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell/inner plexiform layers (GCIPL), lateral geniculate nucleus volume (LGN), white matter lesions of the optic radiations (OR-WML), fractional anisotropy of non-lesional optic radiations (NAOR-FA), and to the mean thickness of primary visual cortex (V1). Effect sizes are given as marginal R 2 (mR 2 )., Results: P100-latency, pRNFL, GCIPL and LGN in patients differed from controls. Within patients, P100-latency was significantly associated with GCIPL (mR 2  = 0.26), and less strongly with OR-WML (mR 2  = 0.17), NAOR-FA (mR 2  = 0.13) and pRNFL (mR 2  = 0.08). In multivariate analysis, GCIPL and NAOR-FA remained significantly associated with P100-latency (mR 2  = 0.41). In ON-patients, P100-latency was significantly associated with LGN volume (mR 2  = -0.56)., Conclusions: P100-latency is affected by anterior and posterior visual pathway damage. In ON-patients, damage at the synapse-level (LGN) may additionally contribute to latency delay., Significance: Our findings corroborate post-chiasmatic contributions to the VEP-signal, which may relate to distinct pathophysiological mechanisms in MS., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Histopathologic studies have identified immunoglobulin (Ig) deposition and complement activation as contributors of CNS tissue damage in multiple sclerosis (MS). Intrathecal IgM synthesis is associated with higher MS disease activity and severity, and IgM is the strongest complement-activating immunoglobulin. In this study, we investigated whether complement components (CCs) and complement activation products (CAPs) are increased in persons with MS, especially in those with an intrathecal IgM synthesis, and whether they are associated with disease severity and progression., Methods: CC and CAP levels were quantified in plasma and CSF of 112 patients with clinically isolated syndrome (CIS), 127 patients with MS (90 relapsing-remitting, 14 primary progressive, and 23 secondary progressive), 31 inflammatory neurologic disease, and 44 symptomatic controls from the Basel CSF databank study. Patients with CIS/MS were followed in the Swiss MS cohort study (median 6.3 years). Levels of CC/CAP between diagnosis groups were compared; in CIS/MS, associations of CC/CAP levels with intrathecal Ig synthesis, baseline Expanded Disability Status Scale (EDSS) scores, MS Severity Score (MSSS), and neurofilament light chain (NfL) levels were investigated by linear regression, adjusted for age, sex, and albumin quotient., Results: CSF (but not plasma) levels of C3a, C4a, Ba, and Bb were increased in patients with CIS/MS, being most pronounced in those with an additional intrathecal IgM production. In CIS, doubling of C3a and C4a in CSF was associated with 0.31 (CI 0.06-0.56; p = 0.016) and 0.32 (0.02-0.62; p = 0.041) increased EDSS scores at lumbar puncture. Similarly, doubling of C3a and Ba in CIS/MS was associated with 0.61 (0.19-1.03; p < 0.01) and 0.74 (0.18-1.31; p = 0.016) increased future MSSS. In CIS/MS, CSF levels of C3a, C4a, Ba, and Bb were associated with increased CSF NfL levels, e.g., doubling of C3a was associated with an increase of 58% (Est. 1.58; CI 1.37-1.81; p < 0.0001)., Discussion: CNS-compartmentalized activation of the classical and alternative pathways of complement is increased in CIS/MS and associated with the presence of an intrathecal IgM production. Increased complement activation within the CSF correlates with EDSS, future MSSS, and NfL levels, supporting the concept that complement activation contributes to MS pathology and disease progression. Complement inhibition should be explored as therapeutic target to attenuate disease severity and progression in MS.

Background and Objectives: Progression independent of relapse activity (PIRA) is a crucial determinant of overall disability accumulation in multiple sclerosis (MS). Accelerated brain atrophy has been shown in patients experiencing PIRA. In this study, we assessed the relation between PIRA and neurodegenerative processes reflected by (1) longitudinal spinal cord atrophy and (2) brain paramagnetic rim lesions (PRLs). Besides, the same relationship was investigated in progressive MS (PMS). Last, we explored the value of cross-sectional brain and spinal cord volumetric measurements in predicting PIRA., Methods: From an ongoing multicentric cohort study, we selected patients with MS with (1) availability of a susceptibility-based MRI scan and (2) regular clinical and conventional MRI follow-up in the 4 years before the susceptibility-based MRI. Comparisons in spinal cord atrophy rates (explored with linear mixed-effect models) and PRL count (explored with negative binomial regression models) were performed between: (1) relapsing-remitting (RRMS) and PMS phenotypes and (2) patients experiencing PIRA and patients without confirmed disability accumulation (CDA) during follow-up (both considering the entire cohort and the subgroup of patients with RRMS). Associations between baseline MRI volumetric measurements and time to PIRA were explored with multivariable Cox regression analyses., Results: In total, 445 patients with MS (64.9% female; mean [SD] age at baseline 45.0 [11.4] years; 11.2% with PMS) were enrolled. Compared with patients with RRMS, those with PMS had accelerated cervical cord atrophy (mean difference in annual percentage volume change [MD-APC] -1.41; p = 0.004) and higher PRL load (incidence rate ratio [IRR] 1.93; p = 0.005). Increased spinal cord atrophy (MD-APC -1.39; p = 0.0008) and PRL burden (IRR 1.95; p = 0.0008) were measured in patients with PIRA compared with patients without CDA; such differences were also confirmed when restricting the analysis to patients with RRMS. Baseline volumetric measurements of the cervical cord, whole brain, and cerebral cortex significantly predicted time to PIRA (all p ≤ 0.002)., Discussion: Our results show that PIRA is associated with both increased spinal cord atrophy and PRL burden, and this association is evident also in patients with RRMS. These findings further point to the need to develop targeted treatment strategies for PIRA to prevent irreversible neuroaxonal loss and optimize long-term outcomes of patients with MS.

Introduction: Hyperthyroidism, characterized by excessive thyroid hormone production, is a common endocrine disorder that affects various physiological processes, including brain function. Recent advancements in neuroimaging techniques have enabled researchers to investigate structural alterations in the brain associated with hyperthyroidism. This study aimed to examine regional cortical thickness and cortical volume differences across the brain between hyperthyroid patients and control subjects., Methods: We examined localized cortical thicknesses and volumes in 34 hyperthyroid patients and 35 control subjects with high-resolution T1-weighted images using FreeSurfer software and assessed group differences with analysis of covariance (covariates: age, sex, education, and total intracranial volume). Spearman and partial correlations were performed between clinical variables and cortical thicknesses/volumes and between neuropsychological scores and cortical thicknesses/volumes, respectively., Results: Hyperthyroid patients exhibited significantly increased cortical thickness in bilateral superior temporal and superior frontal gyri, along with higher cortical volumes in various regions, including the right superior temporal gyrus, right superior parietal gyrus, right rostral and caudal middle frontal gyrus, and left superior frontal gyrus. Notably, thyroid hormones (fT3, fT4) correlated positively with cortical thicknesses and volumes in the superior temporal gyrus and superior frontal gyrus. Additionally, recognition memory scores negatively correlated with the right superior temporal gyrus and right superior frontal gyrus cortical thickness., Conclusion: The observed cortical thickening and increased cortical volume in specific brain areas provide new insights into the pathophysiological mechanism associated with brain impairment in hyperthyroidism., (© 2024 S. Karger AG, Basel.)

Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)