Adipose tissue from children with obesity demonstrates a dysregulation of key modulators of MB and organelle structure, and displays hyperacetylation of key proteins and altered expression of upstream regulators of cell metabolism.

Dear Editor, Although dexamethasone is approved for the hyperinflammation treatment of hospitalised COVID-19 patients, nonhospitalised patients do not benefit from this therapy. 1 A potential drug for treating COVID-19 patients is polymerised type I collagen (PTIC). A downregulator of proinflammatory cytokines, adhesion molecules (ELAM-1, VCAM-1, and ICAM-1), cyclooxygenase (Cox)-1 enzyme and the collagenases expression through the modulation of transcription of factor NF-kB. [2][3][4][5][6] The intramuscular or subcutaneous administration of PTIC to patients with active RA (Phase II studies) improved the count of swollen joints and morning stiffness; 57% of patients achieved an ACR score of 50, and 30% had disease remission with this therapeutic combination. PTIC was safe and well-tolerated in long-term treatment, without adverse effects. [7][8][9] A double-blind, randomised, placebo-controlled clinical trial evaluated the PTIC intramuscular administration's safety and efficacy on hyperinflammation, oxygen saturation and symptom improvement in adult symptomatic COVID-19 outpatients (https://www.medrxiv.org/content/ 10.1101/2021.05.12.21257133v1).Eighty-nine participants with a confirmed COVID-19 diagnosis (mild to moderate disease) were included from August 31 to November 7, 2020, and followed for 12 weeks. Patients were randomly assigned to receive either 1.5 ml of PTIC intramuscularly every 12 h for 3 days and then every 24 h for 4 days (n = 45) or a matching placebo (n = 44) (sample size is describe in Methodology S1). Demographics, clinical characteristics, coexisting conditions and symptoms are described in Table 1. Ninety-eight per cent of patients in the PTIC group and 95.5% in the placebo group were analysed by the intention-to-treat principle (Figure S1). Of 89 patients at baseline, 64 (72%) were being treated with acetaminophen, 28 (31.5%) with acetylsalicylic acid, 5 (5.6%) with antivirals and 36 (40.4%) with antibiotics. The use of acetaminophen (71% vs. 73%), acetylsalicylic acid (27% vs. 39%), antivirals (7% vs. 5%) and antibiotics (40% vs. 41%) were similar in the PTIC andThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Taxane‐based chemotherapy regimens are used as first‐line treatment for breast cancer. Neurotoxicity, mainly taxane‐induced peripheral neuropathy (TIPN), remains the most important dose‐limiting adverse event. Multiple genes may be associated with TIPN; however, the strength and direction of the association remain unclear. For this reason, we systematically reviewed observational studies of TIPN pharmacogenetic markers in breast cancer treatment. We conducted a systematic search of terms alluding to breast cancer, genetic markers, taxanes, and neurotoxicity in Ovid, ProQuest, PubMed, Scopus, Virtual Health, and Web of Science. We assessed the quality of evidence and bias profile. We extracted relevant variables and effect measures. Whenever possible, we performed random‐effects gene meta‐analyses and examined interstudy heterogeneity with meta‐regression models and subgroup analyses. This study follows the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) and STrengthening the REporting of Genetic Association Studies (STREGA) reporting guidance. A total of 42 studies with 19,431 participants were included. These evaluated 262 single‐nucleotide polymorphisms (SNPs) across 121 genes. We conducted meta‐analyses on 23 genes with 60 SNPs (19 studies and 6246 participants). Thirteen individual SNPs (ABCB1‐rs2032582, ABCB1‐rs3213619, BCL6/‐rs1903216, /CAND1‐rs17781082, CYP1B1‐rs1056836, CYP2C8‐rs10509681, CYP2C8‐rs11572080, EPHA5‐rs7349683, EPHA6‐rs301927, FZD3‐rs7001034, GSTP1‐rs1138272, TUBB2A‐rs9501929, and XKR4‐rs4737264) and the overall SNPs' effect in four genes (CYP3A4, EphA5, GSTP1, and SLCO1B1) were statistically significantly associated with TIPN through meta‐analysis. In conclusion, through systematic review and meta‐analysis, we found that polymorphisms, and particularly 13 SNPs, are associated with TIPN, suggesting that genetics does play a role in interindividual predisposition. Further studies could potentially use these findings to develop individual risk profiles and guide decision making.