Nevin Manimala

Syst Rev. 2024 Jul 15;13(1):180. doi: 10.1186/s13643-024-02605-1.

ABSTRACT

BACKGROUND: The emergence of HIV drug resistance presents a substantial challenge. Current antiretroviral treatments, along with current classes, face the danger of becoming partially or entirely inactive. As a result, alternative treatment regimens are limited, and treatment choices are complicated. According to the recommendation of the WHO, nations should consider changing their first-line ART regimen if HIV drug resistance exceeds 10%. In spite of the fact that a number of primary studies have been performed on HIV drug resistance in Ethiopia, their pooled prevalence rate has not been determined in a systematic review and meta-analysis, which may provide stronger evidence. Therefore, the objective of this systematic review and meta-analysis will be to estimate the pooled prevalence rate of HIV1 drug resistance in patients with first-line treatment failure in Ethiopia.

METHODS: Primary studies will be identified from PubMed/MEDLINE, Scopus, Embase, Web of Science Core Collection, and Google Scholar. The period of search will be from 01 April to 30 June 2024. Studies identified through the search strategies will first be screened by titles and abstracts. Included studies meeting established criteria will be evaluated for risk of bias using the JBI checklist. Data will be extracted, and the pooled prevalence rate of HIV drug resistance will be computed using STATA 14 software. Random effect models will be used when heterogeneity is suspected. The I² statistic and its corresponding P value will be checked to distinguish heterogeneity. Additionally, publication bias and heterogeneity will be checked using visual funnel plots, Egger’s test, trim-and-fill tests, meta-regression, and subgroup analysis. To present and synthesize the results, narrative synthesis will be performed to describe study characteristics and findings, and forest plots will be used to visually represent effect sizes and confidence intervals from individual studies.

DISCUSSION: Estimating the pooled prevalence rate of HIV drug resistance through a systematic review and meta-analysis improves the reliability of the evidence, the availability of effective HIV treatment options, and the ability to assist in making decisions for both clinical practice and public health policy in Ethiopia.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42024533975.

PMID:39010186 | DOI:10.1186/s13643-024-02605-1

BMC Pharmacol Toxicol. 2024 Jul 15;25(1):42. doi: 10.1186/s40360-024-00763-5.

ABSTRACT

BACKGROUND: A global increase in cannabis use has led to questions about its effects on fertility. The rise in consumption amongst women of reproductive age is a growing concern, as this group is vulnerable in terms of reproductive health. Ample evidence suggests that the psychoactive component of cannabis, Δ⁹-Tetrahydrocannabinol (THC), interacts with the endocannabinoid system (ECS), that helps regulate mammalian reproduction. This study aimed to research the epigenetic effects of THC in bovine granulosa cells (GCs) by (1) investigating global DNA methylation via measuring 5-mC and 5-hmC levels; (2) measuring key methylation regulators, including the methylating enzymes DNMT1, DNMT3a, DNMT3b and the demethylases TDG and TET1/2/3; and (3) assessing fertility-associated miRNAs key in developmental competency, including miR-21, -155, -33b, -324 and -346.

METHODS: Bovine GCs were used as a translational model for reproductive toxicity in humans. To determine THC effects, GCs were isolated from Cumulus-Oocyte-Complexes (COCs) from bovine ovaries, cultured in vitro for 7 days, or until confluent, and cryopreserved at passage 1 (P1). For experimentation, cells were thawed, cultured until passage 2 (P2), serum restricted for 24-h and treated for 24-h in one of five groups: control, vehicle (1:1:18 ethanol: tween: saline) and three clinically relevant THC doses (0.032, 0.32 and 3.2 μM). Global methylation was assessed by measuring 5-mC and 5-hmC levels with flow cytometry. To assess mRNA and protein expression of methylation regulators and miRNA profiles, qPCR and Western Blotting were utilized. Shapiro-Wilk test was used to determine normality within datasets. One-way ANOVA was applied to determine statistical significance using GraphPad Prism 6.0.0.

RESULTS: Results indicate a significant decrease (p = 0.0435) in 5-mC levels following low THC exposure, while no changes were observed in 5-hmC levels. A significant increase in DNMT1 following high THC exposure at the RNA level (p < 0.05) and a significant increase following low THC exposure at the protein level (p = 0.0048) were also observed. No significant differences were observed in DNMT3a/3b, TDG, TET1/2/3 mRNAs or in any of the miRNAs analyzed.

CONCLUSIONS: This research suggests that THC mainly affects DNA methylation, but not miRNA profiles, ultimately altering gene expression and likely impairing oocyte competence, maturation, and fertilization potential.

PMID:39010179 | DOI:10.1186/s40360-024-00763-5

Trials. 2024 Jul 15;25(1):480. doi: 10.1186/s13063-024-08311-6.

ABSTRACT

BACKGROUND: Postoperative sleep disturbance has a potentially detrimental effect on postoperative recovery. Perioperative patients are affected by several factors. General anesthesia induces a non-physiological state that does not resemble natural sleep. Exposure to propofol/sevoflurane can lead to desynchronization of the circadian rhythm, which may result in postoperative sleep disturbance characterized by mid-cycle advancement of sleep and daytime sleepiness. Dexmedetomidine is a highly selective α2-adrenoceptor agonist with a unique sedative effect that facilitates the transition from sleep to wakefulness. Basic research has shown that dexmedetomidine induces deep sedation, similar to physical sleep, and helps maintain forebrain connectivity, which is likely to reduce delirium after surgery. The aim of this study is to evaluate the influence of exposure to the mono-anesthetic propofol on the development of postoperative sleep disturbance in young and middle-aged female patients undergoing hysteroscopy and whether prophylactic administration of dexmedetomidine influences reducing postoperative sleep disturbance.

METHODS: This prospective randomized controlled trial (RCT) will include 150 patients undergoing hysteroscopy at the First Affiliated Hospital of Xiamen University. Participants will be randomly assigned to three groups in a 1:1:1 ratio. The dexmedetomidine group will have two subgroups and will receive a nasal spray of 0.2 µg/kg or 0.5 µg/kg 25 min before surgery, while the control group will receive a saline nasal spray. Three groups will undergo hysteroscopy with propofol-based TIVA according to the same scheme. Sleep quality will be measured using a wearable device and double-blind sleep assessments will be performed before surgery and 1, 3, and 7 days after surgery. SPSS 2.0 is used for statistical analysis. A χ² test is used to compare groups, and t-test is used to determine statistical the significance of continuous variables.

DISCUSSION: The purpose of this study is to investigate the incidence of propofol-associated sleep disorders and to test a combination of dexmedetomidine anesthesia regimen for the prevention of postoperative sleep disorders. This study will help to improve patients’ postoperative satisfaction and provide a new strategy for comfortable perioperative medical treatment.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06281561. Registered on February 24, 2024.

PMID:39010171 | DOI:10.1186/s13063-024-08311-6

J Oral Sci. 2024;66(3):189-192. doi: 10.2334/josnusd.24-0078.

ABSTRACT

PURPOSE: To investigate the influence of various nickel-titanium (Ni-Ti) files on debris extrusion during the retreatment of teeth with simulated lateral root perforation, focusing on root resorption.

METHODS: Sixty human mandibular premolar teeth were divided into groups with and without perforation and further subdivided based on the retreatment technique. Lateral root perforations were created in one group (Group 1), while the other group had no perforations (Group 2). Two retreatment techniques were compared: Remover (RE)+One RECI (OR) and ProTaper Universal Retreatment (PTUR)+WaveOne Gold (WOG). The weight of the extruded debris was determined. The time of both retreatment procedures was measured. Statistical analyses were performed using a two-way analysis of variance (ANOVA) test (P < 0.05).

RESULTS: Teeth with simulated lateral root perforation exhibited higher extrusion of debris during retreatment. In both groups, RE+OR files led to more extruded debris than PTUR+WOG files. However, this difference was statistically significant in Group 2 (P < 0.001). Compared to PTUR+WOG files, RE+OR files showed a statistically significant longer time to remove obturation material (P < 0.001).

CONCLUSION: Perforated teeth exhibited significantly higher debris extrusion. While both file systems demonstrated similar debris extrusion in perforated teeth, the RE+OR files significantly increased debris extrusion in non-perforated teeth compared to the PTUR+WOG files.

