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Sports Medicine (Auckland, N.Z.) Dec 2023This narrative review evaluated the evidence for buffering agents (sodium bicarbonate, sodium citrate and beta-alanine), with specific consideration of three discrete... (Review)
Review
This narrative review evaluated the evidence for buffering agents (sodium bicarbonate, sodium citrate and beta-alanine), with specific consideration of three discrete scenarios: female athletes, extreme environments and combined buffering agents. Studies were screened according to exclusion and inclusion criteria and were analysed on three levels: (1) moderating variables (supplement dose and timing, and exercise test duration and intensity), (2) design factors (e.g., use of crossover or matched group study design, familiarisation trials) and (3) athlete-specific factors (recruitment of highly trained participants, buffering capacity and reported performance improvements). Only 19% of the included studies for the three buffering agents reported a performance benefit, and only 10% recruited highly trained athletes. This low transferability of research findings to athletes' real-world practices may be due to factors including the small number of sodium citrate studies in females (n = 2), no studies controlling for the menstrual cycle (MC) or menstrual status using methods described in recently established frameworks, and the limited number of beta-alanine studies using performance tests replicating real-world performance efforts (n = 3). We recommend further research into buffering agents in highly trained female athletes that control or account for the MC, studies that replicate the demands of athletes' heat and altitude camps, and investigations of highly trained athletes' use of combined buffering agents. In a practical context, we recommend developing evidence-based buffering protocols for individual athletes which feature co-supplementation with other evidence-based products, reduce the likelihood of side-effects, and optimise key moderating factors: supplement dose and timing, and exercise duration and intensity.
Topics: Humans; Female; Athletes; Sodium Bicarbonate; Exercise; Sodium Citrate; beta-Alanine; Extreme Environments; Athletic Performance
PubMed: 37878211
DOI: 10.1007/s40279-023-01872-7 -
Neurology and Therapy Dec 2023Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on...
INTRODUCTION
Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression.
METHODS
This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed.
RESULTS
A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not.
CONCLUSION
Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.
PubMed: 37861931
DOI: 10.1007/s40120-023-00557-7 -
Journal of Translational Medicine Oct 2023Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options,...
BACKGROUND
Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options, CRC shows a poor prognosis with a 5 year survival rate of ~ 45%. PRDM2/RIZ, a member of PR/SET domain family (PRDM), expresses two main molecular variants, the PR-plus isoform (RIZ1) and the PR-minus (RIZ2). The imbalance in their expression levels in favor of RIZ2 is observed in many cancer types. The full length RIZ1 has been extensively investigated in several cancers where it acts as a tumor suppressor, whereas few studies have explored the RIZ2 oncogenic properties. PRDM2 is often target of frameshift mutations and aberrant DNA methylation in CRC. However, little is known about its role in CRC.
METHODS
We combined in-silico investigation of The Cancer Genome Atlas (TCGA) CRC datasets, cellular and molecular assays, transcriptome sequencing and functional annotation analysis to assess the role of RIZ2 in human CRC.
RESULTS
Our in-silico analysis on TCGA datasets confirmed that PRDM2 gene is frequently mutated and transcriptionally deregulated in CRC and revealed that a RIZ2 increase is highly correlated with a significant RIZ1 downregulation. Then, we assayed several CRC cell lines by qRT-PCR analysis for the main PRDM2 transcripts and selected DLD1 cell line, which showed the lowest RIZ2 levels. Therefore, we overexpressed RIZ2 in these cells to mimic TCGA datasets analysis results and consequently to assess the PRDM2/RIZ2 role in CRC. Data from RNA-seq disclosed that RIZ2 overexpression induced profound changes in CRC cell transcriptome via EGF pathway deregulation, suggesting that RIZ2 is involved in the EGF autocrine regulation of DLD1 cell behavior. Noteworthy, the forced RIZ2 expression increased cell viability, growth, colony formation, migration and organoid formation. These effects could be mediated by the release of high EGF levels by RIZ2 overexpressing DLD1 cells.
