Chemical and Protein Characterization of Two Varieties of Chickpea (Cicer Arietinum): Costa 2004 and El Patrón.

The objective of this study was to evaluate the chemical composition of two chickpea varieties, 'Costa 2004' and 'El Patrón', and to characterize their proteins to determine their technological potential for the food industry. For this purpose, chickpea samples of both varieties from the 2019 harvest region of Guanajuato, Mexico, were obtained and chemically characterized to determine the protein fractions using electrophoretic and amino acid profiling. The chickpea variety 'Costa 2004' contained 3% less protein and 7% less dietary fiber content than the variety 'El Patrón'; whereas, the carbohydrate content of 'Costa 2004' was 4% greater. Additionally, the chickpeas demonstrated an antioxidant capacity ranging from 319 to 387 µMET/g and total phenol levels exceeding 500 mg/g. Among the protein fractions, globulins represented the highest proportion in both varieties of chickpea, at approximately 8.73 g/100 g ('Costa 2004') and 10.42 g/100 g ('El Patrón'), followed by albumin, at approximately 1.24 g/100 g and 1.47 g/100 g, respectively. The chickpea proteins ranged in molecular weight between 100 and 25 kDa, with particularly strong signals in the albumin and globulin bands. Regarding the amino acid profile, histidine was predominant in both varieties. In conclusion, both varieties of chickpea have high nutritional value and broad potential for technological use in the food industry.

Metabolic dysregulation of tricarboxylic acid cycle and oxidative phosphorylation in glioblastoma.

Glioblastoma multiforme (GBM) exhibits genetic alterations that induce the deregulation of oncogenic pathways, thus promoting metabolic adaptation. The modulation of metabolic enzyme activities is necessary to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates essential for fulfilling the biosynthetic needs of glioma cells. Moreover, the TCA cycle produces intermediates that play important roles in the metabolism of glucose, fatty acids, or non-essential amino acids, and act as signaling molecules associated with the activation of oncogenic pathways, transcriptional changes, and epigenetic modifications. In this review, we aim to explore how dysregulated metabolic enzymes from the TCA cycle and oxidative phosphorylation, along with their metabolites, modulate both catabolic and anabolic metabolic pathways, as well as pro-oncogenic signaling pathways, transcriptional changes, and epigenetic modifications in GBM cells, contributing to the formation, survival, growth, and invasion of glioma cells. Additionally, we discuss promising therapeutic strategies targeting key players in metabolic regulation. Therefore, understanding metabolic reprogramming is necessary to fully comprehend the biology of malignant gliomas and significantly improve patient survival.

Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations in the hypoxic tumor microenvironment, as well as in transcriptional and signaling networks, which result in changes in global genetic expression. The signaling pathways PI3K/AKT/mTOR and RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, by modulating the transcriptional factors p53, HIF1, and c-Myc. The overexpression of HIF1 and c-Myc, master regulators of cellular metabolism, is a key contributor to the synthesis of bioenergetic molecules that mediate glioma cell transformation, proliferation, survival, migration, and invasion by modifying the transcription levels of key gene groups involved in metabolism. Meanwhile, the tumor-suppressing protein p53, which negatively regulates HIF1 and c-Myc, is often lost in glioblastoma. Alterations in this triad of transcriptional factors induce a metabolic shift in glioma cells that allows them to adapt and survive changes such as mutations, hypoxia, acidosis, the presence of reactive oxygen species, and nutrient deprivation, by modulating the activity and expression of signaling molecules, enzymes, metabolites, transporters, and regulators involved in glycolysis and glutamine metabolism, the pentose phosphate cycle, the tricarboxylic acid cycle, and oxidative phosphorylation, as well as the synthesis and degradation of fatty acids and nucleic acids. This review summarizes our current knowledge on the role of HIF1, c-Myc, and p53 in the genic regulatory network for metabolism in glioma cells, as well as potential therapeutic inhibitors of these factors.

