Multisensory gamma stimulation mitigates the effects of demyelination induced by cuprizone in male mice.

Demyelination is a common pathological feature in a wide range of diseases, characterized by the loss of myelin sheath and myelin-supporting oligodendrocytes. These losses lead to impaired axonal function, increased vulnerability of axons to damage, and result in significant brain atrophy and neuro-axonal degeneration. Multiple pathomolecular processes contribute to neuroinflammation, oligodendrocyte cell death, and progressive neuronal dysfunction. In this study, we use the cuprizone mouse model of demyelination to investigate long-term non-invasive gamma entrainment using sensory stimulation as a potential therapeutic intervention for promoting myelination and reducing neuroinflammation in male mice. Here, we show that multisensory gamma stimulation mitigates demyelination, promotes oligodendrogenesis, preserves functional integrity and synaptic plasticity, attenuates oligodendrocyte ferroptosis-induced cell death, and reduces brain inflammation. Thus, the protective effects of multisensory gamma stimulation on myelin and anti-neuroinflammatory properties support its potential as a therapeutic approach for demyelinating disorders.

Single-cell multiregion dissection of Alzheimer's disease.

Alzheimer's disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood1-3. Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer's disease. We identify 76 cell types, including region-specific subtypes of astrocytes and excitatory neurons and an inhibitory interneuron population unique to the thalamus and distinct from canonical inhibitory subclasses. We identify vulnerable populations of excitatory and inhibitory neurons that are depleted in specific brain regions in Alzheimer's disease, and provide evidence that the Reelin signalling pathway is involved in modulating the vulnerability of these neurons. We develop a scalable method for discovering gene modules, which we use to identify cell-type-specific and region-specific modules that are altered in Alzheimer's disease and to annotate transcriptomic differences associated with diverse pathological variables. We identify an astrocyte program that is associated with cognitive resilience to Alzheimer's disease pathology, tying choline metabolism and polyamine biosynthesis in astrocytes to preserved cognitive function late in life. Together, our study develops a regional atlas of the ageing human brain and provides insights into cellular vulnerability, response and resilience to Alzheimer's disease pathology.

The Impact of Non-bone Metastatic Cancer on Musculoskeletal Health.

PURPOSE OF REVIEW: The purpose of this review is to discuss the musculoskeletal consequences of cancer, including those that occur in the absence of bone metastases. RECENT FINDINGS: Cancer patients frequently develop cachexia, a debilitating condition reflected by weight loss and skeletal muscle wasting. The negative effects that tumors exert on bone health represents a growing interest amongst cachexia researchers. Recent clinical and pre-clinical evidence demonstrates cancer-induced bone loss, even in the absence of skeletal metastases. Together with muscle wasting, losses in bone demonstrates the impact of cancer on the musculoskeletal system. Identifying therapeutic targets that comprehensively protect musculoskeletal health is essential to improve the quality of life in cancer patients and survivors. IL-6, RANKL, PTHrP, sclerostin, and TGF-ß superfamily members represent potential targets to counteract cachexia. However, more research is needed to determine the efficacy of these targets in protecting both skeletal muscle and bone.

Single-nucleus multiregion transcriptomic analysis of brain vasculature in Alzheimer's disease.

Cerebrovascular dysregulation is a hallmark of Alzheimer's disease (AD), but the changes that occur in specific cell types have not been fully characterized. Here, we profile single-nucleus transcriptomes in the human cerebrovasculature in six brain regions from 220 individuals with AD and 208 age-matched controls. We annotate 22,514 cerebrovascular cells, including 11 subtypes of endothelial, pericyte, smooth muscle, perivascular fibroblast and ependymal cells. We identify 2,676 differentially expressed genes in AD, including downregulation of PDGFRB in pericytes, and of ABCB1 and ATP10A in endothelial cells, and validate the downregulation of SLC6A1 and upregulation of APOD, INSR and COL4A1 in postmortem AD brain tissues. We detect vasculature, glial and neuronal coexpressed gene modules, suggesting coordinated neurovascular unit dysregulation in AD. Integration with AD genetics reveals 125 AD differentially expressed genes directly linked to AD-associated genetic variants. Lastly, we show that APOE4 genotype-associated differences are significantly enriched among AD-associated genes in capillary and venule endothelial cells, as well as subsets of pericytes and fibroblasts.

Evaluating Ligand Modifications of the Titanocene and Auranofin Moieties for the Development of More Potent Anticancer Drugs.

