Adult aberrant astrocytes submitted to late passage cultivation lost differentiation markers and decreased their pro-inflammatory profile.

In amyotrophic lateral sclerosis (ALS), astrocytes are considered key players in some non-cell non-neuronal autonomous mechanisms that underlie motor neuron death. However, it is unknown how much of these deleterious features were permanently acquired. To assess this point, we evaluated if the most remarkable features of neurotoxic aberrant glial phenotypes (AbAs) isolated from paralytic rats of the ALS model G93A Cu/Zn superoxide dismutase 1 (SOD1) could remain upon long lasting cultivation. Real time PCR, immunolabelling and zymography analysis showed that upon many passages, AbAs preserved the cell proliferation capacity, mitochondrial function and response to different compounds that inhibit some key astrocyte functions but decreased the expression of parameters associated to cell lineage, homeostasis and inflammation. As these results are contrary to the sustained inflammatory status observed along disease progression in SOD1G93A rats, we propose that the most AbAs remarkable features related to homeostasis and neurotoxicity were not permanently acquired and might depend on the signaling coming from the injuring microenvironment present in the degenerating spinal cord of terminal rats.

A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals.

BACKGROUND: Alcohol consumption is associated with numerous negative social and health outcomes. These associations may be direct consequences of drinking, or they may reflect common genetic factors that influence both alcohol consumption and other outcomes. METHODS: We performed exploratory phenome-wide association studies (PheWAS) of three of the best studied protective single nucleotide polymorphisms (SNPs) in genes encoding ethanol metabolising enzymes (ADH1B: rs1229984-T, rs2066702-A; ADH1C: rs698-T) using up to 1109 health outcomes across 28 phenotypic categories (e.g., substance-use, mental health, sleep, immune, cardiovascular, metabolic) from a diverse 23andMe cohort, including European (N ≤ 2,619,939), Latin American (N ≤ 446,646) and African American (N ≤ 146,776) populations to uncover new and perhaps unexpected associations. These SNPs have been consistently implicated by both candidate gene studies and genome-wide association studies of alcohol-related behaviours but have not been investigated in detail for other relevant phenotypes in a hypothesis-free approach in such a large cohort of multiple ancestries. To provide insight into potential causal effects of alcohol consumption on the outcomes significant in the PheWAS, we performed univariable two-sample and one-sample Mendelian randomisation (MR) analyses. FINDINGS: The minor allele rs1229984-T, which is protective against alcohol behaviours, showed the highest number of PheWAS associations across the three cohorts (N = 232, European; N = 29, Latin American; N = 7, African American). rs1229984-T influenced multiple domains of health. We replicated associations with alcohol-related behaviours, mental and sleep conditions, and cardio-metabolic health. We also found associations with understudied traits related to neurological (migraines, epilepsy), immune (allergies), musculoskeletal (fibromyalgia), and reproductive health (preeclampsia). MR analyses identified evidence of causal effects of alcohol consumption on liability for 35 of these outcomes in the European cohort. INTERPRETATION: Our work demonstrates that polymorphisms in genes encoding alcohol metabolising enzymes affect multiple domains of health beyond alcohol-related behaviours. Understanding the underlying mechanisms of these effects could have implications for treatments and preventative medicine. FUNDING: MVJ, NCK, SBB, SSR and AAP were supported by T32IR5226 and 28IR-0070. SSR was also supported by NIDA DP1DA054394. NCK and RBC were also supported by R25MH081482. ASH was supported by funds from NIAAA K01AA030083. JLMO was supported by VA 1IK2CX002095. JLMO and JJMM were also supported by NIDA R21DA050160. JJMM was also supported by the Kavli Postdoctoral Award for Academic Diversity. EGA was supported by K01MH121659 from the NIMH/NIH, the Caroline Wiess Law Fund for Research in Molecular Medicine and the ARCO Foundation Young Teacher-Investigator Fund at Baylor College of Medicine. MSA was supported by the Instituto de Salud Carlos III and co-funded by the European Union Found: Fondo Social Europeo Plus (FSE+) (P19/01224, PI22/00464 and CP22/00128).

Prevalence and Consequences of a Delayed Diagnosis in Multiple Myeloma: A Single Institution Experience.

