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Hypermethylation of ACADVL is involved in the high-intensity interval training-associated reduction of cardiac fibrosis in heart failure patients

J Transl Med. 2023 Mar 10;21(1):187. doi: 10.1186/s12967-023-04032-7.

ABSTRACT

BACKGROUND: Emerging evidence suggests that DNA methylation can be affected by physical activities and is associated with cardiac fibrosis. This translational research examined the implications of DNA methylation associated with the high-intensity interval training (HIIT) effects on cardiac fibrosis in patients with heart failure (HF).

METHODS: Twelve HF patients were included and received cardiovascular magnetic resonance imaging with late gadolinium enhancement for cardiac fibrosis severity and a cardiopulmonary exercise test for peak oxygen consumption ([Formula: see text]O2peak). Afterwards, they underwent 36 sessions of HIIT at alternating 80% and 40% of [Formula: see text]O2peak for 30 min per session in 3-4 months. Human serum from 11 participants, as a means to link cell biology to clinical presentations, was used to investigate the exercise effects on cardiac fibrosis. Primary human cardiac fibroblasts (HCFs) were incubated in patient serum, and analyses of cell behaviour, proteomics (n = 6) and DNA methylation profiling (n = 3) were performed. All measurements were conducted after completing HIIT.

RESULTS: A significant increase (p = 0.009) in [Formula: see text]O2peak (pre- vs. post-HIIT = 19.0 ± 1.1 O2 ml/kg/min vs. 21.8 ± 1.1 O2 ml/kg/min) was observed after HIIT. The exercise strategy resulted in a significant decrease in left ventricle (LV) volume by 15% to 40% (p < 0.05) and a significant increase in LV ejection fraction by approximately 30% (p = 0.010). LV myocardial fibrosis significantly decreased from 30.9 ± 1.2% to 27.2 ± 0.8% (p = 0.013) and from 33.4 ± 1.6% to 30.1 ± 1.6% (p = 0.021) in the middle and apical LV myocardium after HIIT, respectively. The mean single-cell migration speed was significantly (p = 0.044) greater for HCFs treated with patient serum before (2.15 ± 0.17 μm/min) than after (1.11 ± 0.12 μm/min) HIIT. Forty-three of 1222 identified proteins were significantly involved in HIIT-induced altered HCF activities. There was significant (p = 0.044) hypermethylation of the acyl-CoA dehydrogenase very long chain (ACADVL) gene with a 4.474-fold increase after HIIT, which could activate downstream caspase-mediated actin disassembly and the cell death pathway.

CONCLUSIONS: Human investigation has shown that HIIT is associated with reduced cardiac fibrosis in HF patients. Hypermethylation of ACADVL after HIIT may contribute to impeding HCF activities. This exercise-associated epigenetic reprogramming may contribute to reduce cardiac fibrosis and promote cardiorespiratory fitness in HF patients.

TRIAL REGISTRATION: NCT04038723. Registered 31 July 2019, https://clinicaltrials.gov/ct2/show/NCT04038723 .

PMID:36894992 | DOI:10.1186/s12967-023-04032-7

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Novel Plasmodium falciparum k13 gene polymorphisms from Kisii County, Kenya during an era of artemisinin-based combination therapy deployment

Malar J. 2023 Mar 9;22(1):87. doi: 10.1186/s12936-023-04517-2.

ABSTRACT

BACKGROUND: Currently, chemotherapy stands out as the major malaria intervention strategy, however, anti-malarial resistance may hamper global elimination programs. Artemisinin-based combination therapy (ACT) stands as the drug of choice for the treatment of Plasmodium falciparum malaria. Plasmodium falciparum kelch13 gene mutations are associated with artemisinin resistance. Thus, this study was aimed at evaluating the circulation of P. falciparum k13 gene polymorphisms from Kisii County, Kenya during an era of ACT deployment.

METHODS: Participants suspected to have malaria were recruited. Plasmodium falciparum was confirmed using the microscopy method. Malaria-positive patients were treated with artemether-lumefantrine (AL). Blood from participants who tested positive for parasites after day 3 was kept on filter papers. DNA was extracted using chelex-suspension method. A nested polymerase chain reaction (PCR) was conducted and the second-round products were sequenced using the Sanger method. Sequenced products were analysed using DNAsp 5.10.01 software and then blasted on the NCBI for k13 propeller gene sequence identity using the Basic Local Alignment Search Tool (BLAST). To assess the selection pressure in P. falciparum parasite population, Tajima’ D statistic and Fu & Li’s D test in DnaSP software 5.10.01 was used.