CONCLUSIONS
Our findings add novel insights on the putative RIZ2 tumor-promoting functions in CRC, although additional efforts are warranted to define the underlying molecular mechanism.
Topics: Humans; Cell Line, Tumor; Colorectal Neoplasms; Epidermal Growth Factor; ErbB Receptors; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Tumor Cells, Cultured
PubMed: 37853459
DOI: 10.1186/s12967-023-04621-6 -
Seizure Dec 2023We investigated the value of automated enlarged perivascular spaces (ePVS) quantification to distinguish chronic traumatic brain injury (TBI) patients with...
BACKGROUND
We investigated the value of automated enlarged perivascular spaces (ePVS) quantification to distinguish chronic traumatic brain injury (TBI) patients with post-traumatic epilepsy (PTE) from chronic TBI patients without PTE (PTE) in a feasibility study.
METHODS
Patients with and without PTE were recruited and underwent an MRI post-TBI. Multimodal auto identification of ePVS algorithm was applied to T1-weighted MRIs to segment ePVS. The total number of ePVS was calculated and corrected for white matter volume, and an asymmetry index (AI) derived.
RESULTS
PTE was diagnosed in 7 out of the 99 participants (male=69) after a median time of less than one year since injury (range 10-22). Brain lesions were observed in all 7 PTE cases (unilateral=4, 57%; bilateral=3, 43%) as compared to 40 PTE cases (total 44%; unilateral=17, 42%; bilateral=23, 58%). There was a significant difference between PTE (M=1.21e, IQR [8.89e]) and PTE cases (M=2.79e, IQR [6.25e]) in total corrected numbers of ePVS in patients with unilateral lesions (p=0.024). No differences in AI, trauma severity and lesion volume were seen between groups.
CONCLUSION
This study has shown that automated quantification of ePVS is feasible and provided initial evidence that individuals with PTE with unilateral lesions may have fewer ePVS compared to TBI patients without epilepsy. Further studies with larger sample sizes should be conducted to determine the value of ePVS quantification as a PTE-biomarker.
Topics: Humans; Male; Epilepsy, Post-Traumatic; Feasibility Studies; Brain Injuries, Traumatic; Magnetic Resonance Imaging; White Matter; Nervous System Malformations
PubMed: 37847935
DOI: 10.1016/j.seizure.2023.10.006 -
Current Diabetes Reviews 2024Prediabetes is a reversible condition before the onset of Type 2 Diabetes Mellitus. Untreated condition of prediabetes will develop into diabetes and its complications....
BACKGROUND
Prediabetes is a reversible condition before the onset of Type 2 Diabetes Mellitus. Untreated condition of prediabetes will develop into diabetes and its complications. The prevalence of prediabetes has been emerging worldwide and has a considerable socioeconomic impact. The current study reviews the roles of early detection, educational models, life modification, and prophylaxis of individuals with prediabetes in preventing the progression of prediabetes into Type 2 Diabetes Mellitus and complications in the future.
METHODS
This study included published articles from several electronic databases. The obtained articles were limited to March 2023. Articles that were not open access and not in Indonesian or English were excluded. The protocol for this study used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020.
RESULTS
Of 39627 articles, 39601 were excluded due to duplication and did not meet the eligibility criteria. At the final, there were 26 articles that were eligible for systematic review.
CONCLUSION
Prevention of the development of prediabetes into diabetes is essential. A comprehensive understanding and training on intensive lifestyle modification protocols from local and national experts in diabetes prevention through digital-based education models and linguistically and culturally approach can be considered. Intensive lifestyle modification and pharmacological approaches may improve the outcome. Regular monitoring of glycemic control is also important for early diagnosis of diabetes, especially in patients with special conditions.
Topics: Humans; Prediabetic State; Diabetes Mellitus, Type 2; Patient Education as Topic; Models, Educational; Early Diagnosis; Disease Progression
PubMed: 37818560
DOI: 10.2174/0115733998275518231006074504 -
Heliyon Sep 2023Hepatitis C is still a serious liver case of health. Up to now the development of anti-Hepatitis C Virus (HCV) drugs is challenging, especially the development of...