PMID:39010167 | DOI:10.2334/josnusd.24-0078

J Oral Sci. 2024;66(3):163-168. doi: 10.2334/josnusd.24-0031.

ABSTRACT

PURPOSE: Using X-ray micro-computed tomography (micro-CT), the aim of this study was to measure the porosity of two tricalcium silicate sealers (EndoSequence BC and NeoSealer Flo) applied using three obturation techniques (single-cone, warm-vertical, and cold-lateral) to six single-rooted human teeth.

METHODS: Six extracted, single-rooted human teeth were shaped with ProTaper Next rotary files and obturated with EndoSequence BC or NeoSealer Flo sealers and gutta-percha (GP) using one of the three techniques above. Micro-CT was used to map the full length of the canals. Deep learning cross-sectional segmentation was used to analyze image slices of the apical (0-2 mm) and coronal (14-16 mm from the apex) regions (n = 230-261 per tooth) for the areas of GP and sealer, as well as porosity. Median (%) with interquartile range of porosity were calculated , and the results were statistically analyzed with the Kruskal-Wallis test.

RESULTS: In the apical region, EndoSequence BC had significantly fewer pores than NeoSealer Flo with the single-cone obturation (% median-interquartile range, IQR: 0.00-1.62) and warm-vertical condensation (5.57-10.32) techniques, whereas in the coronal region, NeoSealer Flo had significantly fewer pores than EndoSequence BC with these two techniques (0.39-5.02) and (0.10-0.19), respectively. There was no significant difference in porosity between the two sealers for the cold-lateral condensation technique in both the apical and coronal regions.

CONCLUSION: For optimal obturation, the choice of technique and sealer is critical.

PMID:39010164 | DOI:10.2334/josnusd.24-0031

Health Res Policy Syst. 2024 Jul 15;22(1):84. doi: 10.1186/s12961-024-01177-9.

ABSTRACT

BACKGROUND: Health policymaking is a critical aspect of governmental decision-making that shapes the well-being of populations. In the Middle East and North Africa, particularly in Kuwait, limited attention has been given to exploring the research capacities, engagement, and utilization among health policymakers. This study aims to bridge this gap by investigating how Kuwaiti health policymakers incorporate evidence-based research into the formulation of health-related policies.

METHODS: This cross-sectional study targeted health policymakers in leadership positions within the Kuwait Ministry of Health (MOH). Using the Seeking, Engaging with and Evaluating Research (SEER) questionnaire, participants’ capacities, engagement, and use of research were assessed. The targeted sample was all health policymakers in leadership positions, starting from the head of departments and above. The questionnaire comprises four domains, 14 sections, and 50 questions and utilizes Likert and binary scales, with aggregate scores predicting engagement actions and research use. The data were collected between March and July 2023. All the statistical analyses were performed using SPSS v27, and the numerical and categorical variables were analyzed using appropriate statistical tests, including t-tests, ANOVA, and Pearson’s correlation.

RESULTS: Out of 205 policymakers, 88 participated (42.9% response rate): predominantly male (51.1%) and married (78.4%). The mean age was 49.84 ± 7.28 years, with a mean MOH tenure of 24.39 ± 6.80 years. Participants demonstrated high value for research (mean score 4.29 ± 0.55) and expressed confidence in the research utilization. Organizational emphasis on research use exhibited nuanced perceptions, identifying areas where MOH support may be lacking. Access to research resources and processes for policy development guidance were highlighted as challenges.

CONCLUSIONS: This study provides crucial insights into the research capacities and engagement of Kuwaiti health policymakers. It emphasizes the need for targeted interventions to align individual perceptions with organizational expectations, address confidence disparities, and enhance collaborative efforts. Organizational investments are crucial for fostering a dynamic research ecosystem to improve evidence-based policy development in Kuwait’s healthcare landscape.

PMID:39010161 | DOI:10.1186/s12961-024-01177-9

Perioper Med (Lond). 2024 Jul 15;13(1):74. doi: 10.1186/s13741-024-00428-1.

