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The article "The rise of non-typhoidal Salmonella: an emerging global public health concern" published in Frontiers in Microbiology discusses the increasing threat of non-typhoidal Salmonella infections, primarily transmitted through contaminated food. The paper highlights the rising incidence rates of NTS infections globally, focusing on regions like Sub-Saharan Africa, Asia, the United States, and Europe. It also addresses the challenges posed by antibiotic resistance in NTS strains and the economic burden associated with healthcare expenditures and productivity losses. The article concludes with recommendations for enhancing global efforts to monitor and control NTS outbreaks, emphasizing the importance of improving food safety standards, managing antibiotic resistance, and promoting public health interventions like clean water and sanitation. [Extracted from the article] more...

The rapid increase in the production and global use of chemicals and their mixtures has raised concerns about their potential impact on human and environmental health. With advances in analytical techniques, in particular, high-resolution mass spectrometry (HRMS), thousands of compounds and transformation products with potential adverse effects can now be detected in environmental samples. However, identifying and prioritizing the toxicity drivers among these compounds remain a significant challenge. Effect-directed analysis (EDA) emerged as an important tool to address this challenge, combining biotesting, sample fractionation, and chemical analysis to unravel toxicity drivers in complex mixtures. Traditional EDA workflows are labor-intensive and time-consuming, hindering large-scale applications. The concept of high-throughput (HT) EDA has recently gained traction as a means of accelerating these workflows. Key features of HT-EDA include the combination of microfractionation and downscaled bioassays, automation of sample preparation and biotesting, and efficient data processing workflows supported by novel computational tools. In addition to microplate-based fractionation, high-performance thin-layer chromatography (HPTLC) offers an interesting alternative to HPLC in HT-EDA. This review provides an updated perspective on the state-of-the-art in HT-EDA, and novel methods/tools that can be incorporated into HT-EDA workflows. It also discusses recent studies on HT-EDA, HT bioassays, and computational prioritization tools, along with considerations regarding HPTLC. By identifying current gaps in HT-EDA and proposing new approaches to overcome them, this review aims to bring HT-EDA a step closer to monitoring applications. [ABSTRACT FROM AUTHOR] more...

Abstract Circadian regulation of autonomic tone and reflex pathways pairs physiological processes with the daily light cycle. However, the underlying mechanisms mediating these changes on autonomic neurocircuitry are only beginning to be understood. The brainstem nucleus of the solitary tract (NTS) and adjacent nuclei, including the area postrema and dorsal motor nucleus of the vagus, are key candidates for rhythmic control of some aspects of the autonomic nervous system. Recent findings have contributed to a working model of circadian regulation in the brainstem which manifests from the transcriptional, to synaptic, to circuit levels of organization. Vagal afferent neurons and the NTS possess rhythmic clock gene expression, rhythmic action potential firing, and our recent findings demonstrate rhythmic spontaneous glutamate release. In addition, postsynaptic conductances also vary across the day producing subtle changes in membrane depolarization which govern synaptic efficacy. Together these coordinated pre‐ and postsynaptic changes provide nuanced control of synaptic transmission across the day to tune the sensitivity of primary afferent input and likely govern reflex output. Further, given the important role for the brainstem in integrating cues such as feeding, cardiovascular function and temperature, it may also be an underappreciated locus in mediating the effects of such non‐photic entraining cues. This short review focuses on the neurophysiological principles that govern NTS synaptic transmission and how circadian rhythms impacted them across the day. more...

Non-targeted screening (NTS) technology has been showing significant potential in identifying contaminants of emerging concern (CECs) in water and has attracted great attention in academia in recent years. It is a method that analyzes samples without pre-selecting substances, enabling the detection and identification of unknown compounds, which is crucial for environmental health and public protection. This study uses the Bibliometrix package in R 4.4.1 and CiteSpace 6.3.R1 software to statistically analyze 589 relevant publications from the Web of Science Core Collection from 2007 to 2024. Our work concentrates on NTS of water bodies; thus, articles that only analyze water sediments without analyzing the water were not considered for inclusion. By conducting a quantitative analysis and visualizing the publication trends, countries, authors, journals, and keywords, the present study identifies research hotspots, compositions, and paradigms within this field, trying to analyze the horizontal and vertical development trends and structural evolution of the research area. The research found that the application of NTS in water pollution studies has progressed through three phases: theoretical exploration, rapid development, and steady progress. From the national level, China leads with the highest number of publications (131), followed by Germany (105), Spain (50), and the United States (39). The top three authors by publication volume are J. Hollender, Nikolaos S. Thomaidis, and Emma L. Schymanski, while the top three by citation count are J. Hollender, Emma L. Schymanski, and M. Krauss. However, international collaboration between countries and researchers still remains an area for improvement. Science of the Total Environment is the journal with the highest number of publications (81), and Environmental Science & Technology holds the highest number of citations. Research on NTS methodologies, suspect screening, and health risk assessments are hot topics in the academic community. Future research is expected to be multidisciplinary, with emerging hotspots likely to focus on including the identification of novel pollutants through NTS, toxicity assessments of biotransformed compounds, and the health impacts and mechanisms of related compounds. [ABSTRACT FROM AUTHOR] more...

