Tag: nevin manimala

Am J Chin Med. 2023 Apr 29:1-26. doi: 10.1142/S0192415X23500386. Online ahead of print.

ABSTRACT

Current medical treatments for endometriosis-associated pain (EAP) have limitations, including symptom recurrence and hormonal side effects. For this reason, it is important to elucidate any alternative or complementary treatments available, while Chinese herbal medicine (CHM) shows potential to be this treatment. This study aims to provide evidence for the efficacy and safety of CHM for EAP. Randomized control trials comparing CHM to other treatments for EAP in women with endometriosis were considered eligible, and they were searched for in Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, as well as in the Chinese databases Sino-Med and CNKI, from inception to October 2021. Numerous outcomes were put through meta-analysis using a weighted mean difference and a 95% CI, and the results of dichotomous data were presented as a pooled RR with a 95% CI. A total of 34 eligible studies with 3389 participants were included. Compared with no treatment, there was a statistically significant pooled benefit of CHM on dysmenorrhea at the end of 3-month treatment, and these effects continued for 3 months, but not 9 months, after treatment. Compared with conventional therapy, a significant difference was found in the levels of pelvic pain with a lower rate of hot flush and irregular vaginal bleeding at the end of treatment for 3 months, but not after treatment. Comparing combined treatment with CHM and conventional therapy with conventional therapy alone, significant decreases were found in dysmenorrhea, dyspareunia, and pelvic pain after a 3-month treatment cycle, and in dysmenorrhea after a 4-month treatment cycle with a lower hot flash rate. In conclusion, CHM, used alone or in combination with conventional therapies, appears to have benefits in relieving EAP with fewer side effects than traditional treatment.

PMID:37120704 | DOI:10.1142/S0192415X23500386

Sci Rep. 2023 Apr 29;13(1):7021. doi: 10.1038/s41598-023-34250-4.

ABSTRACT

Healthcare workers are susceptible to blood borne pathogens, such as human immunodeficiency virus (HIV). Occupational exposure to HIV infection among healthcare workers is becoming a global public health concern. However, there is limited evidence about occupational exposure of healthcare workers to HIV and utilization of post-exposure prophylaxis in Addis Ababa, Ethiopia. Accordingly, this study was conducted to assess the prevalence of occupational exposure to HIV and utilization of post exposure prophylaxis among healthcare workers at St. Peter’s specialized hospital, Addis Ababa, Ethiopia. A health facility-based cross-sectional study was conducted among 308 randomly selected healthcare workers in April 2022. Structured and pretested self-administered questioner was used to collect data. Occupational exposure to HIV was taken as any percutaneous injury or blood or other body fluids exposure while administering medications, specimen collection, and other procedures with HIV confirmed patients. Multivariable binary logistic regression analysis was used to identify factors associated with occupational exposure to HIV and utilization of post-exposure prophylaxis. Statistically significant association was declared on the basis of adjusted odds ratio with 95% confidence interval and p-value less than 0.05. The study found that 42.3% (95% CI 36.6, 47.9%) of the healthcare workers had occupational exposure to HIV during their career time, out of whom 16.1% (95% CI 11.9, 20.3%) used post-exposure prophylaxis. Healthcare workers with lower-level education such as diploma (AOR: 0.41, 95% CI 0.17, 0.96) and BSc (AOR: 0.51, 95% CI 0.26, 0.92), and healthcare workers who received infection prevention training (AOR: 0.55, 95% CI 0.33, 0.90) had less risk of exposure to HIV. On the other hand, nurses (AOR: 1.98, 95% CI 1.07, 3.67), midwifes (AOR: 3.79, 95% CI 1.21, 11.9), and physicians (AOR: 2.11, 95% CI 1.05, 4.22) had high risk of exposure to HIV compared with other professionals. Moreover, healthcare workers with BSc degree compared with healthcare workers with masters degree (AOR: 3.69, 95% CI 1.08, 12.6), healthcare workers with long service year (AOR: 3.75, 95% CI 1.64, 8.57), and healthcare workers who are working in facilities where prophylaxis is available (AOR: 3.41, 95% CI 1.47, 7.91) had higher odds to utilize post-exposure prophylaxis. Significant proportion of healthcare workers included in the current study had occupational exposure to HIV and very few of them used post-exposure prophylaxis. Healthcare workers need to use appropriate personal protective equipment, safely manage contaminated equipment, and safely administered medications and collect specimen to protect themselves from exposure to HIV. Moreover, use of post-exposure prophylaxis should be promoted when exposure exists.

PMID:37120700 | DOI:10.1038/s41598-023-34250-4

Osteoporos Int. 2023 Apr 29. doi: 10.1007/s00198-023-06761-3. Online ahead of print.

ABSTRACT

Previous randomized controlled trials have reported inconsistent findings regarding the effects of high-dose vitamin D supplementation on a risk of falls and fractures. This meta-analysis of 15 trials shows that intermittent or single high-dose vitamin D supplementation had no preventive effect on the risk of falls and fractures and might even increase the risk of falls.

PURPOSE: Randomized controlled trials (RCTs) have reported controversial findings regarding the associations between intermittent or single high-dose vitamin D supplementation and a risk of falls and fractures in adults. This study aimed to investigate those associations using a systematic review and meta-analysis.

METHODS: We searched PubMed, EMBASE, and Cochrane Library from inception to May 25, 2022. Data were extracted for a random-effects meta-analysis to calculate a pooled relative risk (RR) with a 95% confidence interval (CI).

RESULTS: Out of 527 articles, a total of 15 RCTs were included in the final analysis. In a meta-analysis of RCTs, intermittent or single high-dose vitamin D supplementation showed no significant beneficial effect in the prevention of either falls (RR, 1.03 [95% CI, 0.98-1.09]; I² = 56.6%; n = 11) or fractures (RR, 0.99 [95% CI, 0.87-1.14]; I² = 48.3%; n = 11). Among the subgroup meta-analyses by various factors, intermittent or single high-dose vitamin D supplementation reduced the risk of fractures in the subgroup meta-analysis of RCTs that included fewer than 1000 participants (RR, 0.74 [95% CI 0.57-0.96]; I² = 0.0%; n = 5). However, its beneficial effect was not observed in those including 1000 or more participants (RR, 1.06 [95% CI 0.92-1.21]; I² = 57.5%; n = 6). In contrast, intermittent or single high-dose vitamin D3 supplementation increased the risk of falls on the borderline of statistical significance (RR, 1.06 [95% CI 0.99-1.15]; P = 0.051; I² = 50.0%; n = 7).

CONCLUSIONS: Intermittent or single high-dose vitamin D supplementation had no preventive effect on the risk of falls and fractures and might even increase the risk of falls.

PMID:37120684 | DOI:10.1007/s00198-023-06761-3

J Hum Hypertens. 2023 Apr 29. doi: 10.1038/s41371-023-00833-x. Online ahead of print.

ABSTRACT

Hypertension is a leading cause of non-communicable morbidity in Sub Saharan Africa. Recent studies suggest and increase in the prevalence of hypertension in rural Sub-Saharan Africa. Using a three-phase approach, a structured questionnaire was used to determine the prevalence of hypertension in a rural settlement is Enugu State, Southeast Nigeria. Blood pressure measurement was done according to the guidelines of the European Society of Hypertension. Out of 1576 participants aged 18 years and above, 1082 (68.7%) completed the full survey, their blood pressure was measured, and data analyzed. The prevalence of hypertension in this study was 27.6%, (95%CI 25-30.4), similar in males 29.2, (95%CI 24.7-30.4) and females 26.8%, (95%CI 23.5-30.2). p = 0.39. The prevalence of hypertension increased with age reaching a peak of 32.8% (95%CI 26.2-40) in the 40-49 age group, however this was not statistically significant P = 0.22. This age-related increase in the prevalence of hypertension tended towards significance in males (p = 0.05) but not in females (p = 0.44). Awareness of hypertension was 7.2%. Systolic blood pressure positively correlated with older age, higher blood glucose levels and waist-hip ratio. Diastolic blood pressure correlated with the type of work the patients is involved in and blood glucose levels. In conclusion, the prevalence of hypertension in a rural southeastern Nigeria community was 27.6%, however awareness was very low (7.9%). Most participants had mild hypertension thus offering a window of opportunity for public health educators in preventing the complications of hypertension. There is therefore the need for awareness campaigns to be intensified in rural communities.

PMID:37120682 | DOI:10.1038/s41371-023-00833-x

Nat Methods. 2023 Apr 29. doi: 10.1038/s41592-023-01887-y. Online ahead of print.

NO ABSTRACT

PMID:37120675 | DOI:10.1038/s41592-023-01887-y

Sci Rep. 2023 Apr 29;13(1):7049. doi: 10.1038/s41598-023-34161-4.

ABSTRACT

Discovering synthetic lethal (SL) gene partners of cancer genes is an important step in developing cancer therapies. However, identification of SL interactions is challenging, due to a large number of possible gene pairs, inherent noise and confounding factors in the observed signal. To discover robust SL interactions, we devised SLIDE-VIP, a novel framework combining eight statistical tests, including a new patient data-based test iSurvLRT. SLIDE-VIP leverages multi-omics data from four different sources: gene inactivation cell line screens, cancer patient data, drug screens and gene pathways. We applied SLIDE-VIP to discover SL interactions between genes involved in DNA damage repair, chromatin remodeling and cell cycle, and their potentially druggable partners. The top 883 ranking SL candidates had strong evidence in cell line and patient data, 250-fold reducing the initial space of 200K pairs. Drug screen and pathway tests provided additional corroboration and insights into these interactions. We rediscovered well-known SL pairs such as RB1 and E2F3 or PRKDC and ATM, and in addition, proposed strong novel SL candidates such as PTEN and PIK3CB. In summary, SLIDE-VIP opens the door to the discovery of SL interactions with clinical potential. All analysis and visualizations are available via the online SLIDE-VIP WebApp.

PMID:37120674 | DOI:10.1038/s41598-023-34161-4

Eye (Lond). 2023 Apr 29. doi: 10.1038/s41433-023-02549-1. Online ahead of print.

ABSTRACT

PURPOSE: This study compared the efficiency of diabetic retinopathy (DR) diagnosis and differences in the relative visible retinal area among the Early Treatment Diabetic Retinopathy Study (ETDRS) seven-field, ultra-widefield (UWF)-Optos, and UWF-Clarus fundus imaging methods.

METHODS: This was a prospective and clinic-based comparative study. All patients underwent three fundus examinations, and all images were graded using the ETDRS severity scale. We compared and analysed the agreement of DR severity and the relative visible retinal area among the three fundus examination methods, and the number and type of lesions outside the ETDRS seven-field (peripheral lesions) between the two UWF imaging methods.

RESULTS: A total of 202 patients (386 eyes) were included. Weighted kappa for the agreement between ETDRS seven-field and blinded Optos images was 0.485; between ETDRS seven-field and blinded Clarus images, 0.924; and between blinded Optos and Clarus images, 0.461. Blinded Clarus showed excellent performance when a ETDRS scale was used for grading the images. The relative visible retinal area for ETDRS seven-field images was 195 ± 28 disc area (DA); single Optos images, 371 ± 69 DA; single Clarus images, 261 ± 65 DA; two-montage Clarus images, 462 ± 112 DA; and four-montage Clarus images, 598 ± 139 DA. The relative visible retinal area was statistically significant between any two of the imaging systems used. In total, 2015 and 4200 peripheral lesions were detected in single Optos and Clarus images, respectively (P < 0.001). These peripheral lesions on two UWF images suggested a more severe DR level in approximately 10% and 12% of eyes, respectively.

CONCLUSION: UWF-Clarus fundus imaging offers a suitable assessment approach for DR severity; it could improve DR diagnosis and has the potential to replace ETDRS seven-field imaging after additional clinical trials.

PMID:37120657 | DOI:10.1038/s41433-023-02549-1

Sci Rep. 2023 Apr 29;13(1):7055. doi: 10.1038/s41598-023-34305-6.

