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Comparative Analysis of Nanos and Ago Genes Expression in the Germinative Cells Isolated from Germinal Layer and the Neck Region of Echinococcus granulosus

Iran J Parasitol. 2024 Apr-Jun;19(2):131-139. doi: 10.18502/ijpa.v19i2.15849.

ABSTRACT

BACKGROUND: We aimed to evaluate the differential expression of nanos and ago genes in the protoscoleces, germinal layer, the neck, and the sucker regions of adult Echinococcus granulosus.

METHODS: The study was conducted in 2018 at the Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran. In the present study E. granulosus protoscoleces were cultured in a di-phasic medium to obtain strobilated worms. The strobilated worms were harvested and using a sterile razor blade, the neck region was separated. In the molecular study the neck sections were compared with the tissues derived from the suckers from the same worm. The primers were specifically designed for RT-qPCR on nanos and ago. The germinative cells were isolated from the cyst germinal layer and cultured in DMEM for further molecular studies. The Immunohisto-chemical profile was designed to explore the nature of nanos protein in the strobilated worms. Differences between and within groups were statistically assessed relative to the protoscoleces.

RESULTS: An increasing nanos gene expressions were found in sucker, neck, cells and germinal layer in comparison to the protoscoleces. The expression of ago gene was decreased in sucker, cell and germinal layer, and increased in the neck region in comparison to the protoscoleces. The results showed that both genes were expressed in all developmental stages of E. granulosus.

CONCLUSION: nanos and ago genes were differentially expressed at different developmental stages of E. granulosus and may contribute to differentiation of the parasite.

PMID:39011528 | PMC:PMC11246205 | DOI:10.18502/ijpa.v19i2.15849

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Application of metagenomic next-generation sequencing for rapid molecular identification in spinal infection diagnosis

Front Cell Infect Microbiol. 2024 Jul 1;14:1382635. doi: 10.3389/fcimb.2024.1382635. eCollection 2024.

ABSTRACT

OBJECTIVE: This study aimed to determine the sensitivity and specificity of metagenomic next-generation sequencing (mNGS) for detecting pathogens in spinal infections and to identify the differences in the diagnostic performance between mNGS and targeted next-generation sequencing (tNGS).

METHODS: A total of 76 consecutive patients with suspected spinal infections who underwent mNGS, culture, and histopathological examinations were retrospectively studied. The final diagnosis of the patient was determined by combining the clinical treatment results, pathological examinations, imaging changes and laboratory indicators. The sensitivity and specificity of mNGS and culture were determined.

RESULTS: The difference between the two detection rates was statistically significant (p < 0.001), with mNGS exhibiting a significantly higher detection rate (77.6% versus 18.4%). The average diagnosis time of mNGS was significantly shorter than that of bacterial culture (p < 0.001, 1.65 versus 3.07 days). The sensitivity and accuracy of mNGS were significantly higher than that of the culture group (p < 0.001, 82.3% versus 17.5%; 75% versus 27.6%), whereas the specificity of mNGS (42.9%) was lower than that of the culture group (p > 0.05, 42.9% versus 76.9%). The sensitivity, specificity, accuracy, and positive predictive value (PPV) of pus were higher than those of tissue samples for mNGS, whereas for culture, the sensitivity, specificity, accuracy, and PPV of tissue samples were higher than those of pus. tNGS demonstrated higher sensitivity and accuracy in diagnosing tuberculosis (TB) than mNGS (80% versus 50%; 87.5% versus 68.8%).

CONCLUSION: mNGS for spinal infection demonstrated better diagnostic value in developing an antibiotic regimen earlier, and it is recommended to prioritize pus samples for testing through mNGS. Moreover, tNGS outperformed other methods for diagnosing spinal TB and identifying antibiotic-resistance genes in drug-resistant TB.

PMID:39011516 | PMC:PMC11247381 | DOI:10.3389/fcimb.2024.1382635

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Different approach, similar outcomes: the impact of surgical access routes in minimally invasive cardiac surgery on enhanced recovery after surgery

Front Cardiovasc Med. 2024 Jul 1;11:1412829. doi: 10.3389/fcvm.2024.1412829. eCollection 2024.

