Effect of carbohydrate mouth rinse on muscle strength and muscular endurance: A systematic review with meta-analysis.

The present systematic review with meta-analysis summarized studies that investigated the effect of carbohydrate (CHO) mouth rinse on muscle strength and muscular endurance. The search was performed in six databases. Thirteen randomized clinical trials were selected and the standardized mean difference between CHO mouth rinse and placebo for maximal strength and muscular endurance was determined via a random-effects model using Review Manager 5.4 software. Meta-regression was also performed to explore the influence of load, number of sets, number of exercises, fasting time, CHO concentration, and number of mouth rinses on the main outcomes. There was no significant effect of CHO mouth rinse on maximal strength (mean difference= 0.25 kg, 95%CI - 1.81 to 2.32 kg, z = 0.24, p = 0.810). However, there was a significant positive effect of CHO mouth rinse on muscular endurance (mean difference = 1.24 repetitions, 95%CI 0.70 to 1.77 repetitions, z = 4.55, p < 0.001). Meta-regression identified that CHO mouth rinse has greater benefits on muscular endurance when using high workloads, multiple exercises, and a smaller number of mouth rinses (p = 0.001). In conclusion, CHO mouth rinse has no effect on maximal muscle strength but has a positive effect on muscular endurance and seems to optimize when fewer mouth rinses, high workloads and numbers of exercises are used.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2057417.

Genetic Association and Differential RNA Expression of Histone (De)Acetylation-Related Genes in Pemphigus Foliaceus-A Possible Epigenetic Effect in the Autoimmune Response.

Pemphigus foliaceus (PF) is an autoimmune skin blistering disease characterized by antidesmoglein-1 IgG production, with an endemic form (EPF) in Brazil. Genetic and epigenetic factors have been associated with EPF, but its etiology is still not fully understood. To evaluate the genetic association of histone (de)acetylation-related genes with EPF susceptibility, we evaluated 785 polymorphisms from 144 genes, for 227 EPF patients and 194 controls. Carriers of HDAC4_rs4852054*A were more susceptible (OR = 1.79, p = 0.0038), whereas those with GSE1_rs13339618*A (OR = 0.57, p = 0.0011) and homozygotes for PHF21A_rs4756055*A (OR = 0.39, p = 0.0006) were less susceptible to EPF. These variants were not associated with sporadic PF (SPF) in German samples of 75 SPF patients and 150 controls, possibly reflecting differences in SPF and EPF pathophysiology. We further evaluated the expression of histone (de)acetylation-related genes in CD4+ T lymphocytes, using RNAseq. In these cells, we found a higher expression of KAT2B, PHF20, and ZEB2 and lower expression of KAT14 and JAD1 in patients with active EPF without treatment compared to controls from endemic regions. The encoded proteins cause epigenetic modifications related to immune cell differentiation and cell death, possibly affecting the immune response in patients with PF.

Multidisciplinary management of idiopathic intracranial hypertension in pregnancy: case series and narrative review

Abstract Idiopathic intracranial hypertension (IIH) is a neurological condition characterized by raised intracranial pressure of unknown etiology with normal cerebrospinal fluid (CSF) composition and no brain lesions. It occurs in pregnant patients at approximately the same frequency as in general population, but obstetric and anesthetic management of the pregnancy and labor remains controversial. In this article we provide a multidisciplinary review of the main aspects of IIH in pregnancy including treatment options, mode of delivery and anesthetic techniques. Additionally, we report three cases of pregnant women diagnosed with IIH between 2012 and 2019 in our institution.

Genetic Associations and Differential mRNA Expression Levels of Host Genes Suggest a Viral Trigger for Endemic Pemphigus Foliaceus.

The long search for the environmental trigger of the endemic pemphigus foliaceus (EPF, fogo selvagem) has not yet resulted in any tangible findings. Here, we searched for genetic associations and the differential expression of host genes involved in early viral infections and innate antiviral defense. Genetic variants could alter the structure, expression sites, or levels of the gene products, impacting their functions. By analyzing 3063 variants of 166 candidate genes in 227 EPF patients and 194 controls, we found 12 variants within 11 genes associated with differential susceptibility (p < 0.005) to EPF. The products of genes TRIM5, TPCN2, EIF4E, EIF4E3, NUP37, NUP50, NUP88, TPR, USP15, IRF8, and JAK1 are involved in different mechanisms of viral control, for example, the regulation of viral entry into the host cell or recognition of viral nucleic acids and proteins. Only two of nine variants were also associated in an independent German cohort of sporadic PF (75 patients, 150 controls), aligning with our hypothesis that antiviral host genes play a major role in EPF due to a specific virus−human interaction in the endemic region. Moreover, CCL5, P4HB, and APOBEC3G mRNA levels were increased (p < 0.001) in CD4+ T lymphocytes of EPF patients. Because there is limited or no evidence that these genes are involved in autoimmunity, their crucial role in antiviral responses and the associations that we observed support the hypothesis of a viral trigger for EPF, presumably a still unnoticed flavivirus. This work opens new frontiers in searching for the trigger of EPF, with the potential to advance translational research that aims for disease prevention and treatment.

