The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

[Therapeutic effectiveness of modified endoscopic retrograde appendicitis therapy for acute appendicitis of different severities in children].

Objective: To investigate the effects of modified endoscopic retrograde appendicitis therapy (mERAT) on the treatment of children with different severities of acute appendicitis. Methods: This study was a case-control study. A total of 586 children with acute appendicitis, who were admitted to the Pediatric Department of Second Affiliated Hospital of Air Force Medical University between January 2019 and November 2023, were selected as the research subjects. According to the severity of the disease, the patients were divided into simple appendicitis group, suppurative appendicitis group and perforated appendicitis group. The baseline data, hospitalization treatment and costs, outcomes, and recurrence in each group were analyzed, and the difference in the effectiveness of mERAT between the groups were compared by Kruskal-Wallis H test and χ2 test. Results: Among 586 children, there were 338 males and 248 females. The age at onset was 7.0 (4.6, 9.4) years. There were 475 cases of simple appendicitis, 78 cases of suppurative appendicitis, and 33 cases of perforated appendicitis. There were no significant differences in age and gender among the three groups (F=0.59, χ2=3.31, both P>0.05). However, there were statistically significant differences in body temperature, white blood cell counts, neutrophil percentage, lymphocyte percentage, nausea or vomiting, right lower abdominal pain, umbilical pain, right lower abdominal tenderness, and right lower abdominal rebound pain (H=7.56, 161.52, 169.11, and 169.61, χ2=12.05, 13.82, 12.05, 7.74, 20.35, and 94.61, all P<0.05). Also, the treatment time, postoperative hospital stay, total hospital stay, and cost showed statistically significant differences (H=4.70, 33.66, 34.99, 30.37, all P<0.05). There was no significant difference in the initial treatment success rate (98.1% (466/475) vs. 98.7% (77/78) vs. 90.9% (30/33), P=0.057). During the 30 (23, 36) months of follow-up, the recurrence rate was 7.9% (35/433) in the simple appendicitis group, 20.8% (15/72) in the suppurative appendicitis group, and 30.0% (9/30) in the perforated appendicitis group, with a statistically significant difference (χ2=23.56, P<0.001). Among the children with recurrent appendicitis, 15 cases still chose mERAT, of them 11 cases (31.2%) had simple appendicitis, 2 cases (2/15) had suppurative appendicitis, and 2 cases (2/9) had perforated appendicitis.The latest time to recurrence in the 3 groups was 32, 35 and 10 months, respectively. Conclusion: Treatment with mERAT has a good effect in pediatric simple appendicitis, but has a higher recurrence rate despite a better initial treatment success rate in suppurative appendicitis and perforated appendicitis.

[Analysis of the relationship between intestinal segmented filamentous bacteria and rotavirus infection in children].