Circadian regulation of autonomic tone and reflex pathways pairs physiological processes with the daily light cycle. However, the underlying mechanisms mediating these changes on autonomic neurocircuitry are only beginning to be understood. The brainstem nucleus of the solitary tract (NTS) and adjacent nuclei, including the area postrema and dorsal motor nucleus of the vagus, are key candidates for rhythmic control of some aspects of the autonomic nervous system. Recent findings have contributed to a working model of circadian regulation in the brainstem which manifests from the transcriptional, to synaptic, to circuit levels of organization. Vagal afferent neurons and the NTS possess rhythmic clock gene expression, rhythmic action potential firing, and our recent findings demonstrate rhythmic spontaneous glutamate release. In addition, postsynaptic conductances also vary across the day producing subtle changes in membrane depolarization which govern synaptic efficacy. Together these coordinated pre‐ and postsynaptic changes provide nuanced control of synaptic transmission across the day to tune the sensitivity of primary afferent input and likely govern reflex output. Further, given the important role for the brainstem in integrating cues such as feeding, cardiovascular function and temperature, it may also be an underappreciated locus in mediating the effects of such non‐photic entraining cues. This short review focuses on the neurophysiological principles that govern NTS synaptic transmission and how circadian rhythms impacted them across the day. What is the topic of this review?Synaptic encoding of brainstem circadian rhythms.What advances does it highlight?Rhythmic changes in fast neurotransmission span the time frames between transcription/translation and physiological/behavioural responses. Coordinated pre‐ and postsynaptic neurophysiological changes provide nuanced circadian control to synaptic throughput. Spontaneous vesicle release is a unique cellular mechanism for encoding circadian changes to synaptic and circuit function. [ABSTRACT FROM AUTHOR] more...

Copyright of Revista Didasc@lia: Didáctica y Educación is the property of Universitaria de Las Tunas, Centro de Estudios de Didactica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...

Neurons of the subpostremal nucleus of the solitary tract (NTS) respond to changes in extracellular glucose with alterations in membrane potential with both depolarization and hyperpolarization. From 5 mM glucose, a rapid shift to 0.5 mM glucose produces a membrane depolarization by an unknown mechanism in most neurons. However, the mechanism involved in this response needs to be known. Here, we investigated if the low glucose-induced depolarization could be mimicked by reducing ATP synthesis and possible mediators of this effect. We showed that applying the mitochondrial uncoupler CCCP (1 µM) reproduced the effects of low glucose depolarizing the membrane, generating an inward current, and decreasing membrane resistance. On the other hand, activation of AMPK did not alter these parameters. To test if low glucose and CCCP could depolarize the membrane by affecting the ionic gradient, we inhibited the electrogenic Na/K pump with 10 µM of ouabain. We observed a similar membrane depolarization but not a decrease in membrane resistance. We conclude that perfusion of neurons of the subpostremal NTS with a low glucose solution depolarizes the membrane by probably reducing intracellular ATP, but not by activating AMPK or decreasing the ionic gradient across the membrane. [ABSTRACT FROM AUTHOR] more...

There is evidence that astrocytes modulate synaptic transmission in the nucleus tractus solitarius (NTS) interacting with glutamatergic and purinergic mechanisms. Here, using in situ working heart-brainstem preparations, we evaluated the involvement of astrocyte and glutamatergic/purinergic neurotransmission in the processing of autonomic and respiratory pathways in the NTS of control and rats exposed to sustained hypoxia (SH). Baseline autonomic and respiratory activities and the responses to chemoreflex activation (KCN) were evaluated before and after microinjections of fluorocitrate (FCt, an astrocyte metabolic inhibitor), kynurenic acid, and pyridoxalphosphate-6-azophenyl-2′,4′-disulfonate (PPADS) (nonselective antagonists of glutamatergic and purinergic receptors) into the rostral aspect of the caudal commissural NTS. FCt had no effects on the baseline parameters evaluated but reduced the bradycardic response to chemoreflex activation in SH rats. FCt combined with kynurenic acid and PPADS in control rats reduced the baseline duration of expiration, which was attenuated after SH. FCt produced a large increase in PN frequency discharge in control rats, which was reduced after SH, indicating a reduction in the astrocyte modulation after SH. The data show that 1) the bradycardic component of the peripheral chemoreflex is reduced in SH rats after astrocytes inhibition, 2) the inhibition of astrocytes in the presence of double antagonists in the NTS affects the modulation of baseline duration of expiration in control but not in SH rats, and 3) the autonomic and respiratory responses to chemoreflex activation are mediated by glutamatergic and purinergic receptors in the rostral aspect of the caudal commissural NTS. NEW & NOTEWORTHY: Our findings indicate that the neurotransmission of autonomic and respiratory components of the peripheral chemoreflex in the nucleus tractus solitarius (NTS) is mediated by glutamatergic and purinergic mechanisms and reveal a selective involvement of NTS astrocytes in controlling the chemoreflex parasympathetic response in rats exposed to sustained hypoxia (SH) and the baseline duration of expiration mainly in control rats, indicating a selective role for astrocytes modulation in the NTS of control and SH rats. [ABSTRACT FROM AUTHOR] more...

Functional magnetic resonance imaging (fMRI) suggests that the hypoxic ventilatory response is facilitated by the AMP-activated protein kinase (AMPK), not at the carotid bodies, but within a subnucleus (Bregma -7.5 to -7.1 mm) of the nucleus tractus solitarius that exhibits right-sided bilateral asymmetry. Here, we map this subnucleus using cFos expression as a surrogate for neuronal activation and mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic cells by Cre expression via the tyrosine hydroxylase promoter. Comparative analysis of brainstem sections, relative to controls, revealed that AMPK-α1/α2 deletion inhibited, with right-sided bilateral asymmetry, cFos expression in and thus activation of a neuronal cluster that partially spanned three interconnected anatomical nuclei adjacent to the area postrema: SolDL (Bregma -7.44 mm to -7.48 mm), SolDM (Bregma -7.44 mm to -7.48 mm) and SubP (Bregma -7.48 mm to -7.56 mm). This approximates the volume identified by fMRI. Moreover, these nuclei are known to be in receipt of carotid body afferent inputs, and catecholaminergic neurons of SubP and SolDL innervate aspects of the ventrolateral medulla responsible for respiratory rhythmogenesis. Accordingly, AMPK-α1/α2 deletion attenuated hypoxia-evoked increases in minute ventilation (normalised to metabolism), reductions in expiration time, and increases sigh frequency, but increased apnoea frequency during hypoxia. The metabolic response to hypoxia in AMPK-α1/α2 knockout mice and the brainstem and spinal cord catecholamine levels were equivalent to controls. We conclude that within the brainstem an AMPK-dependent, hypoxia-responsive subnucleus partially spans SubP, SolDM and SolDL, namely SubSol-HIe, and is critical to coordination of active expiration, the hypoxic ventilatory response and defence against apnoea. [ABSTRACT FROM AUTHOR] more...

