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Bioaccumulation of Chloropyrifos Organo-pesticide and Its Toxicogenic Association with Antioxidant GSTP1 in Pakistani Pest Control Workers

Appl Biochem Biotechnol. 2023 Aug 30. doi: 10.1007/s12010-023-04649-w. Online ahead of print.

ABSTRACT

Synthetic pesticides are employed to enhance agricultural production. Chronic exposure to organophosphate (OP) pesticides may be a source of health problems. The present study was designed to examine an association of GSTP1 (rs1695) polymorphism with OP pesticide chronic exposure. A case-control study was recruited with 250 subjects comprising exposed (n = 100) and controls (n = 150). A survey was conducted to determine the pesticide type to which workers had exposed. According to recorded survey assessment, two compounds of OP pesticides chloropyrifos and malathion were investigated in the blood samples of exposed study subjects using high-performance liquid chromatography (HPLC). For screening of genetic polymorphism in GSTP1 (rs1695) polymerase chain reaction, restriction length polymorphism (PCR-RFLP) and agarose gel electrophoresis were performed. Statistically, data were analyzed using SPSS v. 20.0 and MedCal© software. Total chrom© navigator programmer was used for detection of OP residues in serum and local pesticide solution. chloropyrifos-OP pesticide residues were detected in serum of estimated chronically exposed subjects at 206 nm HPLC optimal conditions. The pattern of GSTP1 (rs1695) genotypic frequencies depicted that heterozygous genotype was higher in Chloropyrifos exposed subjects (0.56) when compared with controls (0.44). Statistical outcomes showed an insignificant association with GSTP1 (rs1695) polymorphism and chloropyrifos-OP pesticide toxicity (Fisher’s exact test 1.0, p = 0.25). An insignificant allelic investigation reflected a protective effect of mutant allele G against chloropyrifos-OP pesticide toxicity in exposed subjects. Findings may be helpful in identifying bioaccumulated pesticide residues, but in studied Pakistani exposed workers, no significant association of GSTP1 (rs1695) variant with chloropyrifos-OPs was demonstrated.

PMID:37646887 | DOI:10.1007/s12010-023-04649-w

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Clinical characterization of patients with HLA-B27-associated uveitis and evaluation of the impact of systemic treatment on the recurrence rate: a cross-sectional study

J Ophthalmic Inflamm Infect. 2023 Aug 30;13(1):38. doi: 10.1186/s12348-023-00352-3.

ABSTRACT

INTRODUCTION: Despite HLA-B27-associated uveitis is one of the most frequent etiologies of uveitis worldwide, there are scarce studies on the clinical spectrum of this disease and the implications of therapeutic strategies used in the Latin-American population, with none conducted in Colombia. Thus, this study aimed to describe the clinical characteristics of a cohort of patients with positive HLA-B27-associated uveitis in Colombia and evaluate the impact of systemic treatment on the recurrence rate.

METHODS: We retrospectively reviewed 490 clinical charts of patients with uveitis, searching for those with positive HLA-B27-associated uveitis over eight years in a referral center in Bogotá, Colombia. We used descriptive statistics to summarize demographic and clinical characteristics and conducted a Chi-square test, Fisher Exact test, Spearman correlation, and Mann-Whitney test to assess associations between treatment strategies and the recurrences rate.

RESULTS: We analyzed 39 patients (59% females) with positive HLA-B27-associated uveitis, with a median age at the first consultation of 44.5 years (Range: 2-80) and a mean follow-up time of 86.4 weeks (1.65 years). Most patients had unilateral uveitis (53.8%) and an anterior anatomical diagnosis (76.6%); two had anterior chamber fibrinous reaction, and only one had hypopyon. Most patients did not show associated systemic symptoms (66.7%). Topical corticosteroids, NSAIDs, methotrexate, mydriatics, and adalimumab were the most used treatments. The most common complications included cataracts, posterior synechiae, and macular edema. We identified that the rate of recurrences decreases over time (r = -0.6361, P = 0.002571), and this decrease seems to be associated with the initiation of disease-modifying antirheumatic drugs (DMARDs) in chronic and recurrent cases.