Algorithms for predicting COVID outcome using ready-to-use laboratorial and clinical data.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging crisis affecting the public health system. The clinical features of COVID-19 can range from an asymptomatic state to acute respiratory syndrome and multiple organ dysfunction. Although some hematological and biochemical parameters are altered during moderate and severe COVID-19, there is still a lack of tools to combine these parameters to predict the clinical outcome of a patient with COVID-19. Thus, this study aimed at employing hematological and biochemical parameters of patients diagnosed with COVID-19 in order to build machine learning algorithms for predicting COVID mortality or survival. Patients included in the study had a diagnosis of SARS-CoV-2 infection confirmed by RT-PCR and biochemical and hematological measurements were performed in three different time points upon hospital admission. Among the parameters evaluated, the ones that stand out the most are the important features of the T1 time point (urea, lymphocytes, glucose, basophils and age), which could be possible biomarkers for the severity of COVID-19 patients. This study shows that urea is the parameter that best classifies patient severity and rises over time, making it a crucial analyte to be used in machine learning algorithms to predict patient outcome. In this study optimal and medically interpretable machine learning algorithms for outcome prediction are presented for each time point. It was found that urea is the most paramount variable for outcome prediction over all three time points. However, the order of importance of other variables changes for each time point, demonstrating the importance of a dynamic approach for an effective patient's outcome prediction. All in all, the use of machine learning algorithms can be a defining tool for laboratory monitoring and clinical outcome prediction, which may bring benefits to public health in future pandemics with newly emerging and reemerging SARS-CoV-2 variants of concern.

Clinical characteristics, diagnosis, treatment and outcomes of patients living with HIV and co-infected with tuberculosis and histoplasmosis: a 5-y retrospective case series.

BACKGROUND: In Latin America, tuberculosis (TB) and histoplasmosis are two of the most frequent opportunistic infections affecting people living with human immunodeficiency virus (HIV). However, there are limited data on the clinical characteristics and outcomes of patients with concurrent TB and histoplasmosis infections. METHODS: This was a retrospective observational study to describe the clinical, epidemiological and laboratory characteristics and outcomes of 21 patients living with HIV (PLHIV) who were diagnosed with concurrent histoplasmosis and TB between 2017 and 2021 in Guatemala City, Guatemala. RESULTS: Most patients were male and were newly diagnosed with HIV. All patients had advanced HIV disease (AHD). They presented with a median CD4 count of 20 cells/µl. The most common symptoms reported by the patients were fever, weight loss, cough and diarrhoea. Twelve patients died within 6 months of baseline evaluation, for a mortality rate of 57.1%. CONCLUSIONS: PLHIV with concurrent TB and histoplasmosis infections are characterised by AHD, predominantly presenting with disseminated forms of these infections and with unspecific symptoms and signs. This evidence calls for early HIV and opportunistic infection screening and insights into the challenges and opportunities for the efficient diagnostic and therapeutic management of patients with AHD with concurrent histoplasmosis and TB infections.

Reirradiation salvage radiotherapy for recurrent prostate cancer after primary low-dose brachytherapy.

PURPOSE: Local recurrence of prostate cancer after low-dose rate brachytherapy is a clinical problem with limited salvage treatment options. This prospective study evaluated the tolerability and outcome of salvage external beam radiation therapy (S-EBRT) for locally recurrent prostate cancer after primary low-dose rate prostate brachytherapy (LDR-BT). MATERIALS AND METHODS: Between October 2012 and 2022, 18 patients with biopsy-proven locally recurrent prostate cancer after primary LDR-BT and received S-EBRT. We evaluated biochemical failure (BF), overall survival (OS) and acute/late gastrointestinal and urinary toxicities (CTCAE v5.0 or CTCAE v4, only before 2017). RESULTS: Median follow-up was 32 months (range, 5-124). The median age was at S-EBRT 68 years (range 59-79). 34% (6/18) were low risk, 44% (8/18) intermediate risk, 5% (1/18) high risk, and 17% (3/18) not specified. All patients were treated with IMRT/VMAT and received 60 Gy (2.5 Gy/fraction) to the prostate and 40% (7/18) 55.2 Gy (2,3 Gy/fx) to the seminal vesicles. 56% received ADT The 3-year OS and biochemical relapse-free survival after S-EBRT were 100% and 89%, respectively, with a median PSA nadir 0,035 ng/mL (0,01-0,34). Acute cystitis was present in 72% (13/18) of patients (27% of Grade > 2). Urethritis was present in 78% (14/18) patients (16% of cases Grade > 3), and acute rectitis occurred in 22% (4/18) of patients (no cases Grade > 3). CONCLUSIONS: Our data suggest that the treatment of locally recurrent prostate cancer with S-EBRT could provide adequate disease control safely and be used as an additional treatment in the natural history of prostate cancer patients. However, the results are still early and the sample is small; larger studies with longer follow-up would be mandatory.