BACKGROUND: Multiple myeloma (MM) is a disease with unspecific initial symptoms which may lead into a delay in the diagnosis, seemingly increasing the risk of complications and in turn reducing the overall survival (OS). OBJECTIVE: To analyze the consequences of a delayed diagnosis of MM in both the OS and the progression-free survival (PFS) of the patients in a single center in México. METHODS: The study included patients with MM who were diagnosed at Clínica Ruiz, Puebla, México, between 1983 and 2022. According to the time elapsed between the onset of symptoms to the establishment of the definite diagnosis of MM, 4 groups were constructed: 1) Less than 3 months, 2) 3-6 months, 3) 6-12 months, and 4) More than 12 months. RESULTS: About 136 patients had a complete clinical record and at least a 3-month follow up period. A delay in the diagnosis of MM (more than 3 months from the onset of symptoms) was recorded in 92/136 persons (68%). The median follow-up for the whole group was 24.7 months, median OS was 131.4 months, whereas median PFS was 85.4 months. There was a significant trend for being in earlier stages of the disease and being diagnosed within 3 months from the onset of symptoms (P = .049). Both OS and PFS were similar in the patients diagnosed before or after 3 months from the symptoms onset (P = .772). The 6-12 months group was the group with the better median both OS (197.4 months) and DFS (197.4) from the diagnosis. The median OS for the other groups were similar among them. CONCLUSION: A delay in the diagnosis of MM is very frequent in México (68% of cases); despite the fact that there was a significant trend for being in earlier stages of the disease and being diagnosed within 3 months from the onset of symptoms, we did not find a relationship between a delay on the diagnosis of the disease and a higher risk of complications and/or poor prognosis. Possible explanations to these findings are discussed.

EZH2 inhibition reactivates epigenetically silenced FMR1 and normalizes molecular and electrophysiological abnormalities in fragile X syndrome neurons.

Fragile X Syndrome (FXS) is a neurological disorder caused by epigenetic silencing of the FMR1 gene. Reactivation of FMR1 is a potential therapeutic approach for FXS that would correct the root cause of the disease. Here, using a candidate-based shRNA screen, we identify nine epigenetic repressors that promote silencing of FMR1 in FXS cells (called FMR1 Silencing Factors, or FMR1- SFs). Inhibition of FMR1-SFs with shRNAs or small molecules reactivates FMR1 in cultured undifferentiated induced pluripotent stem cells, neural progenitor cells (NPCs) and post-mitotic neurons derived from FXS patients. One of the FMR1-SFs is the histone methyltransferase EZH2, for which an FDA-approved small molecule inhibitor, EPZ6438 (also known as tazemetostat), is available. We show that EPZ6438 substantially corrects the characteristic molecular and electrophysiological abnormalities of cultured FXS neurons. Unfortunately, EZH2 inhibitors do not efficiently cross the blood-brain barrier, limiting their therapeutic use for FXS. Recently, antisense oligonucleotide (ASO)-based approaches have been developed as effective treatment options for certain central nervous system disorders. We therefore derived efficacious ASOs targeting EZH2 and demonstrate that they reactivate FMR1 expression and correct molecular and electrophysiological abnormalities in cultured FXS neurons, and reactivate FMR1 expression in human FXS NPCs engrafted within the brains of mice. Collectively, our results establish EZH2 inhibition in general, and EZH2 ASOs in particular, as a therapeutic approach for FXS.

Noribogaine acute administration in rats promotes wakefulness and suppresses REM sleep.

Ibogaine is a potent atypical psychedelic that has gained considerable attention due to its antiaddictive and antidepressant properties in preclinical and clinical studies. Previous research from our group showed that ibogaine suppresses sleep and produces an altered wakefulness state, which resembles natural REM sleep. However, after systemic administration, ibogaine is rapidly metabolized to noribogaine, which also shows antiaddictive effects but with a distinct pharmacological profile, making this drug a promising therapeutic candidate. Therefore, we still ignore whether the sleep/wake alterations depend on ibogaine or its principal metabolite noribogaine. To answer this question, we conducted polysomnographic recordings in rats following the administration of pure noribogaine. Our results show that noribogaine promotes wakefulness while reducing slow-wave sleep and blocking REM sleep, similar to our previous results reported for ibogaine administration. Thus, we shed new evidence on the mechanisms by which iboga alkaloids work in the brain.

Risk factors contributing to infection with SARS-CoV-2 are modulated by sex.

Throughout the early stages of the COVID-19 pandemic in Mexico (August-December 2020), we closely followed a cohort of n = 100 healthcare workers. These workers were initially seronegative for Immunoglobulin G (IgG) antibodies against SARS-CoV-2, the virus that causes COVID-19, and maintained close contact with patients afflicted by the disease. We explored the database of demographic, physiological and laboratory parameters of the cohort recorded at baseline to identify potential risk factors for infection with SARS-CoV-2 at a follow-up evaluation six months later. Given that susceptibility to infection may be a systemic rather than a local property, we hypothesized that a multivariate statistical analysis, such as MANOVA, may be an appropriate statistical approach. Our results indicate that susceptibility to infection with SARS-CoV-2 is modulated by sex. For men, different physiological states appear to exist that predispose to or protect against infection, whereas for women, we did not find evidence for divergent physiological states. Intriguingly, male participants who remained uninfected throughout the six-month observation period, had values for mean arterial pressure and waist-to-hip ratio that exceeded the normative reference range. We hypothesize that certain risk factors that worsen the outcome of COVID-19 disease, such as being overweight or having high blood pressure, may instead offer some protection against infection with SARS-CoV-2.

Neutrophil to lymphocyte ratio and systemic immune-inflammatory index as markers of response to autologous hematopoietic stem cell transplantation in persons with multiple sclerosis.

INTRODUCTION: Biomarkers that help to evaluate the immune system and could be useful in multiple sclerosis (MS) are the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). The objective of this work is to evaluate the significance of the SII index, PLR, and NLR before and after transplantation in individuals with MS who underwent autologous hematopoietic stem cell transplant (aHSCT) at a single institution. METHODS: Patients with MS who received an aHSCT between 2017 and 2022 were included in the study. NLR, PLR, and SII index were calculated prior to the transplant and 100 days after, and evaluation of the expanded disability status scale (EDSS) was done before the transplant and 12 months after. The cohort was divided into two groups: aHSCT responders (R) and nonresponders (NR). RESULTS: Fifty-eight individuals were examined: 37 patients in the responders group R group and 21 in NR group. There was no statistically significant difference in the SII, NLR, and PLR prior to the transplant, however at 100 days post-HSCT, NLR in the R group was 1.8 versus 3.1 in the NR group (p = 0.003), PLR was 194 versus 295, respectively (p = 0.024), meanwhile SII index was 489.5 versus 729.3 (p < 0.001). CONCLUSION: High NLR and SII index values after the aHSCT were associated with a worsening in the EDSS score. However, since this is the first ever study that compared NLR and SII index with the aHSCT response in persons with MS, further studies must be performed to corroborate this information.

Achalasia alters physiological networks depending on sex.

Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. While the infection is eventually resolved, genetically susceptible individuals may still be at risk of developing achalasia. This study aimed to determine whether immunological and physiological networks differ between male and female patients with achalasia. This cross-sectional study included 189 preoperative achalasia patients and 500 healthy blood donor volunteers. Demographic, clinical, laboratory, immunological, and tissue biomarkers were collected. Male and female participants were evaluated separately to determine the role of sex. Correlation matrices were constructed using bivariate relationships to generate complex inferential networks. These matrices were filtered based on their statistical significance to identify the most relevant relationships between variables. Network topology and node centrality were calculated using tools available in the R programming language. Previous occurrences of chickenpox, measles, and mumps infections have been proposed as potential risk factors for achalasia, with a stronger association observed in females. Principal component analysis (PCA) identified IL-22, Th2, and regulatory B lymphocytes as key variables contributing to the disease. The physiological network topology has the potential to inform whether a localized injury or illness is likely to produce systemic consequences and the resulting clinical presentation. Here we show that immunological involvement in achalasia appears localized in men because of their highly modular physiological network. In contrast, in women the disease becomes systemic because of their robust network with a larger number of inter-cluster linkages.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review.

Introduction: Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrated brain-specific molecular findings of PTSD from humans and animals. Methods: A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms. Results: Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, with 17 of them significantly enriched for PTSD. Chemical synaptic transmission and signaling by G-protein-coupled receptors were consistently enriched across omics and species. Discussion: Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD's pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Rabies virus in white-nosed coatis (Nasua narica) in Mexico: what do we know so far?