Chronic kidney disease (CKD) is an emerging cause for morbidity and mortality worldwide. Acute kidney injury (AKI) can transition to CKD and finally to end-stage renal disease (ESRD). Targeted treatment is still unavailable. NF-κB signaling is associated with CKD and activated by B cell activating factor (BAFF) via BAFF-R binding. In turn, renal tubular epithelial cells (TECs) are critical for the progression of fibrosis and producing BAFF. Therefore, the direct involvement of the BAFF/BAFF-R system to the pathogenesis of CKD is conceivable. We performed non-accelerated nephrotoxic serum nephritis (NTN) as the CKD model in BAFF KO (B6.129S2-Tnfsf13btm1Msc/J), BAFF-R KO (B6(Cg)-Tnfrsf13ctm1Mass/J) and wildtype (C57BL/6J) mice to analyze the BAFF/BAFF-R system in anti-glomerular basement membrane (GBM) disease using high throughput RNA sequencing. We found that BAFF signaling is directly involved in the upregulation of collagen III as BAFF ko mice showed a reduced expression. However, these effects were not mediated via BAFF-R. We identified several upregulated genes that could explain the effects of BAFF in chronic kidney injury such as Txnip, Gpx3, Igfbp7, Ccn2, Kap, Umod and Ren1. Thus, we conclude that targeted treatment with anti-BAFF drugs such as belimumab may reduce chronic kidney damage. Furthermore, upregulated genes may be useful prognostic CKD biomarkers. [ABSTRACT FROM AUTHOR] more...

Introduction: Sleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation. Methods: Rats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype I receptors (AT1R) in the NTS of rats were assessed. Results: Compared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1-7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation. Discussion: In conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation. [ABSTRACT FROM AUTHOR] more...

Neurotrophins (NTs) are four small proteins produced by both neuronal and non-neuronal cells; they include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). NTs can exert their action through both genomic and non-genomic mechanisms by interacting with specific receptors. Initial studies on NTs have identified them only as functional molecules of the nervous system. However, recent research have shown that some tissues and organs (such as the lungs, skin, and skeletal and smooth muscle) as well as some structural cells can secrete and respond to NTs. In addition, NTs perform several roles in normal and pathological conditions at different anatomical sites, in both fetal and postnatal life. During pregnancy, NTs are produced by the mother, placenta, and fetus. They play a pivotal role in the pre-implantation process and in placental and embryonic development; they are also involved in the development of the brain and respiratory system. In the postnatal period, it appears that NTs are associated with some diseases, such as sudden infant death syndrome (SIDS), asthma, congenital central hypoventilation syndrome (CCHS), and bronchopulmonary dysplasia (BPD). more...

Non-targeted screening (NTS) technology has been showing significant potential in identifying contaminants of emerging concern (CECs) in water and has attracted great attention in academia in recent years. It is a method that analyzes samples without pre-selecting substances, enabling the detection and identification of unknown compounds, which is crucial for environmental health and public protection. This study uses the Bibliometrix package in R 4.4.1 and CiteSpace 6.3.R1 software to statistically analyze 589 relevant publications from the Web of Science Core Collection from 2007 to 2024. Our work concentrates on NTS of water bodies; thus, articles that only analyze water sediments without analyzing the water were not considered for inclusion. By conducting a quantitative analysis and visualizing the publication trends, countries, authors, journals, and keywords, the present study identifies research hotspots, compositions, and paradigms within this field, trying to analyze the horizontal and vertical development trends and structural evolution of the research area. The research found that the application of NTS in water pollution studies has progressed through three phases: theoretical exploration, rapid development, and steady progress. From the national level, China leads with the highest number of publications (131), followed by Germany (105), Spain (50), and the United States (39). The top three authors by publication volume are J. Hollender, Nikolaos S. Thomaidis, and Emma L. Schymanski, while the top three by citation count are J. Hollender, Emma L. Schymanski, and M. Krauss. However, international collaboration between countries and researchers still remains an area for improvement. Science of the Total Environment is the journal with the highest number of publications (81), and Environmental Science & Technology holds the highest number of citations. Research on NTS methodologies, suspect screening, and health risk assessments are hot topics in the academic community. Future research is expected to be multidisciplinary, with emerging hotspots likely to focus on including the identification of novel pollutants through NTS, toxicity assessments of biotransformed compounds, and the health impacts and mechanisms of related compounds. more...

Non-typhoidal Salmonella associated with multidrug resistance cause invasive disease in sub-Saharan Africa. Specific lineages of serovars Typhimurium and Enteritidis have been implicated. Here we characterized the genomic diversity of 100 clinical non-typhoidal Salmonella collected from 93 patients in 2001 from the eastern, and in 2006-2018 from the western regions of The Gambia respectively. A total of 93 isolates (64 invasive, 23 gastroenteritis and six other sites) representing a single infection episode were phenotypically tested for antimicrobial susceptibility using the Kirby-Bauer disc diffusion technique. Whole genome sequencing of 100 isolates was performed using Illumina, and the reads were assembled and analysed using SPAdes. The Salmonella in Silico Typing Resource (SISTR) was used for serotyping. SNP differences among the 93 isolates were determined using Roary, and phylogenetic analysis was performed in the context of 495 African strains from the European Nucleotide Archive. Salmonella serovars Typhimurium (26/64; 30.6 %) and Enteritidis (13/64; 20.3 %) were associated with invasive disease, whilst other serovars were mainly responsible for gastroenteritis (17/23; 73.9 %). The presence of three major serovar Enteritidis clades was confirmed, including the invasive West African clade, which made up more than half (11/16; 68.8 %) of the genomes. Multidrug resistance was confined among the serovar Enteritidis West African clade. The presence of this epidemic virulent clade has potential for spread of resistance and thus important implications for systematic patient management. Surveillance and epidemiological investigations to inform control are warranted. more...

