Orexinergic Input to Dopaminergic Neurons of the Human Ventral Tegmental Area

The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA, 15.062.8% of TH-IR perikarya in humans and 3.260.3% in rats received orexin B-IR afferent contacts. On average, 0.2460.05 and 0.0560.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority(86–88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavierorexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established well in rodents

Socioeconomic inequalities in low birth weight risk before and during the COVID-19 pandemic in Argentina: A cross-sectional study

Background: The coronavirus disease 2019 (COVID-19) pandemic may have exacerbated existing socioe- conomic inequalities in health. In Argentina, public hospitals serve the poorest uninsured segment of the population, while private hospitals serve patients with health insurance. This study aimed to assess whether socioeconomic inequalities in low birth weight (LBW) risk changed during the first wave of the COVID-19 pandemic. Methods: This multicenter cross-sectional study included 15929 infants. A difference-in-difference (DID) analysis of socioeconomic inequalities between public and private hospitals in LBW risk in a pandemic cohort (March 20 to July 19, 2020) was compared with a prepandemic cohort (March 20 to July 19, 2019) by using medical records obtained from ten hospitals. Infants were categorized by weight as LBW < 2500 g, very low birth weight (VLBW) < 1500 g and extremely low birth weight (ELBW) < 1000 g. Log binomial regression was performed to estimate risk differences with an interaction term representing the DID estimator. Covariate-adjusted models included potential perinatal confounders. Findings: Of the 8437 infants in the prepandemic cohort, 4887 (57 ? 9%) were born in public hospitals. The pandemic cohort comprised 7492 infants, 4402 (58 ? 7%) of whom were born in public hospitals. The DID estimators indicated no differences between public versus private hospitals for LBW risk ( −1 ? 8% [95% CI −3 ? 6, 0 ? 0]) and for ELBW risk ( −0 ? 1% [95% CI −0 ? 6, 0 ? 3]). Significant differences were found between public versus private hospitals in the DID estimators ( −1 ? 2% [95% CI, −2 ? 1, −0 ? 3]) for VLBW risk. The results were comparable in covariate-adjusted models. Interpretation: In this study, we found evidence of decreased disparities between public and private hos- pitals in VLBW risk. Our findings suggest that measures that prioritize social spending to protect the most vulnerable pregnant women during the pandemic contributed to better birth outcomes. Funding: No funding was secured for this study.Fil: Cuestas, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Gómez Flores, Martha E.. Gobierno de la Provincia de Buenos Aires. Hospital Doctor Ramón Carrillo; ArgentinaFil: Charras, María D.. Gobierno de la Provincia de Buenos Aires. Hospital Doctor Ramón Carrillo; ArgentinaFil: Peyrano, Alberto J.. Hospital Materno Provincial Dr. Raúl Felipe Lucini; ArgentinaFil: Montenegro, Clara. Hospital Materno Provincial Dr. Raúl Felipe Lucini; ArgentinaFil: Sosa Boye, Ignacio. No especifíca;Fil: Burgos, Verónica. Universidad Católica de Córdoba. Facultad de Medicina. Clínica Universitaria Reina Fabiola; ArgentinaFil: Giusti, Graciela. Clínica y Maternidad del Sol; ArgentinaFil: Espósito, Mario. Clínica y Maternidad del Sol; ArgentinaFil: Blanco Pool, Silvyana S.. Hospital Misericordia Nuevo Siglo ; Gobierno de la Provincia de Cordoba; ArgentinaFil: Gurevich, Debora P.. Hospital Misericordia Nuevo Siglo ; Gobierno de la Provincia de Cordoba; ArgentinaFil: Ahumada, Luis A.. Hospital Misericordia Nuevo Siglo ; Gobierno de la Provincia de Cordoba; ArgentinaFil: Pontoriero, Ricardo D.. Hospital Misericordia Nuevo Siglo ; Gobierno de la Provincia de Cordoba; ArgentinaFil: Rizzotti, Alina. Hospital Privado Universitario de Córdoba; ArgentinaFil: Bas, José I.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Vaca, María B.. Hospital Universitario de Maternidad y Neonatología; ArgentinaFil: Miranda, María J.. Hospital Universitario de Maternidad y Neonatología; ArgentinaFil: Ferreyra, Mirta E.. Hospital Misericordia Nuevo Siglo ; Gobierno de la Provincia de Cordoba; ArgentinaFil: Moreno, Gabriela C.. Gobierno de la Provincia de Buenos Aires. Hospital Doctor Ramón Carrillo; ArgentinaFil: Pedicino, Héctor. Hospital Italiano; ArgentinaFil: Rojas Rios, Melvy. Hospital Italiano; Argentin