ABSTRACT

BACKGROUND: Thyroid diseases are one of the most common health problems worldwide. Although they represent a necessary step in order to perform thyroidectomy, hyperextension of the neck can potentially increase postoperative pain. The aim of this study is to determine a correlation between the degree of neck hyperextension on the operative table and the postoperative pain in patients undergoing open thyroidectomy.

METHODS: Patients were prospectively enrolled from the cohort of patients operated at the Endocrine Surgery Unit of the University Hospital of Pisa, between May and July 2021. Both of patients who underwent total thyroidectomy or hemi-thyroidectomy were recruited. The following data were analysed in order to find a correlation with postoperative pain at 24 h: age, gender, type of surgery, BMI, operative time, and degree of neck extension.

RESULTS: Overall, 195 patients were enrolled. A direct, statistically significant correlation emerged between the degree of neck hyperextension and the postoperative pain 24 h after surgery, regardless of the pain of the surgical wound (p < 0.001; beta 0.270).

CONCLUSIONS: A direct correlation emerges between neck tilt angle and postoperative neck pain. Moreover, total thyroidectomy (TT) predisposes more to postoperative neck pain, considering the type of surgery.

PMID:39010151 | DOI:10.1186/s13741-024-00428-1

J Ovarian Res. 2024 Jul 15;17(1):146. doi: 10.1186/s13048-024-01466-5.

ABSTRACT

BACKGROUND: The relationship between leukocyte telomere length (LTL) and female reproductive endocrine diseases has gained significant attention and research interest in recent years. However, there is still limited understanding of the exact impacts of LTL on these diseases. Therefore, the primary objective of this study was to investigate the genetic causal association between LTL and female reproductive endocrine diseases by employing Mendelian randomization (MR) analysis.

METHODS: Instruments for assessing genetic variation associated with exposure and outcome were derived from summary data of published genome-wide association studies (GWAS). Inverse-variance weighted (IVW) was utilized as the main analysis method to investigate the causal relationship between LTL and female reproductive endocrine diseases. The exposure data were obtained from the UK Biobanks GWAS dataset, comprising 472,174 participants of European ancestry. The outcome data were acquired from the FinnGen consortium, including abnormal uterine bleeding (menorrhagia and oligomenorrhea), endometriosis (ovarian endometrioma and adenomyosis), infertility, polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) and premenstrual syndrome (PMS). Furthermore, to account for potential confounding factors such as smoking, alcohol consumption, insomnia, body mass index (BMI) and a history of pelvic inflammatory disease (PID), multivariable MR (MVMR) analysis was also conducted. Lastly, a series of pleiotropy tests and sensitivity analyses were performed to ensure the reliability and robustness of our findings. P < 0.0063 was considered to indicate statistically significant causality following Bonferroni correction.

RESULTS: Our univariable MR analysis demonstrated that longer LTL was causally associated with an increased risk of menorrhagia (IVW: odds ratio [OR]: 1.1803; 95% confidence interval [CI]: 1.0880-1.2804; P = 0.0001) and ovarian endometrioma (IVW: OR: 1.2946; 95%CI: 1.0970-1.5278; P = 0.0022) at the Bonferroni significance level. However, no significant correlation was observed between LTL and oligomenorrhea (IVW: OR: 1.0124; 95%CI: 0.7350-1.3946; P = 0.9398), adenomyosis (IVW: OR: 1.1978; 95%CI: 0.9983-1.4372; P = 0.0522), infertility (IVW: OR: 1.0735; 95%CI: 0.9671-1.1915; P = 0.1828), PCOS (IVW: OR: 1.0633; 95%CI: 0.7919-1.4278; P = 0.6829), POI (IVW: OR: 0.8971; 95%CI: 0.5644-1.4257; P = 0.6459) or PMS (IVW: OR: 0.7749; 95%CI: 0.4137-1.4513; P = 0.4256). Reverse MR analysis indicated that female reproductive endocrine diseases have no causal effect on LTL. MVMR analysis suggested that the causal effect of LTL on menorrhagia and ovarian endometrioma remained significant after accounting for smoking, alcohol consumption, insomnia, BMI and a history of PID. Pleiotropic and sensitivity analyses also showed robustness of our results.

CONCLUSION: The results of our bidirectional two-sample MR analysis revealed that genetically predicted longer LTL significantly increased the risk of menorrhagia and ovarian endometrioma, which is consistent with the findings from MVMR studies. However, we did not notice any significant effects of LTL on oligomenorrhea, adenomyosis, infertility, PCOS, POI or PMS. Additionally, reproductive endocrine disorders were found to have no impact on LTL. To enhance our understanding of the effect and underlying mechanism of LTL on female reproductive endocrine diseases, further large-scale studies are warranted in the future.

PMID:39010148 | DOI:10.1186/s13048-024-01466-5

BMC Psychol. 2024 Jul 15;12(1):390. doi: 10.1186/s40359-024-01884-6.

ABSTRACT

INTRODUCTION: Fear-avoidance beliefs (FAB) play a crucial role in the treatment outcomes of post-surgery patients. These beliefs can lead to activity avoidance, increased pain, and decreased quality of life. Therefore, accurately measuring these beliefs in Iranian patients is of significant importance. The Fear-Avoidance Belief Questionnaire (FABQ) is a patient-reported questionnaire that evaluates individuals’ FAB. Since the validity and reliability of the Persian version of FABQ (FABQ-P) have not been assessed based on the Iranian population and sociocultural contexts, the current study has been implemented to determine the reliability and validity of the FABQ-P among Iranian post-operative patients by translation and psychometric properties.

METHODS: This methodological study conducted in 2023, a sample of 400 patients who had undergone surgery were selected using a convenience sampling method. The scale used in the study was translated and its psychometric properties were evaluated through network analysis and assessments of construct validity (including exploratory and confirmatory factor analysis), convergent validity, and discriminant validity. Additionally, the study assessed the internal consistency of the scale.

RESULTS: The MLEFA results with Promax and Kaiser Normalization rotation yielded two factors explaining 57.91% of the variance, encompassing 13 items. Also, the model was approved by CFA. Convergent and discriminant validity have been confirmed through the following criteria: Average Variance Extracted (AVE) exceeding 0.5, Composite Reliability (CR) surpassing 0.7, and Heterotrait-Monotrait Ratio of Correlations (HTMT) equating to 0.597. As for reliability, Cronbach’s alpha, composite reliability (CR), and MaxR for all constructs were greater than 0.7, demonstrating good internal consistency.

CONCLUSION: As demonstrated by the results, the FABQ-P has a satisfactory level of reliability along with authentic validity according to the sociocultural contexts of Iranian post-operative patients.

PMID:39010142 | DOI:10.1186/s40359-024-01884-6

Orphanet J Rare Dis. 2024 Jul 15;19(1):265. doi: 10.1186/s13023-024-03254-2.

ABSTRACT

BACKGROUND: Globally, researchers are working on projects aiming to enhance the availability of data for rare disease research. While data sharing remains critical, developing suitable methods is challenging due to the specific sensitivity and uniqueness of rare disease data. This creates a dilemma, as there is a lack of both methods and necessary data to create appropriate approaches initially. This work contributes to bridging this gap by providing synthetic datasets that can form the foundation for such developments.

METHODS: Using a hierarchical data generation approach parameterised with publicly available statistics, we generated datasets reflecting a random sample of rare disease patients from the United States (US) population. General demographics were obtained from the US Census Bureau, while information on disease prevalence, initial diagnosis, survival rates as well as race and sex ratios were obtained from the information provided by the US Centers for Disease Control and Prevention as well as the scientific literature. The software, which we have named SynthMD, was implemented in Python as open source using libraries such as Faker for generating individual data points.

RESULTS: We generated three datasets focusing on three specific rare diseases with broad impact on US citizens, as well as differences in affected genders and racial groups: Sickle Cell Disease, Cystic Fibrosis, and Duchenne Muscular Dystrophy. We present the statistics used to generate the datasets and study the statistical properties of output data. The datasets, as well as the code used to generate them, are available as Open Data and Open Source Software.

CONCLUSION: The results of our work can serve as a starting point for researchers and developers working on methods and platforms that aim to improve the availability of rare disease data. Potential applications include using the datasets for testing purposes during the implementation of information systems or tailored privacy-enhancing technologies.

PMID:39010138 | DOI:10.1186/s13023-024-03254-2