Adoptive T-cell immunotherapy holds great promise for the treatment of viral complications in immunocompromised patients resistant to standard anti-viral strategies. We present a retrospective analysis of 78 patients from 19 hospitals across Australia and New Zealand, treated over the last 15 years with "off-the-shelf" allogeneic T cells directed to a combination of Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK polyomavirus (BKV), John Cunningham virus (JCV) and/or adenovirus (AdV) under the Australian Therapeutic Goods Administration's Special Access Scheme. Most patients had severe post-transplant viral complications, including drug-resistant end-organ CMV disease, BKV-associated haemorrhagic cystitis and EBV-driven post-transplant lymphoproliferative disorder.
View Article and Find Full Text PDFChedíak-Higashi Syndrome (CHS) is a rare autosomal recessive disorder caused by mutations in the Lysosomal Trafficking Regulator (LYST) gene, leading to defective lysosomal function in immune cells, melanocytes, and neurons. Clinically, CHS is characterized by a spectrum of symptoms, including immunodeficiency, partial oculocutaneous albinism, bleeding tendencies, neurodevelopmental deficits and progressive neurodegenerative symptoms. The severity of CHS correlates with the type of LYST mutation: the classic form, linked to nonsense or frameshift mutations, presents early in childhood with severe immune dysfunction, recurrent infections, and a high risk of hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory state.
View Article and Find Full Text PDFTraumatic spinal cord injury (SCI) results in the disruption of physiological systems below the level of the spinal lesion. Connexin hemichannels (CxHCs) are membrane-bound, non-selective pore proteins that are lost in mature myofibers but reappear on the sarcolemma after peripheral denervation, chronic SCI, diabetes, and severe systemic stress such as sepsis. Cx43 and Cx45 have been implicated as the major CxHCs present in diseased muscle, and muscle-restricted knockout of these genes reduces muscle atrophy after denervation, likely by reducing excess calcium influx with resultant inflammasome activation.
View Article and Find Full Text PDFOver the past decade, boldine, a naturally occurring alkaloid found in several plant species including the Chilean Boldo tree, has garnered attention for its efficacy in rodent models of human disease. Some of the properties that have been attributed to boldine include antioxidant activities, neuroprotective and analgesic actions, hepatoprotective effects, anti-inflammatory actions, cardioprotective effects and anticancer potential. Compelling data now indicates that boldine blocks connexin (Cx) hemichannels (HCs) and that many if not all of its effects in rodent models of injury and disease are due to CxHC blockade.
View Article and Find Full Text PDFEur J Breast Health
September 2024
We present the case of a forty-year-old asymptomatic female with no personal or family history of breast cancer, who underwent a core needle biopsy (CNB) following the identification of a focal asymmetry in the right breast on screening mammography. Eight months later, a prominent adjacent vascular structure with a round outpouching was detected on breast ultrasound, confirmed as a post-biopsy pseudoaneurysm. Breast pseudoaneurysms, although exceedingly rare, result from inadvertent vessel puncture during core needle biopsies, particularly when larger gauge needles are used.
View Article and Find Full Text PDFA growing body of research has provided evidence that de novo expression of connexin hemichannels and upregulation of pannexin hemichannels (Cx HCs and Panx HCs, respectively) in the cytoplasmic membrane of skeletal muscle (sarcolemma) are critical steps in the pathogenesis of muscle dysfunction of many genetic and acquired muscle diseases. This review provides an overview of the current understanding of the molecular mechanisms regulating the expression of Cx and Panx HCs in skeletal muscle, as well as their roles in both muscle physiology and pathologies. Additionally, it addresses existing gaps in knowledge and outlines future challenges in the field.
View Article and Find Full Text PDFBackground: Childhood and adolescence are the life stages where eating habits related to the development of cardiovascular risk factors are usually established.
Objective: To classify cardiovascular risk in school adolescents from Villavicencio (Colombia) and, additionally, to estimate its association with food intake frequency according to food kind.
Methodology: This is an analytical cross-sectional study developed in 1,504 adolescents of 13 to 17 years of age schooling in Villavicencio.
Background: The evolution of ischemic stroke is different accordin'g to sex and is one of the main causes of death in women. Previous studies have shown that women are less likely to receive acute treatment, and stroke center type is an important predictor of door-to-needle times. We investigated whether women are attended in a similar way to men in the telestroke network with specialized stroke physicians.
View Article and Find Full Text PDFIntroduction: Variants of uncertain significance (VUS) surged with affordable genetic testing, posing challenges for determining pathogenicity. We examine the pathogenicity of a novel VUS P93S in Annexin A11 (ANXA11) - an amyotrophic lateral sclerosis/frontotemporal dementia-associated gene - in a corticobasal syndrome kindred. Established ANXA11 mutations cause ANXA11 aggregation, altered lysosomal-RNA granule co-trafficking, and transactive response DNA binding protein of 43 kDa (TDP-43) mis-localization.
View Article and Find Full Text PDFAtmos Environ (1994)
June 2024
The US Environmental Protection Agency (EPA) estimates on-road vehicles emissions using the Motor Vehicle Emission Simulator (MOVES). We developed updated ammonia emission rates for MOVES based on road-side exhaust emission measurements of light-duty gasoline and heavy-duty diesel vehicles. The resulting nationwide on-road vehicle ammonia emissions are 1.
View Article and Find Full Text PDFThis review describes the use of tissue dielectric constant (TDC) measurements mainly in the assessment of breast cancer-related lymphedema (BCRL). PubMed, Web of Science, and EMBASE databases were initially searched using criteria that included the terms "dielectric" and "lymphedema." The initial search yielded a total of 131 titles.
View Article and Find Full Text PDFHere, we investigated the mechanisms by which aging-related reductions of the levels of in skeletal muscle fibers contribute to loss of muscle strength and power, two critical features of sarcopenia. Numb is an adaptor protein best known for its critical roles in development, including asymmetric cell division, cell-type specification, and termination of intracellular signaling. expression is reduced in old humans and mice.
View Article and Find Full Text PDFLower extremity swelling may be broadly characterized as due to edema, lymphedema, or lipedema. Differentiation between these three conditions is important for providing appropriate treatment. This review analyzes and compares different clinical diagnostic modalities for these conditions, with the aim of assisting in the process of choosing the most appropriate diagnostic modality by highlighting the advantages and limitations of each.
View Article and Find Full Text PDFObjective: The COVID-19 pandemic accelerated changes to clinical research methodology, with clinical studies being carried out via online/remote means. This mixed-methods study aimed to identify which digital tools are currently used across all stages of clinical research by stakeholders in clinical, health and social care research and investigate their experience using digital tools.
Design: Two online surveys followed by semistructured interviews were conducted.
Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections.
View Article and Find Full Text PDFMobile sources are responsible for a substantial controllable portion of the reactive organic carbon (ROC) emitted to the atmosphere, especially in urban environments of the United States. We update existing methods for calculating mobile source organic particle and vapor emissions in the United States with over a decade of laboratory data that parameterize the volatility and organic aerosol (OA) potential of emissions from on-road vehicles, nonroad engines, aircraft, marine vessels, and locomotives. We find that existing emission factor information from Teflon filters combined with quartz filters collapses into simple relationships and can be used to reconstruct the complete volatility distribution of ROC emissions.
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