Rabies is a neglected disease that affects all mammals. To determine the appropriate sanitary measures, the schedule of preventive medicine campaigns requires the proper identification of the variants of the virus circulating in the outbreaks, the species involved, and the interspecific and intraspecific virus movements. Urban rabies has been eradicated in developed countries and is being eradicated in some developing countries. In Europe and North America, oral vaccination programs for wildlife have been successful, whereas in Latin America, Asia, and Africa, rabies remains a public health problem due to the habitation of a wide variety of wild animal species that can act as rabies virus reservoirs in their environment. After obtaining recognition from the WHO/PAHO as the first country to eliminate human rabies transmitted by dogs, Mexico faces a new challenge: the control of rabies transmitted by wildlife to humans and domestic animals. In recent years, rabies outbreaks in the white-nosed coati (Nasua narica) have been detected, and it is suspected that the species plays a significant role in maintaining the wild cycle of rabies in the southeast of Mexico. In this study, we discussed cases of rabies in white-nosed coatis that were diagnosed at InDRE (in English: Institute of Epidemiological Diagnosis and Reference; in Spanish: Instituto de Diagnostico y Referencia Epidemiologicos) from 1993 to 2022. This study aimed to determine whether white-nosed coatis might be an emergent rabies reservoir in the country. A total of 13 samples were registered in the database from the Rabies laboratories of Estado de Mexico (n = 1), Jalisco (n = 1), Quintana Roo (n = 5), Sonora (n = 1), and Yucatan (n = 5). Samples from 1993 to 2002 from Estado de Mexico, Jalisco, and Sonora were not characterized because we no longer had any samples available. Nine samples were antigenically and genetically characterized. To date, coatis have not been considered important vectors of the rabies virus. The results from our research indicate that the surveillance of the rabies virus in coatis should be relevant to prevent human cases transmitted by this species.

Lobectomías pulmonares en Colombia: una caracterización demográfica y clínico-patológica / Pulmonary lobectomies in Colombia: a demographic and clinicopathological characterization

Introducción. La lobectomía pulmonar es uno de los procedimientos más frecuentes en la cirugía torácica en Colombia y a nivel mundial. El objetivo de este estudio fue proporcionar información sobre el comportamiento clínico de los individuos sometidos a este tipo de cirugías. Métodos. Estudio observacional retrospectivo en un Hospital Universitario de Cali, Colombia, que incluyó todos los pacientes sometidos a lobectomía pulmonar, por causas benignas o malignas, entre los años 2010 y 2020. La información se extrajo del registro institucional de cirugía de tórax, obteniendo datos demográficos, clínicos y patológicos. Resultados. Se evaluaron los registros clínicos de 207 individuos. El 55,5 % eran mujeres, la edad promedio fue 58 años y el 41 % tuvieron antecedente de tabaquismo. En el 51,6 % de los casos se diagnosticaron neoplasias, de las cuales el 47,8 % eran primarias de pulmón, siendo el adenocarcinoma el subtipo más común. Las enfermedades benignas no tumorales representaron el 48,3 % de los casos y la causa más frecuente fueron las infecciones, dentro de las que se incluyeron 17 casos de tuberculosis pulmonar. La técnica más frecuente fue la cirugía toracoscópica video asistida (82,6 %). Presentaron un porcentaje de reintervención del 5,8 %, 10,6 % de complicaciones severas y una mortalidad hospitalaria del 4,3 %. Conclusión. La población evaluada muestra una carga alta de comorbilidades y riesgo operatorio elevado; de forma consecuente, al compararla con otras series internacionales, se encontró un porcentaje mayor de complicaciones perioperatorias y mortalidad.

Introduction. The pulmonary lobectomies is one of the most common procedures in thoracic surgery in Colombia and worldwide. The objective of this study is to provide information on the clinical behavior of individuals who underwent this type of surgeries. Methods. Retrospective observational study at a University Hospital in Cali, Colombia, including all individuals who had pulmonary lobectomies, between the years 2010 to 2020 for benign and malignant causes. The information was extracted from the institutional registry of thoracic surgery, obtaining demographic, clinical and pathological data. Results. The clinical records of 207 individuals were evaluated, 55.5% were women, the average age was 58 years, and 41% had a history of smoking. Of these cases, 51.6% were diagnosed with neoplasms, of which 47.8% were primary lung neoplasms, with adenocarcinoma being the most common subtype. As for benign diseases, they represented 48.3% of the cases and the most frequent cause was infections, including 17 cases of pulmonary tuberculosis. The most frequent technique was video-assisted thoracoscopic surgery in 82.6%, with a reoperation rate of 5.8%, up to 10.6% of severe complications, a median hospital stay of 6 days, and a hospital mortality of 4.3%.Conclusion. The population evaluated shows a high burden of comorbidities and high operative risk; consequently, when compared with other international series, it shows a higher percentage of perioperative complications, hospital stay, and mortality.