Over time platinum-based anticancer drugs have dominated the market, but their side effects significantly impact the quality of life of patients. Alternative treatments are being developed all over the world. The titanocene and auranofin families of compounds, discovered through an empirical search for other metal-based therapeutics, hold tremendous promise to improve the outcomes of cancer treatment. Herein we present a historical perspective of these compounds and review current efforts focused on the evolution of their ligands to improve their physiological solution stability, cancer selectivity, and antiproliferative performance, guided by a clear understanding of the coordination chemistry and aqueous speciation of the metal ions, of the cytotoxic mechanism of action of the compounds, and the external factors that limit their therapeutic potential. Newer members of these families of compounds and their combination in novel bimetallic complexes are the result of years of scientific research. We believe that this review can have a positive impact in the development and understanding of the metal-based drugs of gold, titanium, and beyond.

Seroepidemiología de la toxocariasis en una comunidad indígena Yucpa de la Sierra de Perijá al occidente de Venezuela / Seroepidemilogy of toxocariasis in a Yucpa amerindian community from the Perijá Mountains, western Venezuela

El propósito de este estudio fue determinar la seroprevalencia de infección por Toxocara spp en una comunidad indígena de la sierra de Perijá, al occidente de Venezuela, identificando el efecto de los cambios socioculturales sobre los factores de riesgo. Se estudió el 75,4% del total de la comunidad (110 individuos). La determinación de anticuerpos anti-Toxocara spp se realizó a través de una técnica de ELISA comercial. El análisis estadístico se realizó a través de la prueba de Chi cuadrado y la correlación de Spearman. El porcentaje general de infección fue de 21,7%, la más alta prevalencia se observó en el grupo de mayores de 50 años (37,5%). No se apreciaron diferencias estadísticamente significativas con relación al sexo. La prevalencia encontrada fue más alta que la apreciada en poblaciones urbanas y más baja que en otras comunidades indígenas. El proceso de transculturización en esta comunidad indígena es un factor de riesgo para la infección por Toxocara spp

The aim of this study was to determine the Toxocara spp infection seroprevalence in an Amerindian community from western Venezuela, identifying the effect of socio-cultural changes on the risk factors. 75.4% of the community, 110 individuals, were studied. Blood samples were gathered by venous puncture. Determination of anti-Toxocara spp antibodies was carried out using a commercial ELISA technique. The overall prevalence was 21.7%. Higher prevalence was observed in the age group >50 years old (37.5%). There were no statistically significant differences with regard to sex. The prevalence found was higher than that of an urban population and lower than in other indigenous communities. The transculturization process in this indigenous community is a risk factor for Toxocara spp infection

Frecuencia de intoxicación con Karwinskia humboldtiana en México / Frequency of intoxication with Karwinskia humboldtiana in Mexico

La intoxicación con la Karwinskia humboldtiana presenta un cuadro neurológico similar a la poliomielitis, al síndrome de Guillain-Barré y a otras polirradiculoneuritis con las que suele confundirse. El objetivo de este trabajo fue conocer la frecuencia de esta intoxicación, mediante el antecedente de la ingestión del fruto y la detección de toxinas en sangre por cromatografía en capa fina. Se recibieron 154 muestras de casos con parálisis fláccida aguda procedentes de 18 estados de la República. Se corroboró el antecedente de ingestión en 56 de ellos y la detección fue positiva en 50 de los mismos. En 98 pacientes no hubo antecedentes de ingestión y la detección fue negativa en 95 de ellos. Se obtuvo con este método una sensibilidad de 89 por ciento y una especificidad de 96.9 por ciento

Intoxication produced by Karwinskia humboldtiana presents a neurological picture similar to that of poliomyelitis,Guillain-Barre syndrome or other polyradiculoneuritis with which it is frequently confused. The purpose of this paper is to report the frequency of this intoxication, by means of the antecedent of ingestion of the fruit and the detection of toxins in blood using a thin layer chromatography method. One hundred fifty four samples of cases with acute flaccid paralysis from 18 states of the country were received. The antecedent of ingestion in 56 of them was corroborated and the detection was positive in 50 of these. In 98 patients there was not antecedent of ingestion and detection was negative in 95 of them. We estimated that the sensibility and specificity of detection method are 89% and 96.9% respectively.

Intoxicación de una familia por Karwinskia humboldtiana (tullidora) / Familial intoxication by Karwinskia humboldtiana (tullidora)

La ingestión del fruto maduro de la Karwinskia humboldtiana, arbusto comúnmente conocido como tullidora o coyotillo, provoca una intoxicación descrita en la bibliografía como una parálisis fláccida, simétrica de los miembros inferiores, progresiva y ascendente, que en casos graves puede causar parálisis bulbar y muerte. Se presenta el caso de una familia en la que diez de sus trece miembros ingirieron accidentalmente el fruto de la tullidora; tres fallecieron: el padre y dos hijas. Además, se describe por primera vez, la determinación de las toxinas en sangre por medio de cromatografía en capa fina. Este método resulta útil para el diagnóstico diferencial con otras polirradiculoneuritis, v.gr. poliomielitis y Síndrome de Guillain-Barre