ABSTRACT

OBJECTIVES: Enhanced recovery after surgery (ERAS) is a growing phenomenon in all surgical disciplines and aims to achieve a faster functional recovery after major operations. Minimally invasive cardiac surgery (MICS) therefore integrates well into core ERAS values. Surgical access routes in MICS include right anterolateral mini-thoracotomy (MT) as well as partial upper mini-sternotomy (PS). We seek to compare outcomes in these two cohorts, both of which were enrolled in an ERAS scheme.

METHODS: 358 consecutive patients underwent MICS and perioperative ERAS at our institution between 01/2021 and 03/2023. Patients age >80 years, with BMI > 35 kg/m², LVEF ≤ 35%, endocarditis or stroke with residuum were excluded. Retrospective cohort analysis and statistical testing was performed on the remaining 291 patients. The primary endpoint was successful ERAS, secondary endpoints were the occurrence of major bleeding, ERAS-associated complications (reintubation, return to ICU) as well as access-related complications (wound infection, pleural and pericardial effusions).

RESULTS: 170 (59%) patients received MT for mitral and/or tricuspid valve surgery (n = 162), closure of atrial septal defect (n = 4) or resection of left atrial tumor (n = 4). The remaining 121 (41%) patients had PS for aortic valve repair/replacement (n = 83) or aortic root/ascending surgery (n = 22) or both (n = 16). MT patients’ median age was 63 years (IQR 56-71) and 65% were male, PS patients’ median age was 63 years (IQR 51-69) and 74% were male. 251 (MT 88%, PS 83%, p = 0.73) patients passed through the ERAS program successfully. There were three instances of reintubation (2 MT, 1 PS), and three instances of readmission to ICU (2 MT, 1 PS). Bleeding requiring reexploration occurred six times (3 MT, 3 PS). There was one death (PS), one stroke (MT), and one myocardial infarction requiring revascularization (MT). There were no significant differences in any of the post-operative outcomes recorded, except for the incidence of pericardial effusions (MT 0%, PS 3%, p = 0.03).

CONCLUSIONS: Despite different surgical access routes and underlying pathologies, results in both the MT and the PS cohort were generally comparable for the recorded outcomes. ERAS remains safe and feasible in these patient groups.

PMID:39011491 | PMC:PMC11247003 | DOI:10.3389/fcvm.2024.1412829

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Low progesterone receptor levels in high-grade DCIS correlate with HER2 upregulation and the presence of invasive components

Front Oncol. 2024 Jun 26;14:1347166. doi: 10.3389/fonc.2024.1347166. eCollection 2024.

ABSTRACT

OBJECTIVE: In this study, we investigated pivotal molecular markers in human high-grade breast ductal carcinoma in situ (DCIS). Expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2) was measured among various subtypes (Luminal (Lum) A, LumB HER2, LumB HER2+, HER2-enriched and triple-negative).

METHODS: In total, 357 DCIS cases were classified into respective subtypes, according to the 2013 St. Gallen guidelines. Each subtype was categorized into three subcategories: “Pure” (those without an invasive component), “W/invasive” (those with an invasive component), and “All” (the entire group of the given subtype). ER and PR expression were registered as intervals. Equivocal HER2 immunohistochemistry (IHC) cases (2+) were further investigated using dual-color in situ hybridization.

RESULTS: The majority of patients (71%) were over the age of 50. We discovered no significant differences in the proportion of age between the “Pure” and “W/invasive” groups. There was no significant difference in ER/PR expression between “Pure” luminal subtypes of DCIS and “W/invasive” cases. We compared the HER2 IHC scores of “0”, “1+”, and “2+” among LumA and LumB HER2 subtypes and identified no statistically significant differences between “Pure” and “W/invasive” (p = 0.603). ER and PR expression ≥ 50% cutoff value was present in > 90% of all LumA cases. The incidences of cases with ER expression at cutoff values of < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). The proportion of cases with PR expression < 20% showed significant differences in the various luminal subtypes. In luminal B subtypes, low PR expression (< 20%) was significantly associated with both strong HER2 expression (3+) and the presence of an invasive component (p = 0.0001 and p = 0.0365, respectively).

CONCLUSIONS: ER and PR expression at ≥ 50% cutoff values were found in more than 90% of LumA cases. Samples with ER < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). Low PR expression in high-grade DCIS was strongly associated with HER2 overexpression (3+) and an invasive component (p = 0.0001 and p = 0.0365, respectively).