CONCLUSION: The clinical spectrum of HLA-B27-associated uveitis in Colombian patients is distinct from other latitudes. Notably, we found a female predominance, older age at presentation, higher frequency of bilateral and vitreous involvement, and lower frequency of concomitant systemic diseases. Additionally, our results suggest that DMARDs such as methotrexate and biologic agents are good therapeutic options to avoid recurrences in chronic and recurrent cases.

PMID:37646883 | DOI:10.1186/s12348-023-00352-3

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Heavyweight versus non-heavyweight mesh in ventral hernia repair: a systematic review and meta-analysis

Hernia. 2023 Aug 30. doi: 10.1007/s10029-023-02865-1. Online ahead of print.

ABSTRACT

PURPOSE: There is considerable variability among surgeons regarding the type of mesh used in ventral hernia repair. There has been an increasing incidence of mesh fractures with lightweight (LW) and mediumweight (MW) meshes. However, HW mesh has been associated with a greater foreign body sensation and chronic pain. This meta-analysis aims to compare the outcomes of HW and non-heavyweight (NHW) meshes in ventral hernia repair.

METHODS: We systematically reviewed the PubMed, Embase, Cochrane, and Scopus databases to identify studies comparing HW with NHW meshes in hernia repair. Outcomes analyzed included hernia recurrence, seroma, hematoma, foreign body sensation, postoperative pain, and wound infection. We performed two subgroup analyses focusing on randomized controlled trials and open retromuscular repairs. Statistical analysis was performed using RevMan 5.4.

RESULTS: We screened 1704 studies. Nine studies were finally included in this meta-analysis and comprised 3001 patients from 4 RCTs and 5 non-randomized. The majority of patients (57.1%) underwent open retromuscular repair. HW mesh was significantly associated with increased in foreign body sensation (OR 3.71; 95% CI 1.40-9.84; p = 0.008), but there was no difference in other outcomes. In RCTs analysis, there was no difference between meshes. In open retromuscular repairs, HW mesh was associated with more seromas (OR 1.48; 95% CI 1.01-2.17; p = 0.05).

CONCLUSION: Our study found that HW mesh was associated with more foreign body sensation. Also, open retromuscular repairs analysis showed that HW was associated with more seromas. Further randomized studies are needed to understand better the role of HW mesh in ventral hernia repair.

PMID:37646880 | DOI:10.1007/s10029-023-02865-1

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Outcomes following surgical resection of trigeminal schwannomas: a systematic review and meta-analysis

Neurosurg Rev. 2023 Aug 30;46(1):215. doi: 10.1007/s10143-023-02121-1.

ABSTRACT

Although typically benign, trigeminal schwannomas (TS) may require surgical resection when large or symptomatic and can cause significant morbidity. This study aims to summarize the literature and synthesize outcomes following surgical resection of TS. A systematic review was performed according to PRISMA guidelines. Data extracted included patient and tumor characteristics, surgical approaches, and postoperative outcomes. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were used for outcome analysis. The initial search yielded 1838 results, of which 26 studies with 974 patients undergoing surgical resection of TS were included. The mean age was 42.9 years and 58.0% were female. The mean tumor diameter was 4.7 cm, with Samii type A, B, C, and D tumors corresponding to 33.4%, 15.8%, 37.2%, and 13.6%, respectively. Over a mean symptom duration of 29 months, patients presented with trigeminal hypesthesia (58.7%), headache (32.8%), trigeminal motor weakness (22.8%), facial pain (21.3%), ataxia (19.4%), diplopia (18.7%), and visual impairment (12.0%). Surgical approaches included supratentorial (61.4%), infratentorial (15.0%), endoscopic (8.6%), combined/staged (5.3%), and anterior (5.7%) or posterior (4.0%) petrosectomy. Postoperative improvement of facial pain (83.9%) was significantly greater than trigeminal motor weakness (33.0%) or hypesthesia (29.4%). The extent of resection (EOR) was reported as gross total (GTR), near total, and subtotal in 77.7%, 7.7%, and 14.6% of cases, respectively. Over a mean follow-up time of 62.6 months, recurrence/progression was noted in 7.4% of patients at a mean time to recurrence of 44.9 months. Patients with GTR had statistically significantly lower odds of recurrence/progression (OR: 0.07; 95% CI: 0.04-0.15) compared to patients with non-GTR. This systematic review and meta-analysis report patient outcomes following surgical resection of TS. EOR was found to be an important predictor of the risk of recurrence. Facial pain was more likely to improve postoperatively than facial hypesthesia. This work reports baseline rates of post-operative complications across studies, establishing benchmarks for neurosurgeons innovating and working to improve surgical outcomes for TS patients.