Hepatitis C is still a serious liver case of health. Up to now the development of anti-Hepatitis C Virus (HCV) drugs is challenging, especially the development of natural material compounds as anti-HCV. In the present study, we evaluated the probability of α-mangostin, piperine, and β-sitosterol as anti-HCV with the in silico and in vitro approaches. Molecular docking was performed between nonstructural protein 5B (NS5B, PDB ID 3FQL) with α-mangostin, piperine, and β-sitosterol by Autodock Tools® and BIOVIA Discovery Studio®. Subsequently, molecular dynamics simulations were conducted for 200 ns, evaluating the dynamic interaction between the ligands and the viral protein NS5B. Furthermore, compound characterization at the hepatocarcinoma cell line was employed. α-Mangostin with NS5B complex demonstrated the most negative binding free energy value based on MM-PBSA calculation with a value of -9.13 kcal/mol. In vitro test showed that IC of α -mangostin was 2.70 ± 0.92 μM, IC of piperine was 52.18 ± 3.21 μM, IC of β-sitosterol was >100 μM. α-Mangostin can serve as a valuable lead compound for further development of the anti-HCV.
PubMed: 37809693
DOI: 10.1016/j.heliyon.2023.e20141 -
Journal of Feline Medicine and Surgery Oct 2023The present study aimed to determine the inheritance pattern and genetic cause of congenital radial hemimelia (RH) in cats.
OBJECTIVES
The present study aimed to determine the inheritance pattern and genetic cause of congenital radial hemimelia (RH) in cats.
METHODS
Clinical and genetic analyses were conducted on a Siamese cat family (n = 18), including two siblings with RH. Radiographs were obtained for the affected kittens and echocardiograms of an affected kitten and sire. Whole genome sequencing was completed on the two cases and the parents. Genomic data were compared with the 99 Lives Cat Genome data set of 420 additional domestic cats with whole genome and whole exome sequencing data. Variants were considered as homozygous in the two cases of the siblings with RH and heterozygous in the parents. Candidate variants were genotyped by Sanger sequencing in the extended pedigree.
RESULTS
Radiographs of the female kitten revealed bilateral absence of the radii and bowing of the humeri, while the male kitten showed a dysplastic right radius. Echocardiography suggested the female kitten had restrictive cardiomyopathy with a positive left atrial-to-aortic root ratio (LA:Ao = 1.83 cm), whereas hypertrophic cardiomyopathy was more likely in the sire, showing diastolic dysfunction using tissue Doppler imaging (59.06 cm/s). Twenty-two DNA variants were unique and homozygous in the affected kittens and heterozygous in the parents. Seven variants clustered in one chromosomal region, including two frameshift variants in () and five variants in , ( ), including a missense and an in-frame deletion.
CONCLUSIONS AND RELEVANCE
The present study suggested an autosomal recessive mode of inheritance with variable expression for RH in the Siamese cat family. Candidate variants for the phenotype were identified, implicating their roles in bone development. These genes should be considered as potentially causal for other cats with RH. Siamese cat breeders should consider genetically testing their cats for these variants to prevent further dissemination of the suspected variants within the breed.
Topics: Female; Male; Cats; Animals; Ectromelia; Cardiomyopathies; Risk Factors; Cardiomyopathy, Hypertrophic; Humerus; Cat Diseases
PubMed: 37791865
DOI: 10.1177/1098612X231193557 -
Acta Informatica Medica : AIM : Journal... 2023COVID-19 is a virulent viral infection by SARS-CoV-2 which caused pandemic and high mortality. One of the numerous risk factors for worse clinical outcomes in COVID-19...
BACKGROUND
COVID-19 is a virulent viral infection by SARS-CoV-2 which caused pandemic and high mortality. One of the numerous risk factors for worse clinical outcomes in COVID-19 patients is the presence of comorbidity. Diabetes Mellitus is a chronic metabolic disease frequently in COVID-19 patients. Insulin resistance, causes chronic inflammation in the body, may aggravate the clinical outcome COVID-19 patients.