The article is devoted to the history of the functioning of the movement «Democratic Russia» and, first of all, the Nizhny Novgorod branch of this structure. The aim of the work is to identify the features of the political activity of the movement «Democratic Russia» in 1990–1992 in the Nizhny Novgorod region. The tasks of the work are related to the identification of the most significant Nizhny Novgorod representatives of the movement, as well as the causes of splits in the organization. It is revealed that the reasons for the weakening and extinction of the movement «Democratic Russia» are almost the same both in the center and at the regional level. more...

[Display omitted] • Hypoxia and A 2A receptors knockout do not affect the neuronal membrane properties. • A 2A receptors modulate the spontaneous glutamatergic currents. • Hypoxia enhances the evoked glutamatergic currents by a non-presynaptic mechanism. • A 2A receptors do not modulate the evoked glutamatergic currents under normoxia. • A 2A receptors are required to enhance evoked glutamatergic currents after hypoxia. The first synapses of the afferents of peripheral chemoreceptors are located in the Nucleus Tractus Solitarius (NTS) and there is evidence that short-term sustained hypoxia (SH – 24 h, FiO 2 0.1) facilitates glutamatergic transmission in NTS neurons of rats. Adenosine is an important neuromodulator of synaptic transmission and hypoxia contributes to increase its extracellular concentration. The A 2A receptors mediate the excitatory actions of adenosine and are active players in the modulation of neuronal networks in the NTS. Herein, we used knockout mice for A 2A receptors (A 2A KO) and electrophysiological recordings of NTS neurons were performed to evaluate the contribution of these receptors in the changes in synaptic transmission in NTS neurons of mice submitted to SH. The membrane passive properties and excitability of NTS neurons were not affected by SH and were similar between A 2A KO and wild-type mice. The overall amplitude of spontaneous glutamatergic currents in NTS neurons of A 2A KO mice was lower than in Balb/c WT mice. SH increased the amplitude of evoked glutamatergic currents of NTS neurons from WT mice by a non-presynaptic mechanism, but this enhancement was not observed in NTS neurons of A 2A KO mice. Under normoxia, the amplitude of evoked glutamatergic currents was similar between WT and A 2A KO mice. The data indicate that A 2A receptors (a) modulate spontaneous glutamatergic currents, (b) do not modulate the evoked glutamatergic transmission in the NTS neurons under control conditions, and (c) are required for the enhancement of glutamatergic transmission observed in the NTS neurons of mice submitted to SH. [ABSTRACT FROM AUTHOR] more...

The neurovascular unit (NVU) refers to the functional building unit of the brain and the retina, where neurons, glia, and microvasculature orchestrate to meet the demand of the retina's and brain's function. Neurotrophins (NTs) are structural families of secreted proteins and are known for exerting neurotrophic effects on neuronal differentiation, survival, neurite outgrowth, synaptic formation, and plasticity. NTs include several molecules, such as nerve growth factor, brain-derived neurotrophic factor, NT-3, NT-4, and their precursors. Furthermore, NTs are involved in signaling pathways such as inflammation, apoptosis, and angiogenesis in a nonneuronal cell type. Interestingly, NTs and the precursors can bind and activate the p75 neurotrophin receptor (p75NTR) at low and high affinity. Mature NTs bind their cognate tropomyosin/tyrosine-regulated kinase receptors, crucial for maintenance and neuronal development in the brain and retina axis. Activation of p75NTR results in neuronal apoptosis and cell death, while tropomysin receptor kinase upregulation contributes to differentiation and cell growth. Recent findings indicate that modulation of NTs and their receptors contribute to neurovascular dysfunction in the NVU. Several chronic metabolic and acute ischemic diseases affect the NVU, including diabetic and ischemic retinopathy for the retina, as well as stroke, acute encephalitis, and traumatic brain injury for the brain. This work aims to review the current evidence through published literature studying the impact of NTs and their receptors, including the p75NTR receptor, on the injured and healthy brain-retina axis. [ABSTRACT FROM AUTHOR] more...

Non-Typhoidal Salmonellas (NTSs) are diffused worldwide. In Italy, more than 3500 cases are notified each year, but despite this, data about salmonellosis are scarce. Our multi-center, retrospective, descriptive study selected 252 patients with positive cultures for Salmonella spp. (feces 79.8%, blood 8.7%, feces and blood 7.5%), aiming to describe the epidemiological and clinical characteristics of this population. Bacteremic infections constituted 16.3% (41/252) of patients. Extreme ages (≤12 and ≥65 years old) accounted for 79.7%, but only elder ages were strongly associated with bacteremic infections (aOR 5.78). Invasive infections had a 7-fold higher mortality rate than non-invasive disease (9.8% vs. 1.4%, p = 0.013), with an overall rate of 2.8%. The two more represented serogroups were O:4 (52.8%) and O:9 (22.2%). The O:9 serogroup was strongly associated with a higher frequency of invasive infection (aOR 2.96, 95% CI 1.17–7.63). In particular, S. napoli, an emerging serovar in Europe, accounted for 31.7% of bacteremic infections and only 9.5% of non-bacteremic ones (p < 0.001). Antibiotic microbial resistance (AMR) observed a steep increasing trend and was detected in 60.4% of cases (122/202): amoxicillin/clavulanate, ampicillin, and gentamicin were most commonly involved (26.7%, 21.8%, 14.3%, respectively), while TMP/SMX, ciprofloxacin, and ceftriaxone were <10%. Resistance was, in general, less common in the O:9 serogroup, while amikacin resistance was significantly more common. Factors associated with an MDR Salmonella acquisition were time (OR 1.37 per year more), O:4 serogroup (OR 2.67), and being a woman (OR 2.11). The most frequent symptoms were diarrhea (90.5%) and fever (81.7%). In conclusion, our study highlights a high burden of NTS infections, leading to severe or fatal outcomes in frail patients. Furthermore, AMR shows an increasing trend with a concerning high prevalence of cephalosporine resistance compared to the rest of Europe. [ABSTRACT FROM AUTHOR] more...

