COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor ...involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood.
We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells.
Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2).
The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy.
Key messages
Critically ill COVID-19 patients show emergency myelopoiesis.
HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets.
HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.
Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell ...adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as
,
and
. The
variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in
and
SNV were present.
and
SNVs were present in all three SCA, whereas in two of these tumors SNV in
and
were found. None of the analyzed tumors showed SNV in
or
. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors.
Anemia represents a global health problem that negatively impacts quality of life in elderly population; however, its impact on the geriatric syndrome of frailty is unclear. We examined the ...prevalence of anemia among elderly and sought a relationship between hemoglobin and the phenotype of frailty. Baseline hemoglobin quintiles and anemia were assessed in relation to frailty status in a prospective study with 1,933 older community-dwelling adults enrolled in the Study on Aging and Dementia in Mexico (SADEM). Logistic regression was used to model the relationship between frailty and Hb, adjusting for risk factors of frailty, sociodemographic data, cognitive decline, chronic diseases, and some risky habits. Prevalence of frailty was 8.3 %. Frailty risk was highest at the lowest hemoglobin quintile (<14.3 g/dL for men; <13.3 g/dL for women), and 160 (8.3 %) were anemic (<13 g/dL for men; <12 g/dL for women). The relationship between frailty and Hb levels, adjusted for age and sex, observed in the first and fifth quintiles, compared with the fourth quintile, were 1.53 (95 % confidence interval (CI), 1.46–1.60) and 1.05 (95 % CI, 1.01–1.15). After multivariate adjustment, the odds ratios (ORs) were 1.23 (95 % CI, 1.17–1.13) and 1.06 (95 % CI, 1.01–1.11). The association was not diminished by risk factors for frailty (body mass index (BMI), comorbidity, cognitive decline, smoking, alcohol consumption, etc.). In community-dwelling older adults, low hemoglobin concentrations and anemia were independently associated with increased frailty risk. This suggests that mild anemia and low Hb levels are independent, modifiable risk factors for frailty.
Endothelial dysfunction and subsequent inflammation contribute to the development of vascular cognitive impairment (VCI). Soluble intercellular adhesion molecule-1 (sICAM-1) is upregulated in ...endothelial dysfunction and promotes an inflammatory response; however, the relationship between sICAM-1 and VCI remains equivocal.
To determine whether sICAM-1 contributes to the prediction of VCI.
Community-dwelling older adults (n = 172) from the "Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults" (COSFOMA) study were identified as VCI or controls using standard neuropsychological evaluations and neuroimaging. sICAM-1 was quantified using ELISA, and multivariate logistic regression determined the association between sICAM-1 and VCI.
A total of 31 VCI cases were identified. sICAM-1 was higher in VCI (VCI: 450.7 241.6 ng/mL vs. controls: 296.9 140.9 ng/mL). sICAM-1 concentrations above the 90th percentile (464.1 ng/mL) were associated with VCI group membership in all models (OR: 6.9, 95% CI: 1.1-42.2). The final saturated model explained 64% of the variance in VCI group membership.
High concentrations of sICAM-1 are independently associated with VCI group membership. Efforts to further characterize the relationship between indices of endothelial dysfunction and pathological changes to the aging brain should be further pursued.
IntroductionCognitive and physical declines are frequent causes of disability among older adults (OAs) in Mexico that imposes significant burden on the health system and OAs’ families. Programmes to ...prevent or delay OAs’ cognitive and physical decline are scarce.Methods and analysisA double-blind randomised clinical trial will be conducted. The study will aim to evaluate two 24-week double-task (aerobic and cognitive) square-stepping exercise programmes for OAs at risk of cognitive decline—one programme with and another without caregiver participation—and to compare these with an aerobic-balance-stretching exercise programme (control group). 300 OAs (100 per group) affiliated with the Mexican Institute of Social Security (IMSS) between 60 and 65 years of age with self-reported cognitive concerns will participate. They will be stratified by education level and randomly allocated to the groups. The intervention will last 24 weeks, and the effect of each programme will be evaluated 12, 24 and 52 weeks after the intervention. Participants’ demographic and clinical characteristics will be collected at baseline. The outcomes will include: (1) general cognitive function; (2) specific cognitive functions; (3) dual-task gait; (4) blood pressure; (5) carotid intima–media thickness; (6) OAs’ health-related quality of life; and (7) caregiver burden. The effects of the interventions on each outcome variable will be examined using a repeated-measures analysis of variance (ANOVA), with study groups as the between-subjects variable and time as the within-subject variable.Ethics and disseminationThe study was approved by the IMSS Ethics and Research Committees (registration number: 2018-785-095). All participants will sign a consent form prior to their participation. The study results will be disseminated to the IMSS authorities, healthcare providers and the research community.Trial registration numberClinicalTrials.gov (NCT04068376).
El exceso de tejido adiposo representa una de las principales causas de las enfermedades metabólicas y cardiovasculares. Inicialmente al tejido adiposo se le consideró el almacén de lípidos y energía ...del organismo. Posteriormente se descubrió que presentaba otras funciones, como la endocrina, controlando diferentes procesos metabólicos e inmunitarios. Por sus características funcionales y estructurales, se reconocen varios tipos de tejido adiposo. El adipocito blanco representa la reserva energética y el adipocito marrón se encarga de la oxidación de los lípidos para la termogénesis. El adipocito beige se origina del adipocito blanco, mediante un proceso que conduce a la lipólisis y la termogénesis. A los anteriores se han sumado el adipocito azul, en el hígado, que interviene en la homeostasis de retinoides, y el adipocito rosa, que participa en la lactogénesis y se ha identificado en la glándula mamaria de animales. La irisina es una hormona secretada principalmente por el músculo esquelético, que promueve el pardeamiento del tejido adiposo blanco a beige, favoreciendo así la termogénesis. Otro aspecto interesante de esta hormona es que representa una conexión entre la actividad muscular y la lipólisis. Por lo anterior, la irisina puede ser una clave en la prevención y el tratamiento de la obesidad.
Antecedentes: El síndrome metabólico (SM) es un conjunto de alteraciones metabólicas que aumentan el riesgo de aparición de enfermedad cardiovascular (ECV) y diabetes. El exceso de lípidos en el ...tejido adiposo visceral (TAV) inicia la cascada de cambios metabólicos. Sin embargo, la información de la relación entre el tejido adiposo perirrenal (TAPR) y la disfunción metabólica es limitada. Objetivo: Analizar las diferencias del TAPR en individuos con y sin SM, en ausencia de diagnóstico de diabetes y ECV. Método: Estudio transversal de 108 pacientes, 72 mujeres y 36 hombres, de 30-50 años. Se midieron parámetros metabólicos, antropométricos, TAV por bioimpedancia y TAPR por medio de tomografía computarizada. Resultados: Los pacientes con SM, en comparación con los pacientes sin SM, presentaron incremento del TAPR (133.6 ± 92.4 vs. 102.9 ± 72.9 mm3; p = 0.006). Además, se encontró correlación del TAPR con índice de masa corporal, perímetro de cintura, glucosa, lípidos y microalbuminuria. Conclusiones: En pacientes con SM sin diabetes preexistente ni ECV se encontró un aumento de TAPR. Estos datos sugieren que aun en etapas previas al desarrollo de la diabetes y ECV, los pacientes con SM presentan incremento en el TAPR.
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