Objective: To investigate the association between intestinal colonization of segmented filamentous bacteria (SFB) and the risk of rotavirus infection, and the possible mechanisms by which SFB resist rotavirus infection. Methods: This case-control study enrolled 50 children aged 0 to 5 years who present to the outpatient Department of Children's Hospital, Zhejiang University School of Medicine with diarrhea and positive stool tests for rotavirus. The children were divided into rotavirus enteritis group and control group consisting of 55 children with non-gastrointestinal and non-infectious surgical diseases.The age and sex composition of the two groups was matched. The DNA of the fecal flora was extracted and SFB was detected by real-time fluorescence quantitative PCR analysis. The children in the rotavirus enteritis group and the control group were subgrouped by age and sex to analyze the differences in SFB positivity rates between different groups, and further compare and analyze the differences in SFB positivity rates between these two groups of children in the ≤2 years old subgroup and the >2-5 years old subgroup. Neutralization test was performed with p3340 protein and rotavirus to determine the relationship between rotavirus infection rate and p3340 concentration in Vero cells. χ2 test or Fisher's exact probability method was used for comparison between the two groups. Results: There were 50 children in the rotavirus enteritis group with an age of (1.7±0.9) years, and 55 children in the control group with an age of (1.8±1.1) years. The positive rate of SFB in children with rotavirus enteritis showed a declining trend across ages groups, with the highest rate of 10/14 in the ≤1 year old group, followed by 67% (14/21) in the >1-2 years old group, 9/15 in the >2-5 years old group, and there was no statistically significant difference (P=0.867). The positive rate of SFB in the control group was 12/15 in the ≤1 year old group, 95% (19/20) in the >1-2 years old group, 50% (10/20) in the >2-5 years old group, with statistical significance (P=0.004). The positive rate of SFB in children with rotavirus enteritis was 74% (20/27) in males and 56% (13/23) in females (χ2=1.71, P=0.192). In the control group, it was 79% (22/28) in males and 70% (19/27) in females (χ2=0.49, P=0.485). The positive rate of SFB was 66% (33/50) in the rotavirus enteritis group and 75% (41/55) in the control group, with no statistically significant (χ2=0.56, P=0.454). In the children ≤2 years old, the SFB positivity rate was 69% (24/35) in the rotavirus enteritis group and 89% (31/35) in the control group, with a statistically significant difference (χ2=4.16, P=0.041). However, in the children >2-5 years old, no statistically significant difference was observed, with the positive rate of SFB being 9/15 in the rotavirus enteritis group and 50% (10/20) in the control group (P=0.734). Pearson correlation analysis revealed a negative correlation between rotavirus infection and SFB positivity (r=-0.87,P<0.001). As the concentration of the p3340 specific protein increased, the luminescence intensity of the luciferase in the Vero cells, which were suitable for cultivating rotavirus, exhibited a decreasing trend (F=4.17, P=0.001). Conclusions: SFB colonization in infants less than 2 years old is associated with a reduced risk of rotavirus infection. Cloning of specific SFB functional protein p3340 neutralizes rotavirus infection of Vero cells, and this mechanism of targeting rotavirus infection differs from the common antiviral mechanism.

Neurite orientation dispersion and density imaging reveals abnormal white matter and glymphatic function in active young boxers.

The neurological effects and underlying pathophysiological mechanisms of sports-related concussion (SRC) in active young boxers remain poorly understood. This study aims to investigate the impairment of white matter microstructure and assess changes in glymphatic function following SRC by utilizing neurite orientation dispersion and density imaging (NODDI) on young boxers who have sustained SRC. A total of 60 young participants were recruited, including 30 boxers diagnosed with SRC and 30 healthy individuals engaging in regular exercise. The assessment of whole-brain white matter damage was conducted using diffusion metrics, while the evaluation of glymphatic function was performed through diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS) index. A two-sample t-test was utilized to examine group differences in DTI and NODDI metrics. Spearman correlation and generalized linear mixed models were employed to investigate the relationship between clinical assessments of SRC and NODDI measurements. Significant alterations were observed in DTI and NODDI metrics among young boxers with SRC. Additionally, the DTI-ALPS index in the SRC group exhibited a significantly higher value than that of the control group (left side: 1.58 vs. 1.48, PFDR = 0.009; right side: 1.61 vs. 1.51, PFDR = 0.02). Moreover, it was observed that the DTI-ALPS index correlated with poorer cognitive test results among boxers in this study population. Repetitive SRC in active young boxers is associated with diffuse white matter injury and glymphatic dysfunction, highlighting the detrimental impact on brain health. These findings highlight the importance of long-term monitoring of the neurological health of boxers.

Is Type 2 Diabetes Mellitus Associated with Spinal Degenerative Disorders?: Evidence from Observational and 2-Sample Mendelian Randomization Analyses.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Exploring the role of vitamin D-VDR pathway in pemphigus foliaceous: a novel perspective on disease pathogenesis.