We categorized levels of self-reported stress, anxiety, worry, and sleep among US college and university students during the COVID-19 pandemic. We conducted an anonymous online survey between May 7 and June 21, 2020. Nearly all participants reported worry about the pandemic. Nearly half (95% CI: 43.3–51.3) reported moderate-to-severe anxiety, and 42.0% (95% CI: 38.0–45.9) reported experiencing poor sleep quality. Those with moderate-to-severe anxiety were more likely (OR: 3.3; 95% CI: 2.4–4.7) to report poor sleep quality than those with less anxiety. Moderate or extreme worry about the pandemic was associated with poor sleep quality (OR: 1.5; 95% CI: 1.1–2.1). Our survey found high levels of stress, worry, anxiety, and poor sleep among US college and university students during the early months of the pandemic. Universities should prioritize access to resources for healthy coping to help students manage anxiety and improve sleep quality as the pandemic continues. [ABSTRACT FROM AUTHOR] more...

Precise neural regulation is required for maintenance of energy homeostasis. Essential to this are the hypothalamic and brainstem nuclei which are located adjacent and supra-adjacent to the circumventricular organs. They comprise multiple distinct neuronal populations which receive inputs not only from other brain regions, but also from circulating signals such as hormones, nutrients, metabolites and postprandial signals. Hence, they are ideally placed to exert a multi-tier control over metabolism. The neuronal sub-populations present in these key metabolically relevant nuclei regulate various facets of energy balance which includes appetite/satiety control, substrate utilization by peripheral organs and glucose homeostasis. In situations of heightened energy demand or excess, they maintain energy homeostasis by restoring the balance between energy intake and expenditure. While research on the metabolic role of the central nervous system has progressed rapidly, the neural circuitry and molecular mechanisms involved in regulating distinct metabolic functions have only gained traction in the last few decades. The focus of this review is to provide an updated summary of the mechanisms by which the various neuronal subpopulations, mainly located in the hypothalamus and the brainstem, regulate key metabolic functions. [ABSTRACT FROM AUTHOR] more...

The vagus nerve conveys gastrointestinal cues to the brain to control eating behavior. In obesity, vagally mediated gut-brain signaling is disrupted. Here, we show that the cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide synthesized proportional to the food consumed in vagal afferent neurons (VANs) of chow-fed rats. CART injection into the nucleus tractus solitarii (NTS), the site of vagal afferent central termination, reduces food intake. Conversely, blocking endogenous CART action in the NTS increases food intake in chow-fed rats, and this requires intact VANs. Viral-mediated Cartpt knockdown in VANs increases weight gain and daily food intake via larger meals and faster ingestion rate. In obese rats fed a high-fat, high-sugar diet, meal-induced CART synthesis in VANs is blunted and CART antibody fails to increase food intake. However, CART injection into the NTS retains its anorexigenic effect in obese rats. Restoring disrupted VAN CART signaling in obesity could be a promising therapeutic approach. more...

The integration of new renewable power capacity into the grid constitutes an important challenge. Control issues become more complex, and the behavior of the new installations must be carefully assessed. In this sense, countries are establishing strict technical requirements when integrating new generation facilities into networks. Within this framework, given the great importance of photovoltaic solar energy as a clean electricity generation technology that is experiencing an unstoppable increase, the present paper evaluates the compliance of a real solar photovoltaic power plant with a number of technical requirements established in the new Spanish grid code. The analyses are performed by means of a photovoltaic power plant simulation model representing the actual facility. Thus, the main contribution of the present work consists of mitigating the lack of information about the performance of real experiences on the commissioning process of new renewable power plants, as well as demonstrating the usefulness of simulation models towards the modernization of grid codes. The results reveal the compliance of the renewable facility with the requirements analyzed, showing a maximum deviation of 0.47% in the case of the power–frequency requirements, and very accurate responses of the power plant under the reactive power control requisites. The results also reveal the facility fully covers the reactive power capability requirements. This paper has served not only to deepen the process of compliance with grid codes, but also to obtain approval from the Spanish transmission system operator, Red Eléctrica de España, to commission the power plant under consideration, this being a contribution of special interest to industry. more...

Background: Previous studies have shown a significant response to acute transcutaneous vagus nerve stimulation (taVNS) in regions of the vagus nerve pathway, including the nucleus tractus solitarius (NTS), raphe nucleus (RN) and locus coeruleus (LC) in both healthy human participants and migraine patients. This study aims to investigate the modulation effect of repeated taVNS on these brainstem regions by applying seed-based resting-state functional connectivity (rsFC) analysis. Methods: 70 patients with migraine were recruited and randomized to receive real or sham taVNS treatments for 4 weeks. fMRI data were collected from each participant before and after 4 weeks of treatment. The rsFC analyses were performed using NTS, RN and LC as the seeds. Results: 59 patients (real group: n = 33; sham group: n = 29) completed two fMRI scan sessions. Compared to sham taVNS, real taVNS was associated with a significant reduction in the number of migraine attack days (p = 0.024) and headache pain intensity (p = 0.008). The rsFC analysis showed repeated taVNS modulated the functional connectivity between the brain stem regions of the vagus nerve pathway and brain regions associated with the limbic system (bilateral hippocampus), pain processing and modulation (bilateral postcentral gyrus, thalamus, and mPFC), and basal ganglia (putamen/caudate). In addition, the rsFC change between the RN and putamen was significantly associated with the reduction in the number of migraine days. Conclusion: Our findings suggest that taVNS can significantly modulate the vagus nerve central pathway, which may contribute to the potential treatment effects of taVNS for migraine. [ABSTRACT FROM AUTHOR] more...

This research provides new evidence about the relationship between online and in-store shopping. This article uses data for England from the UK National Travel Survey (NTS) which covers a full week and also provides information about grocery shopping practices (online and in-store). We examine the effects of online purchases on the grocery shopping practices of working couples and their related CO2 emissions. Our analysis reveals a substitution effect between in-store trips and online shopping combined with home delivery and a 37% reduction in household CO2 emissions for grocery shopping. It appears that buying groceries online combined with a home delivery system makes it possible to significantly cut emissions for grocery shopping trips, or at least to offset the effects of in-store trips by the households with the highest emissions. No rebound effect is observed for other trip motives, i.e. it is not because people make fewer trips for in-store grocery shopping that they make more trips for leisure, personal or other motives. [ABSTRACT FROM AUTHOR] more...