Cáncer de mama en el norte del Perú: subtipos moleculares y HER2 low / Breast cancer in northern Peru: molecular subtypes and HER2 low

RESUMEN El objetivo del estudio fue conocer el perfil inmunohistoquímico del cáncer de mama e identificar el subgrupo HER2 low en la macrorregión norte del Perú. Se realizó un estudio transversal con una muestra de 1176 pacientes atendidos en el Instituto Regional de Enfermedades Neoplásicas Norte del Perú desde enero de 2016 a diciembre de 2023. Los datos recolectados (edad, tipo histológico, grado y resultados complementarios), se analizaron con frecuencias y porcentajes. El perfil correspondió a: luminal B (45,6%); luminal A (24,7%); triple negativo (18,2%); y HER2 positivo no luminal (11,5%). Además, HER2 low fueron 215 pacientes (25,1% de los considerados previamente negativos). Este estudio proporciona evidencia que la subtipificación de cáncer de mama ha cambiado, siendo luminal B más frecuente, y es esencial involucrar a políticas de salud para adquirir terapias dirigidas considerando a pacientes HER2 low.

ABSTRACT This study aimed to understand the immunohistochemical profile of breast cancer and to identify the HER2 low subgroup in the northern macro-region of Peru. A cross-sectional study was conducted in 1176 patients from the Regional Institute of Neoplastic Diseases Northern Peru, from January 2016 to December 2023. We analyzed the data (age, histological type, grade and complementary results), with frequencies and percentages. The profile corresponded to: luminal B (45.6%); luminal A (24.7%); triple negative (18.2%); and HER2 positive non luminal (11.5%). In addition, 215 patients presented HER2 low (25.1% of those previously considered negative). This study provides evidence that the subtyping of breast cancer has changed, being luminal B the most frequent. It is essential to involve health policies to acquire targeted therapies considering HER2 low patients.

Light Microscopic, Ultrastructure Analysis and Functional Morphology of Cornu aspersum Spermatozoa Contained in the Frozen Hermaphroditic Duct / Análisis de Microscopía de Luz, Ultraestructura y Morfología Funcional de Espermatozoides de Cornu aspersum Contenidos en el Conducto Hermafrodita Congelado

SUMMARY: In this study we describe the functional morphology of Cornu aspersum (Helix aspersa), spermatozoa using light, scanning (SEM) and transmission electron (TEM) microscopies. The studies were performed with sperm located in the frozen hermaphroditic duct. Our results showed that the head presents an elongated conical shape slightly coiled in a corkscrew, with the nucleus partially covered by an acrosome, where an apical vesicle is located at the lateralized apex. This peculiar shape suggests the helical displacement movement of the spermatozoa. The head and the nucleus are slightly larger size compared to those of other gastropod species. The intermediate tract is surrounded by a mitochondrial complex and a glycogen helix. The glycogen helix is coiled helically along the intermediate tract, presenting at least five twists of glycogen helices. The complexity of both the mitochondrial complex and the glycogen helix suggests a high metabolic consumption considering the long period of time until fertilization occurs. Our findings on the detailed characterization of Cornu aspersum spermatozoa, obtained from a frozen hermaphroditic duct can contribute to a better understanding of the functional morphology of sperm and serve as a reference for future studies.

En este estudio describimos la morfología funcional de Cornu aspersum (Helix aspersa), espermatozoides utilizando microscopías de luz, barrido (SEM) y electrónica de transmisión (TEM). Los estudios se realizaron con espermatozoides localizados en el conducto hermafrodita congelado. Nuestros resultados mostraron que la cabeza presenta una forma cónica alargada ligeramente enrollada en un tirabuzón, con el núcleo parcialmente cubierto por un acrosoma, donde se ubica una vesícula apical en el ápice lateralizado. Esta peculiar forma sugiere el movimiento de desplazamiento helicoidal de los espermatozoides. La cabeza y el núcleo son de un tamaño ligeramente mayor en comparación con los de otras especies de gasterópodos. El tracto intermedio está rodeado por un complejo mitocondrial y una hélice de glucógeno. La hélice de glucógeno se enrolla helicoidalmente a lo largo del tracto intermedio, presentando al menos cinco giros de hélices de glucógeno. La complejidad tanto del complejo mitocondrial como de la hélice de glucógeno sugiere un alto consumo metabólico considerando el largo período de tiempo hasta que ocurre la fecundación. Nuestros hallazgos sobre la caracterización detallada de los espermatozoides de Cornu aspersum, obtenidos de un conducto hermafrodita congelado, pueden contribuir a una mejor comprensión de la morfología funcional de los espermatozoides y servir como referencia para futuros estudios.