PMID:37646878 | DOI:10.1007/s10143-023-02121-1

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A systemic review and meta-analysis of pararectus versus ilioinguinal approach for the management of acetabular fractures

Eur J Orthop Surg Traumatol. 2023 Aug 30. doi: 10.1007/s00590-023-03700-0. Online ahead of print.

ABSTRACT

PURPOSE: The complex anatomy of acetabular fracture needs a surgical approach that can achieve anatomical reduction with fewer complications for the fixation of these fractures. Current literature suggests that both Pararectus (PR) approach and Ilioinguinal (IL) approach can be used for the fixation of these fractures safely. However, superiority of the PR approach over the IL approach is not established. Hence, this meta-analysis aimed to compare the PR versus IL approach.

METHODOLOGY: A literature search was performed on five databases Medline/PubMed, Scopus Embase, Cinhal, and Cochrane Library, from the inception to January 14, 2023. A qualitative and quantitative analysis was done for the five eligible studies from the literature search. Individual study characteristics data and outcomes were extracted, and Software version 5.4.1 of Review Manager was used for statistical analysis.

RESULTS: Five articles, one Randomized trial (RCT), and four retrospective articles were included and analyzed in this meta-analysis. PR approach has a shorter surgical time [mean difference (MD) -48.4 with 95% CI -74.49, -22.30; p = 0.0003], less intraoperative blood loss (MD -123.22 with 95% CI -212.28, -34.15; p = 0.007), and smaller surgical incision (MD -9.87 with 95% CI -15.21, -4.52; p = 0.0003) than the IL approach. However, the meta-analysis failed to show a difference between the two surgical approaches concerning the quality of reduction, overall complications, nerve injury, vascular injury, heterotopic ossification, deep vein thrombosis, and pulmonary embolism.

CONCLUSION: The PR approach has a shorter surgical duration, less blood loss, and a smaller surgical incision than the IL approach. However, both surgical approaches have equivocal results regarding fracture reduction quality, complication rates, and functional outcomes for acetabular fracture fixation. Hence, for acetabular fractures fixation, PR approach can be considered a safe and feasible alternative to the IL approach.

PMID:37646876 | DOI:10.1007/s00590-023-03700-0

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Differential Treatment and Outcomes for Patients With Heart Attacks in Advantaged and Disadvantaged Communities

J Am Heart Assoc. 2023 Aug 30:e030506. doi: 10.1161/JAHA.122.030506. Online ahead of print.

ABSTRACT

Background Racially and ethnically minoritized groups, people with lower income, and rural communities have worse access to percutaneous coronary intervention (PCI) than their counterparts, but PCI hospitals have preferentially opened in wealthier areas. Our study analyzed disparities in PCI access, treatment, and outcomes for patients with acute myocardial infarction based on the census-derived Area Deprivation Index. Methods and Results We obtained patient-level data on 629 419 patients with acute myocardial infarction in California between January 1, 2006 and December 31, 2020. We linked patient data with population characteristics and geographic coordinates, and categorized communities into 5 groups based on the share of the population in low or high Area Deprivation Index neighborhoods to identify differences in PCI access, treatment, and outcomes based on community status. Risk-adjusted models showed that patients in the most advantaged communities had 20% and 15% greater likelihoods of receiving same-day PCI and PCI during the hospitalization, respectively, compared with patients in the most disadvantaged communities. Patients in the most advantaged communities also had 19% and 16% lower 30-day and 1-year mortality rates, respectively, compared with the most disadvantaged, and a 15% lower 30-day readmission rate. No statistically significant differences in admission to a PCI hospital were observed between communities. Conclusions Patients in disadvantaged communities had lower chances of receiving timely PCI and a greater risk of mortality and readmission compared with those in more advantaged communities. These findings suggest a need for targeted interventions to influence where cardiac services exist and who has access to them.