Multidisciplinary management of idiopathic intracranial hypertension in pregnancy: case series and narrative review.

Idiopathic intracranial hypertension (IIH) is a neurological condition characterized by raised intracranial pressure of unknown etiology with normal cerebrospinal fluid (CSF) composition and no brain lesions. It occurs in pregnant patients at approximately the same frequency as in general population, but obstetric and anesthetic management of the pregnancy and labor remains controversial. In this article we provide a multidisciplinary review of the main aspects of IIH in pregnancy including treatment options, mode of delivery and anesthetic techniques. Additionally, we report three cases of pregnant women diagnosed with IIH between 2012 and 2019 in our institution.

Genetic variability of immune-related lncRNAs: polymorphisms in LINC-PINT and LY86-AS1 are associated with pemphigus foliaceus susceptibility.

Pemphigus foliaceus (PF) is an autoimmune blistering disease of the skin, clinically characterized by erosions and, histopathologically, by acantholysis. PF is endemic in the Brazilian Central-Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibility for PF, including SNPs at long non-coding RNA (lncRNA) genes, which are known to participate in many physiological and pathogenic processes, such as autoimmunity. Here, we investigated whether the genetic variation of immune-related lncRNA genes affects the risk for endemic and sporadic forms of PF. We analysed 692 novel SNPs for PF from 135 immune-related lncRNA genes in 227 endemic PF patients and 194 controls. The SNPs were genotyped by Illumina microarray and analysed by applying logistic regression at additive model, with correction for sex and population structure. Six associated SNPs were also evaluated in an independent German cohort of 76 sporadic PF patients and 150 controls. Further, we measured the expression levels of two associated lncRNA genes (LINC-PINT and LY86-AS1) by quantitative PCR, stratified by genotypes, in peripheral blood mononuclear cells of healthy subjects. We found 27 SNPs in 11 lncRNA genes associated with endemic PF (p < .05 without overlapping with protein-coding genes). Among them, the LINC-PINT SNP rs10228040*A (OR = 1.47, p = .012) was also associated with increased susceptibility for sporadic PF (OR = 2.28, p = .002). Moreover, the A+ carriers of LY86-AS1*rs12192707 mark lowest LY86-AS1 RNA levels, which might be associated with a decreasing autoimmune response. Our results suggest a critical role of lncRNA variants in immunopathogenesis of both PF endemic and sporadic forms.

Interaction of Long Noncoding RNAs and Notch Signaling: Implications for Tissue Homeostasis Loss.

The Notch signaling is a crucial pathway involved in cellular development, progression, and differentiation. Deregulation of Notch signaling pathway commonly impacts tissue homeostasis, being highly associated with proliferative disorders. The long noncoding RNAs (lncRNAs), which are transcripts with more than 200 nucleotides that do not code for proteins, were already described as Notch signaling pathway-interacting molecules. Many of them act as important transcriptional and posttranscriptional regulators, affecting gene expression and targeting other regulatory molecules, such as miRNAs. Due to their strong impact on function and gene expression of Notch-related molecules, lncRNAs influence susceptibility to cancer and other diseases, and can be regarded as potential biomarkers and therapeutic targets. Along this chapter, we summarize the cross talk between the Notch signaling pathway and their most important modulating lncRNAs, as well as the pathological consequences of these interactions, in different tissues.

Region 1p13.2 including the RSBN1, PTPN22, AP4B1 and long non-coding RNA genes does not bear risk factors for endemic pemphigus foliaceus (fogo selvagem).

Pemphigus foliaceus (PF) is an autoimmune skin disease characterized by autoantibodies directed mainly against desmoglein-1. The purpose of this study was to determine whether differential susceptibility to endemic PF in Brazil (fogo selvagem) is associated with polymorphisms at the cytogenetic location 1p13.2. Four single nucleotide polymorphisms that together tag 28 SNPs on a segment of approximately 312,000 bp encompassing the protein-coding genes MAGI3, PHTF1, RSBN1, PTPN22, BCL2L15, AP4B1, DCLRE1B, the pseudogenes MTND5P20, RPS2P14 (AL133517.1) and the long non-coding RNA genes AL137856.1, and AP4B1-AS1 were used as markers for association analysis in a case-control study. Allele, genotype and haplotype frequencies of rs33996649, rs2476601, rs3789604 and rs3195954 were compared between patient and control samples. No significant association was found. Lack of association with rs2476601 of the PTPN22 gene agrees with previous results for pemphigus vulgaris and the Tunisian form of endemic pemphigus foliaceus. The other three SNPs had never been analysed before in any form of pemphigus. We conclude that variants in structural and regulatory sites of region 1p13.2 are not susceptibility factors for fogo selvagem. We suggest careful investigation of this genomic region in diseases that had been previously associated with PTPN22, since there are several other genes relevant for immune-mediated diseases located in 1p13.2.

"Our Voices, Our Meaning": The Social Representations of Sports for Brazilian Athletes With Disabilities.

This study aimed to identify the social representations of sports for Brazilian athletes with disabilities and to understand the extent to which sports can contribute to their empowerment. A total of 153 Brazilian athletes of various sports and with different types of disabilities took part in the study (122 men and 31 women; M = 31.91 years, SD = 9.46). The research was performed by an online survey by means of the free word association technique. All analyses were carried out using the Iramuteq computer program. The results indicated that the social representations of sports are related to individual and collective gains derived from practicing sports and that the representations are distinct according to the discipline practiced by the athlete. These results are discussed in light of the advantages of valuing the collective experience of athletes with disabilities as a group rather than as cases of individual overcoming. Social implications and possible future directions for research are presented.

Long non-coding RNAs in cancer: Another layer of complexity.

We review the most well characterized long non-coding RNAs (lncRNAs) with important roles in hallmarks of cancer, additionally including lncRNAs with a higher potential for clinical application. LncRNAs are transcripts larger than 200 nucleotides in length that do not appear to have protein-coding potential, although some of those may produce small functional peptides. These transcripts have attracted significant attention from researchers as a result of their role in genetic regulation, including epigenetic, transcriptional and post-transcriptional regulation, being involved in numerous biological processes, as well as being associated with multifactorial diseases, including tumorigenesis. The hallmarks of cancer include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis and activating invasion/metastasis. Additionally, genome instability, inflammation, reprogramming of energy metabolism and evading immune destruction and lncRNAs are implicated in all hallmarks of cancer. Based on the great number of studies describing lncRNAs associated with diverse aspects of most tumor types, lncRNAs have essential roles in potentially all biological features of cancer cells and show great utility as diagnostic and prognostic markers, as exemplified by PCA3 lncRNA detection in prostate cancer diagnosis.

Long Non-Coding RNAs in Multifactorial Diseases: Another Layer of Complexity.

Multifactorial diseases such as cancer, cardiovascular conditions and neurological, immunological and metabolic disorders are a group of diseases caused by the combination of genetic and environmental factors. High-throughput RNA sequencing (RNA-seq) technologies have revealed that less than 2% of the genome corresponds to protein-coding genes, although most of the human genome is transcribed. The other transcripts include a large variety of non-coding RNAs (ncRNAs), and the continuous generation of RNA-seq data shows that ncRNAs are strongly deregulated and may be important players in pathological processes. A specific class of ncRNAs, the long non-coding RNAs (lncRNAs), has been intensively studied in human diseases. For clinical purposes, lncRNAs may have advantages mainly because of their specificity and differential expression patterns, as well as their ideal qualities for diagnosis and therapeutics. Multifactorial diseases are the major cause of death worldwide and many aspects of their development are not fully understood. Recent data about lncRNAs has improved our knowledge and helped risk assessment and prognosis of these pathologies. This review summarizes the involvement of some lncRNAs in the most common multifactorial diseases, with a focus on those with published functional data.

Besides Pathology: Long Non-Coding RNA in Cell and Tissue Homeostasis.

A significant proportion of mammalian genomes corresponds to genes that transcribe long non-coding RNAs (lncRNAs). Throughout the last decade, the number of studies concerning the roles played by lncRNAs in different biological processes has increased considerably. This intense interest in lncRNAs has produced a major shift in our understanding of gene and genome regulation and structure. It became apparent that lncRNAs regulate gene expression through several mechanisms. These RNAs function as transcriptional or post-transcriptional regulators through binding to histone-modifying complexes, to DNA, to transcription factors and other DNA binding proteins, to RNA polymerase II, to mRNA, or through the modulation of microRNA or enzyme function. Often, the lncRNA transcription itself rather than the lncRNA product appears to be regulatory. In this review, we highlight studies identifying lncRNAs in the homeostasis of various cell and tissue types or demonstrating their effects in the expression of protein-coding or other non-coding RNA genes.

A 3'UTR polymorphism marks differential KLRG1 mRNA levels through disruption of a miR-584-5p binding site and associates with pemphigus foliaceus susceptibility.

Genetic variations mapping to 3' untranslated regions (3'UTRs) may overlap with microRNA (miRNA) binding sites, therefore potentially interfering with translation inhibition or messenger RNA (mRNA) degradation. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) located within the 3'UTRs of six candidate genes and predicted to interfere with miRNA ligation could account for disease-relevant differential mRNA levels. Focusing on pemphigus foliaceus (PF) - an autoimmune blistering skin condition with unique endemic patterns - we investigated whether nine 3'UTR SNPs from the CD1D, CTLA4, KLRD1, KLRG1, NKG7, and TNFSF13B genes differentially expressed in PF were disease-associated. The heterozygous genotype of the KLRG1 rs1805672 polymorphism was associated with increased predisposition to PF (A/G vs. A/A: P=0.038; OR=1.60), and a trend for augmented susceptibility was observed for carriers of the G allele (P=0.094; OR=1.44). In silico analyses suggested that rs1805672 G allele could disrupt binding of miR-584-5p, and indicated rs1805672 as an expression Quantitative Trait Locus (eQTL), with an effect on KLRG1 gene expression. Dual-luciferase assay showed that miR-584-5p mediated approximately 50% downregulation of the reporter gene's activity through the 3'UTR of KLRG1 harboring rs1805672 A allele (vs. miRNA-negative condition, P=0.006). This silencing relationship was lost after site-directed mutation to G allele (vs. miRNA-negative condition, P=0.391; vs. rs1805672 A allele, P=0.005). Collectively, these results suggest that a disease-associated SNP located within the 3'UTR of KLRG1 directly interferes with miR-584-5p binding, allowing for KLRG1 mRNA differential accumulation, which in turn may contribute to pathogenesis of autoimmune diseases, such as pemphigus.

Pneumatosis intestinalis and volvulus: a rare association / Pneumatose intestinal e volvo: uma associação rara

Pneumatosis intestinalis (PI) is a rare condition, especially when associated with volvulus; it is often misdiagnosed and inappropriately treated. We present the case of a 27 year-old woman suffering from an acute abdomen. An abdominal tomography was performed revealing Pneumatosis intestinalis. Once in the operating theatre sigmoid volvulus was diagnosed and Hartmann surgery performed. Histology showed intestinal ischemia. During the hospital stay, evolution was favourable. The authors present this case and a brief theoretical review, due to its rarity and clinical interest.

A pneumatose intestinal (PI) é uma condição pouco frequente, sendo ainda mais rara em associação com volvo; sendo muitas vezes mal diagnosticada e tratada inapropriadamente. Apresentamos o caso de uma mulher de 27 anos com um quadro de abdómen agudo. Realizou TAC abdominal que demonstrou pneumatose intestinal. Intra-operatoriamente foi diagnosticado volvo da sigmoideia e optado por cirurgia de Hartmann. O resultado anatomo-patológico da peça foi compatível com isquémia intestinal. Durante o internamento hospital, a doente evoluiu favoravelmente. Os autores apresentam este caso e uma breve revisão teórica, pela sua raridade e interesse clínico.

Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo.