Perceived Social Support and Mental Health Indicators of a Mexican LGBT Sample During the COVID-19 Pandemic.

The COVID-19 pandemic created mental health challenges for LGBTQ + communities worldwide, however there is a paucity of research on Mexican populations. Existing data show that LGBTQ + people in Mexico experience acute forms of violence and discrimination that impact their mental health. This article explores the relationship between social support, discrimination, and mental health for LGBTQ + populations in Mexico (N = 1525) during the COVID-19 lockdown. Utilizing social media recruitment strategies, participants answered an online survey exploring five mental health indicators: depression, anxiety, stress, suicidal ideation, and suicide attempt during lockdown. Mediating, and multiple regression analyses revealed that neuroticism is the most important variable in predicting poor mental health, and that perceived social support plays a mediating role in the case of depression. Discomfort with one's own family holds positive correlations with mental health indicators, showing that the greater the discomfort, higher levels of depression, anxiety, stress, and suicidal ideation. Results also showed that discrimination, and drug use hold significant relationships to suicidal attempt. Practice recommendations for Mexican LGBTQ + communities are offered.

Erythrose inhibits the progression to invasiveness and reverts drug resistance of cancer stem cells of glioblastoma.

Glioblastoma (GBM) is the most frequent brain cancer and more lethal than other cancers. Characteristics of this cancer are its high drug resistance, high recurrence rate and invasiveness. Invasiveness in GBM is related to overexpression of matrix metalloproteinases (MMPs) which are mediated by wnt/ß-catenin and induced by the activation of signaling pathways extracellularly activated by the cytokine neuroleukin (NLK) in cancer stem cells (CSC). Therefore, in this work we evaluated the effect of the tetrose saccharide, erythrose (Ery), a NLK inhibitor of invasiveness and drug sensitization in glioblastoma stem cells (GSC). GSC were obtained from parental U373 cell line by a CSC phenotype enrichment protocol based on microenvironmental stress conditions such as hypoxia, hipoglycemia, drug exposition and serum starvation. Enriched fraction of GSC overexpressed the typical markers of brain CSC: low CD133+ and high CD44; in addition, epithelial to mesenchyme transition (EMT) markers and MMPs were increased several times in GSC vs. U373 correlating with higher invasiveness, elongated and tubular mitochondrion and temozolomide (TMZ) resistance. IC50 of Ery was found at nM concentration and at 24 h induced a severe diminution of EMT markers, MMPs and invasiveness in GSC. Furthermore, the phosphorylation pattern of NLK after Ery exposition also was affected. In addition, when Ery was administered to GSC at subIC50, it was capable of reverting TMZ resistance at concentrations innocuous to non-tumor cancer cells. Moreover, Ery added daily induced the death of all GSC. Those findings indicated that the phytodrug Ery could be used as adjuvant therapy in GBM.

Emotions, Agency, and Materiality: Embodiment of Homophobic Discrimination Amongst Mexican LGBTQ+ Youth.

Embodiment refers to understanding the body as the object and subject of culture, a process that allows an understanding of political, cultural, social, and emotional processes in the assemblage of a particular identity. We describe a qualitative-narrative study utilizing focus groups and interviews in three Mexican cities with 75 LGBTQ+ youth to understand the effects of discrimination and how this impacts subjectivity through embodied affection. Through axial and line-by-line analysis, we describe the process of embodiment through four dimensions: violence, emotions, agency, and materiality. Violence operates as the sediment for LGBTQ+ youth's subjective, social, and political life, and paves the way for particular emotions, such as guilt, shame, fear, sadness, and pain, that directly relates to material aspects such as gender expression and body presentation, beauty standards and a discourse around perversion and promiscuity. Finally, the combination of emotions and materiality prove relevant for certain expressions of agency and resilience.