PMID:37646213 | DOI:10.1161/JAHA.122.030506

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Beta-cell death and dysfunction drives hyperglycaemia in organ donors

Diabetes Obes Metab. 2023 Aug 30. doi: 10.1111/dom.15248. Online ahead of print.

ABSTRACT

BACKGROUND: Donor hyperglycaemia following brain death has been attributed to reversible insulin resistance. However, our islet and pancreas transplant data suggest that other mechanisms may be predominant. We aimed to determine the relationships between donor insulin use and markers of beta-cell death and beta-cell function in pancreas donors after brain death.

METHODS: In pancreas donors after brain death, we compared clinical and biochemical data in ‘insulin-treated’ and ‘not insulin-treated donors’ (IT vs. not-IT). We measured plasma glucose, C-peptide and levels of circulating unmethylated insulin gene promoter cell-free DNA (INS-cfDNA) and microRNA-375 (miR-375), as measures of beta-cell death. Relationships between markers of beta-cell death and islet isolation outcomes and post-transplant function were also evaluated.

RESULTS: Of 92 pancreas donors, 40 (43%) required insulin. Glycaemic control and beta-cell function were significantly poorer in IT donors versus not-IT donors [median (IQR) peak glucose: 8 (7-11) vs. 6 (6-8) mmol/L, p = .016; C-peptide: 3280 (3159-3386) vs. 3195 (2868-3386) pmol/L, p = .046]. IT donors had significantly higher levels of INS-cfDNA [35 (18-52) vs. 30 (8-51) copies/ml, p = .035] and miR-375 [1.050 (0.19-1.95) vs. 0.73 (0.32-1.10) copies/nl, p = .05]. Circulating donor miR-375 was highly predictive of recipient islet graft failure at 3 months [adjusted receiver operator curve (SE) = 0.813 (0.149)].

CONCLUSIONS: In pancreas donors, hyperglycaemia requiring IT is strongly associated with beta-cell death. This provides an explanation for the relationship of donor IT with post-transplant beta-cell dysfunction in transplant recipients.

PMID:37646197 | DOI:10.1111/dom.15248

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Microbiome analysis of circulating bacterial extracellular vesicles in obsessive-compulsive disorder

Psychiatry Clin Neurosci. 2023 Aug 30. doi: 10.1111/pcn.13593. Online ahead of print.

ABSTRACT

AIM: The present study examined the microbiome abundance and composition of drug-naïve or drug-free patients with obsessive-compulsive disorder (OCD) compared to healthy controls. In addition, in the OCD group, the microbiome composition was compared between early-onset and late-onset OCD.

METHODS: Serum samples were collected from 89 patients with OCD and 107 age- and sex-matched healthy controls. Bacterial DNA was isolated from bacteria-derived extracellular vesicles in serum and then amplified and quantified using primers specific to the V3-V4 hypervariable region of the 16S rDNA gene. The 16S rRNA gene amplicon sequencing was performed.

RESULTS: The pooled estimate showed that alpha diversity was significantly reduced in patients with OCD compared to that in healthy controls (pShannon = 0.00015). In addition, a statistically significant difference was observed in beta diversity between patients with OCD and healthy controls at the order (p = 0.012), family (p = 0.003), genus (p < 0.001), and species (p = 0.005) levels. In the microbiome composition, Pseudomonas, Caulobacteraceae(f), Streptococcus, Novosphingobium, and Enhydrobacter at the genus level were significantly less prevalent in patients with OCD than in controls. In addition, among patients with OCD, the microbial composition in the early-onset versus late-onset types was significantly different with respect to the genera Corynebacterium and Pelomonas.

