The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo.

Naive T cells undergo metabolic reprogramming to support the increased energetic and biosynthetic demands of effector T cell function. However, how nutrient availability influences T cell metabolism and function remains poorly understood. Here we report plasticity in effector T cell metabolism in response to changing nutrient availability. Activated T cells were found to possess a glucose-sensitive metabolic checkpoint controlled by the energy sensor AMP-activated protein kinase (AMPK) that regulated mRNA translation and glutamine-dependent mitochondrial metabolism to maintain T cell bioenergetics and viability. T cells lacking AMPKα1 displayed reduced mitochondrial bioenergetics and cellular ATP in response to glucose limitation in vitro or pathogenic challenge in vivo. Finally, we demonstrated that AMPKα1 is essential for T helper 1 (Th1) and Th17 cell development and primary T cell responses to viral and bacterial infections in vivo. Our data highlight AMPK-dependent regulation of metabolic homeostasis as a key regulator of T cell-mediated adaptive immunity.

Virtual Reality Breathing Interventions for Mental Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Breathing exercises have been shown to reduce mental health problems among clinical and non-clinical populations. Although virtual reality (VR) breathing interventions are assumed to have potential benefits, it remains unclear whether VR breathing interventions are more effective at improving mental health than non-VR breathing interventions. We conducted a systematic literature search in six electronic databases (Web of Science, PsycINFO, Embase, Cochrane Central Register of Controlled Trials, Scopus, and PubMed) from inception to 30th September, 2022. We included randomized controlled trials in adults evaluating effects of VR compared to non-VR breathing interventions on primary outcomes of mental health (stress, anxiety and mood), and secondary outcomes of physiological stress measures (e.g., heart rate (HR), heart rate variability (HRV)). Within these selected studies, we explored differences in likeability and future use between VR and non-VR breathing interventions. 2.848 records were identified of which 65 full-text articles were assessed. Six RCTs were included, of which five were suitable for meta-analyses. Comparing VR to non-VR breathing interventions, there were no significant differences in overall mental health, stress, anxiety or mood, nor in HR or HRV. There was no evidence that participants liked VR breathing interventions more than non-VR, nor would use them more in the future. These results suggest that there is no evidence that VR breathing interventions are more effective than non-VR in improving mental health outcomes, HR, HRV. Further research is required to determine whether there may be advantages to longer-term VR-implementation and practice, and explore possible mechanisms.

Magnesium-sensitive upstream ORF controls PRL phosphatase expression to mediate energy metabolism.

Phosphatases of regenerating liver (PRL-1, PRL-2, and PRL-3, also known as PTP4A1, PTP4A2, and PTP4A3) control magnesium homeostasis through an association with the CNNM magnesium transport regulators. Although high PRL levels have been linked to cancer progression, regulation of their expression is poorly understood. Here we show that modulating intracellular magnesium levels correlates with a rapid change of PRL expression by a mechanism involving its 5'UTR mRNA region. Mutations or CRISPR-Cas9 targeting of the conserved upstream ORF present in the mRNA leader derepress PRL protein synthesis and attenuate the translational response to magnesium levels. Mechanistically, magnesium depletion reduces intracellular ATP but up-regulates PRL protein expression via activation of the AMPK/mTORC2 pathway, which controls cellular energy status. Hence, altered PRL-2 expression leads to metabolic reprogramming of the cells. These findings uncover a magnesium-sensitive mechanism controlling PRL expression, which plays a role in cellular bioenergetics.

Primary Care Population Management for COVID-19 Patients.

BACKGROUND: Most patients infected with SARS-CoV-2 have mild to moderate symptoms manageable at home; however, up to 20% develop severe illness requiring additional support. Primary care practices performing population management can use these tools to remotely assess and manage COVID-19 patients and identify those needing additional medical support before becoming critically ill. AIM: We developed an innovative population management approach for managing COVID-19 patients remotely. SETTING: Development, implementation, and evaluation took place in April 2020 within a large urban academic medical center primary care practice. PARTICIPANTS: Our panel consists of 40,000 patients. By April 27, 2020, 305 had tested positive for SARS-CoV-2 by RT-qPCR. Outreach was performed by teams of doctors, nurse practitioners, physician assistants, and nurses. PROGRAM DESCRIPTION: Our innovation includes an algorithm, an EMR component, and a twice daily population report for managing COVID-19 patients remotely. PROGRAM EVALUATION: Of the 305 patients with COVID-19 in our practice at time of submission, 196 had returned to baseline; 54 were admitted to hospitals, six of these died, and 40 were discharged. DISCUSSION: Our population management strategy helped us optimize at-home care for our COVID-19 patients and enabled us to identify those who require inpatient medical care in a timely fashion.

The effect of respiratory viral assay panel on antibiotic prescription patterns at discharge in adults admitted with mild to moderate acute exacerbation of COPD: a retrospective before- after study.

BACKGROUND: Despite well-defined criteria for use of antibiotics in patients presenting with mild to moderate Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD), their overuse is widespread. We hypothesized that following implementation of a molecular multiplex respiratory viral panel (RVP), AECOPD patients with viral infections would be more easily identified, limiting antibiotic use in this population. The primary objective of our study was to investigate if availability of the RVP decreased antibiotic prescription at discharge among patients with AECOPD. METHODS: This is a single center, retrospective, before (pre-RVP) - after (post-RVP) study of patients admitted to a tertiary medical center from January 2013 to March 2016. The primary outcome was antibiotic prescription at discharge. Groups were compared using univariable and multivariable logistic-regression. RESULTS: A total of 232 patient-episodes were identified, 133 following RVP introduction. Mean age was 68.1 (pre-RVP) and 68.3 (post-RVP) years respectively (p = 0.88). Patients in pre-RVP group were similar to the post-RVP group with respect to gender (p = 0.54), proportion of patients with BMI < 21(p = 0.23), positive smoking status (p = 0.19) and diagnoses of obstructive sleep apnea (OSA, p = 0.16). We found a significant reduction in antibiotic prescription rate at discharge in patients admitted with AECOPD after introduction of the respiratory viral assay (pre-RVP 77.8% vs. post-RVP 63.2%, p = 0.01). In adjusted analyses, patients in the pre-RVP group [OR 2.11 (CI: 1.13-3.96), p = 0.019] with positive gram stain in sputum [OR 4.02 (CI: 1.61-10.06), p = 0.003] had the highest odds of antibiotic prescription at discharge. CONCLUSIONS: In patients presenting with mild to moderate Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD), utilization of a comprehensive respiratory viral panel can significantly decrease the rate of antibiotic prescription at discharge.

eIF4AII is dispensable for miRNA-mediated gene silencing.

MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression through partial complementary base-pairing to the 3' untranslated region (UTR) of target mRNAs. Inhibition of translation initiation has been identified as an early event of miRNA-mediated gene repression, but the underlying mechanistic details of this process are not well understood. Recently, eukaryotic initiation factor (eIF) 4AII was identified as a critical modulator of miRNA activity with depletion of this factor alleviating miRNA-mediated gene repression. Using the CRISPR/Cas9-editing system, we generated a novel cell line in which expression of eIF4AII was eliminated. The absence of eIF4AII does not affect cell viability, proliferation, or global mRNA translation. Importantly, we show that eIF4AII is dispensable for miRNA-mediated gene silencing.

[Responsible ownership of dogs and human health in neighborhoods of San Carlos de Bariloche, Argentina]. / Tenencia responsable de perros y salud humana en barrios de San Carlos de Bariloche, Argentina.