Nudo verdadero como causa de taquicardia fetal persistente Reporte de un caso / True Knot as a Cause of Persistent Fetal Tachycardia. Case Report

Resumen Las anomalías del cordón umbilical están asociadas a efectos adversos durante el embarazo. El nudo verdadero del cordón umbilical está presente en el 0.3-2.1% de los embarazos y se ha asociado a muerte fetal. Dentro de los factores de riesgo se incluye, la edad materna, índice de masa corporal (IMC) elevado, multiparidad, trastornos hipertensivos, tabaquismo, polihidramnios, diabetes gestacional, sexo masculino del feto y otras malformaciones. El diagnóstico prenatal del nudo verdadero es raro y un desafío. La mayoría se diagnostica durante el nacimiento y sólo el 0.08% de los nudos verdaderos son diagnosticados de manera prenatal. El registro cardiotocográfico puede registrar trazos no tranquilizadores que reflejan que hay un estrés hipóxico o mecánico que interrumpe la oxigenación fetal. El objetivo de este reporte es mostrar un caso de nudo verdadero del cordón umbilical que presentó taquicardia fetal persistente durante el trabajo de parto con terminación del embarazo vía vaginal.

Abstract Umbilical cord abnormalities are associated with adverse effects during pregnancy. The true umbilical cord knot is present in 0.3-2.1% of pregnancies and has been associated with fetal death. Risk factors include maternal age, high BMI, multiparity, hypertensive disorders, smoking, polyhydramnios, gestational diabetes, male sex of the fetus, and other malformations. Prenatal diagnosis of the true knot is rare and challenging. Most are diagnosed at birth and only 0.08% of true knots are diagnosed prenatally. Non-reassuring cardiotocography traces may be present, reflecting hypoxic or mechanical stress disrupting fetal oxygenation. The aim of this case report is to present a case of true umbilical cord knot presenting with persistent fetal tachycardia during labor, resolved by vaginal delivery.

Epidemiology and Mortality of Cryptococcal Disease in Guatemala: Two-Year Results of a Cryptococcal Antigen Screening Program.

Cryptococcal disease is an important opportunistic infection among people living with HIV. The cryptococcal antigen (CrAg) can be detected before the clinical onset of meningitis and its screening is recommended. Here, we evaluated CrAg frequency, and describe the epidemiological characteristics and mortality at 180 days in a cohort of HIV patients from Guatemala. A total of 3457 patients were screened with a CrAg lateral flow assay in serum between January 2017 and December 2018. CrAg positivity was 11.5% in patients with ≤100 CD4/mm3, 8.7% in patients with <200 CD4/mm3, and 6.3% in patients with <350 CD4/mm3. In Latin America, we estimated 9.2% CrAg positivity (IC95% 7.9−10.7%) in patients with ≤100 CD4/mm3. Among patients newly diagnosed with HIV, we estimated 4416 incident cases per year in Latin America in those with <200 CD4/mm3 and 5289 in those with <350 CD4/mm3. In addition, we calculated the burden in people not on ARV or without viral suppression and found 28,672 cases. CrAg screening should be considered in patients who have a CD4 cell count < 350 cells/mm3. Cryptococcal meningitis was associated with 30.8% mortality in Guatemala. Global access to diagnosis as well as to liposomal amphotericin B and flucytosine is a priority.

Colorectal cancer: comparative analysis between two series of patients separated by more than three decades

Abstract Aim This study characterizes Colorectal Cancer (CRC) incidence in the University Hospital Ramon and Cajal, Madrid, and analyzes variations over time. It establishes risk groups, aiming to discover whether diagnosis can be determined in less advanced stages of disease. Method Evolutionary epidemiological study of genetic and environmental factors contributing to the development of CRC in this district that enables the comparison of two cohorts of patients separated by 37 years: G1 (patients of current group) and G2 (patients of historical group). The main risk variables gleaned retrospectively were analyzed and the statistical association between cohorts was determined. Results The mean age of patients increased significantly from 64 to 71 along with the incidence of ascending colon cancer. G1 scored higher than G2 for: the incidence of colon cancer in men, detection of adenomatous polyps (48.1%), percentage of resectability with curative intent (80.4%), and Dukes A stage (34.1%) (p < 0.001). Conclusion Biological aspects of CRC have been compared against its profile three decades earlier. We can confirm the existence of concrete changes in the manifestation and staging at the time of diagnosis or following earlier treatment. (AU)