ABSTRACT

With the rapid rate of SARS-CoV-2 Main protease (M^pro) structures deposition, a computational method that can combine all the useful structural features becomes crucial. This research focuses on the frequently occurring atoms and residues to find a generalized strategy for inhibitor design given a large amount of protein complexes from SARS-CoV in contrast to SARS-CoV-2 M^pro. By superposing large numbers of the ligands onto the protein template and grid box, we can analyse which part of the structure is conserved from position-specific interaction for both data sets for the development of pan-M^pro antiviral design. The difference in conserved recognition sites from the crystal structures can be used to determine specificity determining residues for designing selective drugs. We can display pictures of the imaginary shape of the ligand by unionising all atoms from the ligand. We also pinpoint the most probable atom adjustments to imitate the frequently found densities from the ligand atoms statistics. With molecular docking, Molecular Dynamics simulation, and MM-PBSA methods, a carbonyl replacement at the nitrile warhead (N5) of Paxlovid’s Nirmatrelvir (PF-07321332) was suggested. By gaining insights into the selectivity and promiscuity regions for proteins and ligands, crucial residues are highlighted, and the antiviral design strategies are proposed.

PMID:37120654 | DOI:10.1038/s41598-023-34305-6

Transl Psychiatry. 2023 Apr 29;13(1):141. doi: 10.1038/s41398-023-02443-0.

ABSTRACT

Treatment effect in clinical trials for major depressive disorders (RCT) can be viewed as the resultant of treatment specific and non-specific effects. Baseline individual propensity to respond non-specifically to any treatment or intervention can be considered as a major non-specific confounding effect. The greater is the baseline propensity, the lower will be the chance to detect any treatment-specific effect. The statistical methodologies currently applied for analyzing RCTs doesn’t account for potential unbalance in the allocation of subjects to treatment arms due to heterogenous distributions of propensity. Hence, the groups to be compared may be imbalanced, and thus incomparable. Propensity weighting methodology was used to reduce baseline imbalances between arms. A randomized, double-blind, placebo controlled, three arms, parallel group, 8-week, fixed-dose study to evaluate efficacy of paroxetine CR 12.5 and 25 mg/day is presented as a cases study. An artificial intelligence model was developed to predict placebo response at week 8 in subjects assigned to placebo arm using changes from screening to baseline of individual Hamilton Depression Rating Scale items. This model was used to predict the probability to respond to placebo in each subject. The inverse of the probability was used as weight in the mixed-effects model applied to assess treatment effect. The analysis with and without propensity weight indicated that the weighted analysis provided an estimate of treatment effect and effect-size about twice larger than the non-weighted analysis. Propensity weighting provides an unbiased strategy to account for heterogeneous and uncontrolled placebo effect making patients’ data comparable across treatment arms.

PMID:37120641 | DOI:10.1038/s41398-023-02443-0

Clin Epigenetics. 2023 Apr 29;15(1):73. doi: 10.1186/s13148-023-01482-0.

ABSTRACT

BACKGROUND: Epigenetic silencing of tumor suppressor genes (TSGs) is a key feature of oncogenesis in hepatocellular carcinoma (HCC). Liver-targeted delivery of CRISPR-activation (CRISPRa) systems makes it possible to exploit chromatin plasticity, by reprogramming transcriptional dysregulation.

RESULTS: Using The Cancer Genome Atlas HCC data, we identify 12 putative TSGs with negative associations between promoter DNA methylation and transcript abundance, with limited genetic alterations. All HCC samples harbor at least one silenced TSG, suggesting that combining a specific panel of genomic targets could maximize efficacy, and potentially improve outcomes as a personalized treatment strategy for HCC patients. Unlike epigenetic modifying drugs lacking locus selectivity, CRISPRa systems enable potent and precise reactivation of at least 4 TSGs tailored to representative HCC lines. Concerted reactivation of HHIP, MT1M, PZP, and TTC36 in Hep3B cells inhibits multiple facets of HCC pathogenesis, such as cell viability, proliferation, and migration.

CONCLUSIONS: By combining multiple effector domains, we demonstrate the utility of a CRISPRa toolbox of epigenetic effectors and gRNAs for patient-specific treatment of aggressive HCC.

PMID:37120619 | DOI:10.1186/s13148-023-01482-0