CONCLUSION: The present study showed an aberrant microbiome in patients with OCD, suggesting a role of the microbiota-brain interaction in the pathophysiology of OCD. Further longitudinal studies with larger sample sizes adjusting for various confounders are warranted. This article is protected by copyright. All rights reserved.

PMID:37646189 | DOI:10.1111/pcn.13593

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Meta-Analysis of the Impact of Four Advanced Primary Care Redesign Initiatives on Medicare Expenditures

Med Care Res Rev. 2023 Aug 30:10775587231194658. doi: 10.1177/10775587231194658. Online ahead of print.

ABSTRACT

We conducted a secondary analysis of the evaluations of 22 sites participating in four primary care redesign initiatives funded by the Centers for Medicare and Medicaid Services or the Center for Medicare and Medicaid Innovation. Our objectives were to determine the overall impact of the initiatives on Medicare expenditures and whether specific site-level program features influenced expenditure findings. Averaged over sites, the mean intervention effect was a statistically insignificant US$26 per beneficiary per year. Policy implications from meta-regression results suggest that funders should consider supporting technical assistance efforts and pay for performance incentives to increase savings. There was no evidence that paying for medical home transformation produced savings in total cost of care. We estimate that in future evaluations, data from 35 sites would be needed to detect feature effects of US$300 per beneficiary per year.

PMID:37646166 | DOI:10.1177/10775587231194658

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Delta tocotrienol as a supplement to FOLFOXIRI in first-line treatment of metastatic colorectal cancer. A randomized, double-blind, placebo-controlled phase II study

Acta Oncol. 2023 Aug 30:1-10. doi: 10.1080/0284186X.2023.2249225. Online ahead of print.

ABSTRACT

PURPOSE: Triplet chemotherapy might be more effective than doublet chemotherapy in metastatic colorectal cancer (mCRC), but it may also be marked by increased toxicity. To investigate whether δ-tocotrienol, a vitamin E analogue, with possible neuroprotective and anti-inflammatory effects, reduces the toxicity of triplet chemotherapy, we conducted a randomized, double-blind, placebo-controlled trial in mCRC patients receiving first-line 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI).

MATERIAL AND METHODS: Seventy patients with mCRC were randomly assigned (1:1) to receive FOLFOXIRI plus either δ-tocotrienol or placebo at the Department of Oncology, Vejle Hospital, Denmark. Eligibility criteria were adenocarcinoma in the colon or rectum, age 18-75 years and ECOG performance status 0-1. FOLFOXIRI was given in eight cycles followed by four cycles of 5-fluorouracil. δ-tocotrienol 300 mg or placebo × 3 daily was added during chemotherapy and for a maximum of two years. The primary endpoint was time to hospitalization or death during treatment with chemotherapy.

RESULTS: Median time to first hospitalization or death was 3.7 months in the placebo group (95% CI 1.93-not reached (NR)), and was NR in the δ-tocotrienol group (95% CI 1.87-NR) with a hazard ratio of 0.70 (95% CI 0.36-1.36). Grade 3-4 toxicities were uncommon in both groups, except for neutropenia, which occurred in 19 patients (58%) in the placebo group and 17 patients (50%) in the δ-tocotrienol group. There were no grade 3 or 4 peripheral sensory neuropathy. In the placebo group, 24 patients (71%) had oxaliplatin dose reductions compared to 17 patients (47%) in the δ-tocotrienol group (p = 0.047).

CONCLUSION: The addition of δ-tocotrienol to FOLFOXIRI did not statistically significant prolong the time to first hospitalization or death compared to FOLFOXIRI plus placebo. Toxicity was manageable and not statistically different. There was a statistically significant difference in dose reductions of oxaliplatin pointing to a possible neuroprotective effect of δ-tocotrienol.

PMID:37646150 | DOI:10.1080/0284186X.2023.2249225