Intervención educativa para el afrontamiento de la hipertensión arterial en adultos mayores de Alamar

RESUMEN Fundamento: la hipertensión arterial constituye uno de los problemas médico-sanitarios más prevalentes. Las estrategias de afrontamiento y el apoyo social desempeñan un rol importante en la adaptación y manejo de esta enfermedad crónica. Objetivo evaluar la efectividad de una intervención educativa para favorecer el afrontamiento de la hipertensión arterial en adultos mayores. Método: se realizó un estudio de intervención, entre enero y marzo de 2020. El universo estuvo constituido por 253 adultos mayores hipertensos del consultorio médico de familia 19, perteneciente al Policlínico Docente Mario Escalona Reguera de Alamar. La muestra fue de tipo no probabilística y estuvo conformada por 13 pacientes. Se analizaron como variables cualitativas: conocimiento de la enfermedad, estilos de vida, autocuidado, afrontamiento, recursos personológicos, autocontrol emocional, apoyo social, comunicación y adherencia terapéutica. Se calcularon las frecuencias absolutas y porcentajes de las variables cualitativas. Resultados con la aplicación del programa de intervención educativa los ancianos lograron cumplir los objetivos propuestos en cada sesión, adquirieron nuevos conocimientos y reflexionaron sobre la necesidad de modificar estilos de vida, ejercer mayor control sobre las emociones negativas, desarrollar el autocuidado y la adherencia terapéutica, para afrontar de una mejor manera la enfermedad. Conclusiones el programa de intervención educativa fue efectivo y tuvo un progreso favorable, en tanto modificó los estilos de afrontamiento a la enfermedad identificados. Se logró de ese modo, transformar en ellos, el problema de salud sobre el cual se intervino.

Background: arterial hypertension constitutes one of the most prevalent medical-sanitary problems. Coping strategies and social support play an important role in the adaptation and management of this chronic disease. Objective: to evaluate the effectiveness of an educational intervention to promote coping with the disease in hypertensive older adults. Method: an intervention study was carried out between January and March 2020. The 253 hypertensive older adults from the family doctor's office 19, belonging to the Mario Escalona Reguera Teaching Polyclinic in Alamar, were the universe. The sample was non-probabilistic with 13 patients. Qualitative variables were analyzed: knowledge of the disease, lifestyles, self-care, coping, personological resources, emotional self-control, social support, communication and therapeutic adherence. The absolute frequencies and percentages of the qualitative variables were calculated. Results: with the application of the educational intervention program, the elderly managed to meet the objectives proposed in each session, acquired new knowledge and reflected on the need to modify lifestyles, exercise greater control over negative emotions, develop self-care and therapeutic adherence, to better cope with the disease. Conclusions: the educational intervention program was effective and had a favorable progress, while it modified the identified styles of coping with the disease. In this way, it was possible to modify in them the health problem.

Regulatory role of acetylation on enzyme activity and fluxes of energy metabolism pathways.

BACKGROUND: Most of the enzymes involved in the central carbon metabolism are acetylated in Lys residues. It has been claimed that this covalent modification represents a novel regulatory mechanism by which both enzyme/transporter activities and pathway fluxes can be modulated. METHODS: To establish which enzymes are regulated by acetylation, a systematic experimental analysis of activities and acetylation profile for several energy metabolism enzymes and pathway fluxes was undertaken in cells and mitochondria. RESULTS: The majority of the glycolytic and neighbor enzymes as well as mitochondrial enzymes indeed showed Lys-acetylation, with GLUT1, HPI, CS, ATP synthase displaying comparatively lower acetylation patterns. The incubation of cytosolic and mitochondrial fractions with recombinant Sirt-3 produced lower acetylation signals, whereas incubation with acetyl-CoA promoted protein acetylation. Significant changes in acetylation levels of MDH and IDH-2 from rat liver mitochondria revealed no change in their activities. Similar observations were attained for the cytosolic enzymes from AS-30D and HeLa cells. A minor but significant (23%) increase in the AAT-MDH complex activity induced by acetylation was observed. To examine this question further, AS-30D and HeLa cells were treated with nicotinamide and valproic acid. These compounds promoted changes in the acetylation patterns of glycolytic proteins, although their activities and the glycolytic flux (as well as the OxPhos flux) revealed no clear correlation with acetylation. CONCLUSION: Acetylation seems to play no predominant role in the control of energy metabolism enzyme activities and pathway fluxes. GENERAL SIGNIFICANCE: The physiological function of protein acetylation on energy metabolism pathways remains to be elucidated.

