Mixed-Dimensional van der Waals Heterostructure (2D ReS2/0D MoS2 Quantum Dots)-Based Broad Spectral Range with Ultrahigh-Responsive Photodetector.

The remarkable properties of two-dimensional (2D) materials have led to significant advancements in photodetection and optoelectronics research. Currently, there are many successful methods that are employed to improve the responsivity of photodetectors, but the limited spectral range of the device remains a limitation. This work demonstrates the development of a mixed-dimensional (2D/0D) hybrid photodetector device fabricated using chemical vapor deposition (CVD)-grown monolayer ReS2 and solution-processed MoS2 quantum dots (QDs). The mixed dimensionality of 2D (ReS2) and zero-dimensional (0D) MoS2 QDs assist in improving the spectral range of the device [ultraviolet (360 nm) to near-infrared (780 nm)]. Further, due to the work function difference between ReS2 and MoS2 QDs, the built-in electric field across the mixed-dimensional interface promotes effective charge separation and migration, resulting in improved responsivities of the device. The calculated responsivities of the fabricated photodetector are 5.4 × 102, 3.3 × 102, and 2.6 × 102 A/W when subjected to visible, UV, and NIR light illumination, which is remarkable when compared to the existing reports on broadband photodetection. The mixed-dimensionality heterostructure coupled with contact engineering paves the way for highly responsive broadband photodetectors for potential applications in security, healthcare, etc.

Circadian Variation of Immune Cell Populations in Preterm Human Milk: A Preliminary Study.

Introduction: Breast milk contains both nutritional and non-nutritional components for the newborn, with some of the latter exhibiting marked diurnal variations in concentration. This study aimed to analyze the circadian behavior of specific immune cell populations and proinflammatory cytokines present in the transitional milk of premature infants. Methods: The study quantified cellular components, including stem and immune cells, using flow cytometry. Additionally, ELISA assays were employed to measure proinflammatory cytokine concentrations. Results: Flow cytometry analyses revealed a diurnal rise in the percentage of CD23+, CD32+, CD36+, CD2+, and Tγδ cell populations. Conversely, nocturnal increases were observed in the percentage of CD16+, CD19+, and CD4+ populations. Notably, CD3+ and CD8+ populations did not exhibit any rhythmic variations. Proinflammatory cytokine concentrations were found to be higher in daytime milk samples compared to those collected at night. Conclusion: This study demonstrates rhythmic fluctuations in both immune cell populations and proinflammatory cytokine concentrations within the transitional milk of premature mothers.

Mixed-Mode Solar Drying and its Effect on Physicochemical and Colorimetric Properties of Zompantle (Erythrina Americana).

A mixed-mode solar drying was developed to evaluate the physicochemical and colorimetric properties of Zompantle (Erythrina americana). A 22-factorial design was used; the operation mode (mesh shade and direct) and airflow (natural convection and forced convection) were established as factors in this design. The initial moisture content in the Zompantle flower was reduced from 89.03% (w.b) to values that ranged from 3.84% to 5.84%; depending on the operation mode of the dryer, the final water activity ranged from 0.25 to 0.33. The Zompantle's components as proteins (4.28%), antioxidant activity (18.8%), carbohydrates (4.83%), fat (0.92%), fiber (3.71%), ash (0.94%), and total soluble solids (3°Brix) increased as the water was evaporated during the drying. The increment in the Zompantle's components depends on the operation mode; in direct mode and natural convection, the proteins, antioxidant activity, carbohydrates, fat, fiber, ash, and total soluble solids were 6.99%, 61.69%, 79.05%, 1.20%, 3.84%, 8.70%, and 45 °Brix, respectively. The total drying efficiency was 14.84% with the direct mode and natural convection (DM-NC) and 17.10% with the mesh shade and natural convection (MS-NC). The Hue angle measures the property of the color; the indirect mode and natural convection keep the hue angle close to the initial value (29.2 °). The initial chroma value of the Zompantle flower was 55.07; the indirect mode and natural convection kept high saturation (37.58); these dry conditions ensured a red color in the dehydrated Zompantle. Dehydrated Zompantle's flowers could have several practical applications, such as an additive in traditional Mexican cuisine.