Association between COVID-19 mandatory lockdown and decreased incidence of preterm births and neonatal mortality

Previous studies suggest a decrease in preterm births (PTB) during de coronavirus disease 2019 (COVID-19), possibly due to the effect of the mandatory lockdown. Nevertheless, other reports have been unable to confirm this finding. Most of these studies originated in high-income countries and evaluated a limited number of potential confounders, and all of them assessed a short lockdown period. In addition, an important question remains unanswered: How can we be sure that the observed changes are due to lockdown, when most of the pregnancies delivered in the lockdown period were conceived prior to it?To date there is insufficient evidence to support the notion that public health interventions during the lockdown prevent PTB . The aim of this study was to compare the incidence of PTB, neonatal mortality (NM) and stillbirths adjusted by potential confounders during the lockdown period assessing a time window of nine and a half months during which all the pregnancies analyzed in the exposed group were conceived after the lockdown, with the corresponding incidence in the previous year where all the unexposed pregnancies analyzed were conceived before the lockdown.publishedVersionFil: Cuestas, Eduardo. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Cuestas, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Gómez Flores, Martha E. Gobierno de la Provincia de Buenos Aires. Hospital Doctor Ramon Carrillo; Argentina.Fil: Charras, María D. Gobierno de la Provincia de Buenos Aires. Hospital Doctor Ramon Carrillo; Argentina.Fil: Peyrano, Alberto J. Hospital Materno Provincial Dr. Raúl Felipe Lucini; Argentina.Fil: Montenegro, Clara. Hospital Materno Provincial Dr. Raúl Felipe Lucini; Argentina.Fil: Sosa-Boye, Ignacio. Clínica Universitaria Reina Fabiola; Argentina.Fil: Burgos, Verónica. Clínica Universitaria Reina Fabiola; Argentina.Fil: Giusti, Graciela. Clínica y Maternidad del Sol; Argentina.Fil: Espósito, Mario. Clínica y Maternidad del Sol; Argentina.Fil: Blanco Pool, Silvyana S. Hospital Misericordia Nuevo Siglo; Argentina.Fil: Blanco Pool, Silvyana S. Sanatorio Allende; Argentina.Fil: Gurevich, Debora P. Sanatorio Allende; Argentina.Fil: Gurevich, Debora P. Hospital Misericordia Nuevo Siglo; Argentina.Fil: Ahumada, Luis A. Sanatorio Allende; Argentina.Fil: Ahumada, Luis A. Hospital Misericordia Nuevo Siglo; Argentina.Fil: Pontoriero, Ricardo D. Hospital Misericordia Nuevo Siglo; Argentina.Fil: Rizzotti, Alina. Hospital Privado Universitario de Córdoba; Argentina.Fil: Bas, José I. Hospital Privado Universitario de Córdoba; Argentina.Fil: Vaca, María B. Hospital Universitario de Maternidad y Neonatología; Argentina.Fil: Miranda, María J. Hospital Universitario de Maternidad y Neonatología; Argentina.Fil: Ferreyra, Mirta E. Sanatorio del Salvador; Argentina.Fil: Ferreyra, Mirta E. Hospital Misericordia Nuevo Siglo; Argentina.Fil: Moreno, Gabriela C. Sanatorio del Salvador; Argentina.Fil: Pedicino, Héctor. Instituto Universidad Escuela de Medicina del Hospital Italiano; Argentina.Fil: Rojas-Rios, Melvy. Instituto Universidad Escuela de Medicina del Hospital Italiano; Argentina

Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment Elevation Myocardial Infarction Patients

Aims: Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression. Methods and Results: We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P &lt; 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P &lt; 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences. Conclusions: Our study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies

CD8 lymphocytes and plaque erosion: A new piece in the jigsaw

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Takotsubo Syndrome in Intensive Cardiac Care Unit: Challenges in Diagnosis and Management

Takotsubo syndrome (TTS) is an acute reversible form of myocardial dysfunction that is often associated with serious adverse in-hospital complications, including acute heart failure, cardiogenic shock and life-threatening arrythmias. In the absence of randomized clinical trials, its management in the acute phase is based on empirical supportive pharmacological and non-pharmacological measures.In this review article, we aimed at providing an overview of the acute clinical manifestations of patients presenting with TTS, highlighting the predictors of a worse short-term outcome, along with the challenges in therapeutic management of TTS-related complications in the acute care setting