RESULTS: Out of 275 enrolled participants, 231 completed the follow-up schedule. 13 (5.6%) had parasites on day 28 hence characterized for recrudescence. Out of the 13 samples suspected of recrudescence, 5 (38%) samples were positively amplified as P. falciparum, with polymorphisms in the k13-propeller gene detected. Polymorphisms detected in this study includes R539T, N458T, R561H, N431S and A671V, respectively. The sequences have been deposited in NCBI with bio-project number PRJNA885380 and accession numbers SAMN31087434, SAMN31087433, SAMN31087432, SAMN31087431 and SAMN31087430 respectively.

CONCLUSIONS: WHO validated polymorphisms in the k13-propeller gene previously reported to be associated with ACT resistance were not detected in the P. falciparum isolates from Kisii County, Kenya. However, some previously reported un-validated k13 resistant single nucleotide polymorphisms were reported in this study but with limited occurrences. The study has also reported new SNPs. More studies need to be carried out in the entire country to understand the association of reported mutations if any, with ACT resistance.

PMID:36894982 | DOI:10.1186/s12936-023-04517-2

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Gut colonization with vancomicyn-resistant enterococci among patients with hematologic malignancies

Gut Pathog. 2023 Mar 9;15(1):12. doi: 10.1186/s13099-023-00538-z.

ABSTRACT

BACKGROUND: Vancomycin-resistant enterococci (VRE) are well known agents that colonize the gastrointestinal tract of immunocompromised patients, especially those with hematologic malignancies. The aim of the current study was to determine the incidence of and risk factors for colonization with VRE among patients with hematologic malignancies.

MATERIALS: For a nine-month period, all patients admitted to the Hematology ward at University Hospital in Pleven, Bulgaria who had hematologic malignancy and duration of hospitalization of more than 48 h were screened for colonization with VRE. The data collected from patients and their medical records during the entire hospital stay included: demographic characteristics, clinical information and information about all antimicrobials used. A longitudinal study was used to assesses the risk factors and statistical analysis was performed using SPSS version 27.0.

RESULTS: A total of 119 patients were enrolled in the study. Colonization with VRE was established in 18 of them. One patient carried two species, resulting in a total of 19 VRE: 12 Enterococcus gallinarum, 4 Enterococcus casseliflavus, 2 Enterococcus faecium and 1 Enterococcus faecalis. VanA phenotype, with high-level resistance of vancomycin (MIC ≥ 256 μg/ml) and teicoplanin (MIC = 96 μg/ml), was demonstrated by one E. faecium, which carried vanA. The other E. faecium and E. faecalis expressed low-level resistance to vancomycin (MICs: 8 μg/ml and 12 μg/ml), susceptibility to teicoplanin (MICs = 0.5 μg/ml) and vanB was detected. All E. gallinarum and E. casseliflavus showed low-level resistance to vancomycin and susceptibility to teicoplanin. E. gallinarum strains were positive for vanC1 and E. casseliflavus for vanC2. Only two patients were colonized with vanA or vanB enterococci and the rest 16 were positive for vanC. The univariate analysis revealed that patient’s age (70-79 years; p = 0.025) and multiple myeloma (p = 0.001) are risk factors for VRE acquisition among the investigated patients. In addition, the multivariate analysis confirmed that patient’s age (70-79 years) is an independent risk factor for VRE colonization.

CONCLUSIONS: Our results showed that 15.1% of patients with hematologic malignancies were colonized with VRE. There was a distinct prevalence of vanC enterococci. Among the analyzed risk factors, advanced age and multiple myeloma contributed to VRE acquisition.

PMID:36894979 | DOI:10.1186/s13099-023-00538-z

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Prevalence, indications and fetal outcomes of operative vaginal delivery in Sub-Saharan Africa, systematic review, and meta-analysis

BMC Womens Health. 2023 Mar 9;23(1):95. doi: 10.1186/s12905-023-02224-3.

ABSTRACT

PURPOSE: This systematic review and meta-analysis is intended to assess the prevalence, indications, and fetal outcome of operative vaginal delivery in sub-Saharan Africa.