ABSTRACT: Objectives: Antimicrobial-resistant livestock-associated Salmonella enterica serovar Agona infection poses a significant public health threat worldwide. The present study aimed to identify antibiotic resistance genes in livestock-associated S. Agona strains isolated from chickens and associated food products (meat and eggs) in Pakistan via whole-genome sequencing. Methods: The genomic DNAs of S. Agona strains (n=25) were sequenced using an Illumina MiSeq platform. The generated reads were trimmed and de novo assembled using CLC Genomics Workbench v.7. The draft genomes were annotated using the National Centre for Biotechnology Information (NCBI) Prokaryotic Genome Annotation Pipeline and were characterised by multilocus sequence typing (MLST). The antimicrobial-resistance genes (acquired and chromosomal mutations), extrachromosomal plasmids and Salmonella pathogenicity islands were predicted using ResFinder and CARD, PlasmidFinder and SPIFinder, respectively. Results: The genome size of S. Agona ranges from 4.9 to 5.1 Mb with 52.1% GC contents. The strains belong to ST13 and harbour several antibiotic-resistance genes, including aac (6′)-Iaa, aadA1, aadA2, bla OXA-10, qnrS1, cmlA, floR, tet(A), dfrA12 and point mutations in gyrB, gyrA, ParC conferring antibiotic resistance to fluoroquinolones. The strains also contain several plasmids and Salmonella pathogenicity islands. Conclusion: This study reports draft genomes of multidrug-resistant S. Agona from Pakistan isolated from chickens and associated food products. The data may help with understanding the antimicrobial resistance mechanisms and transmission dynamics of this serovar in poultry and associated food products and their possible transmission to humans. more...

The rhythmicity of breath is vital for normal physiology. Even so, breathing is enriched with multifunctionality. External signals constantly change breathing, stopping it when under water or deepening it during exertion. Internal cues utilize breath to express emotions such as sighs of frustration and yawns of boredom. Breathing harmonizes with other actions that use our mouth and throat, including speech, chewing, and swallowing. In addition, our perception of breathing intensity can dictate how we feel, such as during the slow breathing of calming meditation and anxiety-inducing hyperventilation. Heartbeat originates from a peripheral pacemaker in the heart, but the automation of breathing arises from neural clusters within the brainstem, enabling interaction with other brain areas and thus multifunctionality. Here, we document how the recent transformation of cellular and molecular tools has contributed to our appreciation of the diversity of neuronal types in the breathing control circuit and how they confer the multifunctionality of breathing. [ABSTRACT FROM AUTHOR] more...

Introduction: Non-typhoidal Salmonella (NTS), are frequently found in sewage and are one of the main causes of diarrhea in developed and developing countries due to poor sanitation conditions. In addition, NTS can potentially act as reservoirs and vehicles for the transmission of antimicrobial resistance (AMR), which can be facilitated by the discharge of sewage effluents into environmental matrices. This study aimed to analyze a NTS Brazilian collection, focusing on their antimicrobial susceptibility profile and the presence of clinically relevant AMRencoding genes. Methodology: Forty-five non-clonal NTS strains from serotypes Salmonella enteritidis (n = 6), Salmonella enterica serovar 1,4,[5],12:i:- (S. 1,4,[5],12:i:-) (n = 25), Salmonella cerro (n = 7), Salmonella typhimurium (n = 3) and Salmonella braenderup (n = 4) were studied. Antimicrobial susceptibility testing was done using the Clinical and Laboratory Standards Institute guidelines (2017) and genes encoding resistance to beta-lactams, fluoroquinolones and aminoglycosides were identified by polymerase chain reaction and sequencing. Results: Resistance to ß-lactams, fluoroquinolones, tetracyclines and aminoglycosides was frequent. The highest rates were observed for nalidixic acid (89.0%), followed by tetracycline (67.0%), ampicillin (67.0%), amoxicillin + clavulanic acid (64.0%); ciprofloxacin (47.0%) and streptomycin (42.0%). The AMR-encoding genes detected were qnrB, oqxAB, blaCTX-M and rmtA. Conclusions: Raw sewage has been considered a valuable tool to evaluate epidemiological population patterns and this study supports the view that NTS with pathogenic potential and resistance to antimicrobials are circulating in the studied region. This is worrisome due to the dissemination of these microorganisms throughout the environment. [ABSTRACT FROM AUTHOR] more...

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, heightened chemosensory discharges of the carotid body (CB), which contributes to potentiate the ventilatory hypoxic response and elicits hypertension. We aimed to determine 1 ) whether the persistence of cardiorespiratory alterations found in long-term CIH depends on the inputs from the CB and 2 ) in what extension the activation of glial cells and neuroinflammation in the caudal region of the nucleus of the solitary tract (NTS) require functional CB chemosensory activity. To evaluate these hypotheses, we exposed male mice to CIH for 60 days. At 50 days of CIH, CBs were denervated and animals were kept in CIH for 10 additional days. At the end of the experiments, we measured arterial blood pressure, breathing regularity, and hypoxic ventilatory response (HVR) and assessed astrocyte and microglia cell activation. Compared to sham treatment, CIH induced hypertension [mean arterial blood pressure (MABP): 83.47 ± 1.39 vs. 95.00 ± 2.18 mmHg] and disordered breathing [irregularity score (IS): 7.77 ± 0.49 vs. 12.56 ± 1.66], increased the HVR [1.69 ± 0.17 vs. 4.31 ± 0.87 change in minute ventilation (ΔV̇e)/min], and produced an early transient activation of astrocytes followed by a late and persistent activation of microglia in the NTS. In addition, CIH increased IL-1β, IL-6, and TNF-α levels in the NTS. Bilateral CB denervation after 50 days of CIH results in the restoration of normal glial cell activation in the NTS, lower levels of IL-6 and TNF-α, and reductions in arterial blood pressure (83.47 ± 1.38 mmHg) and HVR (1.63 ± 0.43 ΔV̇e/min). The present results suggest that CB inputs to the NTS during long-term CIH contribute to maintain the cardiorespiratory alterations and the formation of a neuroinflammatory niche at the NTS by modifying glial cell activity. NEW & NOTEWORTHY Chronic intermittent hypoxia (CIH), a feature of obstructive sleep apnea, causes cardiorespiratory alterations (i.e. hypertension) linked to oxidative stress, inflammation, and sympathoexcitation. In the present study, we highlight the role of enhanced carotid body (CB) chemosensory afferent discharges to the nucleus of the solitary tract (NTS) in long-term CIH-induced cardiorespiratory disorders. Indeed, we provide evidence that supports the notion that increased CB afferent activity contributes to persistent CIH-induced hypertension, likely triggering neuroinflammation in the NTS. more...