Several auto-immune diseases have been linked to vitamin D deficiency as a contributing environmental factor. Its pleiotropic effects on the immune system, especially its essential role in maintaining immune tolerance, make the vitamin D pathway of great interest. In this study, we focused on Pemphigus foliaceous (PF) in Tunisian population. we aimed to quantify the Serum 25[OH]D levels using chemiluminescence assay and to analyze the differential expression of the VDR, CYP27B1 and CYP24A1 genes in the circulating blood cells and lesional skin tissue of PF patients using Q-PCR. A genetic explanation was then sought to explore any direct relationship between tag polymorphisms and the inherited features of PF. Results confirmed a vitamin D hypovitaminosis in Tunisian PF patients. Interestingly, a differential gene expression correlated to the disease stratification was noted. Indeed, at the systemic level, an upregulation of VDR and CYP27B1 genes was observed in healthy controls compared to PF patients. Notably, in lesional skin tissue, the clinical and serological remission phase was correlated with high transcriptional levels of the VDR gene and conversely a drop in expression of the CYP24A1 gene. Genetic analysis indicated the involvement of the most appealing polymorphisms, rs2228570 and poly (A) microsatellite, in PF etiopathogenesis. Indeed, CAC13 haplotype was associated with a higher risk of PF development. Our findings suggest that alterations in the vitamin D-VDR pathway may influence PF physiopathology, making this pathway a potential target for pharmacological modulation, especially for cortico-resistant PF patients.

Changes in the serum metabolomics of polycystic ovary syndrome before and after compound oral contraceptive treatment.

Background: Polycystic ovary syndrome (PCOS) is both a common endocrine syndrome and a metabolic disorder that results in harm to the reproductive system and whole-body metabolism. This study aimed to investigate differences in the serum metabolic profiles of patients with PCOS compared with healthy controls, in addition to investigating the effects of compound oral contraceptive (COC) treatment in patients with PCOS. Materials and methods: 50 patients with PCOS and 50 sex-matched healthy controls were recruited. Patients with PCOS received three cycles of self-administered COC treatment. Clinical characteristics were recorded, and the laboratory biochemical data were detected. We utilized ultra-performance liquid chromatography-high-resolution mass spectrometry to study the serum metabolic changes between patients with PCOS, patients with PCOS following COC treatment, and healthy controls. Result: Patients with PCOS who received COC treatment showed significant improvements in serum sex hormone levels, a reduction in luteinising hormone levels, and a significant reduction in the levels of biologically active free testosterone in the blood. Differential metabolite correlation analysis revealed differences between PCOS and healthy control groups in N-tetradecanamide, hexadecanamide, 10E,12Z-octadecadienoic acid, and 13-HOTrE(r); after 3 months of COC treatment, there were significant differences in benzoic acid, organic acid, and phenolamides. Using gas chromatography-mass spectrometry to analyse blood serum in each group, the characteristic changes in PCOS were metabolic disorders of amino acids, carbohydrates, and purines, with significant changes in the levels of total cholesterol, uric acid, phenylalanine, aspartic acid, and glutamate. Conclusion: Following COC treatment, improvements in sex hormone levels, endocrine factor levels, and metabolic levels were better than in the group of PCOS patients receiving no COC treatment, indicating that COC treatment for PCOS could effectively regulate the levels of sex hormones, endocrine factors, and serum metabolic profiles.

[Association of the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene with preeclampsia among Chinese women].

OBJECTIVE: To assess the association of -c.108C>T and c.192Q>R polymorphisms of paraoxonase 1 (PON1) gene with preeclampsia (PE) and the influence of genotypes on the metabolic and oxidative stress indexes among Chinese women. METHODS: This case-control study has included 334 patients with PE and 1337 healthy pregnant women. The -c.108C>T and c.192Q>R genotypes were determined by PCR and restriction fragment length polymorphism method. Metabolic and oxidative stress parameters were also analyzed. RESULTS: No statistical difference in the genotypic and allelic frequencies for the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene was found between the PE patients and the healthy controls (P > 0.05). Nevertheless, the 192Q-108T haplotype of these polymorphisms was associated with an increased risk of PE (P = 0.007). Total antioxidant capacity (TAC) and atherosderosis index were higher in patients with the -108TT genotype compared with those with a CT genotype (P < 0.05); whilst total oxidant status was lower in patients with a CT genotype compared with those with a CC genotype (P = 0.036). Malondialdehyde level was higher in patients with a 192RR genotype compared with those with a QQ genotype (P = 0.019). TAC level was higher in patients with a RR genotype compared with those with a QR genotype (P = 0.015). CONCLUSION: The 192Q-108T haplotype of the PON1 gene is associated with the risk for PE. These polymorphisms may be associated with abnormal lipid metabolism and oxidative stress among Chinese PE patients.

Evaluation of interleukin-18 levels in patients affected by multiple myeloma and monoclonal gammopathy of undetermined significance: analysis and review of the literature.

OBJECTIVE: Monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic disease that often precedes multiple myeloma. The multistep evolutionary pattern of multiple myeloma is driven by genetic instability, a pro-inflammatory and immunosuppressive microenvironment, and tumor growth. Inflammation has long been recognized as a factor in both the onset and progression of cancer. PATIENTS AND METHODS: In this study, interleukin-18 plasma levels were compared in patients with multiple myeloma and monoclonal gammopathy of undetermined significance, as well as in a group of healthy controls. RESULTS: Our study shows that monoclonal gammopathy of undetermined significance patients have lower levels of interleukin-18 than healthy controls (521.657 ± 168.493 pg/ml vs. 1,266.481 ± 658.091 pg/ml for controls, p < 0.001). Thus, we discovered a significant difference in interleukin-18 levels between multiple myeloma patients and controls (418.177 ± 197.837 pg/ml; p = 0.001). CONCLUSIONS: In our work, we identified a reduction of interleukin-18 in monoclonal gammopathies. Furthermore, in this paper, we aimed to evaluate the existing literature on the potential mechanisms of action of this pro-inflammatory cytokine in the development of these diseases.

Reinforcement learning for individualized lung cancer screening schedules: A nested case-control study.

BACKGROUND: The current guidelines for managing screen-detected pulmonary nodules offer rule-based recommendations for immediate diagnostic work-up or follow-up at intervals of 3, 6, or 12 months. Customized visit plans are lacking. PURPOSE: To develop individualized screening schedules using reinforcement learning (RL) and evaluate the effectiveness of RL-based policy models. METHODS: Using a nested case-control design, we retrospectively identified 308 patients with cancer who had positive screening results in at least two screening rounds in the National Lung Screening Trial. We established a control group that included cancer-free patients with nodules, matched (1:1) according to the year of cancer diagnosis. By generating 10,164 sequence decision episodes, we trained RL-based policy models, incorporating nodule diameter alone, combined with nodule appearance (attenuation and margin) and/or patient information (age, sex, smoking status, pack-years, and family history). We calculated rates of misdiagnosis, missed diagnosis, and delayed diagnosis, and compared the performance of RL-based policy models with rule-based follow-up protocols (National Comprehensive Cancer Network guideline; China Guideline for the Screening and Early Detection of Lung Cancer). RESULTS: We identified significant interactions between certain variables (e.g., nodule shape and patient smoking pack-years, beyond those considered in guideline protocols) and the selection of follow-up testing intervals, thereby impacting the quality of the decision sequence. In validation, one RL-based policy model achieved rates of 12.3% for misdiagnosis, 9.7% for missed diagnosis, and 11.7% for delayed diagnosis. Compared with the two rule-based protocols, the three best-performing RL-based policy models consistently demonstrated optimal performance for specific patient subgroups based on disease characteristics (benign or malignant), nodule phenotypes (size, shape, and attenuation), and individual attributes. CONCLUSIONS: This study highlights the potential of using an RL-based approach that is both clinically interpretable and performance-robust to develop personalized lung cancer screening schedules. Our findings present opportunities for enhancing the current cancer screening system.

Epigenetic and sex differences in opioid use disorder in chronic pain: A real-world study linked with OPRM1 DNA methylation.

Opioid use disorder (OUD) is a multifaceted condition influenced by sex, genetic and environmental factors that could be linked with epigenetic changes. Understanding how these factors interact is crucial to understand and address the development and progression of this disorder. Our aim was to elucidate different potential epigenetic and genetic mechanisms between women and men that correlate with OUD under real-world pain unit conditions. Associations between analgesic response and the DNA methylation level of the opioid mu receptor (OPRM1) gene (CpG sites 1-5 selected in the promoter region) were evaluated in 345 long opioid-treated chronic non cancer pain: cases with OUD (n = 67) and controls (without OUD, n = 278). Cases showed younger ages, low employment status and quality of life, but higher morphine equivalent daily dose and psychotropic use, compared to the controls. The patients with OUD showed a significant decrease in OPRM1 DNA methylation, which correlated with clinical outcomes like pain relief, depression and different adverse events. Significant differences were found at the five CpG sites studied for men, and exclusively in women for CpG site 3, in relation to OUD diagnosis. These findings support the importance of epigenetics and sex as biological variables to be considered toward efficient OUD understanding and therapy development.

High prevalence of long-term olfactory disorders in healthcare workers after COVID-19: A case-control study.

BACKGROUND: More than a year after recovering from COVID-19, a large proportion of individuals, many of whom work in the healthcare sector, still report olfactory dysfunctions. However, olfactory dysfunction was common already before the COVID-19 pandemic, making it necessary to also consider the existing baseline prevalence of olfactory dysfunction. To establish the adjusted prevalence of COVID-19 related olfactory dysfunction, we assessed smell function in healthcare workers who had contracted COVID-19 during the first wave of the pandemic using psychophysical testing. METHODS: Participants were continuously tested for SARS-CoV-2 IgG antibodies since the beginning of the pandemic. To assess the baseline rate of olfactory dysfunction in the population and to control for the possibility of skewed recruitment of individuals with prior olfactory dysfunction, consistent SARS-CoV-2 IgG naïve individuals were tested as a control group. RESULTS: Fifteen months after contracting COVID-19, 37% of healthcare workers demonstrated a quantitative reduction in their sense of smell, compared to only 20% of the individuals in the control group. Fifty-one percent of COVID-19-recovered individuals reported qualitative symptoms, compared to only 5% in the control group. In a follow-up study 2.6 years after COVID-19 diagnosis, 24% of all tested recovered individuals still experienced parosmia. CONCLUSIONS: In summary, 65% of healthcare workers experienced parosmia/hyposmia 15 months after contracting COVID-19. When compared to a control group, the prevalence of olfactory dysfunction in the population increased by 41 percentage points. Parosmia symptoms were still lingering two-and-a half years later in 24% of SARS-CoV-2 infected individuals. Given the amount of time between infection and testing, it is possible that the olfactory problems may not be fully reversible in a plurality of individuals.

Risk factors for toxoplasmosis in people living with HIV in the Asia-Pacific region.

INTRODUCTION: Toxoplasma gondii can cause symptomatic toxoplasmosis in immunodeficient hosts, including in people living with human immunodeficiency virus (PLWH), mainly because of the reactivation of latent infection. We assessed the prevalence of toxoplasmosis and its associated risk factors in PLWH in the Asia-Pacific region using data from the TREAT Asia Human Immunodeficiency Virus (HIV) Observational Database (TAHOD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA) Asia-Pacific. METHODS: This study included both retrospective and prospective cases of toxoplasmosis reported between 1997 and 2020. A matched case-control method was employed, where PLWH diagnosed with toxoplasmosis (cases) were each matched to two PLWH without a toxoplasmosis diagnosis (controls) from the same site. Sites without toxoplasmosis were excluded. Risk factors for toxoplasmosis were analyzed using conditional logistic regression. RESULTS: A total of 269/9576 (2.8%) PLWH were diagnosed with toxoplasmosis in 19 TAHOD sites. Of these, 227 (84%) were reported retrospectively and 42 (16%) were prospective diagnoses after cohort enrollment. At the time of toxoplasmosis diagnosis, the median age was 33 years (interquartile range 28-38), and 80% participants were male, 75% were not on antiretroviral therapy (ART). Excluding 63 out of 269 people without CD4 values, 192 (93.2%) had CD4 ≤200 cells/µL and 162 (78.6%) had CD4 ≤100 cells/µL. By employing 538 matched controls, we found that factors associated with toxoplasmosis included abstaining from ART (odds ratio [OR] 3.62, 95% CI 1.81-7.24), in comparison to receiving nucleoside reverse transcriptase inhibitors plus non-nucleoside reverse transcriptase inhibitors, HIV exposure through injection drug use (OR 2.27, 95% CI 1.15-4.47) as opposed to engaging in heterosexual intercourse and testing positive for hepatitis B virus surface antigen (OR 3.19, 95% CI 1.41-7.21). Toxoplasmosis was less likely with increasing CD4 counts (51-100 cells/µL: OR 0.41, 95% CI 0.18-0.96; 101-200 cells/µL: OR 0.14, 95% CI 0.06-0.34; >200 cells/µL: OR 0.02, 95% CI 0.01-0.06), when compared to CD4 ≤50 cells/µL. Moreover, the use of prophylactic cotrimoxazole was not associated with toxoplasmosis. CONCLUSIONS: Symptomatic toxoplasmosis is rare but still occurs in PLWH in the Asia-Pacific region, especially in the context of delayed diagnosis, causing advanced HIV disease. Immune reconstitution through early diagnosis and ART administration remains a priority in Asian PLWH.

The Comparison of Irisin, Subfatin, and Adropin in Normal-Weight and Obese Polycystic Ovary Syndrome Patients.

Background: A combination of genetic and environmental factors contribute to the highly common, complex, and varied endocrine condition known as polycystic ovary syndrome (PCOS) in women. PCOS primarily affects women between the ages of 15 and 35 who are in the early to late stages of pregnancy. Thus, this study aimed to evaluate the serum levels of irisin, subfatin, and adropin in PCOS with and without obesity compared to the control group. Methods: The present cross-sectional study was conducted in 2022 at Al-Nahrain University/Department of Chemistry (Baghdad, Iraq). The serum levels of irisin, subfatin, and adropin were measured with the enzyme-linked immunosorbent assay (ELISA) method. Body mass index, lipid profile, insulin, fasting glucose, follicle-stimulating hormone, and luteinizing hormone levels were also evaluated. The data were analyzed using one-way analysis of variance (ANOVA) by GraphPad Prism software version 8.0.2. A P<0.05 was considered statistically significant. Results: The study population comprised PCOS patients (n=90, divided into 45 obese and 45 normal weight) and healthy women (n=30). According to the results, the serum levels of irisin were significantly higher (P<0.001) in obese and normal-weight PCOS patients than controls. While adropin and subfatin were significantly lower in PCOS than controls (P<0.001). Moreover, there are higher levels of serum insulin, fasting glucose, and luteinizing hormone in PCOS women than in healthy women. Conclusion: According to the findings, PCOS patients had a higher level of irisin than the controls. In addition, decreased subfatin and adropin levels were observed in PCOS patients compared with healthy women. Further research is required to confirm these results in the future.

Association of diet and outdoor time with inflammatory bowel disease: a multicenter case-control study using propensity matching analysis in China.

Objective: To investigate the association between dietary and some other environmental factors and the risk of inflammatory bowel diseases (IBD) in Chinese population. Materials and methods: A multicenter case-control study was conducted involving 11 hospitals across China. A total of 1,230 subjects were enrolled consecutively, and diet and environmental factor questionnaires were collected. IBD patients were matched with healthy controls (HC) using propensity-score matching (PSM) at a 1:1 ratio with a caliper value of 0.02. Multivariate conditional logistic regression analyses were performed to evaluate the associations between diet, environmental factors, and IBD. Results: Moderate alcohol and milk consumption, as well as daily intake of fresh fruit, were protective factors for both Crohn's disease (CD) and ulcerative colitis (UC). Conversely, the consumption of eggs and chocolate increased the risk of IBD. Outdoor time for more than 25% of the day was a protective factor only for CD. In eastern regions of China, CD patients had higher egg consumption and less outdoor time, while UC patients consumed more chocolate. IBD patients from urban areas or with higher per capita monthly income consumed more fruit, eggs, and chocolate. Conclusions: This study reveals an association between specific foods, outdoor time, and the emergence of IBD in the Chinese population. The findings emphasize the importance of a balanced diet, sufficient outdoor time and activities, and tailored prevention strategies considering regional variations.

COVID-19 Vaccine Effectiveness in Autumn and Winter 2022 to 2023 Among Older Europeans.

Importance: In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination campaigns. Objective: To estimate the effectiveness of COVID-19 vaccines administered in autumn and winter 2022 to 2023 against symptomatic SARS-CoV-2 infection (with all circulating viruses and XBB lineage in particular) among people aged 60 years or older in Europe, and to compare different CVE approaches across the exposed and reference groups used. Design, Setting, and Participants: This case-control study obtained data from VEBIS (Vaccine Effectiveness, Burden and Impact Studies), a multicenter study that collects COVID-19 and influenza data from 11 European sites: Croatia; France; Germany; Hungary; Ireland; Portugal; the Netherlands; Romania; Spain, national; Spain, Navarre region; and Sweden. Participants were primary care patients aged 60 years or older with acute respiratory infection symptoms who were recruited at the 11 sites after the start of the COVID-19 vaccination campaign from September 2022 to August 2023. Cases and controls were defined as patients with positive and negative, respectively, reverse transcription-polymerase chain reaction (RT-PCR) test results. Exposures: The exposure was COVID-19 vaccination. The exposure group consisted of patients who received a COVID-19 vaccine during the autumn and winter 2022 to 2023 vaccination campaign and 14 days or more before symptom onset. Reference group included patients who were not vaccinated during or in the 6 months before the 2022 to 2023 campaign (seasonal CVE), those who were never vaccinated (absolute CVE), and those who were vaccinated with at least the primary series 6 months or more before the campaign (relative CVE). For relative CVE of second boosters, patients receiving their second booster during the campaign were compared with those receiving 1 booster 6 months or more before the campaign. Main Outcomes and Measures: The outcome was RT-PCR-confirmed, medically attended, symptomatic SARS-CoV-2 infection. Four CVE estimates were generated: seasonal, absolute, relative, and relative of second boosters. CVE was estimated using logistic regression, adjusting for study site, symptom onset date, age, chronic condition, and sex. Results: A total of 9308 primary care patients were included, with 1687 cases (1035 females; median [IQR] age, 71 [65-79] years) and 7621 controls (4619 females [61%]; median [IQR] age, 71 [65-78] years). Within 14 to 89 days after vaccination, seasonal CVE was 29% (95% CI, 14%-42%), absolute CVE was 39% (95% CI, 6%-60%), relative CVE was 31% (95% CI, 15% to 44%), and relative CVE of second boosters was 34% (95% CI, 18%-47%) against all SARS-CoV-2 variants. In the same interval, seasonal CVE was 44% (95% CI, -10% to 75%), absolute CVE was 52% (95% CI, -23% to 82%), relative CVE was 47% (95% CI, -8% to 77%), and relative CVE of second boosters was 46% (95% CI, -13% to 77%) during a period of high XBB circulation. Estimates decreased with time since vaccination, with no protection from 180 days after vaccination. Conclusions and Relevance: In this case-control study among older Europeans, all CVE approaches suggested that COVID-19 vaccines administered in autumn and winter 2022 to 2023 offered at least 3 months of protection against symptomatic, medically attended, laboratory-confirmed SARS-CoV-2 infection. The effectiveness of new COVID-19 vaccines against emerging SARS-CoV-2 variants should be continually monitored using CVE seasonal approaches.