Although HLA-A3 and A11 have been reported to be ligands for KIR3DL2, evidence for any in vivo relevance of this interaction is still missing. To explore the functional importance of KIR3DL2 allelic variation, we analyzed the autoimmune disease pemphigus foliaceus, previously associated (lower risk) with activating KIR genes. KIR3DL2*001 was increased in patients (odds ratio (OR) = 2.04; p = 0.007). The risk was higher for the presence of both KIR3DL2*001 and HLA-A3 or A11 (OR = 3.76, p = 0.013), providing the first evidence that HLA-A3 and A11 may interact with KIR3DL2 in vivo. The nonsynonymous single nucleotide polymorphism 1190T (rs3745902) was associated with protection (OR = 0.52, p = 0.018). This SNP results in a threonine-to-methionine substitution. Individuals who have methionine in this position exhibit a lower percentage of KIR3DL2-positive natural killer (NK) cells and also lower intensity of KIR3DL2 on expressing natural killer cells; additionally, we show that the expression of KIR3DL2 is independent of other killer cell immunoglobulin-like receptors. Pemphigus foliaceus is a very unique complex disease strongly associated with immune-related genes. It is the only autoimmune disease known to be endemic, showing a strong correlation with environmental factors. Our data demonstrate that this relatively unknown autoimmune disease may facilitate understanding of the molecular mechanisms of KIR3DL2 ligand recognition.

Metástase óssea como forma de apresentação de carcinoma hepatocelular / Bone metastasis as the presenting symptom of hepatocellular carcinoma

O carcinoma hepatocelular (CHC) é o tumor maligno primário do fígado mais frequente, apresentando na maioria das vezes em doentes cirróticos. O espectro de apresentação é muito variado e as manifestações clínicas dependem da fase evolutiva da doença. A progressão local e sistémica do carcinoma hepatocelular é frequente e as metástases ósseas não são incomuns. Apesar de as metástases ósseas serem uma forma de apresentação rara de carcinoma hepatocelular, por vezes estas precedem as manifestações hepáticas pelo que o carcinoma hepatocelular deve ser incluído no diagnóstico diferencial de lesões ósseas osteolíticas. Os autores apresentam um caso clínico e uma breve revisão teórica, pela sua raridade e importância clínica, sublinhando a importância do diagnóstico diferencial de carcinoma hepatocelular um doente previamente assintomático, sem doença hepática conhecida anteriormente, com um fractura patológica...

Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver, presenting most often in cirrhotic patients. The spectrum of presentation is very varied and clinical manifestations depend on the phase of the disease. The local and systemic progression of hepatocellular carcinoma is frequent and bone metastases are not uncommon. Although bone metastases are a rare form of presentation of hepatocellular carcinoma, sometimes they precede hepatic manifestations and that's way hepatocellular carcinoma should be included in the differential diagnosis of osteolytic bone lesions. The authors present a case report and a brief literature review, due to its rarity and clinical importance, stressing the importance of the differential diagnosis of hepatocellular carcinoma in a previously healthy patient without previously known liver disease, with a pathological fracture...

Activating KIR and HLA Bw4 ligands are associated to decreased susceptibility to pemphigus foliaceus, an autoimmune blistering skin disease.

The KIR genes and their HLA class I ligands have thus far not been investigated in pemphigus foliaceus (PF) and related autoimmune diseases, such as pemphigus vulgaris. We genotyped 233 patients and 204 controls for KIR by PCR-SSP. HLA typing was performed by LABType SSO reagent kits. We estimated the odds ratio, 95% confidence interval and performed logistic regression analyses to test the hypothesis that KIR genes and their known ligands influence susceptibility to PF. We found significant negative association between activating genes and PF. The activating KIR genes may have an overlapping effect in the PF susceptibility and the presence of more than three activating genes was protective (OR=0.49, p=0.003). A strong protective association was found for higher ratios activating/inhibitory KIR (OR=0.44, p=0.001). KIR3DS1 and HLA-Bw4 were negatively associated to PF either isolated or combined, but higher significance was found for the presence of both together (OR=0.34, p<10(-3)) suggesting that the activating function is the major factor to interfere in the PF pathogenesis. HLA-Bw4 (80I and 80T) was decreased in patients. There is evidence that HLA-Bw4(80T) may also be important as KIR3DS1 ligand, being the association of this pair (OR=0.07, p=0.001) stronger than KIR3DS1-Bw4(80I) (OR=0.31, p=0.002). Higher levels of activating KIR signals appeared protective to PF. The activating KIR genes have been commonly reported to increase the risk for autoimmunity, but particularities of endemic PF, like the well documented influence the environmental exposure in the pathogenesis of this disease, may be the reason why activated NK cells probably protect against pemphigus foliaceus.

Factores que intervienen en la relacion medico-paciente; trabajo practico de epidemiologia Carrera de Medicina

Trabajo de la materia de epidemiologia realizado en medicos y pacientes de la Caja Petrolera de Salud y Cossmil en Cochabamba