Preterm Delivery in Obese Mothers Predicts Tumor Necrosis Factor-α Levels in Breast Milk.

Background: Breast milk (BM) is a nutritive fluid that is rich in bioactive components such as hormones and cytokines that can shape the newborn's feeding habits and program the newborn's immature immune system. BM components can change under different scenarios that include maternal body mass index (BMI) and premature birth. This study aimed to study the interaction of premature status or maternal obesity on the hormonal and cytokine profile in BM according to the sex of the offspring. Materials and Methods: We recruited 31 women with preterm births from the Centro de Alta Especialidad Dr. Rafael Lucio in Mexico. Luminex multiplexing assay was used for quantifying cytokine profile of monocyte chemoattractant protein-1, tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)1-ß, IL-2, IL-4, IL-6, IL-7, and hormones insulin, ghrelin, leptin, and glucagon in mature BM samples. Biological modeling was performed to predict the interaction between cytokines and hormones, maternal BMI status, infant birth sex, parity, and gestational age. Results: BM multiplex analysis showed positive correlations for TNF-α and increasing prematurity and for higher maternal BMI and IL-2, IL-4, and IL-6 cytokines. Multiple regression models identified an interaction between maternal BMI and gestational weeks in male infants that is associated to TNF-α accumulation in BM. Biological modeling predicts that preterm delivery in mothers with obesity modulates TNF- α levels in mature BM of women with male offspring. Conclusion: Prematurity and obesity modify BM's immune profile. TNF- α expression increases as prematurity increases, and maternal BMI correlates positively with increases in IL-2, IL-6, and IL-4. Our multiple regression model also shows that maternal BMI and gestational weeks in male infants predict TNF-α.

Tigecycline Tango: A Case of Antibiotic-Induced Pancreatitis.

Acute pancreatitis is a frequent cause of hospitalization, with the most common triggers being alcohol consumption and gallstones. Although the incidence of drug-induced pancreatitis remains low, it is steadily increasing due to the advent of newly discovered broad-spectrum antibiotics targeting multi-drug resistant organisms. Tigecycline, a broad-spectrum intravenous antibiotic derived from the tetracycline class, was approved by the FDA in 2005 for the treatment of complicated skin and skin structure infections, complicated intra-abdominal infections, and community-acquired pneumonia. It has activity against vancomycin-resistant Enterococcus, Methicillin-resistant Staphylococcus aureus, multi-drug-resistant Acinetobacter baumannii, multi-drug-resistant Stenotrophomonas maltophilia, and Extended Spectrum Beta-lactamase (ESBL) producing Enterobacter species. However, it was later discovered that tigecycline can cause acute pancreatitis. We present a case of a 27-year-old female patient who was admitted to the emergency department with abdominal pain and was subsequently diagnosed with tigecycline-induced pancreatitis based on the clinical resolution after withdrawal of the drug.

Micro problems with macro consequences: accumulation of persistent organic pollutants and microplastics in human breast milk and in human milk substitutes.

Industrial activities provide a modern human lifestyle with advances and comforts in every field. However, such scenario has brought several negative issues. Persistent organic pollutants (POPs) and a growing plastic usage together with the degradation byproducts, namely microplastics (MPs), are current environmental problems present in every ecosystem, disturbing all forms of life. POPs and MPs are also found in human consumption products including animal and vegetal derivatives, human milk substitutes, and in human breast milk. To date, it is currently unknown what are the effects of MPs and POPs when ingested during the first and most important stage for health programming of the offspring, the first 1000 days of life. Here, we add epidemiological and clinical evidence supporting major sources of POPs and MPs in the ecosystem; and we will precisely describe the effect of POP and MP accumulation in animal- or plant-based infant formulas and human breast milk, modulating health outcomes in the newborn. This review provides a rational to incentive the POP and MP identification in human breast milk and human milk substitutes for avoiding susceptibility to negative health outcomes for the newborn.