Human relationship with dogs associates with numerous and varied benefits on human health; however, it also presents significant risks. The goal of this study was to describe demographic parameters and characteristics of dog ownership with possible implications on human health and to evaluate the prevalence of dog bites and traffic accidents due to dogs. Interviews were conducted in the neighborhoods of Nuestras Malvinas and Nahuel Hue in San Carlos de Bariloche. The percentage of homes with at least one dog, the average number of dogs per home, the prevalence of dog bites and traffic accidents due to dogs and the general awareness of the population on dog transmitted zoonoses were estimated. Regarding ownership characteristics, the degree of sterilization, vaccination and parasite control and the percentage of dogs allowed to roam freely in public places were evaluated. A total of 141 interviews were conducted; 87% of the households had at least one dog, with an average of 2.2 dogs. In 26% of the households someone had suffered a traffic accident caused by dogs and in 41% someone had been bitten. Antiparasite treatment was administered to 83% of the dogs in the last 12 months, on average 1.4 times (recommended 6 times), 51% were sterilized, 55% were allowed to roam freely. This study shows a disturbing situation regarding the canine population of the evaluated neighborhoods. The number of dogs allowed to roam freely and the low level of parasite control and sterilization provide suitable conditions for the spread of zoonoses.

Evidence from central Mexico supporting the Younger Dryas extraterrestrial impact hypothesis.

We report the discovery in Lake Cuitzeo in central Mexico of a black, carbon-rich, lacustrine layer, containing nanodiamonds, microspherules, and other unusual materials that date to the early Younger Dryas and are interpreted to result from an extraterrestrial impact. These proxies were found in a 27-m-long core as part of an interdisciplinary effort to extract a paleoclimate record back through the previous interglacial. Our attention focused early on an anomalous, 10-cm-thick, carbon-rich layer at a depth of 2.8 m that dates to 12.9 ka and coincides with a suite of anomalous coeval environmental and biotic changes independently recognized in other regional lake sequences. Collectively, these changes have produced the most distinctive boundary layer in the late Quaternary record. This layer contains a diverse, abundant assemblage of impact-related markers, including nanodiamonds, carbon spherules, and magnetic spherules with rapid melting/quenching textures, all reaching synchronous peaks immediately beneath a layer containing the largest peak of charcoal in the core. Analyses by multiple methods demonstrate the presence of three allotropes of nanodiamond: n-diamond, i-carbon, and hexagonal nanodiamond (lonsdaleite), in order of estimated relative abundance. This nanodiamond-rich layer is consistent with the Younger Dryas boundary layer found at numerous sites across North America, Greenland, and Western Europe. We have examined multiple hypotheses to account for these observations and find the evidence cannot be explained by any known terrestrial mechanism. It is, however, consistent with the Younger Dryas boundary impact hypothesis postulating a major extraterrestrial impact involving multiple airburst(s) and and/or ground impact(s) at 12.9 ka.

A cellular response linking eIF4AI activity to eIF4AII transcription.

The recruitment of ribosomes to eukaryotic cellular mRNAs requires the activity of two prototypic RNA helicases, eukaryotic initiation factor (eIF) 4AI and eIF4AII. The eIF4A isoforms are highly conserved, are thought to be functionally interchangeable, and are directed to the 5' m(7)GpppN cap structure of mRNAs during translation initiation by virtue of their assembly into eIF4F, a heterotrimeric complex that also harbors the eIF4E cap binding protein and eIF4G scaffolding unit. During the course of RNA interference experiments aimed at investigating the respective roles of eIF4AI and eIF4AII in translation, we uncovered a cellular response pathway whereby suppression of eIF4AI increases transcription of the eIF4AII gene, leading to elevated eIF4AII mRNA and protein levels. Inhibition of eIF4AI suppresses protein synthesis, and although eIF4AII protein levels increase above and beyond what should be sufficient to compensate for the decrease in eIF4AI levels, there is no corresponding rescue of translation or of the block on cellular proliferation that occurs upon eIF4AI suppression. These results were phenocopied using the small molecule eIF4A inhibitor hippuristanol. Taken together, our results indicate that eIF4AI and eIF4AII expression appear linked and that the two protein isoforms exhibit functional differences.

The communities of helminth parasites of Heterandria bimaculata (Teleostei: Poeciliidae) from the upper Río La Antigua basin, east-central Mexico show a predictable structure.