OBJECTIVE
The aim of the study was to examine factors that impact clinical outcomes in COVID-19 T2DM patients.
METHODS
The method used an analytical method with cross sectional design. Population is inpatients in Haji Adam Malik Hospital diagnosed with COVID-19 and Diabetes Mellitus Type 2 with 99 inpatients as sample. The data used are secondary data obtained through medical records from a hospital covering patients characteristics and laboratory result The data was analyzed using t-independent and chi square test with SPSS program.
RESULTS
Clinical outcomes for 99 patients are 60 patients are cured and 39 patients are dead. analytical study found a significant correlation between factors impacting clinical outcomes on COVID-19 patients with T2DM that are HbA1c level, D-dimer, cholesterol total and COVID-19 degree of severity and the clinical outcomes (p<0,05).
CONCLUSION
HbA1c level, D-dimer, total cholesterol and the infection degree of severity affects the clinical outcomes on COVID-19 with T2DM (p<0,05).
PubMed: 37781495
DOI: 10.5455/aim.2023.31.182-185 -
Acta Informatica Medica : AIM : Journal... 2023Anemia is one of the major global problems that continues to this day. According to World Health Organization (WHO) data, anemia is found in 1.62 billion people or...
BACKGROUND
Anemia is one of the major global problems that continues to this day. According to World Health Organization (WHO) data, anemia is found in 1.62 billion people or equivalent to 24.8% of the world's population while, the prevalence of anemia in children under 6 years of age in Indonesia reached 38.4%. Anemia, if undiagnosed or untreated for a long period of time can lead to multiorgan failure. The cardiovascular system is the most commonly affected system in chronic anemia. Between one-third and two-thirds of patients with severe anemia have cardiomegaly and this will return to normal within a few weeks after the anemia is well managed. This abnormality can be evaluated on chest radiograph or echocardiography.
OBJECTIVE
This study aims to evaluate the association between anemia and cardiomegaly.
METHODS
This was a cross-sectional which was carried out in the pediatric ward and pediatric cardiology outpatient clinic in the year 2022. The research subjects were children diagnosed with anemia, then they would undergo chest radiograph and echocardiography to assess whether there is cardiomegaly or not.
RESULTS
Eighty one children were included in this study. The majority of them were girl, with a total of 43 people (53.1%). The median age of patients in this study was 7.75 years old. In addition, this study also found that the median of patients' body weight and height were 18.3 kg and 116 cm. In this study, the median hemoglobin level was 10.3 g/dL. For the echocardiography parameters in this study, the median of LA/Ao, EF and FS were 1.24, 65% and 35% respectively. There is no association beteween anemia and cardiomegaly based on chest radiograph or echocardiography.
PubMed: 37781491
DOI: 10.5455/aim.2023.31.191-194 -
Microorganisms Sep 2023Guanylate-binding proteins (GBPs) are highly expressed interferon-stimulated genes (ISGs) that play significant roles in protecting against invading pathogens. Although...
Guanylate-binding proteins (GBPs) are highly expressed interferon-stimulated genes (ISGs) that play significant roles in protecting against invading pathogens. Although their functions in response to RNA viruses have been extensively investigated, there is limited information available regarding their role in DNA viruses, particularly poxviruses. Ectromelia virus (ECTV), a member of the orthopoxvirus genus, is a large double-stranded DNA virus closely related to the monkeypox virus and variola virus. It has been intensively studied as a highly effective model virus. According to the study, GBP2 overexpression suppresses ECTV replication in a dose-dependent manner, while GBP2 knockdown promotes ECTV infection. Additionally, it was discovered that GBP2 primarily functions through its N-terminal GTPase activity, and the inhibitory effect of GBP2 was disrupted in the GTP-binding-impaired mutant GBP2. This study is the first to demonstrate the inhibitory effect of GBP2 on ECTV, and it offers insights into innovative antiviral strategies.
PubMed: 37764102
DOI: 10.3390/microorganisms11092258