Memantine protects cholinergic and glutamatergic septal neurons from Aβ1-40-induced toxicity

The medial septal region (medial septum and diagonal band of Broca, MS/DB) controls hippocampal excitability and synaptic plasticity. MS/DB cholinergic neurons degenerate early in Alzheimer’s disease (AD). The presence of MS/DB glutamatergic neurons that project to the hippocampus and are vulnerable to Aβ suggests that excitotoxicity plays a role in AD septal degeneration and hippocampal dysfunction. To demonstrate the presence of excitotoxicity in Aβinduced septal damage, we compared rats injected with Aβ1–40 into the MS/DB with animals treated with memantine prior, during and after Aβ1–40 injections. Controls were injected with phosphate buffered saline (PBS). MS/DB cholinergic, glutamatergic and GABAergic neurons were immunochemically identified. The number of MS/DB neurons was estimated using stereology. Our results show that memantine blocks Aβ1–40-induced septal damage and suggest that excitotoxicity plays a role in basal forebrain neurodegeneration

Memantine protects cholinergic and glutamatergic septal neurons from Aβ1-40-induced toxicity

The medial septal region (medial septum and diagonal band of Broca, MS/DB) controls hippocampal excitability and synaptic plasticity. MS/DB cholinergic neurons degenerate early in Alzheimer\u27s disease (AD). The presence of MS/DB glutamatergic neurons that project to the hippocampus and are vulnerable to Aβ suggests that excitotoxicity plays a role in AD septal degeneration and hippocampal dysfunction. To demonstrate the presence of excitotoxicity in Aβ-induced septal damage, we compared rats injected with Aβ1-40 into the MS/DB with animals treated with memantine prior, during and after Aβ1-40 injections. Controls were injected with phosphate buffered saline (PBS). MS/DB cholinergic, glutamatergic and GABAergic neurons were immunochemically identified. The number of MS/DB neurons was estimated using stereology. Our results show that memantine blocks Aβ1-40-induced septal damage and suggest that excitotoxicity plays a role in basal forebrain neurodegeneration

A Nonsynonymous Change in Adhesion G Protein–Coupled Receptor L3 Associated With Risk for Equine Degenerative Myeloencephalopathy in the Caspian Horse

Equine degenerative myeloencephalopathy (EDM), a neurological disease of young horses, causes progressive development of symmetric ataxia predominantly in the pelvic limbs. Equine degenerative myeloencephalopathy is likely inherited and with no known treatment affected horses frequently need euthanasia. Alpha-tocopherol deficiency during early life appears to contribute to the phenotype. This study sought to identify any genetic variants correlated with EDM in Caspian foals. Two half-sibling EDM-diagnosed cases were genotyped at 52,063 loci and evaluated by the Autozygosity by Difference statistic. Additional horses not affected by EDM were used for genetic comparison to identify regions unique to the case phenotype. The associated region on chromosome 3 contains only one gene encoding adhesion G protein–coupled receptor L3 (ADGRL3). Adhesion G protein–coupled receptor L3 is a member of the latrophilin subfamily of G protein–coupled receptors and may contribute to attention deficit/hyperactivity disorder in humans and hyperactive motor function in mice and zebrafish. Analysis of the predicted coding regions for Equine ADGRL3 in affected horses revealed a nonsynonymous single nucleotide polymorphism at Chr3:71,917,591 bp. Caspian and Caspian cross-relatives (n = 81) of the two initial cases and unrelated horses from similar breeds (n = 130, including Arabians, American Miniatures, and Shetlands) possessed this allele at 5% frequency, with no homozygotes observed within the non-Caspian breeds. This study suggests that a polymorphism in ADGRL3 could contribute to a genetic predisposition to Caspian horse EDM

