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Introduction: Chronic migraine (CM) is at the severe end of the clinical migraine spectrum, but its genetic background is unknown. Our study searched for evidence that genetic factors are involved in the chronification process. Methods:We initially selected 144 single-nucleotide polymorphisms (SNPs) from 48 candidate genes, which we tested for association in two stages: The first stage encompassed 262 CM patients, the second investigated 226 patients with highfrequency migraine (HFM). Subsequently, SNPs with p values<0.05 were forwarded to the replication stage containing 531 patients with CM or HFM. Results: Eight SNPs were significantly associated with CM and HFM in the two-stage phase. None survived replication in the third stage. Discussion: We present the first comprehensive genetic association study for migraine chronification. There were no significant findings. Future studies may benefit from larger, genome-wide data sets or should use other genetic approaches to identify genetic factors involved in migraine chronification. [ABSTRACT FROM AUTHOR]

Introduction According to the IHCD-3β classification, chronic migraine (CM) is headache occurring on 15 or more days/month. Episodic migraine (EM) can be divided into low frequency (LFEM) and high frequency (HFEM) depending on the headache days suffered per month. Methods We performed a clinical comparison of migraine characteristics according to monthly headache days suffered. Patients were divided into three groups: LFEM (1-9 headache days/month), HFEM (10-14 headache days/month) and CM (≥15 headache days/month). Results The analysis included 1109 patients. Previously reported differences between EM and CM were replicated. However, there were three times more clinical differences between LFEM and HFEM than between HFEM and CM (15 vs. 6). A new model that takes 10 headache days as a cut-off value for CM would have a minimally higher predictive capacity (72.8%) and no statistical differences (71.8%) when comparing it to the current classification. Conclusions HFEM patients have few clinical differences compared with CM patients. This includes the poor outcomes regarding headache-related disability and impact on daily life. According to these findings, neurologists and headache specialists should consider that the emotional and functional impact in HFEM patients could be as disabling as in those with CM. [ABSTRACT FROM AUTHOR]

Background: Sodium increases during acute kidney injury (AKI) recovery. Both hypernatremia and positive fluid balances are associated with increased mortality. We aimed to evaluate the association between daily fluid balance and daily plasma sodium during the recovery from AKI among critical patients., Methods: Adult patients with AKI were enrolled in four ICUs and followed up for four days or until ICU discharge or hemodialysis initiation. Day zero was the peak day of creatinine. The primary outcome was daily plasma sodium; the main exposure was daily fluid balance., Results: 93 patients were included. The median age was 66 years; 68% were male. Plasma sodium increased in 79 patients (85%), and 52% presented hypernatremia. We found no effect of daily fluid balance on plasma sodium (β -0.26, IC95%: -0.63-0.13; p = 0.19). A higher total sodium variation was observed in patients with lower initial plasma sodium (β -0.40, IC95%: -0.53 to -0.27; p < 0.01), higher initial urea (β 0.07, IC95%: 0.04-0.01; p < 0.01), and higher net sodium balance (β 0.002, IC95%: 0.0001-0.01; p = 0.05)., Conclusions: The increase in plasma sodium is common during AKI recovery and can only partially be attributed to the water and electrolyte balances. The incidence of hypernatremia in this population of patients is higher than in the general critically ill patient population., Competing Interests: Declaration of competing interest The Authors of this study declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