Molecular and immune signatures, and pathological trajectories of fatal COVID-19 lungs defined by in situ spatial single-cell transcriptome analysis.

Despite intensive studies during the last 3 years, the pathology and underlying molecular mechanism of coronavirus disease 2019 (COVID-19) remain poorly defined. In this study, we investigated the spatial single-cell molecular and cellular features of postmortem COVID-19 lung tissues using in situ sequencing (ISS). We detected 10 414 863 transcripts of 221 genes in whole-slide tissues and segmented them into 1 719 459 cells that were mapped to 18 major parenchymal and immune cell types, all of which were infected by SARS-CoV-2. Compared with the non-COVID-19 control, COVID-19 lungs exhibited reduced alveolar cells (ACs) and increased innate and adaptive immune cells. We also identified 19 differentially expressed genes in both infected and uninfected cells across the tissues, which reflected the altered cellular compositions. Spatial analysis of local infection rates revealed regions with high infection rates that were correlated with high cell densities (HIHD). The HIHD regions expressed high levels of SARS-CoV-2 entry-related factors including ACE2, FURIN, TMPRSS2 and NRP1, and co-localized with organizing pneumonia (OP) and lymphocytic and immune infiltration, which exhibited increased ACs and fibroblasts but decreased vascular endothelial cells and epithelial cells, mirroring the tissue damage and wound healing processes. Sparse nonnegative matrix factorization (SNMF) analysis of niche features identified seven signatures that captured structure and immune niches in COVID-19 tissues. Trajectory inference based on immune niche signatures defined two pathological routes. Trajectory A primarily progressed with increased NK cells and granulocytes, likely reflecting the complication of microbial infections. Trajectory B was marked by increased HIHD and OP, possibly accounting for the increased immune infiltration. The OP regions were marked by high numbers of fibroblasts expressing extremely high levels of COL1A1 and COL1A2. Examination of single-cell RNA-seq data (scRNA-seq) from COVID-19 lung tissues and idiopathic pulmonary fibrosis (IPF) identified similar cell populations consisting mainly of myofibroblasts. Immunofluorescence staining revealed the activation of IL6-STAT3 and TGF-ß-SMAD2/3 pathways in these cells, likely mediating the upregulation of COL1A1 and COL1A2 and excessive fibrosis in the lung tissues. Together, this study provides a spatial single-cell atlas of cellular and molecular signatures of fatal COVID-19 lungs, which reveals the complex spatial cellular heterogeneity, organization, and interactions that characterized the COVID-19 lung pathology.

Effect of Human Adenovirus 36 on Response to Metformin Monotherapy in Obese Mexican Patients with Type 2 Diabetes: A Prospective Cohort Study.

Human adenovirus 36 (HAdV-36) has been associated with obesity and changes in glucose and lipid metabolism. The virus has been reported to increase insulin sensitivity and paradoxically promote weight gain. Because of its effects on metabolism, infection with the virus could alter the response to several drugs used to treat type 2 diabetes (DM2), such as metformin. The aim of this study was to test whether HAdV-36 affects the response to metformin in a group of obese patients with DM2. METHODS: In a prospective cohort study, 103 obese patients with newly diagnosed DM2 were divided into two groups based on their HAdV-36 seropositivity (+HAdV-36 and -HAdV-36). Weight, glucose, cholesterol, triglycerides, body mass index, body fat percentage, and waist and hip circumference were measured and compared in both groups at baseline and after 45 days of metformin treatment. RESULTS: Only glucose was significantly lower in the +HAdV-36 group at baseline, while all other variables were similar between the two study groups. After 45 days of follow-up, it was observed that the effect of metformin did not differ between the groups, but the variables improved significantly after treatment. CONCLUSIONS: In this study, we did not find that HAdV-36 had an effect on the response to metformin in obese patients with DM2.

Approach to Circular Chemistry Preparing New Polyesters from Olive Oil.

The transformation of cooking oils and their waste into polyesters is a challenge for circular chemistry. Herein, we have used epoxidized olive oil (EOO), obtained from cooking olive oil (COO), and various cyclic anhydrides (such as phthalic anhydride PA, maleic anhydride MA, and succinic anhydride SA) as raw materials for the preparation of new bio-based polyesters. For the synthesis of these materials, we have used the bis(guanidine) organocatalyst 1 and tetrabutylammonium iodide (Bu4NI) as cocatalyst. The optimal reaction conditions for the preparation of poly(EOO-co-PA) and poly(EOO-co-MA) were 80 °C for 5 h using toluene as solvent; however, the synthesis of poly(EOO-co-SA) required more extreme reaction conditions. Furthermore, we have exclusively succeeded in obtaining the trans isomer for MA-polyester. The obtained biopolyesters were characterized by NMR, Fourier transform infrared, thermogravimetric analysis, and scanning electron microscopy analyses. Since there are few examples of functionalized and defined compounds based on olive oil, it is innovative and challenging to transform these natural-based compounds into products with high added value.

Activation of the central but not the medial and cortical amygdala during anticipation for daily nursing in the rabbit.

Rabbits have remarkable nursing behavior: after parturition, does visit daily their pups for nursing only once with circadian periodicity. Before the nursing events, they present increased activity and arousal, which shift according to the timing of scheduled nursing, either during the day or night. Brain areas related to maternal behavior and neuroendocrine cells for milk secretion are also entrained. The daily return of the doe for nursing at approximately the same hour suggests a motivational drive with circadian periodicity. Previously, we reported the activation of the mesolimbic system at the time of nursing, but not 12 h before that. Aiming at a better understanding of the mechanism of this anticipatory behavior, we explored the participation of the limbic regions of the amygdala and the bed nucleus of the stria terminalis, as well as the possible activation of the hypothalamic-pituitaryadrenal axis, specifically the corticotropin-releasing factor cells in the hypothalamic paraventricular nucleus of does at different times before and after nursing. The medial and cortical amygdala, the bed nucleus of the stria terminalis, and corticotropin cells showed activation only after nursing. However, the central amygdala was also activated before nursing. We conclude that the medial and the cortical amygdala form part of the afferent olfactory pathway for entrainment, and the central amygdala participates in the anticipatory motivational circuit of the control of periodic nursing. The lack of activation of corticotropin cells before nursing is consistent with the possible harmful effects of the doe's high glucocorticoid levels on the developing pups.

COVID-19 Alcoholic Cirrhosis and Non-Alcoholic Steatohepatitis Cirrhosis Outcomes among Hospitalized Patients in the United States: Insight from National Inpatient Sample Database.

Patients with co-morbidities like cirrhosis are at risk of worse outcome from COVID-19 infection. Given limited prior studies, we evaluated outcomes associated with COVID-19 infection in alcoholic and non-alcoholic steatohepatitis cirrhotic (CC+) versus cirrhotic without COVID-19 (CC−). We performed retrospective analysis of 822,604 patients including 28,610 COVID-19 patients from the National Inpatient Sample database with alcoholic and NASH cirrhosis enrolled between 1 January 2020 to 31 December 2020, with univariate and multivariate regression analyses. Primary outcome was mortality and secondary outcomes was mechanical ventilation, vasopressor use, length of stay, hospitalization expense and predictors of mortality. In-hospital mortality was three time higher in the CC+ group compared to those in the CC− group(18.6% vs. 5.96%, p < 0.001, adjusted odds ratio (OR)3.39 (95% 3.08−3.74 CI). Hospitalization was more likely for underrepresented racial and ethnic groups with COVID-19 and cirrhosis. CC+ group had over twice the rates of mechanical ventilation (19.92% vs. 9.07%, adjusted OR 2.71 2.71 (95% 2.51−2.93 CI)),1.7 times likelihood of receiving vasopressors (4.12% vs. 2.45%, p < 0.001, adjusted OR 1.71 (95% CI 1.46−2.01). COVID-19 is associated with increased mortality in patients with alcoholic and NASH cirrhosis, and patients with alcoholic cirrhosis and COVID-19 have a slightly higher mortality compared to NASH cirrhosis.

Characterizing Macrophages Diversity in COVID-19 Patients Using Deep Learning.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for coronavirus disease 2019 (COVID-19), has affected the lives of billions and killed millions of infected people. This virus has been demonstrated to have different outcomes among individuals, with some of them presenting a mild infection, while others present severe symptoms or even death. The identification of the molecular states related to the severity of a COVID-19 infection has become of the utmost importance to understanding the differences in critical immune response. In this study, we computationally processed a set of publicly available single-cell RNA-Seq (scRNA-Seq) data of 12 Bronchoalveolar Lavage Fluid (BALF) samples diagnosed as having a mild, severe, or no infection, and generated a high-quality dataset that consists of 63,734 cells, each with 23,916 genes. We extended the cell-type and sub-type composition identification and our analysis showed significant differences in cell-type composition in mild and severe groups compared to the normal. Importantly, inflammatory responses were dramatically elevated in the severe group, which was evidenced by the significant increase in macrophages, from 10.56% in the normal group to 20.97% in the mild group and 34.15% in the severe group. As an indicator of immune defense, populations of T cells accounted for 24.76% in the mild group and decreased to 7.35% in the severe group. To verify these findings, we developed several artificial neural networks (ANNs) and graph convolutional neural network (GCNN) models. We showed that the GCNN models reach a prediction accuracy of the infection of 91.16% using data from subtypes of macrophages. Overall, our study indicates significant differences in the gene expression profiles of inflammatory response and immune cells of severely infected patients.

Transformer for Gene Expression Modeling (T-GEM): An Interpretable Deep Learning Model for Gene Expression-Based Phenotype Predictions.

Deep learning has been applied in precision oncology to address a variety of gene expression-based phenotype predictions. However, gene expression data's unique characteristics challenge the computer vision-inspired design of popular Deep Learning (DL) models such as Convolutional Neural Network (CNN) and ask for the need to develop interpretable DL models tailored for transcriptomics study. To address the current challenges in developing an interpretable DL model for modeling gene expression data, we propose a novel interpretable deep learning architecture called T-GEM, or Transformer for Gene Expression Modeling. We provided the detailed T-GEM model for modeling gene-gene interactions and demonstrated its utility for gene expression-based predictions of cancer-related phenotypes, including cancer type prediction and immune cell type classification. We carefully analyzed the learning mechanism of T-GEM and showed that the first layer has broader attention while higher layers focus more on phenotype-related genes. We also showed that T-GEM's self-attention could capture important biological functions associated with the predicted phenotypes. We further devised a method to extract the regulatory network that T-GEM learns by exploiting the attributions of self-attention weights for classifications and showed that the network hub genes were likely markers for the predicted phenotypes.

Validación de un manual sobre la elaboración de una estrategia didáctica para potenciar el nivel de información sobre la COVID-19 en estudiantes de Medicina / Validation of a manual to design a didactic strategy for enhancing the level of information on COVID-19 in the medical students / Validação de um manual sobre o desenvolvimento de uma estratégia didática para aumentar o nível de informação sobre COVID-19 em estudantes de Medicina