Insulin regulates neurovascular coupling through astrocytes

Mice with insulin receptor (IR)-deficient astrocytes (GFAP-IR knockout [KO] mice) show blunted responses to insulin and reduced brain glucose uptake, whereas IRdeficient astrocytes show disturbed mitochondrial responses to glucose. While exploring the functional impact of disturbed mitochondrial function in astrocytes, we observed that GFAP-IR KO mice show uncoupling of brain blood flow with glucose uptake. Since IR-deficient astrocytes show higher levels of reactive oxidant species (ROS), this leads to stimulation of hypoxia-inducible factor-1¿ and, consequently, of the vascular endothelial growth factor angiogenic pathway. Indeed, GFAP-IR KO mice show disturbed brain vascularity and blood flow that is normalized by treatment with the antioxidant N-acetylcysteine (NAC). NAC ameliorated high ROS levels, normalized angiogenic signaling and mitochondrial function in IR-deficient astrocytes, and normalized neurovascular coupling in GFAP-IR KO mice. Our results indicate that by modulating glucose uptake and angiogenesis, insulin receptors in astrocytes participate in neurovascular coupling.We are thankful to M.Garcia and R. Cañadas for technical support. This work was funded by Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) (Instituto de Salud CarlosIII, Spain) to I.T.A., A.G., and T.I.; an Inter-CIBER project (PIE14/00061) to I.T.A.that forms part of the projects PID2019-104376RB-I00 (I.T.A.) and RTI2018-094887-B-I00 (M.N.) funded by MCIN/AEI/10.13039/501100011033; a grant from Junta de Andalucia Consejería de Economía y Conocimiento (P18-RT-2233 to A.G.) cofinanced by Programa Operativo FEDER 2014–2020; a grant from Instituto de Salud Carlos III Spain (cofinanced by FEDER funds from the European Union; PI21/00915 to A.G.); Grant PID2020-115218RB-I00 to T.I. funded by Ministerio de Ciencia e Innovación/Agencia Española de Investigación (MCIN/AEI/10.13039/501100011033); and a grant from Comunidad de Madrid through the European Social Fund (ESF)–financed programme Neurometabolismo-Comunidad de Madrid (NEUROMETAB-CM) (B2017/BMD-3700 to I.T.A.and T.I.). M.N. was also supported by the Spanish Ministry of Science and Innovation (Ramón y Cajal RYC-2016-20414). J.P.-U. was contracted by CIBERNED

Rectovaginal Colonization with Serotypes of Group B Streptococci with Reduced Penicillin Susceptibility among Pregnant Women in Leon, Nicaragua

Group B Streptococci (GBS) are important causes of neonatal sepsis and meningitis globally. To elucidate the potential benefits of maternal GBS vaccines, data is needed on the epidemiology of maternal GBS rectovaginal colonization, distribution of serotypes, and resistance to intrapartum antibiotic prophylaxis (IAP). We collected rectal and vaginal samples from 305 pregnant women in León, Nicaragua between 35 and 40 weeks gestation. Samples were cultured for GBS and confirmed using latex agglutination. GBS isolates underwent serotyping by quantitative polymerase chain reaction, and antimicrobial susceptibility testing by disk diffusion and microdilution following Clinical Laboratory Standard Institute guidelines. Sixty-three women (20.7%) were colonized with GBS in either the rectum or the vagina. Of 91 GBS isolates collected from positive cultures, most were serotypes II (28.6%), Ia (27.5%), and III (20.9%). Most GBS isolates (52.9%) were resistant to penicillin, the first-line prophylactic antibiotic. Penicillin resistance was highly correlated with resistance to vancomycin, ceftriaxone, and meropenem. The results of our study suggest that one-fifth of pregnant women in the urban area of León, Nicaragua are colonized with GBS and risk transmitting GBS to their offspring during labor. High resistance to commonly available antibiotics in the region suggests that prophylactic maternal GBS vaccination would be an effective alternative to IAP

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually

Streptococo del grupo B en mujeres embarazadas atendidas en el Centro de Salud Primero de Mayo. Abril-Agosto 2007

Streptococos del grupo B (SGB) es una de las principales causas de muertes neonatales en todo el mundo y esta directamente relacionada con la colonización materna al momento del parto. Se realizó un estudio descriptivo de corte transversal que incluyó un total de 120 mujeres embarazadas atendidas en el Centro de Salud 1ro. de mayo-León, con el objetivo de identificar la frecuencia de streptococo del grupo B, debido a que la identificación de esta bacteria influye positivamente en la prevención de infecciones perinatales. La frecuencia de SGB encontrada fue del 11%. El 78% de las participantes eran amas de casa. En relación con la colonización de las participantes según su edad encontramos que el 36% de las participantes eran menores de 19 años e iniciaron su vida sexual activa a temprana edad (12-16 años). Además, el 55% de las participantes colonizadas tenían entre 20-29 semanas de gestación. Los procesos patológicos que presentaron las participantes colonizadas fueron 73% Leucorrea y 64% infección de vías urinarias. Los antibióticos de elección para infección por SGB resultaron con una sensibilidad de 77% penicilina, 62% clindamicina y 54% eritromicina; en cuanto a la resistencia antimicrobiana se encontró 92% Gentamicina y 77% Oxacilina. El inicio temprano de vida sexual tiene relación con una alta frecuencia de colonización por SGB. Los procesos patológicos que predominaban en las participantes fueron leucorrea e infecciones de vías urinarias. El tratamiento de elección para infección por SGB que es utilizado en la población involucrada no es 100% sensible

La predisposición a innovar. Análisis cross–cultural entre los jóvenes de Colombia y México

This article is the result of a scientific investigation and has been raised around the objective of analyzing and comparing the influence of personal and social characteristics on the predisposition to innovate in the young consumers of Villavicencio - Colombia and Coatzacoalcos - Mexico. For the development was carried out to survey 1591 university students of the two cities. The age range of the sample was between 17 and 25 years. To this end, the University of Los Llanos and the Universidad Veracruzana collaborated. The results show that there is no association between the predisposition to innovate and the variables of personal or social characteristics studied. This means that a strategy of demographic segmentation is not enough, since the determinants of the behavior of the segment may be influenced by their personal motivations, or by the characteristics of the products.Este artigo é o resultado da investigação científica e tem sido levantada em torno do objetivo analisar e comparar a influência das características pessoais e sociais na predisposição para inovar jovens consumidores de Villavicencio - Colômbia e Coatzacoalcos - México. Desenvolvimento procedeu ao levantamento de 1591 estudantes universitários das duas cidades. A faixa etária da amostra foi de entre 17 e 25 anos. Para fazer isso, ele contou com a colaboração da Universidade do Llanos e Universidad Veracruzana. Os resultados mostram que não existe uma associação entre a vontade de inovar e variáveis de características pessoais ou sociais estudados. Isto significa que uma estratégia de segmentação demográfica não é suficiente, porque os determinantes do segmento de comportamento podem ser influenciadas pelas suas motivações pessoais, ou as características dos produtos.El presente artículo es resultado de una investigación científica y se ha planteado en torno al objetivo de analizar y comparar la influencia de las características personales y sociales en la predisposición a innovar en los consumidores jóvenes de Villavicencio - Colombia y Coatzacoalcos - México. Para el desarrollo se procedió a encuestar a 1591 jóvenes universitarios de las dos ciudades. El rango etario de la muestra fue entre 17 y 25 años. Para ello se contó con la colaboración de la Universidad de los Llanos y la Universidad Veracruzana. Los resultados evidencian que no existe asociación entre la predisposición a innovar y las variables de características personales o sociales estudiadas. Esto significa que una estrategia de segmentación demográfica no es suficiente, pues los determinantes del comportamiento del segmento pueden estar influenciados por sus motivaciones personales, o por las características de los productos

Brain‐based ranking of cognitive domains to predict schizophrenia

Schizophrenia is a devastating brain disorder that disturbs sensory perception, motoraction, and abstract thought. Its clinical phenotype implies dysfunction of variousmental domains, which has motivated a series of theories regarding the underlyingpathophysiology. Aiming at a predictive benchmark of a catalog of cognitive functions,we developed a data-driven machine-learning strategy and provide a proof ofprinciple in a multisite clinical dataset (n = 324). Existing neuroscientific knowledge ondiverse cognitive domains was first condensed into neurotopographical maps. Wethen examined how the ensuing meta-analytic cognitive priors can distinguishpatients and controls using brain morphology and intrinsic functional connectivity.Some affected cognitive domains supported well-studied directions of research onauditory evaluation and social cognition. However, rarely suspected cognitivedomains also emerged as disease relevant, including self-oriented processing of bodilysensations in gustation and pain. Such algorithmic charting of the cognitive landscapecan be used to make targeted recommendations for future mental health research