Preparaciones culinarias ¿cómo determinar cuándo forman parte de una dieta sustentable?

La adopción de formas de consumo y producción sostenibles de alimentos es una necesidad imperiosa, debido a las consecuencias adversas que los sistemas alimentarios actuales tienen para la salud y el planeta. A pesar de que estudios muestran que las personas valoran un menor efecto de la dieta en el ambiente, desconocen cómo evaluar su impacto en este sentido. Esta revisión cualitativa buscó la existencia de indicadores o herramientas que permitan evaluar la sustentabilidad de preparaciones culinarias como parte de una dieta sostenible. Se incluyen definiciones, abordajes y formas de medir y evaluar tanto la dieta como la gastronomía sustentable a nivel mundial y nacional. La búsqueda de artículos científicos se realizó en las bases de datos Medline/PubMed, Scopus, Web of Science y SciELO utilizando como palabras claves "dietas sustentables", "dietas sostenibles", "ecogastronomía", "sustainability assessment", "out of home meals", "sustainable gastronomy", "sustainable diet", "sustainable healthy diets", "sustainability indicators", "sustainable indicators", "sustainability index", "sustainable diets index", "dietas sustentáveis". Toda dieta tiene un impacto en el medio ambiente, sin embargo, factores como su composición y formas de producción determinan la magnitud de dicho impacto. Un tema central gira en torno a las metodologías para medir, analizar y evaluar los diferentes aspectos que componen la sostenibilidad de las dietas, existiendo escasa evidencia respecto de herramientas que permitan calificar las preparaciones culinarias según su nivel de sustentabilidad. Por esto, se requiere mayor investigación en la materia con el propósito de contribuir en la adopción de dietas saludables y sostenibles por parte de la población.

The adoption of sustainable forms of consumption and production is an imminent need due to the adverse consequences that current food systems have on health and the planet. Although studies show that people value a lesser effect of diet on the environment, they do not know how to evaluate its impact in this sense. This qualitative literature review investigated the existence of indicators or tools to assess the sustainability of culinary preparations as part of a sustainable diet. Definitions, approaches, and ways of measuring and evaluating sustainable diets and sustainable gastronomy at the global and national levels were included. The search for scientific articles was carried out in the Medline/PubMed, Scopus, Web of Science and SciELO databases using as keywords "sustainable diets", "sustainable diets", "ecogastronomy", "sustainability assessment", "out of home meals", "sustainable gastronomy", "sustainable diet", "sustainable healthy diets", "sustainability indicators", "sustainable indicators", "sustainability index", "sustainable diets index", "dietas sustentáveis". Every diet has an impact on the environment, however, factors such as its composition and forms of production determine the magnitude of this impact. A central issue revolves around the methodologies to measure, analyze and evaluate the different aspects that make up the sustainability of diets, and there is little evidence regarding tools to qualify culinary preparations according to their level of sustainability. Therefore, further research is required in this area in order to contribute to the adoption of healthy and sustainable diets by the population.

Rare tandem repeat expansions associate with genes involved in synaptic and neuronal signaling functions in schizophrenia.

Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex disorders such as cancer and autism spectrum disorder. The role of TREs in schizophrenia is now emerging. In this study, we have performed a genome-wide investigation of TREs in schizophrenia. Using genome sequence data from 1154 Swedish schizophrenia cases and 934 ancestry-matched population controls, we have detected genome-wide rare (<0.1% population frequency) TREs that have motifs with a length of 2-20 base pairs. We find that the proportion of individuals carrying rare TREs is significantly higher in the schizophrenia group. There is a significantly higher burden of rare TREs in schizophrenia cases than in controls in genic regions, particularly in postsynaptic genes, in genes overlapping brain expression quantitative trait loci, and in brain-expressed genes that are differentially expressed between schizophrenia cases and controls. We demonstrate that TRE-associated genes are more constrained and primarily impact synaptic and neuronal signaling functions. These results have been replicated in an independent Canadian sample that consisted of 252 schizophrenia cases of European ancestry and 222 ancestry-matched controls. Our results support the involvement of rare TREs in schizophrenia etiology.