We investigated a basic generalization in parasite community ecology stating that stochastic processes played a major part in determining the composition of helminth communities of freshwater fish, or on the contrary, if these communities are predictable, diverse and structured species assemblages. We determined the species pool of helminth parasites of a tropical freshwater fish Heterandria bimaculata in its heartland, the upper Río La Antigua basin in east-central Mexico. Approaching our data from the metapopulation standpoint we studied the spatial patterns, and examined the variation in composition and richness of the component communities across different locations. We tested the prediction that helminth species may be recognized as common or rare; and also two hypotheses anticipating depauperate communities and decay of similarity between component communities with increasing distance. We found these communities composed by a highly structured and predictable set of specialist autogenic helminth species that are constant and abundant, dominating all components throughout space. The prediction that it is possible to recognize common and rare species was met. Richer than expected communities were found, as well as highly homogeneous component communities, where neighbouring components were more similar than distant ones. We speculated that the processes shaping the development of these component communities include stable, predictable habitats through time, allowing for a slow gradual dispersion process limited by host and parasite species capabilities. Our study suggests that metapopulation theory can assist in the prediction of community composition and in the understanding of spatial and temporal community variability.

[Leaf litter decomposition in six Cloud Forest streams of the upper La Antigua watershed, Veracruz, Mexico]. / Descomposición de hojarasca en seis arroyos de Bosque Mesófilo de Montaña en la cuenca alta del río La Antigua, Veracruz, México.

Leaf litter decomposition is an important stream ecosystem process. To understand factors controlling leaf decomposition in cloud forest in Mexico, we incubated leaf packs in different streams along a land use cover gradient for 35 days during the dry and wet seasons. We assessed relations between leaf decomposition rates (k), stream physicochemistry, and macroinvertebrates colonizing leaf packs. Physicochemical parameters showed a clear seasonal difference at all study streams. Leaves were colonized by collector-gatherer insects, followed by shredders. Assessment of factors related to k indicated that only forest cover was negatively related to leaf decomposition rates. Thus stream physicochemistry and seasonality had no impact on decomposition rates. We concluded that leaf litter decomposition at our study streams is a stable process over the year. However, it is possible that this stability is the result of factors regulating decomposition during the different seasons and streams.

The Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes (PRIMERO): Design and Baseline Characteristics for a Birth Cohort Study of Early-life Viral Respiratory Illnesses and Airway Dysfunction in Puerto Rican Children.

Epidemiologic studies demonstrate an association between early-life respiratory illnesses (RIs) and the development of childhood asthma. However, it remains uncertain whether these children are predisposed to both conditions or if early-life RIs induce alterations in airway function, immune responses, or other human biology that contribute to the development of asthma. Puerto Rican children experience a disproportionate burden of early-life RIs and asthma, making them an important population for investigating this complex interplay. PRIMERO, the Puerto Rican Infant Metagenomics and Epidemiologic Study of Respiratory Outcomes , recruited pregnant women and their newborns to investigate how the airways develop in early life among infants exposed to different viral RIs, and will thus provide a critical understanding of childhood asthma development. As the first asthma birth cohort in Puerto Rico, PRIMERO will prospectively follow 2,100 term healthy infants. Collected samples include post-term maternal peripheral blood, infant cord blood, the child's peripheral blood at the year two visit, and the child's nasal airway epithelium, collected using minimally invasive nasal swabs, at birth, during RIs over the first two years of life, and at annual healthy visits until age five. Herein, we describe the study's design, population, recruitment strategy, study visits and procedures, and primary outcomes.

Aspirin treatment failure and the risk of recurrent stroke and death among patients with ischemic stroke.

BACKGROUND: The prognostic value of occurrence of ischemic stroke in a patient despite aspirin treatment (aspirin treatment failure) is not known. Our objective was to determine if aspirin treatment failure predicts recurrent ischemic stroke and/or death. METHODS: We performed a post-hoc analysis of data from the National Institute of Neurological Disorders and Stroke (NINDS) intravenous recombinant tissue plasminogen activator (rt-PA) trial and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). Multivariate analysis was used to calculate the odds ratio (OR) of recurrent stroke and recurrent stroke or death for aspirin treatment failure patients for the duration of available follow-up (3 months for TOAST patients; 12 months for NINDS rt-PA trial patients). RESULTS: The rate of aspirin treatment failure was 40% and 35% among 1275 patients and 624 patients recruited in the TOAST and NINDS rt-PA trials, respectively. The risk of stroke and death at 3 months and 1 year was not higher among patients classified as aspirin treatment failures among the TOAST (OR 1.1; 95% confidence interval [CI] 0.8-1.6; P = .7) or NINDS rt-PA trial patients (OR 0.8; 95% CI 0.6-1.3; P = .4), respectively. In subgroup analysis, aspirin treatment failure was not found to be associated with recurrent stroke or with the combined endpoint of stroke and death among categories defined by etiologic subtype, including those with large artery atherosclerosis. CONCLUSIONS: In a post-hoc analysis of 2 randomized ischemic stroke trials, aspirin treatment failure was not found to be associated with an increased risk of recurrent stroke or death.

Determinants of neurologic deterioration and stroke-free survival after spontaneous cervicocranial dissections: a multicenter study.

Patients with spontaneous cervicocranial dissection (SCCD) may experience new or recurrent ischemic events despite antiplatelet or anticoagulant therapy. Treatment with stent placement is an available option; however, the literature on patient selection is limited. Thus, identifying patients at high risk for neurologic deterioration after SCCD is of critical importance. The present study examined the rate of neurologic deterioration in medically treated patients with SCCD and evaluated demographic, clinical, and radiologic factors affecting this deterioration. We retrospectively identified consecutive patients with SCCD over a 7-year period from 3 medical institutions, and evaluated the relationships between demographic data, clinical characteristics, and angiographical findings and subsequent neurologic outcomes. Neurologic deterioration was defined as transient ischemic attack (TIA), ischemic stroke, or death occurring during hospitalization or within 1 year of diagnosis. Kaplan-Meier curves were used to determine neurologic event-free survival up to 12 months. A total of 69 patients (mean age, 47.8 ± 14 years; 45 males) with SCCD were included in the study. Eleven patients (16%) experienced in-hospital neurologic deterioration (TIA in 9, ischemic stroke in 1) or death (1 patient). An additional 8 patients developed neurologic deterioration within 1 year after discharge (TIA in 5, ischemic stroke in 2, and death in 1). The overall 1-year event-free survival rate was 72%. Women (P = .046), patients with involvement of both vertebral arteries (P = .02), and those with intracranial arterial involvement (P = .018) had significantly higher rates of neurologic deterioration. Our findings indicate that neurologic deterioration is relatively common after SCCD despite medical treatment in women, patients with bilateral vertebral artery involvement, and those with intracranial vessel involvement.

Using four capitals to assess watershed sustainability.

The La Antigua watershed drains into the Gulf of Mexico and can be considered as one of the most important areas in Mexico because of its high productivity, history, and biodiversity, although poverty remains high in the area in spite of these positive attributes. In this study, we performed an integrated assessment of the watershed to recommend a better direction toward a sustainable management in which the four capitals (natural, human, social, and built) are balanced. We contrasted these four capitals in the municipalities of the upper, middle and lower watershed and found that natural capital (natural ecosystems and ecosystem services) was higher in the upper and middle watershed, while human and social capitals (literacy, health, education and income) were generally higher downstream. Overall, Human Development Index was negatively correlated with the percentage of natural ecosystems in the watershed, especially in the upper and lower watershed regions. Our results indicate that natural capital must be fully considered in projections for increasing human development, so that natural resources can be preserved and managed adequately while sustaining intergenerational well-being.

Land use scenarios, seasonality, and stream identity determine the water physicochemistry of tropical cloud forest streams.

