Effect of Bacilli Calmette-Guerin vaccine on severe combined immunodeficiency patient: a narrative review and proposed workup algorithm

This systematic review critically investigates the administration of the Bacillus Calmette-Guérin (BCG) vaccine in neonates with severe combined immunodeficiency (SCID). The BCG vaccine, derived from Mycobacterium bovis, is a live attenuated vaccine recognized for its significant role in mitigating the impacts of tuberculosis (TB) in endemic areas. Despite its beneficial effects in controlling TB, safety and efficacy concerns have been raised when the vaccine is administered to SCID patients, who have a severe dysfunction or absence of the immune system. The potential for the vaccine to lead to severe complications due to the immunocompromised state of SCID patients necessitates a comprehensive investigation. To better understand these issues, a thorough literature review was carried out, integrating data from clinical trials and observational studies available on the PubMed database. An extensive review and analysis of 32 relevant articles revealed substantial evidence of complications from BCG vaccination in SCID patients. These findings emphasize the urgency for a more effective pre-vaccination screening process to circumvent potential adverse effects. Given the crucial role of the BCG vaccine in controlling TB, its potential to induce severe complications in SCID patients warrants careful consideration. Therefore, this review proposes an in-depth screening algorithm for newborns before BCG vaccination administration. The goal is to prevent these adverse events, offering critical insights to health policymakers, researchers, and clinicians in the field

Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function

Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. Using fluorescent glucose analog uptake, we defined multiple developmentally independent mouse plasma cell populations with varying life- spans. Long-lived plasma cells imported more fluo- rescent glucose analog, expressed higher surface levels of the amino acid transporter CD98, and had more autophagosome mass than did short-lived cells. Low amino acid concentrations triggered re- ductions in both antibody secretion and mitochon- drial respiration, especially by short-lived plasma cells. To explain these observations, we found that glutamine was used for both mitochondrial respira- tion and anaplerotic reactions, yielding glutamate and aspartate for antibody synthesis. Endoplasmic reticulum (ER) stress responses, which link meta- bolism to transcriptional outcomes, were similar between long- and short-lived subsets. Accordingly, population and single-cell transcriptional compari- sons across mouse and human plasma cell subsets revealed few consistent and conserved dif- ferences. Thus, plasma cell antibody secretion and lifespan are primarily defined by non-transcriptional metabolic traits

Mesoamerican nephropathy: a narrative review

Mesoamerican nephropathy (MeN) also known as chronic kidney disease of unknown etiology (CKDu) is prevalent in agriculturally rich areas. The most widely accepted pathophysiological explanation for MeN is chronic dehydration caused by prolonged exposure to the sun. Other theories include oxidative stress, chronic inflammation, infection and tubulointerstitial fibrosis. The clinical presentation is quite vague and is diagnosed similar to CKD from any cause using blood, urine analysis and ultrasound. The study highlights the need for interdisciplinary cooperation among physicians, epidemiologists, toxicologists, and geneticists while identifying significant research gaps and future objectives. Occupational health related to agriculture is not emphasised enough especially in third world countries where a large chunk of population heavily depend on farming. To safeguard the population at risk, the significance of community-based initiatives, occupational health measures, and regulatory changes is emphasised

ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges

ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed responses by Zbtb32-/- mice or bone marrow chimeras against a panel of chronic and acute challenges. Mixed bone marrow chimeras were established in which all B cells were derived from either Zbtb32-/- mice or control littermates. Chronic infection of Zbtb32-/- chimeras with murine cytomegalovirus led to nearly 20-fold higher antigen-specific IgG2b levels relative to controls by week 9 post-infection, despite similar viral loads. In contrast, IgA responses and specificities in the intestine, where memory B cells are repeatedly stimulated by commensal bacteria, were similar between Zbtb32-/- mice and control littermates. Finally, an infection and heterologous booster vaccination model revealed no role for ZBTB32 in restraining primary or recall antibody responses against influenza viruses. Thus, ZBTB32 does not limit recall responses to a number of physiological acute challenges, but does restrict antibody levels during chronic viral infections that periodically engage memory B cells. This restriction might selectively prevent recall responses against chronic infections from progressively overwhelming other antibody specificities.National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AI99109, R01AI131680, U01AI131349, K08AI04991]; New York Stem Cell FoundationOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

West Nile Virus Isolated from a Virginia Opossum (Didelphis virginiana) in Northwestern Missouri, USA, 2012

We describe the isolation of West Nile virus (WNV; Flaviviridae, Flavivirus) from blood of a Virginia opossum (Didelphis virginiana) collected in northwestern Missouri, USA in August 2012. Sequencing determined that the virus was related to lineage 1a WNV02 strains. We discuss the role of wildlife in WNV disease epidemiology

Defining phenotypic and functional heterogeneity of glioblastoma stem cells by mass cytometry

Most patients with glioblastoma (GBM) die within 2 years. A major therapeutic goal is to target GBM stem cells (GSCs), a subpopulation of cells that contribute to treatment resistance and recurrence. Since their discovery in 2003, GSCs have been isolated using single-surface markers, such as CD15, CD44, CD133, and α6 integrin. It remains unknown how these single-surface marker-defined GSC populations compare with each other in terms of signaling and function and whether expression of different combinations of these markers is associated with different functional capacity. Using mass cytometry and fresh operating room specimens, we found 15 distinct GSC subpopulations in patients, and they differed in their MEK/ERK, WNT, and AKT pathway activation status. Once in culture, some subpopulations were lost and previously undetectable ones materialized. GSCs that highly expressed all 4 surface markers had the greatest self-renewal capacity, WNT inhibitor sensitivity, and in vivo tumorigenicity. This work highlights the potential signaling and phenotypic diversity of GSCs. Larger patient sample sizes and antibody panels are required to confirm these findings

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic