Intro in the BNT162b2 vaccine after a COVID19 elderly care episode

The vast majority of bactericidal antibiotics display poor efficacy against bacterial persisters, cells that are in a metabolically repressed state. Molecules that retain their bactericidal functions against such bacteria often display toxicity to human cells, which limits treatment options for infections caused by persisters. Here, we leverage insight into metabolism-dependent bactericidal antibiotic efficacy to design antibiotic combinations that sterilize both metabolically active and persister cells, while minimizing the antibiotic concentrations required. These rationally designed antibiotic combinations have the potential to improve treatments for chronic and recurrent infections.On Aug 25 2020, the Africa Regional Commission for the Certification of Poliomyelitis Eradication declared that the WHO African region had interrupted transmission of all indigenous wild polioviruses. This declaration marks the African region as the fifth of the six WHO regions to celebrate this extraordinary achievement. Following the Yaoundé Declaration on Polio Eradication in Africa by heads of state and governments in 1996, Nelson Mandela launched the Kick Polio out of Africa campaign. In this Health Policy paper, we describe the long and turbulent journey to the certification of the interruption of wild poliovirus transmission, focusing on 2016-20, lessons learned, and the strategies and analyses that convinced the Regional Commission that the African region is free of wild polioviruses. This certification of the WHO African region shows the feasibility of polio eradication in countries with chronic insecurity, inaccessible and hard-to-reach populations, and weak health systems. Challenges have been daunting and the sacrifices enormous-dozens of health workers and volunteers have lost their lives in the pursuit of a polio-free Africa.Gut microbiota impacts the host metabolome and affects its health span. How bacterial species in the gut influence age-dependent metabolic alteration has not been elucidated. Here we show in Drosophila melanogaster that allantoin, an end product of purine metabolism, is increased during aging in a microbiota-dependent manner. Allantoin levels are low in young flies but are commonly elevated upon lifespan-shortening dietary manipulations such as high-purine, high-sugar, or high-yeast feeding. Removing Acetobacter persici in the Drosophila microbiome attenuated age-dependent allantoin increase. Mono-association with A. persici, but not with Lactobacillus plantarum, increased allantoin in aged flies. A. persici increased allantoin via activation of innate immune signaling IMD pathway in the renal tubules. On the other hand, analysis of bacteria-conditioned diets revealed that L. plantarum can decrease allantoin by reducing purines in the diet. These data together demonstrate species-specific regulations of host purine levels by the gut microbiome.Bystander effects in biological systems are the responses shown by nontargeted neighboring cells, and critical to the bio-nano interface interactions. In addition to direct effects, bystander effects also determine the design, applications and safety of nanomaterials, although the related information of nanomaterial-induced bystander effects remain largely unknown. A coculture system of A549 and THP-1 was established to mimic the lung microenvironment to study the bystander effects of WS2 nanosheets (representative transition-metal dichalcogenide nanosheets) on microenvironment macrophages during the inhalation exposure or the nanomaterial biomedical application in the lung. Lung cells exposed to WS2 nanosheet resulted in an increase in reactive oxygen species and the depolarization of mitochondrial membrane potential in neighboring macrophages. Bystander exposure also induced macrophage polarization toward the anti-inflammatory M2 phenotype, which is adverse to disease therapy. Metabolomics showed that WS2 nanosheets disturbed the energy metabolism and amino acid metabolism of macrophages, consistent with the metabolic characteristics of M2 macrophages. Nitric oxide-transforming growth factor-β1 played an important mediator in the bystander effects. Importantly, WS2 nanosheet bystander exposure affected macrophage phagocytosis and migration and altered the macrophage immune response to endotoxin. This study improves the current understanding of bio-nano interactions and highlights the importance of neighboring cell responses, allowing us to use the maximum benefits of nanomaterials while limiting their adverse bystander effects.Will people use self-driving cars, virtual doctors, and other algorithmic decision-makers if they outperform humans? The answer depends on the uncertainty inherent in the decision domain. We propose that people have diminishing sensitivity to forecasting error and that this preference results in people favoring riskier (and often worse-performing) decision-making methods, such as human judgment, in inherently uncertain domains. In nine studies (N = 4,820), we found that (a) people have diminishing sensitivity to each marginal unit of error that a forecast produces, (b) people are less likely to use the best possible algorithm in decision domains that are more unpredictable, (c) people choose between decision-making methods on the basis of the perceived likelihood of those methods producing a near-perfect answer, and (d) people prefer methods that exhibit higher variance in performance (all else being equal). To the extent that investing, medical decision-making, and other domains are inherently uncertain, people may be unwilling to use even the best possible algorithm in those domains.Purpose The goal of this study was to determine if differences in stress system activation lead to changes in speaking fundamental frequency, average oral airflow, and estimated subglottal pressure before and after an acute, psychosocial stressor. Method Eighteen vocally healthy adult females experienced the Trier Social Stress Test (TSST) to activate the hypothalamic-pituitary-adrenal axis. The TSST includes public speaking and performing mental arithmetic in front of an audience. At seven time points, three before the stressor and four after the stressor, the participants produced /pa/ repetitions, read the Rainbow Passage, and provided a saliva sample. Measures included (a) salivary cortisol level, (b) oral airflow, (c) estimated subglottal pressure, and (d) speaking fundamental frequency from the second sentence of the Rainbow Passage. Results Ten of the 18 participants experienced a hypothalamic-pituitary-adrenal axis response to stress as indicated by a 2.5-nmol/L increase in salivary cortisol from before the TSST to after the TSST. Those who experienced a response to stress had a significantly higher speaking fundamental frequency before and immediately after the stressor than later after the stressor. No other variable varied significantly due to the stressor. Conclusions This study suggests that the idiosyncratic and inconsistent voice changes reported in the literature may be explained by differences in stress system activation. In addition, laryngeal aerodynamic measures appear resilient to changes due to acute stress. Further work is needed to examine the influence of other stress systems and if these findings hold for dysphonic individuals.Prejudice and discrimination toward immigrants, and the consequences of these negative attitudes and behavior, are key determinants of the economic, sociocultural, and civic-political future of receiving societies and of the individuals who seek to make these societies their new home. In this article I review and organize the existing literature on the determinants and nature of prejudice and discrimination toward immigrants, summarizing what we know to date and the challenges in attributing effects to immigrant status per se. I also discuss the consequences of discrimination against immigrants for immigrants themselves, their families, and the societies in which they settle. I conclude by presenting key research questions and topics in this domain that should be at the top of the research agenda for those interested in intergroup relations in this age of mass migration.Mosaicism refers to the occurrence of two or more genomes in an individual derived from a single zygote. Germline mosaicism is a mutation that is limited to the gonads and can be transmitted to offspring. Somatic mosaicism is a postzygotic mutation that occurs in the soma, and it may occur at any developmental stage or in adult tissues. see more Mosaic variation may be classified in six ways (a) germline or somatic origin, (b) class of DNA mutation (ranging in scale from single base pairs to multiple chromosomes), (c) developmental context, (d) body location(s), (e) functional consequence (including deleterious, neutral, or advantageous), and (f) additional sources of mosaicism, including mitochondrial heteroplasmy, exogenous DNA sources such as vectors, and epigenetic changes such as imprinting and X-chromosome inactivation. Technological advances, including single-cell and other next-generation sequencing, have facilitated improved sensitivity and specificity to detect mosaicism in a variety of biological contexts.Purpose We examined indices of narrative microstructure as metrics of language development and impairment in Arabic-speaking children. We examined their age sensitivity, correlations with standardized measures, and ability to differentiate children with average language and language impairment. Method We collected story narratives from 177 children (54.2% boys) between 3.08 and 10.92 years old (M = 6.25, SD = 1.67) divided into six age bands. Each child also received standardized measures of spoken language (Receptive and Expressive Vocabulary, Sentence Imitation, and Pseudoword Repetition). Several narrative indices of microstructure were examined in each age band. Children were divided into (suspected) developmental language disorder and typical language groups using the standardized test scores and compared on the narrative indicators. Sensitivity and specificity of the narrative indicators that showed group differences were calculated. Results The measures that showed age sensitivity included subject omission error rate, number of object clitics, correct use of subject-verb agreement, and mean length of utterance in words. The developmental language disorder group scored higher on subject omission errors (Cohen's d = 0.55) and lower on correct use of subject-verb agreement (Cohen's d = 0.48) than the typical language group. The threshold for impaired performance with the highest combination of specificity and sensitivity was 35th percentile. Conclusions Several indices of narrative microstructure appear to be valid metrics for documenting language development in children acquiring Gulf Arabic. Subject omission errors and correct use of subject-verb agreement differentiate children with typical and atypical levels of language development.
The role of cholinergic neurotransmission in the hippocampus remains controversial since different studies showed either no influence or its modulatory effect on glutamatergic hippocampal synapses. It remains unclear whether septal cholinergic input can modulate plasticity of synapses formed by CA3 pyramids on CA1 neurons. The aim of the study was to clarify the role of septal input in the development of LTP in this synapse.
We recorded
in rats under urethane anesthesia focal excitatory postsynaptic potential (fEPSP) characteristics in CA1 area after stimulation of the ventral hippocampal commissure (VHC), which contains both CA3 axons innervating CA1 neurons and cholinergic axons coming from the medial septum. We performed two series of experiments in which LTP was induced by tetanization of either VHC or medial septal area (MSA). Degeneration of cholinergic neurons in MSA was induced by intraseptal injection of 192IgG-saporin.
In both experimental series, tetanization induced an increase in fEPSP amplitude which lasted for at least 40 min after tetanic stimulation, although tetanization of VHC induced a larger increase in fEPSP amplitude compared to MSA tetanization.