METHOD: In this study, 17 studies with a total population of 190,900 were included in both systematic review and meta-analysis. Search for relevant articles was done by using international online databases (like Google Scholar, PubMed, HINARI, EMBASE, Web of Science, and African journals) and online repositories of Universities in Africa. The JOANNA Briggs Institute standard data extraction format was used to extract and appraise high-quality articles before being included in this study. The Cochran Q and I2 statistical tests were used to test the heterogeneity of the studies. The publication bias was tested by a Funnel plot and Egger’s test. The overall pooled prevalence, indications, and fetal outcome of operative vaginal delivery along a 95% CI using forest plots and tables.

RESULT: The overall pooled prevalence of operative vaginal delivery in sub-Saharan Africa was 7.98% (95% CI; 5.03-10.65; I2 = 99.9%, P < 0.001). The indications of operative vaginal delivery in sub-Saharan African countries include the prolonged second stage of labor 32.81%, non-reassuring fetal heart rate 37.35%, maternal exhaustion 24.81%, big baby 22.37%, maternal cardiac problems 8.75%, and preeclampsia/eclampsia 2.4%. Regarding the fetal outcome, favourable fetal outcomes were 55% (95% CI: 26.04, 84.44), p = < 0.56, I2: 99.9%). From those births with unfavourable outcomes, the need for the resuscitation of new-born was highest 28.79% followed by poor 5th minute Apgar score, NICU admission, and fresh stillbirth, 19.92, 18.8, and 3.59% respectively.

CONCLUSION: The overall prevalence of operative vaginal delivery (OVD) in sub-Saharan Africa was slightly higher compared to other countries. To reduce the increased applications and adverse fetal outcomes of OVD, capacity building for obstetrics care providers and drafting guidelines are required.

PMID:36894978 | DOI:10.1186/s12905-023-02224-3

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Motivating non-physician health workers to reduce the behavioral risk factors of non-communicable diseases in the community: a field trial study

Arch Public Health. 2023 Mar 10;81(1):37. doi: 10.1186/s13690-023-01047-w.

ABSTRACT

BACKGROUND: Non-communicable diseases behavioral risk factors can be improved if effective interventions are designed considering the health system’s capabilities and local resources. This study evaluated the effectiveness of interventions that aimed at increasing non-physician community health workers’ motivation in reducing non-communicable diseases behavioral risk factors in the community.

METHODS: A randomized field trial study was conducted in 32 community health centers in 4 Iranian districts after a baseline population survey on the status of NCDs of 30-70-year-old individuals (n = 1225). The interventions were performed to improve insufficient physical activity, insufficient fruit consumption, insufficient vegetable consumption, high salt intake, and tobacco use. Four intervention packages were implemented in 24 community health centers; the other 8 centers were used as control groups. The non-physician community health workers performed the interventions. The packages additively included goal-setting, evidence-based education, operational planning, and incentive payments. A second survey was conducted 1 year after the start of the interventions to identify the effects on an independent random sample of 30-70-year-old individuals (n = 1221). Difference-in-difference method was used to quantify the interventions’ effects.

RESULTS: The average age of participants in both surveys was about 49 years. Also, about half of the participants were female, and about 43% were illiterate or had a primary school education. The interventions had statistically significant effects only on decreasing the prevalence of insufficient physical activity. The package with all the intervention components decreased the odds of insufficient physical activity to 0.24 (95% CI, 0.08, 0.72). The package with operational planning but no performance-based financing did not change the odds of insufficient physical activity.

CONCLUSIONS: This study highlighted the importance of components, design, and implementation details of interventions intended to reduce NCDs behavioral risk factors. Some risk factors, such as insufficient physical activity, seem more easily modifiable with limited low-cost interventions in a one-year horizon. However, risk factors related to healthy food consumption and tobacco use need more extensive interventions.

TRIAL REGISTRATION: This trial was registered on the Iranian Registry of Clinical Trials (IRCT20081205001488N2) on 3 June 2018 ( https://en.irct.ir/trial/774 ).

PMID:36894971 | DOI:10.1186/s13690-023-01047-w

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“Reply on: statistics on steroids-how recognizing competing risks gets us closer to the truth about COVID-19-associated VAP”

Crit Care. 2023 Mar 9;27(1):100. doi: 10.1186/s13054-023-04351-7.

NO ABSTRACT

PMID:36894967 | DOI:10.1186/s13054-023-04351-7

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Randomized clinical trial with fractional CO2 laser and Clobetasol in the treatment of Vulvar Lichen Sclerosus: a clinic study of feasibility

BMC Res Notes. 2023 Mar 10;16(1):33. doi: 10.1186/s13104-023-06300-7.

ABSTRACT

OBJECTIVES: The main objective of the study was to describe and compare the feasibility of using fractional CO2 laser to the usual treatment with Clobetasol. Randomized clinical trials brought together 20 women from a Brazilian university hospital, 9 of them were submitted to Clobetasol treatment and 11 to laser therapy. Sociodemographic data were obtained and quality of life parameters, vulvar anatomy, self-perception and histopathological analysis of vulvar biopsies were evaluated. Evaluations were made before the beginning of the treatment, during its implementation, right after its completion (3 months), and 12 months after. The SPSS 14.0 software was used, obtaining descriptive measurements. The level of significance adopted was 5%.

RESULTS: The clinical/anatomical characteristics of the vulva did not differ between the treatment groups, as much before as after its performance. There was no statistically significant difference between the treatments performed regarding the impact on the life quality of the patients. A higher satisfaction degree with the treatment was obtained with the patients in the Laser group in the third month of evaluation. Laser therapy also revealed higher occurrence of telangiectasia after treatment completion. Fractional CO2 laser has proven to be well accepted and is a promising therapeutic option. Registration number and name of trial registry The institutional review board status was approved by the Research Ethics Committee of HU/ UFJF under advisory number 2881073 and registered in the Brazilian Clinical Trials, with consent under registration RBR-4p9s5y. Access link: https://ensaiosclinicos.gov.br/rg/RBR-4p9s5y.

PMID:36894959 | DOI:10.1186/s13104-023-06300-7

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Corn360: a method for quantification of corn kernels

Plant Methods. 2023 Mar 9;19(1):23. doi: 10.1186/s13007-023-00995-2.

ABSTRACT

BACKGROUND: The rapidly advancing corn breeding field calls for high-throughput methods to phenotype corn kernel traits to estimate yield and to study their genetic inheritance. Most of the existing methods are reliant on sophisticated setup, expertise in statistical models and programming skills for image capturing and analysis.

RESULTS: We demonstrated a portable, easily accessible, affordable, panoramic imaging capturing system called Corn360, followed by image analysis using freely available software, to characterize total kernel count and different patterned kernel counts of a corn ear. The software we used did not require programming skills and utilized Artificial Intelligence to train a model and to segment the images of mixed patterned corn ears. For homogeneously patterned corn ears, our results showed accuracies of 93.7% of total kernel count compared to manual counting. Our method allowed to save an average of 3 min 40 s per image. For mixed patterned corn ears, our results showed accuracies of 84.8% or 61.8% of segmented kernel counts. Our method has the potential to greatly decrease counting time per image as the number of images increases. We also demonstrated a case of using Corn360 to count different categories of kernels on a mixed patterned corn ear resulting from a cross of sweet corn and sticky corn and showed that starch:sweet:sticky segregated in a 9:4:3 ratio in its F2 population.

CONCLUSIONS: The panoramic Corn360 approach enables for a portable low-cost high-throughput kernel quantification. This includes total kernel quantification and quantification of different patterned kernels. This can allow for quick estimate of yield component and for categorization of different patterned kernels to study the inheritance of genes controlling color and texture. We demonstrated that using the samples resulting from a sweet × sticky cross, the starchiness, sweetness and stickiness in this case were controlled by two genes with epistatic effects. Our achieved results indicate Corn360 can be used to effectively quantify corn kernels in a portable and cost-efficient way that is easily accessible with or without programming skills.

PMID:36894953 | DOI:10.1186/s13007-023-00995-2

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Deep phenotyping towards precision psychiatry of first-episode depression – the Brain Drugs-Depression cohort

BMC Psychiatry. 2023 Mar 9;23(1):151. doi: 10.1186/s12888-023-04618-x.

ABSTRACT

BACKGROUND: Major Depressive Disorder (MDD) is a heterogenous brain disorder, with potentially multiple psychosocial and biological disease mechanisms. This is also a plausible explanation for why patients do not respond equally well to treatment with first- or second-line antidepressants, i.e., one-third to one-half of patients do not remit in response to first- or second-line treatment. To map MDD heterogeneity and markers of treatment response to enable a precision medicine approach, we will acquire several possible predictive markers across several domains, e.g., psychosocial, biochemical, and neuroimaging.