RESUMEN Introducción: Las estrategias didácticas, en su conjunto, demandan establecer una relación dialógica, constante y triangular entre educadores, educandos y metodologías, aunque el educando ignore o no las metodologías que utiliza el docente para tal fin. Objetivo: validar un manual para el diseño y elaboración de una estrategia didáctica para potenciar el nivel de información sobre COVID-19 en estudiantes de Medicina. Método: Se elaboró un manual sobre el diseño de una estrategia didáctica empleada para incrementar el conocimiento de los estudiantes de Medicina del segundo año de la Universidad de Ciencias Médicas de Sancti Spíritus, Cuba, sobre los signos, síntomas y métodos de prevención de la COVID-19 durante el inicio de la pandemia en el país. Treinta expertos nacionales en ciencias de la educación médica emitieron sus dictámenes sobre la pertinencia de la estrategia didáctica y del manual sobre su diseño, y fueron analizados por el método Delphi. El éxito de la aplicación de la estrategia didáctica se valoró mediante la aplicación de exámenes a la población del estudio antes y después de la introducción de la estrategia didáctica en el período 2021-2022. Resultados: El consenso general de los expertos fue de Muy de acuerdo para los fundamentos que sustentan la estrategia didáctica para la educación médica superior y la calidad del manual propuesto. Conclusiones: Tanto la estrategia educativa como el manual sobre su elaboración fueron validadas por los expertos para su aplicación en la educación médica superior y, particularmente, para la detección y contención de la COVID-19.

ABSTRACT Introduction: Didactic strategies, as a whole, demand the establishment of a dialogical, constant and triangular relationship between educators, learners and methodologies, even though the learner is unaware or not of the methodologies used by the professor for purpose required. Objective: To validate a manual for designing and elaborating a didactic strategy to enhance the information level for medical students concerning COVID-19. Method: A manual based on a didactic strategy structural design was elaborated with the porpuse of increase the knowledge for the second year medical students at the Universidad de Ciencias Médicas de Sancti Spíritus, Cuba, on the signs, symptoms of COVID-19 and the prevention methods used at the beginning of the pandemic in the country. Thirty national experts in medical education sciences gave their opinions on the relevance of the didactic strategy and about the structural design of the manual, which were analyzed by the Delphi method. The success of the strategy implementation was assessed implementing tests to the studied population before and after the introduction of the didactic strategy in the period 2021- 2022. Results: The experts' opinion concerning the fundamentals underpinning the didactic strategy for higher medical education and the quality of the proposed manual was highly favorable in general consensus. Conclusions: Both the educational strategy and the elaboration of the manual were validated by the experts for its application in higher medical education and in particularly for the detection and containment of COVID-19.

RESUMO Introdução: As estratégias didáticas, como um todo, demandam estabelecer uma relação dialógica, constante e triangular entre educadores, educandos e metodologias, independentemente de o educando ignorar ou não as metodologias utilizadas pelo professor para esse fim. Objetivo: Submeter um manual para a concepção e desenvolvimento de uma estratégia didática para melhorar o nível de informação sobre COVID-19 em estudantes de medicina para validação. Método: Foi elaborado um manual sobre o desenho de uma estratégia didática utilizada para aumentar o conhecimento dos alunos do segundo ano de Medicina da Universidad de Ciencias Médicas de Sancti Spíritus, Cuba, sobre os sinais, sintomas e métodos de prevenção da COVID. -19 durante o início da pandemia no país. Trinta especialistas nacionais em ciências da educação médica emitiram suas opiniões sobre a relevância da estratégia didática e do manual sobre seu desenho, e foram analisados pelo método Delphi. O sucesso da aplicação da estratégia didática foi avaliado por meio da aplicação de testes à população do estudo antes e após a introdução da estratégia didática no período 2021-2022. Resultados: O consenso geral dos especialistas foi Fortemente concordante para os fundamentos que sustentam a estratégia didática para a formação médica superior e a qualidade do manual proposto. Conclusões: Tanto a estratégia educativa como o manual sobre a sua elaboração foram validados por especialistas para a sua aplicação no ensino superior médico e, em particular, para a deteção e contenção da COVID-19.

Neonatal ventral hippocampus lesion disrupts maternal behavior in rats: An animal model of schizophrenia.

