Age- and Sex-Associated Wnt Signaling Dysregulation is Exacerbated from the Early Stages of Neuropathology in an Alzheimer's Disease Model.

Emerging studies suggest that Wnt signaling is dysregulated in the brains of AD patients, suggesting that this pathway may also contribute to disease progression. However, it remains to be determined whether alterations in the Wnt pathway are the cause or consequence of this disease and which elements of Wnt signaling mainly contribute to the appearance of AD histopathological markers early in disease compared to what occurs during normal aging. The present study aimed to describe the status of several canonical Wnt pathway components and the expression of the AD marker p-tau in the hippocampi of female and male 3xTg-AD mice during disease progression compared to those during normal aging. We analyzed the levels of the canonical Wnt components Wnt7a, Dkk-1, LRP6 and GSK3ß as well as the levels of p-tau and BDNF at 3, 6, 9-12 and 18 months of age. We found a gradual increase in Dkk-1 levels during aging prior to Wnt7a and LRP5/6 depletion, which was strongly exacerbated in 3xTg-AD mice even at young ages and correlated with GSK3ß activation and p-tau-S202/Thr205 expression. Dkk-1 upregulation, as well as the level of p-tau, was significantly greater in females than in males. Our results suggest that Dkk-1 upregulation is involved in the expression of several features of AD at early stages, which supports the possibility of positively modulating the canonical Wnt pathway as a therapeutic tool to delay this disease at early stages.

The enigmatic triad, a clinical challenge.

The concomitant occurrence of diabetic ketoacidosis (DKA), hypertriglyceridemia (HTG) and acute pancreatitis (AP) was first described by Nair et al. as "The Enigmatic Triad", because the causal factor of AP is still not fully established. We recently attended a patient with this triad.

Mixed 4f population of Tm adatoms on insulating Cu2N islands.

The electronic properties of Tm and Lu atoms adsorbed on nanoscale Cu2N insulating islands and on a clean Cu(100) surface have been investigated by scanning tunnelling microscopy and spectroscopy, and density functional calculations modelling the electronic structure of the rare earth atoms were performed. While Lu adatoms display the same spectra on both surfaces, tunnelling spectra of Tm on Cu2N indicate a state at ≃0.8 V or ≃1.9 V bias, depending on the 4f population of the adatom, 4f12 or 4f13, which is not present on Tm atoms adsorbed on Cu(100). Although inelastic 4f-spin-flip excitations were not detected, variation of tunnelling through the strongly correlated d-electrons indicates that the insulating layer opens a pathway to access the electronic state of those 4f electrons in the single adatom.

Health-care guidelines and policies during the COVID-19 pandemic in Mexico: A case of health-inequalities.

BACKGROUND: Heterogeneous government responses have been reported in reaction to COVID-19. The aim of this study is to generate an exploratory review of healthcare policies published during COVID-19 by health-care institutions in Mexico. Analyzing policies within different health sub-systems becomes imperative in the Mexican case due to the longstanding fragmentation of the health-care system and health inequalities. DATA AND METHODS: Policies purposely included in the analysis were published by four public health institutions (IMSS, ISSSTE, SSA and PEMEX) during the COVID-19 epidemic in Mexico (from February 29th to June 15th, 2020) on official institutional websites. Researchers reviewed each document and classified them into seven policy categories set by the Rapid Research Evaluation and Appraisal Lab (RREAL): public health response, health-care delivery, human resources, health-system infrastructure and supplies, clinical response, health-care management, and epidemiological surveillance. RESULTS: Policy types varied by health institution. The largest number of policies were aimed at public health responses followed by health-care delivery and human resources. Policies were mainly published during the community transmission phase. CONCLUSIONS: The pandemic exposed underlying health-care system inequalities and a reactive rather than prepared response to the outbreak. Additionally, this study outlines potential policy gaps and delays in the response that could be avoided in the future.

Impact of natural selection on global patterns of genetic variation, and association with clinical phenotypes, at genes involved in SARS-CoV-2 infection.

We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection ( ACE2, TMPRSS2, DPP4 , and LY6E ). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At ACE2 , we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function. However, three non-synonymous variants were common among Central African hunter-gatherers from Cameroon and are on haplotypes that exhibit signatures of positive selection. We identify strong signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2 , we identified 13 amino acid changes that are adaptive and specific to the human lineage. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19.

Antiferromagnetic Spin Coupling between Rare Earth Adatoms and Iron Islands Probed by Spin-Polarized Tunneling.

High-density magnetic storage or quantum computing could be achieved using small magnets with large magnetic anisotropy, a requirement that rare-earth iron alloys fulfill in bulk. This compelling property demands a thorough investigation of the magnetism in low dimensional rare-earth iron structures. Here, we report on the magnetic coupling between 4f single atoms and a 3d magnetic nanoisland. Thulium and lutetium adatoms deposited on iron monolayer islands pseudomorphically grown on W(110) have been investigated at low temperature with scanning tunneling microscopy and spectroscopy. The spin-polarized current indicates that both kind of adatoms have in-plane magnetic moments, which couple antiferromagnetically with their underlying iron islands. Our first-principles calculations explain the observed behavior, predicting an antiparallel coupling of the induced 5d electrons magnetic moment of the lanthanides with the 3d magnetic moment of iron, as well as their in-plane orientation, and pointing to a non-contribution of 4f electrons to the spin-polarized tunneling processes in rare earths.