Background: Despite the known association between microorganisms and development of inflammatory bowel disease (IBD), the role of nontyphoidal Salmonella (NTS) in IBD is not adequately addressed. We aimed at elucidating the relationship between NTS infection and the risk of IBD., Methods: Based on the National Health Insurance Research Database in Taiwan, this retrospective cohort study enrolled patients with NTS infection (exposure group; n = 4651) and those without NTS infection (comparator group; n = 4651) who were propensity score matched (1:1) by demographic data, medications, comorbidities, and index date. All patients were followed until IBD onset, individual mortality, or December 31, 2018. Cox proportional hazards regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs). Sensitivity analyses were used for cross-validation., Results: The NTS group demonstrated an increased risk of IBD compared with the non-NTS groups (adjusted hazard ratio [aHR], 2.12; 95% CI, 1.62-2.78) with a higher risk of developing ulcerative colitis in the former (aHR, 2.27; 95% CI, 1.69-3.04). Nevertheless, the small sample size may contribute to lack of significant difference in Crohn's disease. Consistent findings were noted after excluding IBD diagnosed within 6 months of NTS infection (aHR, 2.28; 95% CI, 1.71-3.03), excluding those with enteritis/colitis before index date (aHR, 1.85; 95% CI, 1.28-2.68), excluding those using antibiotics for 1 month in the year before IBD onset (aHR, 1.81; 95% CI, 1.34-2.45), inverse probability of treatment weighting (aHR, 1.64; 95% CI, 1.31-2.04), and inclusion of individuals regardless of age (n = 10 431; aHR, 1.83; 95% CI, 1.53-2.19)., Conclusions: Patients with NTS were associated with an increased risk of developing IBD, especially ulcerative colitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) more...

GLP-1 receptor agonists (GLP1RAs) effectively reduce feeding to treat obesity, although nausea and other aversive side effects of these drugs can limit their use. Brainstem circuits that promote satiation and that mediate the physiologic control of body weight can be distinguished from those that cause aversion. It remains unclear whether brainstem Glp1r neurons contribute to the normal regulation of energy balance and whether GLP1RAs control appetite via circuits distinct from those that mediate aversive responses, however. Hence, we defined roles for AP and NTS Glp1r -expressing neurons (AP Glp1r and NTS Glp1r neurons, respectively) in the physiologic control of body weight, the GLP1RA-dependent suppression of food intake, and the GLP1RA-mediated stimulation of aversive responses. While silencing non-aversive NTS Glp1r neurons interfered with the physiologic restraint of feeding and body weight, restoring NTS Glp1r neuron Glp1r expression on an otherwise Glp1r -null background failed to enable long-term body weight suppression by GLP1RAs. In contrast, selective Glp1r expression in AP Glp1r neurons restored both aversive responses and long-term body weight suppression by GLP1RAs. Thus, while non-aversive NTS Glp1r neurons control physiologic feeding, aversive AP Glp1r neurons mediate both the anorectic and weight loss effects of GLP1RAs, dictating the functional inseparability of these pharmacologic GLP1RA responses at a circuit level., Competing Interests: Conflict of Interests Statement: MGM receives research support from AstraZeneca, Eli Lilly, and Novo Nordisk and MGM has served as a paid consultant for Merck. RJS has received research support from Novo Nordisk, Fractyl, Astra Zeneca, Congruence Therapeutics, Eli Lilly, Bullfrog AI, Glycsend Therapeutics and Amgen. RJS has served as a paid consultant for Novo Nordisk, Eli Lilly, CinRx, Fractyl, Structure Therapeutics, Crinetics and Congruence Therapeutics. RJS has equity in Calibrate, Rewind and Levator Therapeutics. Anna Secher and Kirsten Raun work for and hold equity in Novo Nordisk. The authors declare that they have no other conflicts of interest. more...

Non-Typhoidal Salmonellas (NTSs) are diffused worldwide. In Italy, more than 3500 cases are notified each year, but despite this, data about salmonellosis are scarce. Our multi-center, retrospective, descriptive study selected 252 patients with positive cultures for Salmonella spp. (feces 79.8%, blood 8.7%, feces and blood 7.5%), aiming to describe the epidemiological and clinical characteristics of this population. Bacteremic infections constituted 16.3% (41/252) of patients. Extreme ages (≤12 and ≥65 years old) accounted for 79.7%, but only elder ages were strongly associated with bacteremic infections (aOR 5.78). Invasive infections had a 7-fold higher mortality rate than non-invasive disease (9.8% vs. 1.4%, p = 0.013), with an overall rate of 2.8%. The two more represented serogroups were O:4 (52.8%) and O:9 (22.2%). The O:9 serogroup was strongly associated with a higher frequency of invasive infection (aOR 2.96, 95% CI 1.17–7.63). In particular, S. napoli, an emerging serovar in Europe, accounted for 31.7% of bacteremic infections and only 9.5% of non-bacteremic ones (p < 0.001). Antibiotic microbial resistance (AMR) observed a steep increasing trend and was detected in 60.4% of cases (122/202): amoxicillin/clavulanate, ampicillin, and gentamicin were most commonly involved (26.7%, 21.8%, 14.3%, respectively), while TMP/SMX, ciprofloxacin, and ceftriaxone were more...