Although individuals with schizophrenia typically present deficits in social interaction, little is known about the quality of their parent-infant interactions. In the present study, we assessed the behavioral effects of neonatal ventral hippocampus lesion (nVHL) in female rats (nVHL is known to induce schizophrenia-like deficits in males). Sexually naïve adult nVHL or sham female rats received cognitive and social tests, and their maternal behavior was observed in independent groups of adult nVHL and sham rats on postpartum days 2, 6, and 12. Compared to Sham females, naïve nVHL rats displayed elevated locomotor activity, less social interaction, and disrupted habituation of the acoustic startle response (ASR), while dorsal immobility (a defensive behavioral response) and prepulse inhibition of ASR were not affected. Although all nVHL mothers retrieved their pups, adopted the crouching posture, and nursed them, they showed disturbances in the display of pup body licking and nest building. Furthermore, a high proportion of nVHL mothers displayed atypical retrieval of pups and re-retrieving of pups, atypical nest-building, excavation, and cannibalism, as well a high level of these behaviors. These data indicate that cognition, locomotor activity, and maternal care is disrupted in nVHL female, suggesting disturbances in mesocorticolimbic dopaminergic systems and/or in social cognition.

Breast Milk and the Importance of Chrononutrition.

During pregnancy the human fetus receives timed cues from the circadian rhythms of temperature, metabolites, and hormones from the mother. This influence is interrupted after parturition, the infant does not secrete melatonin and their circadian rhythms are still immature. However, evolution provided the solution to this problem. The newborn can continue receiving the mother's timed cues through breastmilk. Colostrum, transitional, and mature human milk are extraordinary complex biofluids that besides nutrients, contain an array of other non-nutritive components. Upon birth the first milk, colostrum, is rich in bioactive, immunological factors, and in complex oligosaccharides which help the proper establishment of the microbiome in the gut, which is crucial for the infants' health. Hormones, such as glucocorticoids and melatonin, transfer from the mother's plasma to milk, and then the infant is exposed to circadian cues from their mother. Also, milk components of fat, proteins, amino acids, and endogenous cannabinoids, among others, have a markedly different concentration between day and night. In the present review, we give an overview of nutritive and non-nutritive components and their daily rhythms in human milk and explore their physiological importance for the infant. Finally, we highlight some interventions with a circadian approach that emphasize the importance of circadian rhythms in the newborn for their survival, proper growth, and development. It is estimated that ~600,000 deaths/year are due to suboptimal breastfeeding. It is advisable to increase the rate of exclusive breastfeeding, during the day and night, as was established by the evolution of our species.

Leptin in the Commissural Nucleus of the Tractus Solitarius (cNTS) and Anoxic Stimulus in the Carotid Body Chemoreceptors Increases cNTS Leptin Signaling Receptor and Brain Glucose Retention in Rats.

Background and Objectives: The commissural nucleus of the tractus solitarius (cNTS) not only responds to glucose levels directly, but also receives afferent signals from the liver, and from the carotid chemoreceptors (CChR). In addition, leptin, through its receptors in the cNTS, regulates food intake, body weight, blood glucose levels, and brain glucose retention (BGR). These leptin effects on cNTS are thought to be mediated through the sympathetic-adrenal system. How these different sources of information converging in the NTS regulate blood glucose levels and brain glucose retention remains largely unknown. The goal of the present study was to determine whether the local administration of leptin in cNTS alone, or after local anoxic stimulation using sodium cyanide (NaCN) in the carotid sinus, modifies the expression of leptin Ob-Rb and of c-Fos mRNA. We also investigated how leptin, alone, or in combination with carotid sinus stimulation, affected brain glucose retention. Materials and Methods: The experiments were carried out in anesthetized male Wistar rats artificially ventilated to maintain homeostatic values for pO2, pCO2, and pH. We had four groups: (a) experimental 1, leptin infusion in cNTS and NaCN in the isolated carotid sinus (ICS; n = 10); (b) experimental 2, leptin infusion in cNTS and saline in the ICS (n = 10); (c) control 1, artificial cerebrospinal fluid (aCSF) in cNTS and NaCN in the ICS (n = 10); (d) control 2, aCSF in cNTS and saline in the ICS (n = 10). Results: Leptin in cNTS, preceded by NaCN in the ICS increased BGR and leptin Ob-Rb mRNA receptor expression, with no significant increases in c-Fos mRNA in the NTSc. Conclusions: Leptin in the cNTS enhances brain glucose retention induced by an anoxic stimulus in the carotid chemoreceptors, through an increase in Ob-Rb receptors, without persistent changes in neuronal activation.