PMID:39011488 | PMC:PMC11247389 | DOI:10.3389/fonc.2024.1347166

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Chronic myelomonocytic leukemia with ring sideroblasts/SF3B1 mutation presents with low monocyte count and resembles myelodysplastic syndromes with-RS/SF3B1 mutation in terms of phenotype and prognosis

Front Oncol. 2024 Jul 1;14:1385987. doi: 10.3389/fonc.2024.1385987. eCollection 2024.

ABSTRACT

INTRODUCTION: Chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) with ring sideroblasts (RS) or SF3B1 mutation (MDS-RS/SF3B1) differ in many clinical features, but share others, such as anemia. RS and SF3B1 mutation can also be found in CMML.

METHODS: We compared CMML with and without RS/SF3B1 and MDS-RS/SF3B1 considering the criteria established by the 2022 World Health Organization classification.

RESULTS: A total of 815 patients were included (CMML, n=319, CMML-RS/SF3B1, n=172 and MDS-RS/SF3B1, n=324). The percentage of RS was ≥15% in almost all CMML-RS/SF3B1 patients (169, 98.3%) and most (125, 72.7%) showed peripheral blood monocyte counts between 0.5 and 0.9 x109/L and low risk prognostic categories. CMML-RS/SF3B1 differed significantly from classical CMML in the main clinical characteristics, whereas it resembled MDS-RS/SF3B1. At a molecular level, CMML and CMML-RS/SF3B1 had a significantly higher frequency of mutations in TET2 (mostly multi-hit) and ASXL1 (p=0.013) and CMML had a significantly lower frequency of DNMT3A and SF3B1 mutations compared to CMML/MDS-RS/SF3B1. Differences in the median overall survival among the three groups were statistically significant: 6.75 years (95% confidence interval [CI] 5.41-8.09) for CMML-RS/SF3B1 vs. 3.17 years (95% CI 2.56-3.79) for CMML vs. 16.47 years (NA) for MDS-RS/SF3B1, p<0.001. Regarding patients with CMML and MDS, both with SF3B1 mutation, survival did not significantly differ. CMML had a higher risk of transformation to acute myeloid leukemia (24% at 8 years, 95%CI 19%-30%).

DISCUSSION: CMML-RS/SF3B1 mutation resembles MDS-RS/SF3B1 in terms of phenotype and clearly differs from CMML. The presence of ≥15% RS and/or SF3B1 in CMML is associated with a low monocyte count. SF3B1 mutation clearly improves the prognosis of CMML.

PMID:39011475 | PMC:PMC11246989 | DOI:10.3389/fonc.2024.1385987

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Association between serum uric acid and colorectal cancer risk in European population: a two-sample Mendelian randomization study

Front Oncol. 2024 Jul 1;14:1394320. doi: 10.3389/fonc.2024.1394320. eCollection 2024.

ABSTRACT

OBJECTIVES: This study aimed to explore the potential causal associations between serum uric acid (SUA) and the risk of colorectal cancer, colon cancer and rectal cancer.

METHODS: Twenty-six SUA-related single nucleotide polymorphisms which were identified by a large meta-analysis of genome-wide association studies (GWASs) were used as instrumental variables in the two-sample Mendelian randomization (MR) study. Meta-analyses were used to synthesize the results of multiple GWASs which were extracted from the MRC Integrative Epidemiology Unit GWAS database for each type of cancer. The inverse variance weighted (IVW) method was used as the primary MR method to analyze the association between SUA and colorectal cancer risk. Several sensitivity analyses were performed to test the robustness of results.

RESULTS: The IVW method showed that there were no causal relationships between SUA and the risk of colorectal cancer [odds ratio (OR): 1.0015; 95% confidence interval (CI): 0.9975-1.0056] and colon cancer (OR: 1.0015; 95% CI: 0.9974-1.0055). The SUA levels were negative correlated with rectal cancer risk (OR: 0.9984; 95% CI: 0.9971-0.9998). The similar results were observed in both males (OR: 0.9987; 95% CI: 0.9975-0.9998) and females (OR: 0.9985; 95% CI: 0.9971-0.9999). The sensitivity analyses suggested no evidence of heterogeneity or horizontal pleiotropy. The leave-one-out analyses showed that one SNP (rs1471633) significantly drove the causal effect of SUA on rectal cancer risk. The MR-Egger regression and weighted median both showed that there were no causal relationships between SUA and the risk of colorectal cancer and its subtypes.