Nesfatin-1, the cleavage product of nucleobindin-2, is an anorexigenic peptide and major regulator of energy homeostasis. Beyond reducing food intake and increasing energy expenditure, it is also involved in regulating the stress response. Interaction of nucleobindin-2/nesfatin-1 and glucose homeostasis has been observed and recent findings suggest a link between the action of the antidiabetic drug metformin and the nesfatinergic system. Hence, this study aimed to clarify the role of nucleobindin-2/nesfatin-1 in the paraventricular nucleus of the hypothalamus in energy homeostasis as well as its involvement in stress- and metformin-mediated changes in energy expenditure. Knockdown of nucleobindin-2/nesfatin-1 in male Wistar rats led to significantly increased food intake, body weight, and reduced energy expenditure compared to controls. Nucleobindin-2/nesfatin-1 knockdown animals developed an obese-like phenotype represented by significantly increased fat mass and overall increase of circulating lipids. Concomitantly, expression of nucleobindin-2 and melanocortin receptor type 3 and 4 mRNA in the paraventricular nucleus was decreased indicating successful knockdown and impairment at the level of the melanocortin system. Additionally, stress induced activation of interscapular brown adipose tissue was significantly decreased in nucleobindin-2/nesfatin-1 knockdown animals and accompanied by lower adrenal weight. Finally, intracerebroventricular administration of metformin significantly increased energy expenditure in controls and this effect was absent in nucleobindin-2/nesfatin-1 knockdown animals. Overall, we clarified the crucial role of nucleobindin-2/nesfatin-1 in the paraventricular nucleus of the hypothalamus in the regulation of energy homeostasis. The nesfatinergic system was further identified as important mediator in stress- and metformin-induced thermogenesis. [ABSTRACT FROM AUTHOR] more...

Objective: To investigate the relationship between neurotensin (NTS), sphingosine-1-phosphate transporter 2 (SPNS2) and Mortalin expression and epithelial-mesenchymal transition (EMT) markers, clinicopathological features and prognosis in hepatocellular carcinoma (HCC). Methods: 90 patients with HCC were selected from Cangshan Hospital of the 900 Hospital of Joint Logistics Support Force from January 2010 to January 2017 were selected, The NTS, SPNS2, Mortalin and EMT markers N-cadherin (N-Cad) and E-cadherin (E-Cad) expression in cancer tissues and corresponding paracancerous tissues were detected by immunohistochemistry. The relationship between the NTS, SPNS2 and Mortalin expression and EMT markers, clinicopathological features and prognosis in patients with HCC were analyzed. Results: The positive expression rates of NTS, SPNS2, Mortalin and N-Cad in HCC cancer tissues were higher than those in paracancerous tissues, and the positive expression rate of E-Cad was lower than that in paracancerous tissues (P<0.05). Pearson correlation analysis showed that the NTS, SPNS2 and Mortalin expression levels in HCC cancer tissues were positively correlated with the N-Cad expression level, and negatively correlated with the E-Cad expression level (P<0.05). The NTS, SPNS2 and Mortalin expressions in HCC cancer tissues were related to Child-Pugh grade, vascular invasion, Barcelona clinical liver cancer (BCLC) stage, lymph node metastasis and distant metastasis (P<0.05). The 5-year overall survival rate of 90 patients with HCC was 48.89% (44 / 90). Kaplan-Meier survival curve analysis showed that the overall survival rate of NTS, SPNS2 and Mortalin positive groups was lower than that of NTS, SPNS2 and Mortalin negative groups respectively (P<0.05). Conclusion: The up-regulated of NTS, SPNS2 and Mortalin expression in HCC cancer tissues, which is related to EMT, Child-Pugh grade, vascular invasion, BCLC stage, lymph node metastasis, distant metastasis and prognosis. It can be used as an auxiliary evaluation index for the condition and prognosis of HCC. [ABSTRACT FROM AUTHOR] more...

Rett syndrome (RTT) is a devastating neurodevelopmental disorder caused by loss-of-function mutations in the X-linked methyl-CpG binding protein 2 (Mecp2) gene. GABAergic dysfunction has been implicated contributing to the respiratory dysfunction, one major clinical feature of RTT. The nucleus tractus solitarius (NTS) is the first central site integrating respiratory sensory information that can change the nature of the reflex output. We hypothesized that deficiency in Mecp2 gene reduces GABAergic neurotransmission in the NTS. Using whole-cell patch-clamp recordings in NTS slices, we measured spontaneous inhibitory postsynaptic currents (sIPSCs), miniature IPSCs (mIPSCs), NTS-evoked IPSCs (eIPSCs), and GABAA receptor (GABAA-R) agonist-induced responses. Compared to those from wild-type mice, NTS neurons from Mecp2-null mice had significantly (p more...

Apoptosis has been implicated in compensatory proliferation signaling (CPS), whereby dying cells induce proliferation in neighboring cells as a means to restore homeostasis. The nature of signaling between apoptotic cells and their neighboring cells remains largely unknown. Here we show that a fraction of apoptotic cells produce and release CrkI-containing microvesicles (distinct from exosomes and apoptotic bodies), which induce proliferation in neighboring cells upon contact. We provide visual evidence of CPS by videomicroscopy. We show that purified vesicles in vitro and in vivo are sufficient to stimulate proliferation in other cells. Our data demonstrate that CrkI inactivation by ExoT bacterial toxin or by mutagenesis blocks vesicle formation in apoptotic cells and inhibits CPS, thus uncoupling apoptosis from CPS. We further show that c-Jun amino-terminal kinase (JNK) plays a pivotal role in mediating vesicle-induced CPS in recipient cells. CPS could have important ramifications in diseases that involve apoptotic cell death. more...