METHODS: All patients are examined before receiving a standardised treatment package for adults aged 18-65 with first-episode depression in six public outpatient clinics in the Capital Region of Denmark. From this population, we will recruit a cohort of 800 patients for whom we will acquire clinical, cognitive, psychometric, and biological data. A subgroup (subcohort I, n = 600) will additionally provide neuroimaging data, i.e., Magnetic Resonance Imaging, and Electroencephalogram, and a subgroup of patients from subcohort I unmedicated at inclusion (subcohort II, n = 60) will also undergo a brain Positron Emission Tomography with the [11C]-UCB-J tracer binding to the presynaptic glycoprotein-SV2A. Subcohort allocation is based on eligibility and willingness to participate. The treatment package typically lasts six months. Depression severity is assessed with the Quick Inventory of Depressive Symptomatology (QIDS) at baseline, and 6, 12 and 18 months after treatment initiation. The primary outcome is remission (QIDS ≤ 5) and clinical improvement (≥ 50% reduction in QIDS) after 6 months. Secondary endpoints include remission at 12 and 18 months and %-change in QIDS, 10-item Symptom Checklist, 5-item WHO Well-Being Index, and modified Disability Scale from baseline through follow-up. We also assess psychotherapy and medication side-effects. We will use machine learning to determine a combination of characteristics that best predict treatment outcomes and statistical models to investigate the association between individual measures and clinical outcomes. We will assess associations between patient characteristics, treatment choices, and clinical outcomes using path analysis, enabling us to estimate the effect of treatment choices and timing on the clinical outcome.

DISCUSSION: The BrainDrugs-Depression study is a real-world deep-phenotyping clinical cohort study of first-episode MDD patients.

TRIAL REGISTRATION: Registered at clinicaltrials.gov November 15th, 2022 (NCT05616559).

PMID:36894940 | DOI:10.1186/s12888-023-04618-x

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Catastrophic health expenditure and associated factors among households of non community based health insurance districts, Ilubabor zone, Oromia regional state, southwest Ethiopia

Int J Equity Health. 2023 Mar 9;22(1):40. doi: 10.1186/s12939-023-01847-0.

ABSTRACT

BACKGROUND: Out-of-pocket health expenditure is the proportion of total health expenditure that is paid by individuals and households at the time of health service. Hence, the objective of this study is to assess the incidence and intensity of catastrophic health expenditure and associated factors among households in non-community-based health insurance districts in the Ilubabor zone, Oromia National Regional State, Ethiopia.

METHOD: A community-based cross-sectional study design was employed in the Ilubabor zone on non-community-based health insurance scheme districts from August 13 to September 2, 2020, and 633 households participated in the study. A multistage one cluster sampling method was used to select three districts out of seven districts. Data was collected by using a structured mix of open and close-ended pre -tested questionnaires by face-to-face interviewing. A micro-costing/bottom up approach was used for all household expenditure. After checking its completeness, all household consumption expenditure was done by mathematical analysis using Microsoft Excel. Binary and multiple logistic were done using 95%CI and significance was declared at P < 0.05.

RESULTS: The number of households that participated in the study was 633, with a response rate of 99.7%. Out of 633 households surveyed, 110 (17.4%) were in catastrophe, which exceeds 10% of total household expenditure. After medical care expenses, about 5% of the households moved downward from the middle poverty line to extreme poverty. Out-of-pocket payment AOR: 31.201: 95% CI (12.965-49.673), daily income less than 1.90 USD AOR: 2.081: 95% CI (1.010-3.670), living a medium distance from a health facility AOR: 6.219: 95% CI (1.632-15.418), and chronic disease AOR: 5.647: 95% CI (1.764-18.075.

CONCLUSION: In this study, family size, average daily income, out of pocket payment and chronic diseases were statistically significant and independent predictors for household catastrophic health expenditure. Therefore, to overcome financial risk, the Federal Ministry of Health should develop different guidelines and modalities by considering household per capita and income to improve the enrolment of community-based health insurance. Also, the regional health bureau should improve their budget share of 10% to increase the coverage of poor households. Strengthening financial risk protection mechanisms, such as community-based health insurance, could help to improve healthcare equity and quality.

PMID:36894937 | DOI:10.1186/s12939-023-01847-0