Background: Land use is a major factor determining stream water physicochemistry. However, most streams move from one land use type to another as they drain their watersheds. Here, we studied three land use scenarios in a tropical cloud forest zone in Mexico. We addressed three main goals, to: (1) assess how land use scenarios generate different patterns in stream physicochemical characteristics; (2) explore how seasonality (i.e., dry, dry-to-wet transition, and wet seasons) might result in changes to those patterns over the year; and (3) explore whether physicochemical patterns in different scenarios resulted in effects on biotic components (e.g., algal biomass). Methods: We studied Tropical Mountain Cloud Forest streams in La Antigua watershed, Mexico. Streams drained different three scenarios, streams with (1) an upstream section draining forest followed by a pasture section (F-P), (2) an upstream section in pasture followed by a forest section (P-F), and (3) an upstream forest section followed by coffee plantation (F-C). Physicochemistry was determined at the upstream and downstream sections, and at the boundary between land uses. Measurements were seasonal, including temperature, dissolved oxygen, conductivity, and pH. Water was analyzed for suspended solids, alkalinity, silica, chloride, sulfate, magnesium, sodium, and potassium. Nutrients included ammonium, nitrate, and phosphorus. We measured benthic and suspended organic matter and chlorophyll. Results: Streams presented strong seasonality, with the highest discharge and suspended solids during the wet season. Scenarios and streams within each scenario had distinct physicochemical signatures. All three streams within each scenario clustered together in ordination space and remained close to each other during all seasons. There were significant scenario-season interactions on conductivity (F = 9.5, P < 0.001), discharge (F = 56.7, P < 0.001), pH (F = 4.5, P = 0.011), Cl- (F = 12.2, P < 0.001), SO42- (F = 8.8, P < 0.001) and NH4+ (F = 5.4, P = 0.005). Patterns within individual scenarios were associated with stream identity instead of land use. Both P-F and F-C scenarios had significantly different physicochemical patterns from those in F-P in all seasons (Procrustes analysis, m12 = 0.05-0.25; R = 0.86-0.97; P < 0.05). Chlorophyll was significantly different among scenarios and seasons (F = 5.36, P = 0.015, F = 3.81, P = 0.42, respectively). Concentrations were related to physicochemical variables more strongly during the transition season. Conclusion: Overall, land use scenarios resulted in distinctive water physicochemical signatures highlighting the complex effects that anthropogenic activities have on tropical cloud forest streams. Studies assessing the effect of land use on tropical streams will benefit from assessing scenarios, rather than focusing on individual land use types. We also found evidence of the importance that forest fragments play in maintaining or restoring stream water physicochemistry.

Establishing a baseline of antibiotic use in Massachusetts jails reveals heterogeneity in quantity of prescriptions and duration of therapy.

Optimizing antibiotic prescribing is a crucial element of the fight against antibiotic resistance. Antibiotic prescribing patterns in jails have not been studied. We established a baseline of antibiotic prescribing between Massachusetts jails. We detected heterogeneity in quantity and duration of antibiotic prescriptions, revealing an opportunity for improved practice.

An unusual outbreak of dermatitis due to rodent mite infestation in an acute-care hospital.

We report an outbreak of dermatitis associated with Ornithonysus bacoti and Liponyssoides sanguineus infestation in an acute ambulatory care setting. Healthcare workers developed dermatitis prior to the identification of the outbreak. A collaborative team effort resulted in complete eradication.

Stream food webs in tropical mountains rely on allochthonous carbon regardless of land use.

The relative importance of allochthonous and autochthonous carbon (C) as sources of energy for tropical stream food webs remains an open question. Allochthonous C might be the main energy source for small and shaded forest streams, while autochthonous C is more likely to fuel food webs draining land uses with less dense vegetation. We studied food webs in cloud forest streams draining watersheds with forests, coffee plantations, and pastures. Our goal was to assess the effects of those land uses on the C source and structure of stream food webs. The study took place in tropical montane streams in La Antigua Watershed, in eastern Mexico. We selected three streams per land use and sampled biofilm and leaf litter as the main food resources, and macroinvertebrates and aquatic vertebrates from different trophic guilds. Samples were analyzed for δ13C and δ15N isotopes. Using a Bayesian mixing model, we estimated the proportional assimilation of autochthonous and allochthonous carbon by each guild. We found that consumers were mostly using allochthonous C in all streams, regardless of watershed land use. Our findings indicate that montane cloud forest streams are dominated by allochthony even in watersheds dominated by pastures. Abundant precipitation in this life zone might facilitate the movement of allochthonous C into streams. While food webs of streams from coffee plantations and pastures also rely on allochthonous resources, other impacts do result in important changes in stream functioning.