Ollas Comunes en Chile. Entendiendo un fenómeno social de organización para enfrentar el hambre durante la pandemia por COVID-19 / Common pots in Chile. Understanding a social phenomenon of organization to face hunger during the COVID-19 pandemic

Fundamentos: La pandemia por COVID-19 ha conducido a una crisis socioeconómica, aumentando lainseguridad alimentaria. Las medidas gubernamentales no han sido suficientes y la comunidad se haorganizado para solucionar sus necesidades alimentarias. En Chile resurgieron las “Ollas Comunes” (OC):organizaciones sociales autogestionadas cuyo propósito es alimentar a miembros de la comunidad ensituación de hambre. El objetivo del estudio es describir los elementos característicos del funcionamiento delas OC en Chile durante la pandemia por COVID-19.Métodos: Estudio descriptivo transversal, que utiliza datos cuantitativos y cualitativos. A través de unformulario online, se recolectó información de 117 OC a nivel nacional.Resultados: En promedio, 9 personas trabajan en las OC, con diferentes tareas. Las OC operabanprincipalmente 3 días a la semana, mayormente en espacios comunitarios en barrios más vulnerables. Los/asvoluntarios/as reconocen que las OC surgen por una necesidad de la comunidad que el gobierno no es capazde atender; las OC promueven la participación social y son una ayuda para la población vulnerable.Conclusiones: Esta investigación podría ayudar a desarrollar políticas públicas que consideren a estasorganizaciones comunitarias y su rol frente a la inseguridad alimentaria, así como aprovechar la capacidad yainstalada por la comunidad. (AU)

Background: The COVID-19 pandemic has led to a socioeconomic crisis, increasing food insecurity.Government measures have not been enough, and the community has organized itself to solve its foodneeds. In Chile, the "Ollas Comunes" (OC) have re-emerged: self-managed social organizations whose purposeis to feed community members in a situation of hunger. The study aims to describe the characteristicelements of the operation of the OC in Chile during the COVID-19 pandemic.Methods: This is a cross-sectional and descriptive study, which uses quantitative and qualitative data.Through an online form, information was collected from 117 OC nationwide.Results: On average, nine people work in the OC, with different tasks. The OC operated mainly three days aweek in community spaces and in the more vulnerable neighborhoods. The volunteers recognized that the OCarose from a community need that the government could not attend to; the OC promoted social participationand helped the vulnerable population.Conclusions: This research could help develop public policies that consider these community organizationsand their role in food insecurity and take advantage of the community capacity. (AU)

Recommendations to encourage participation of individuals from diverse backgrounds in psychiatric genetic studies.

We present innovative research practices in psychiatric genetic studies to ensure representation of individuals from diverse ancestry, sex assigned at birth, gender identity, age, body shape and size, and socioeconomic backgrounds. Due to histories of inappropriate and harmful practices against marginalized groups in both psychiatry and genetics, people of certain identities may be hesitant to participate in research studies. Yet their participation is essential to ensure diverse representation, as it is incorrect to assume that the same genetic and environmental factors influence the risk for various psychiatric disorders across all demographic groups. We present approaches developed as part of the Eating Disorders Genetics Initiative (EDGI), a study that required tailored approaches to recruit diverse populations across many countries. Considerations include research priorities and design, recruitment and study branding, transparency, and community investment and ownership. Ensuring representation in participants is costly and funders need to provide adequate support to achieve diversity in recruitment in prime awards, not just as supplemental afterthoughts. The need for diverse samples in genetic studies is critical to minimize the risk of perpetuating health disparities in psychiatry and other health research. Although the EDGI strategies were designed specifically to attract and enroll individuals with eating disorders, our approach is broadly applicable across psychiatry and other fields.

Assessment of Angiogenesis and Cell Survivability of an Inkjet Bioprinted Biological Implant in an Animal Model.

The rapidly growing field of tissue engineering hopes to soon address the shortage of transplantable tissues, allowing for precise control and fabrication that could be made for each specific patient. The protocols currently in place to print large-scale tissues have yet to address the main challenge of nutritional deficiencies in the central areas of the engineered tissue, causing necrosis deep within and rendering it ineffective. Bioprinted microvasculature has been proposed to encourage angiogenesis and facilitate the mobility of oxygen and nutrients throughout the engineered tissue. An implant made via an inkjet printing process containing human microvascular endothelial cells was placed in both B17-SCID and NSG-SGM3 animal models to determine the rate of angiogenesis and degree of cell survival. The implantable tissues were made using a combination of alginate and gelatin type B; all implants were printed via previously published procedures using a modified HP inkjet printer. Histopathological results show a dramatic increase in the average microvasculature formation for mice that received the printed constructs within the implant area when compared to the manual and control implants, indicating inkjet bioprinting technology can be effectively used for vascularization of engineered tissues.