CONCLUSION: Overall, there was no linear causal association between SUA and the risk of colorectal cancer. However, further research is needed to investigate the role of higher SUA levels such as hyperuricemia or gout in the occurrence of colorectal cancer.

PMID:39011473 | PMC:PMC11246881 | DOI:10.3389/fonc.2024.1394320

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A peer mentoring program for eating disorders: improved symptomatology and reduced hospital admissions, three years and a pandemic on

J Eat Disord. 2024 Jul 15;12(1):99. doi: 10.1186/s40337-024-01051-7.

ABSTRACT

BACKGROUND: Peer support involves people (mentors) using their own experiences to assist others (mentees). The impetus to include peer support in eating disorder recovery is high, however research on implementation of peer roles in eating disorder management is limited. A previous pilot study found positive but preliminary results for a Peer Mentor Program (PMP) for eating disorders. The PMP has since developed over time, including broadening its eligibility criteria and shifting to predominantly online delivery during COVID-19. This study aimed to evaluate the updated version of the PMP, on a larger and more diverse group of mentees.

METHODS: Previously collected PMP service data from July 2020 to April 2022 (during COVID-19 lockdowns) was evaluated for fifty-one mentees using mixed methods. Data from program start (baseline), mid-point (3-months) and end (6-months) for measures of eating disorder symptoms as measured by the Eating Disorder Examination Questionnaire (EDE-Q) and psychological wellbeing as measured by the Depression, Anxiety and Stress Scale (DASS) was evaluated. Frequency of eating disorder-related hospital admissions during PMP participation versus the 6 months prior, direct program costs and qualitative mentee feedback were also analysed. One way ANOVA’s with post hoc tests were used to evaluate symptom change and thematic analysis was conducted on qualitative data.

RESULTS: Program attendance averaged 12.12 (SD ± 1.57) of a possible 13 sessions. Statistically significant and clinically meaningful improvements were demonstrated across all subscales of the eating disorder and psychological wellbeing symptom measures. EDE-Q Global score and DASS scores decreased significantly by program end. Fewer eating disorder-related hospital admissions were reported during PMP than the 6-months prior. Qualitative findings were positive and themed around the unique benefits of lived experience connection, a new kind of space for recovery, hope and motivation for change. Challenges with the time limited nature of the mentee-mentor relationship were expressed.

CONCLUSIONS: The important benefits of a PMP for individuals with eating disorders are further supported. There is a pressing need for high quality, co-produced research, utilising a mixture of designs and fidelity to core peer work principles, to inform further implementation of peer work into eating disorder policy and practice.

PMID:39010230 | DOI:10.1186/s40337-024-01051-7

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The association between diet quality indices and oxidative stress biomarkers in male footballers and healthy active controls

BMC Res Notes. 2024 Jul 15;17(1):195. doi: 10.1186/s13104-024-06858-w.

ABSTRACT

OBJECTIVE: The aim of the present study was the association between the relationship between Dietary Quality Index-International (DQI-I) and Healthy Eating Index (HEI) and the urinary levels of F2alpha-isoprostane (F2a-IP) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) was investigated as indicators of oxidative stress.

RESULTS: Based on HEI (low, moderate, and good), the diet quality of both groups was classified as moderate. In all participants, HEI (β=-0.29; P = 0.04) and DQI-I (β=-0.46; P = 0.005) were inversely associated with 8-OHdG. Furthermore, a negative correlation was found between HEI (mean β=-3.53; P = 0.04) and DQI-I (mean β=-5.53; P = 0.004) with F2a-IP. The quality of the footballers’ diet was higher than that of the control group. Following a high-quality diet, which is rich in antioxidants, is likely to effectively reduce oxidative stress.

PMID:39010209 | DOI:10.1186/s13104-024-06858-w

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Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial

Trials. 2024 Jul 15;25(1):479. doi: 10.1186/s13063-024-08305-4.

ABSTRACT

BACKGROUND: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections.

METHODS: DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts.

CONCLUSION: We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.

PMID:39010208 | DOI:10.1186/s13063-024-08305-4

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HIV1 drug resistance among patients experiencing first-line treatment failure in Ethiopia: protocol for a systematic review and meta-analysis

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