Rabbits can be conditioned in a food-induced place preference paradigm.

The conditioned place preference (CPP) paradigm has been employed in behavioral studies to investigate the responses to an environment where a reinforcing event occurs. It is applied to reveal incentive motivational responses to reward-related stimuli. It is standardized and widely applied in mice and rats, two of the most common species of laboratory animals. However, no studies using the CPP protocol have been performed in rabbits, even though this animal model is commonly used in pharmacological and behavioral research. There are important physiological and behavioral differences between rodents and rabbits. For example, rodents are spontaneous ovulators while rabbits are induced ovulators. In addition, lactation in the rabbit is circadian, which is unique among mammals. The present investigation aims to establish whether rabbits can be conditioned by using a food-induced CPP protocol in subjects with caloric restriction. Adult female rabbits were subjected to a three-compartment CPP protocol. The food produced place preference, demonstrating for the first time that rabbits can be conditioned using the CPP paradigm opening a new field of opportunities for behavioral studies of positive affective states in a species with important behavioral and physiological differences from rodents.

Association between genetic variant rs2267716 of CRHR2 gene with colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and one of the main causes of death around the world. Multiple lines of evidence have suggested the role of the corticotropin-releasing hormone (CRH) family in CRC induction, including the low expression of corticotropin-releasing hormone receptor 2 (CRHR2), which is an angiogenesis inhibitor and inflammatory modulator. Previous research suggests that CRHR2 expression in colonic intestinal cells can regulate migration, proliferation and apoptosis through the modulation of several pathways. The aim of this study was to analyze the association of the rs10250835, rs2267716 and rs2267717 variants of CRHR2 gene with CRC in the Mexican population in order to consider its predictive value in CRC. This cross-sectional study included a group of 187 unrelated patients with sporadic CRC and a control group of 191 healthy blood donors. DNA extraction from peripheral blood was carried out using the Miller method. Identification of the rs10250835 variant was performed using PCR-restriction fragment length polymorphism (RFLP) and the rs2267716 and rs2267717 variants using TaqMan allelic discrimination assay. The minor allele homozygous CC of the rs2267716 variant of CRHR2 showed significant difference between CRC and control group (p=0.025), as well as the GCA haplotype (p=0.007), corresponding to the rs10250835, rs2267716 and rs2267717 variants, respectively. Our results suggest that the rs2267716 variant and GCA haplotype of CRHR2 represent a risk factor for CRC development in Mexican patients.

Deep learning tackles single-cell analysis-a survey of deep learning for scRNA-seq analysis.

Since its selection as the method of the year in 2013, single-cell technologies have become mature enough to provide answers to complex research questions. With the growth of single-cell profiling technologies, there has also been a significant increase in data collected from single-cell profilings, resulting in computational challenges to process these massive and complicated datasets. To address these challenges, deep learning (DL) is positioned as a competitive alternative for single-cell analyses besides the traditional machine learning approaches. Here, we survey a total of 25 DL algorithms and their applicability for a specific step in the single cell RNA-seq processing pipeline. Specifically, we establish a unified mathematical representation of variational autoencoder, autoencoder, generative adversarial network and supervised DL models, compare the training strategies and loss functions for these models, and relate the loss functions of these models to specific objectives of the data processing step. Such a presentation will allow readers to choose suitable algorithms for their particular objective at each step in the pipeline. We envision that this survey will serve as an important information portal for learning the application of DL for scRNA-seq analysis and inspire innovative uses of DL to address a broader range of new challenges in emerging multi-omics and spatial single-cell sequencing.