Acetate Promotes a Differential Energy Metabolic Response in Human HCT 116 and COLO 205 Colon Cancer Cells Impacting Cancer Cell Growth and Invasiveness.

Under dysbiosis, a gut metabolic disorder, short-chain carboxylic acids (SCCAs) are secreted to the lumen, affecting colorectal cancer (CRC) development. Butyrate and propionate act as CRC growth inhibitors, but they might also serve as carbon source. In turn, the roles of acetate as metabolic fuel and protein acetylation promoter have not been clearly elucidated. To assess whether acetate favors CRC growth through active mitochondrial catabolism, a systematic study evaluating acetate thiokinase (AcK), energy metabolism, cell proliferation, and invasiveness was performed in two CRC cell lines incubated with physiological SCCAs concentrations. In COLO 205, acetate (+glucose) increased the cell density (50%), mitochondrial protein content (3-10 times), 2-OGDH acetylation, and oxidative phosphorylation (OxPhos) flux (36%), whereas glycolysis remained unchanged vs. glucose-cultured cells; the acetate-induced OxPhos activation correlated with a high AcK activity, content, and acetylation (1.5-6-fold). In contrast, acetate showed no effect on HCT116 cell growth, OxPhos, AcK activity, protein content, and acetylation. However, a substantial increment in the HIF-1α content, HIF-1α-glycolytic protein targets (1-2.3 times), and glycolytic flux (64%) was observed. Butyrate and propionate decreased the growth of both CRC cells by impairing OxPhos flux through mitophagy and mitochondrial fragmentation activation. It is described, for the first time, the role of acetate as metabolic fuel for ATP supply in CRC COLO 205 cells to sustain proliferation, aside from its well-known role as protein epigenetic regulator. The level of AcK determined in COLO 205 cells was similar to that found in human CRC biopsies, showing its potential role as metabolic marker.

Cutaneous manifestations of COVID-19 in Mexican patients: A case series and review of literature.

China officially recognized atypical pneumonia outbreak in December 2019; on 11 March 2020, the World Health Organization declared COVID-19 as a pandemic that is produced by a new coronavirus, named SARS-CoV-2, of rapid transmissibility, which can be asymptomatic, with mild to severe respiratory symptoms, and with cardiovascular, neurological, gastrointestinal, and cutaneous complications. Considering that the pandemic prolonged more than initially expected was prognostic, it is essential for the medical community to identify the signs and symptoms of COVID-19. Thus, this work's objectives were to present cases of cutaneous lesions observed in COVID-19 Mexican patients. We register cutaneous lesions in COVID-19 patients referred from internal medicine and otorhinolaryngology services to dermatology. We presented four interesting cases with cutaneous lesions, including exanthema morbilliform, urticaria, chilblains, ecchymosis, and facial edema, and review the available literature. The most frequent cutaneous markers are rash, chilblains, and urticaria. Skin lesions may be the first manifestation of COVID-19, accompany initial respiratory symptoms, or appear during the disease course. Symptoms associated with vascular changes (livedo reticularis and vasculitis) are considered of poor prognosis.

Impact of COVID-19 in Minas Gerais, Brazil: Excess deaths, sub-notified cases, geographic and ethnic distribution.

By analysing the evolution of the COVID-19 epidemic in the state of Minas Gerais, Brazil, we showed the importance of considering the sub-notification not only of deaths but also of infected cases. It was shown that the largely used criteria of a historical all-deaths baseline are not approachable in this case, where most of the deaths are associated with causes that should decrease due to social distancing and reduction of economic activities. A quite simple and intuitive model based on the Gompertz function was applied to estimate excess deaths and excess of infected cases. It fits well the data and predicts the evolution of the epidemic adequately. Based on these analyses, an excess of 21.638 deaths and 557.216 infected cases is predicted until the end of 2020, with an upper bound of the case fatality rate of around 2.4% and a prevalence of 2.6%. The geographical distribution of cases and deaths and its ethnic correlation are also presented. This study points out the necessity of governmental and private organizations working together to improve public awareness and stimulate social distancing to curb the viral infection, especially in critical places with high poverty.