This systematic review aimed to evaluate metabolic syndrome as a risk factor for the development of peripheral arterial disease (PAD). We searched in four databases: (1) PubMed, (2) Web of Science, (3) Scopus, and (4) Embase until March 2021. We included cohort studies that evaluated the risk of PAD in patients with and without metabolic syndrome. Study selection, data extraction, and risk of bias analysis were performed independently by 2 authors. We used a random-effects model to conduct a meta-analysis of effect measures [hazard ratio (HR), risk ratio (RR), and odds ratio (OR)]. Individual analyses were performed according to the diagnostic criterion used for metabolic syndrome. We included 7 cohort studies with a total of 43 824 participants. Most of the studies were performed in the general adult population. The metabolic syndrome and PAD diagnostic criteria used in the individual studies were heterogeneous. Almost all studies using RR found an association between metabolic syndrome and the development of PAD (RR: 1.31; confidence interval 95%: 1.03-1.59; I 2 : 15.6%). On the other hand, almost all the studies that used HR found no association between the two variables. All studies had a low risk of bias. In conclusion, available evidence on the association between metabolic syndrome and the risk of developing PAD is inconsistent. However, given the high prevalence of risk factors that patients with metabolic syndrome have, testing to rule out PAD could be recommended. Future studies should analyze each component of the metabolic syndrome separately and according to the severity of PAD., Competing Interests: Disclosure: A.N.S. was supported by a NIH Fogarty Chronic Pulmonary Disease D43 Training Grant (5D43TW011502-02). The funder had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript. For the remaining authors none were declared. The other authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The objective of this systematic review and meta-analysis was to assess the prevalence of hypertension in populations living at altitude in Latin America and the Caribbean., Methods: We conducted a systematic search from January 1, 2000 to January 10, 2023 in Web of Science (WoS)/Core Collection, WoS/Medline, WoS/Scielo, Scopus, PubMed and Embase databases. We included studies that assessed the prevalence of hypertension in altitude populations (>1500 m.a.s.l.) and these were meta-analyzed using a random-effects model. To assess the sources of heterogeneity, we performed subgroup and meta-regression analyses., Results: Thirty cross-sectional studies (117 406 participants) met the inclusion criteria. Studies used different cut-off points. The prevalence of hypertension in the studies that considered the cut-off point of ≥ 140/90 mmHg in the general population was 19.1%, ≥ 130/85 mmHg was 13.1%, and ≥ 130/80 mmHg was 43.4%. There was a tendency for the prevalence of hypertension to be higher in men. In meta-regression analyses, no association was found between altitude, mean age, year of publication, risk of bias and prevalence of hypertension., Conclusion: The prevalence of hypertension in the altitude population of Latin America and the Caribbean is lower than that reported in populations living at sea level and lower than other altitude populations such as Tibetans., Prospero: CRD42021275229., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zila-Velasque et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To evaluate the efficacy of antituberculosis therapy on pregnancy outcomes in infertile women with genital tuberculosis., Design: Systematic review., Data Sources: We searched in PubMed/MEDLINE, CENTRAL and EMBASE up to 15 January 2023. Additionally, we manually search the reference lists of included studies., Eligibility Criteria: We included randomised controlled trials (RCT), non-RCTs (non-RCT) and cohort studies that evaluated the effects of antituberculosis treatment on pregnancy outcomes in infertile women with genital tuberculosis compared with not receiving antituberculosis treatment or receiving the treatment for a shorter period., Data Extraction and Synthesis: Two independent reviewers extracted data. We used Cochrane Risk of Bias 1.0 and Risk Of Bias In Non-randomised Studies tools for risk of bias assessment and meta-analysis was not performed. We used Grading of Recommendations, Assessment, Development and Evaluations approach to assess the certainty of the evidence., Results: Two RCTs and one non-RCT were included. The antituberculosis regimens were based on isoniazid, rifampicin, pyrazinamide and ethambutol for 6-12 months. In women without structural damage, very low certainty of evidence from one RCT showed that the antituberculosis treatment may have little to no effect on pregnancy, full-term pregnancy, abortion or intrauterine death and ectopic pregnancy, but the evidence is very uncertain. In women with structural damage, very low certainty of evidence from one non-RCT showed that the antituberculosis treatment may reduce the pregnancy rate (297 fewer per 1000, 95% CI -416 to -101), but the evidence is very uncertain. In addition, very low certainty of evidence from one RCT compared a 9-month vs 6-month antituberculosis treatment regimen showed similar effects between the schemes, but the evidence is very uncertain. Two RCTs reported that no adverse events of antituberculosis treatment were noted or were similar in both groups., Conclusion: The effect of antituberculosis treatment on pregnancy outcomes in infertile women with genital tuberculosis is very uncertain., Prospero Registration Number: CRD42022273145., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this scoping review was to determine the characteristics of studies evaluating fecal microbiota transplantation (FMT), as well as its effects and safety as a therapeutic intervention for people living with human immunodeficiency virus (HIV). We conducted a scoping review following the methodology of the Joanna Briggs Institute. We searched the following databases: PubMed, Web of Science, Scopus, Embase, Cochrane Library, and Medline until September 19, 2021. Studies that used FMT in people living with HIV and explored its effects on the health of these people were included. Two randomized and 2 uncontrolled clinical trials with a total of 55 participants were included. Participants were well-controlled HIV-infected people. Regarding microbiota changes, three studies found significant post-FMT increases in Fusobacterium , Prevotella , α-diversity, Chao index, and/or Shannon index, and/or decreases in Bacteroides . Regarding markers of intestinal damage, one study found a decrease in intestinal fatty acid binding protein post-FMT, and another study found an increase in zonulin. Other outcomes evaluated by the studies were as follows: markers of immune and inflammatory activation, markers of immunocompetence (CD4 + , and CD8 + T lymphocytes), and HIV viral load; however, none showed significant changes. Clinical outcomes were not evaluated by these studies. Regarding the safety of FMT, only mild adverse events were appreciated. No serious adverse event was reported. The clinical evidence for FMT in people living with HIV is sparse. FMT appears to have good tolerability and, no serious adverse event has been reported so far. Further clinical trials and evaluation of clinically important biomedical outcomes for FMT in people living with HIV are needed.

Aim: Despite the benefits of recombinant t-PA (rt-PA) for stroke patients some of them suffer from adverse hemorrhagic transformations (HTs) following treatment. Our objective is to study the transcriptomics of HTs patients., Methods: We studied by microarrays 11 blood samples from patients with stroke that had received rt-PA of whom six of them had suffered a HT. For replication step RNA was collected from 14 new subjects (seven with HT, seven without) and then analyzed by real-time PCR. Four proteins were measured by ELISA in 72 new subjects to analyze their role as potential protein biomarkers., Results: The microarray analysis revealed that 14 genes were altered among the HT patients. The replication study confirmed these results for six genes. Two of them (BCL2 and OLFM4) are associated with apoptosis, whereas the other four (LTF, LCN2 [also known as NGAL], CEACAM8 and CRISP3) are involved in the regulation of neutrophil processes., Conclusion: Our data revealed that genes related to apoptosis and neutrophil regulation pathways could be associated with HTs after rt-PA.

Background: Genetic factors contribute to the development of ischemic stroke (IS). In order to identify susceptibility variants, we analyzed single nucleotide polymorphisms (SNPs) that had been previously linked to stroke in a genome-wide association study., Methods: We analyzed 12 SNPs in a White population comprising IS patients and healthy controls. The analysis was adjusted for confounding variables and stratified by stroke etiology. Functional studies were then performed to elucidate the role of these variants in IS., Results: In a preliminary analysis of 268 controls and 531 IS cases, the rs10947803 SNP of KCNK17 (p=0.012) and the rs7506045 of IMPA2 (p=0.040) were associated with IS, although only the KCNK17 gene was an independent risk factor for IS. In a second phase, analysis of 271 new IS cases revealed that the A allele of rs10947803 was associated with stroke after correction for Bonferroni (OR=1.48; 95% CI, 1.14-1.91, p=0.003). Gene expression analysis revealed that KCNK17 mRNA levels were higher in the IS cases in the acute phase than in controls (14+/-78% vs. 91+/-41, p=0.002) but not in the chronic phase (56+/-57%; p=0.230). Moreover, RNA levels depended on the alleles of the rs10947803 SNP in the control group (p=0.021) and in the chronic phase (p=0.033)., Conclusions: The A allele of the rs10947803 variant of KCNK17 was associated with increased risk of IS and increased levels of KCNK17 gene expression. The role of this potassium channel gene in IS opens diagnostic and therapeutic expectations and merits further investigation., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Several studies have suggested that the n-3 fatty acids Docosahexaenoic (DHA) and Eicosapentaenoic (EPA) have an important protective effect on colorectal cancer, and this could be at least partly due to their proapoptotic activity. It is unclear, however, how this phenomenon is triggered and what mechanisms are implicated. Here, we show that both DHA and EPA have an important proapoptotic effect on colorectal cancer cells with different molecular phenotypes but not in noncancerous cells. Apoptosis is caspase dependent, and both intrinsic and extrinsic pathways are implicated. The dimerization of Bax and Bak, the depolarization of the mitochondrial membrane, and the subsequent release of cytochrome c and Smac/Diablo to the cytosol evidence the activation of the intrinsic pathway. The implication of the extrinsic pathway is shown by the activation of caspase-8, along with the down-regulation of FLIP. The timing of caspase-8 activation, and the oligomerization of Bid with Bax, suggest a cross-talk with the intrinsic pathway. None of the death receptors that commonly initiate the extrinsic pathway: FAS, TNF-R1, and TRAIL-R2 are found to be responsible for triggering the apoptosis cascade induced by DHA and EPA. Neither PPARgamma nor cyclooxygenase-2, two likely candidates to regulate this process, play a significant role. Our findings suggest that the down-regulation of two key regulatory elements of the extrinsic and intrinsic pathways, FLIP and XIAP, respectively, is determinant in the induction of apoptosis by DHA and EPA. These fatty acids could potentially be useful adjuvant anticancer agents in combination with other chemotherapeutic elements.