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

Accuracy of a novel method for IOP measurement without applying pressure on the cornea.

PURPOSE: To assess the accuracy of a prototype novel instrument for intra ocular pressure (IOP) measurements not involving corneal pressure application. DESIGN: Prospective case control study. METHODS: An institutional study including 16 healthy volunteers without ocular pathology. IOP in both eyes of the participants was measured four times in different body positions with the novel prototype and reference instrument (Goldmann applanation tonometer (GAT) or iCare (iCare Finland OY, Vantaa, Finland)). IOP results were compared between the prototype and the reference instruments in 116 pairs of measurement. RESULTS: Overall no statistically significant difference was found between the presented prototype and the reference instrument. Stratifying measurements by instrument used revealed no significant difference for GAT and statistical significant (yet clinically insignificant) difference for iCare. CONCLUSIONS: The presented prototype demonstrates good clinical agreement of IOP measuring results with reference instruments Further large-scale studies assessing this instrument in glaucoma patients are warranted.

Allergies and risk of head and neck cancer: a case-control study.

Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case-control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58-88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.

Exploration and verification a 13-gene diagnostic framework for ulcerative colitis across multiple platforms via machine learning algorithms.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with intricate pathogenesis and varied presentation. Accurate diagnostic tools are imperative to detect and manage UC. This study sought to construct a robust diagnostic model using gene expression profiles and to identify key genes that differentiate UC patients from healthy controls. Gene expression profiles from eight cohorts, encompassing a total of 335 UC patients and 129 healthy controls, were analyzed. A total of 7530 gene sets were computed using the GSEA method. Subsequent batch correction, PCA plots, and intersection analysis identified crucial pathways and genes. Machine learning, incorporating 101 algorithm combinations, was employed to develop diagnostic models. Verification was done using four external cohorts, adding depth to the sample repertoire. Evaluation of immune cell infiltration was undertaken through single-sample GSEA. All statistical analyses were conducted using R (Version: 4.2.2), with significance set at a P value below 0.05. Employing the GSEA method, 7530 gene sets were computed. From this, 19 intersecting pathways were discerned to be consistently upregulated across all cohorts, which pertained to cell adhesion, development, metabolism, immune response, and protein regulation. This corresponded to 83 unique genes. Machine learning insights culminated in the LASSO regression model, which outperformed others with an average AUC of 0.942. This model's efficacy was further ratified across four external cohorts, with AUC values ranging from 0.694 to 0.873 and significant Kappa statistics indicating its predictive accuracy. The LASSO logistic regression model highlighted 13 genes, with LCN2, ASS1, and IRAK3 emerging as pivotal. Notably, LCN2 showcased significantly heightened expression in active UC patients compared to both non-active patients and healthy controls (P < 0.05). Investigations into the correlation between these genes and immune cell infiltration in UC highlighted activated dendritic cells, with statistically significant positive correlations noted for LCN2 and IRAK3 across multiple datasets. Through comprehensive gene expression analysis and machine learning, a potent LASSO-based diagnostic model for UC was developed. Genes such as LCN2, ASS1, and IRAK3 hold potential as both diagnostic markers and therapeutic targets, offering a promising direction for future UC research and clinical application.