Human genetic adaptation related to cellular zinc homeostasis.

SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.

Pierre Robin Sequence: An Updated Evidence-Based Treatment Proposal.

BACKGROUND: The Pierre Robin sequence (PRS) is characterized by the presence of micrognathia, glossoptosis, and respiratory obstruction during the neonatal period, its prompt recognition allows to mitigate the associated morbidity and mortality. A diagnosis and treatment algorithm was previously proposed based on data from the literature to guide therapeutic efforts; therefore, it was proposed to carry out a new search for relevant evidence to update or complement it. METHODS: A literature review of the subject was conducted in PubMed, Embase, and Cochrane databases, corresponding to the period between November 2016 and September 2021. Using the GRADE methodology, 38 articles from different clinical studies that discussed diagnostic tests or therapeutic approaches, directly or indirectly compared, were selected and evaluated. RESULTS: After evaluating and analyzing the selected articles, the new information was incorporated into an updated algorithm according to the most recent evidence found for the diagnosis and comprehensive management of patients with PRS. CONCLUSION: To date, there is no consensus in the literature on the treatment of patients with PRS nor are there multicenter studies comparing different management modalities. The indications to proceed with surgical strategies do not present changes with respect to the previous article. Nutritional monitoring is the main objective, and the study of oral feeding is essential in all scenarios.

A descriptive literature review of phubbing behaviors.

The practice of phubbing has become an emerging phenomenon of worldwide interest to researchers. The cause is due to the fact that smartphones are ubiquitous and are often used in co-present interactions. This behavior is generally considered inappropriate and is called "phubbing". Phubbing, as described by Chotpitayasunondh and Douglas (2018), is the act of snubbing someone in a social setting by looking at one's phone instead of paying attention to the other person. The aim of this article is to provide an overview of research studies on phubbing through a review of the current literature. To do this, a search was carried out in an international database, finding 84 relevant articles in English that appeared in peer-reviewed journals published between 2012, the year in which the term 'phubbing' appears, and January 2020. The review covers the main fields of research studies on phubbing behaviors. Likewise, the results of the study show the distribution of published articles on phubbing by year that detail the type of study and the methodological approach and, finally, the research journals that have published articles on phubbing. The results of this review are expected to stimulate and guide future research in this field.

Importance of γ-secretase in the regulation of liver X receptor and cellular lipid metabolism.

Presenilins (PS) are the catalytic components of γ-secretase complexes that mediate intramembrane proteolysis. Mutations in the PS genes are a major cause of familial early-onset Alzheimer disease and affect the cleavage of the amyloid precursor protein, thereby altering the production of the amyloid ß-peptide. However, multiple additional protein substrates have been identified, suggesting pleiotropic functions of γ-secretase. Here, we demonstrate that inhibition of γ-secretase causes dysregulation of cellular lipid homeostasis, including up-regulation of liver X receptors, and complex changes in the cellular lipid composition. Genetic and pharmacological inhibition of γsecretase leads to strong accumulation of cytoplasmic lipid droplets, associated with increased levels of acylglycerols, but lowered cholesteryl esters. Furthermore, accumulation of lipid droplets was augmented by increasing levels of amyloid precursor protein C-terminal fragments, indicating a critical involvement of this γ-secretase substrate. Together, these data provide a mechanism that functionally connects γ-secretase activity to cellular lipid metabolism. These effects were also observed in human astrocytic cells, indicating an important function of γ-secretase in cells critical for lipid homeostasis in the brain.

Switching from Premixed Insulin To Basal Insulin Analogue For Type 2 Diabetes and Role of Dipeptidyl Peptidase-4 Inhibitors.

INTRODUCTION: This study aimed to confirm the usefulness of basal insulin analogue plus oral antidiabetic drugs (OADs) for type 2 diabetes (T2D) patients inadequately controlled with premixed insulin with/without OADs and assess the role of dipeptidyl peptidase-4 (DPP-4) inhibitors within this regimen in clinical practice. METHODS: Spanish retrospective observational study that included 186 T2D patients with glycosylated hemoglobin (HbA1c) >7% (53 mmol/mol) despite premixed insulin with/without OADs who had been switched to basal insulin analogue plus OADs. Study data describing the situation before the treatment switch and 6 months later was retrospectively retrieved from patients' medical charts. RESULTS: Switching to a basal insulin plus OADs decreased HbA1c (-1.0%, p<0.001), fasting (-38.1 mg/dl, p<0.001) and postprandial glycemia (-36.1 mg/dl, p<0.001), with reduced body weight (-1.1 kg, p<0.001) and hypoglycemic episodes (-17.5%, p<0.001). 68 (36.6%) patients received a basal insulin plus DPP-4 inhibitor±metformin and 74 (39.8%) plus metformin only. The DPP-4 inhibitor±metformin group showed a greater HbA1c reduction than the metformin group (1.3±1.4% vs. 0.9±1.0%, p=0.022), with no significant differences between groups in hypoglycemic episodes. CONCLUSIONS: Basal insulin analogue plus OADs may be a useful treatment for type 2 diabetes patients inadequately controlled with premixed insulin. Administering DPP-4 inhibitors within this regimen may contribute to improve patients' glycemia, with a favorable weight-change profile and without increasing hypoglycemia risk.

Ritmo hematofágico de Simulium quadrivittum loew, 1862 (Diptera: Simuliidae) / Hematophagic rate of Simulium quadrivittum loew, 1862 (Diptera: Simuliidae)

Se detectó una relación de la actividad hematofágica de Siumuliium quedrivittatum con la variación de la posición solar el norte de la loma "La Cañada" (21- 43- N y 82- 54'0), la zona central de Isla de la Juventud; se obtuvieron 2 parábolas que responden a las ecuaciones y=11.61 + 0,137 S+ (4,727) S* y y=17,6 + 0,415 S + (-9,495)S*, para los valores de la mañana y la tarde respectivamente. Se encontró una mayor actividad hematofágica promedio durante la tarde (U=25, p<0,05)