HLA-DR and HLA-DQ alleles in patients from the south of Brazil: markers for leprosy susceptibility and resistance

<p>Abstract</p> <p>Background</p> <p>Many epidemiological studies have shown that the genetic factors of the host play a role in the variability of clinical response to infection caused by <it>M. leprae</it>. With the purpose of identifying genes of susceptibility, the present study investigated the possible role of HLA-DRB1 and DQA1/DQB1 alleles in susceptibility to leprosy, and whether they account for the heterogeneity in immune responses observed following infection in a Southern Brazilian population.</p> <p>Methods</p> <p>One hundred and sixty-nine leprosy patients and 217 healthy controls were analyzed by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers(One Lambda^®, CA, USA).</p> <p>Results</p> <p>There was a positive association of HLA-DRB1*16 (*1601 and *1602) with leprosy <it>per se </it>(7.3% <it>vs</it>. 3.2%, <it>P </it>= 0.01, OR = 2.52, CI = 1.26–5.01), in accord with previous serological studies, which showed DR2 as a marker of leprosy. Although, HLA-DQA1*05 frequency (29.8% <it>vs</it>. 20.9%, <it>P </it>= 0.0424, OR = 1.61, CI = 1.09–2.39) was higher in patients, and HLA-DQA1*02 (3.0% <it>vs</it>. 7.5%, <it>P </it>= 0.0392, OR = 0.39, CI = 0.16 – 0.95) and HLA-DQA1*04 (4.0% <it>vs</it>. 9.1%, <it>P </it>= 0.0314, OR = 0.42, CI = 0.19 – 0.93) frequencies lower, <it>P</it>-values were not significant after the Bonferroni's correction. Furthermore, HLA-DRB1*1601 (9.0% <it>vs</it>. 1.8%; <it>P </it>= 0.0016; OR = 5.81; CI = 2.05–16.46) was associated with susceptibility to borderline leprosy compared to control group, and while HLA-DRB1*08 (11.2% <it>vs</it>. 1.2%; <it>P </it>= 0.0037; OR = 12.00; CI = 1.51 – 95.12) was associated with susceptibility to lepromatous leprosy, when compared to tuberculoid leprosy, DRB1*04 was associated to protection.</p> <p>Conclusion</p> <p>These data confirm the positive association of HLA-DR2 (DRB1*16) with leprosy <it>per se</it>, and the protector effect of DRB1*04 against lepromatous leprosy in Brazilian patients.</p

Publisher Correction:COVID-19-associated acute kidney injury: consensus report of the 25^th Acute Disease Quality Initiative (ADQI) Workgroup (Nature Reviews Nephrology, (2020), 10.1038/s41581-020-00356-5)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

A Single-Chain Magnet with a Very High Blocking Temperature and a Strong Coercive Field

Two isostructural 1D complexes, [M­(hfac)₂NaphNN]_<i>n</i> [M = Mn^II (<b>1</b>) or Co^II (<b>2</b>); NaphNN = 1-naphthyl nitronylnitroxide], were synthesized and exhibit very strong antiferromagnetic metal–radical exchange coupling. Compound <b>2</b> shows slow magnetic relaxation behavior with a high blocking temperature (<i>T</i>_B ≈ 13.2 K) and a very high coercive field of 49 kOe at 4.0 K

Binuclear Lanthanide-Radical Complexes Featuring Two Centers with Different Magnetic and Luminescence Properties

Binuclear complexes with general formula [Ln₂(hfac)₆­(H₂O)₂­(dppnTEMPO)] (Ln^III = Gd, Tb, and Dy) have been obtained using the paramagnetic ligand 1-piperidinyl-4-[(diphenylphosphinyl)­amino]-2,2,6,6-tetramethyl (dppnTEMPO) as a bridge. One of the lanthanide ions is ferromagnetically coupled with the TEMPO moiety. Two of the complexes (Dy and Tb) show slow relaxation of the magnetization, and the non-magneto-equivalence of the two Ln^III ions was clearly observed. The <i>ab initio</i> CASSCF calculations were employed to confirm this behavior, as well as to rationalize the Ln–Rad interaction. The simulations of the magnetic properties were allowed by the insights given by the calculations. The inequivalence of the Tb^III ions was also proved by emission spectroscopy

Transient gain of function of cannabinoid CB1 receptors in the control of frontocortical glucose consumption in a rat model of Type-1 diabetes

Here we aimed to unify some previous controversial reports on changes in both cannabinoid CB1 receptor (CB1R) expression and glucose metabolism in the forebrain of rodent models of diabetes. We determined how glucose metabolism and its modulation by CB1R ligands evolve in the frontal cortex of young adult male Wistar rats, in the first 8 weeks of streptozotocin-induced type-1 diabetes (T1D). We report that frontocortical CB1R protein density was biphasically altered in the first month of T1D, which was accompanied with a reduction of resting glucose uptake ex vivo in acute frontocortical slices that was normalized after eight weeks in T1D. This early reduction of glucose uptake in slices was also restored by ex vivo treatment with both the non-selective CB1R agonists, WIN55212−2 (500 nM) and the CB1R-selective agonist, ACEA (3 μM) while it was exacerbated by the CB1R-selective antagonist, O-2050 (500 nM). These results suggest a gain-of-function for the cerebrocortical CB1Rs in the control of glucose uptake in diabetes. Although insulin and IGF-1 receptor protein densities remained unaffected, phosphorylated GSKα and GSKβ levels showed different profiles 2 and 8 weeks after T1D induction in the frontal cortex. Altogether, the biphasic response in frontocortical CB1R density within a month after T1D induction resolves previous controversial reports on forebrain CB1R levels in T1D rodent models. Furthermore, this study also hints that cannabinoids may be useful to alleviate impaired glucoregulation in the diabetic cortex

COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI