Age-adjusted Research Articles

Abstract C122: Androgen receptor-mediated regulation of innate immunity in prostate cancer in Black men

Abstract Black men are two times more likely to die from prostate cancer (PCa) than White men. We reported that innate immune cell infiltration varies between races, and others have reported differences in androgen receptor (AR) expression by race or ancestry. Herein, we evaluated AR status and immune cell infiltration in primary and metastatic PCa tissues obtained from Black and White men. RNA in situ hybridization (RISH) AR analysis was done on a tissue microarray (TMA) constructed from radical prostatectomy tissues from 120 Black men matched to 60 White men on age, grade and stage. RISH or immunohistochemistry (IHC) analysis of AR, NKX3.1, prostate specific antigen (PSA), mast cells (tryptase), neutrophils (CD66), and macrophages (CD206, CD68, CD80) was done on a TMA containing rapid autopsy tissues from metastatic sites (n=11) collected from Black (n=5) and White (n=16) men. Multiplexing IHC (mIHC) was used to assess AR, neutrophils (CD66ce), mast cells (tryptase), T-cells (CD4, CD8), and M2 macrophages (CD163) on radical prostatectomy whole-tissue sections obtained at Johns Hopkins Medicine, Baltimore, MD and biopsy tissues obtained from the University of Nairobi, Nairobi, Kenya. Tumor regions on TMAs were annotated by a pathologist and signal intensity per unit area measured using TMAJ and FrIDA software. HALO Image Analysis Platform (version 3.6.4134.137; Indica Labs) was used to analyze mIHC stained tissues. Statistical analysis and graphing were done using GraphPad Prism. There was increased AR mRNA expression in primary cancer tissues from Black men compared to White men (p<0.0001) after negative binomial regression with the adjustment of TMA set, age, grade and stage. There was a negative correlation between AR expression and CD66+ neutrophils in tumor and benign tissues from Black men (R = -0.318;p = 0.002) but this correlation was not significant among White men (R= -0.045; p = 0.765). Interestingly, we measured a positive correlation between AR mRNA expression and tryptase+ mast cells among White men (R= 0.320; p=0.016), but a trend toward a negative relationship among Black men (R= -0.252;p = 0.075) We also measured a positive correlation between AR and CD163+(R= 0.324; p<0.001), CD68+(R= 0.514;p<0.001), and CD80+(R= 0.386;p<0.001) macrophages in primary tumor tissues from all men. NKX3.1 and PSA protein were significantly increased in metastatic tissues from White compared to Black men. Conversely, CD68+ and CD80+ macrophages were increased in Black compared to White men. CD66+ neutrophils and CD206+ macrophages were increased in AR- compared to AR intact metastatic tissues. Immune cells appeared to be primarily void of AR expression in primary cancer tissues by mIHC, but there was a subset CD4+ and CD8+ T-cell clusters that express AR. Immune cell infiltration varies by the presence of AR in both primary and metastatic PCa tissues. We observed differences in AR mRNA and AR-related proteins between Black and White patients which may contribute to the differences observed in immune cell infiltration between the two races Citation Format: Kennedy Rains, Katie M. Farkouh, Taylor N. Godwin, Eric Erak, Aakash Parikh, Michael Considine, Elana Fertig, Jiayun Lu, Charles Waihenya, Valerie Odero-Marah, Karen S. Sfanos, Angelo M. De Marzo, Corinne E. Joshu, Janielle P. Maynard. Androgen receptor-mediated regulation of innate immunity in prostate cancer in Black men [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C122.

Diminished functional segregation and resilience are associated with symptomatic severity and cognitive impairments in schizophrenia: a large-scale study

BackgroundThe research findings on the topological properties of functional connectomes (TP-FCs) in patients with schizophrenia (SZPs) exhibit inconsistencies and contradictions, which can be attributed to limitations such as small sample...

Language-Based Disparities in Route of Hysterectomy for Benign Disease

Study ObjectiveTo assess the association between patient primary language and route of hysterectomy. DesignA retrospective cohort study was conducted using the Healthcare Cost and Utilization Project's State Inpatient Database (SID) and State Ambulatory Surgery and Services Database (SASD). SettingAll inpatient and outpatient hysterectomies from the most recent year of available data (2020–2021) from the six states that record patient primary language in the SID and SASD (Indiana, Iowa, Maryland, Michigan, Minnesota, and New Jersey) were queried. Patients or ParticipantsPatients aged 18 and over undergoing an inpatient or ambulatory hysterectomy for benign indication. InterventionsMinimally invasive hysterectomy compared to abdominal hysterectomy. Measurement and Main ResultsThe association between patient primary language (English vs. non-English) and route of hysterectomy (abdominal vs minimally invasive) was evaluated. The cohort included 52,226 patients who met inclusion criteria. The majority of patients were non-Hispanic White (71%), with a median age of 46 years (IQR 40.0–53.0). 91.4% of patients spoke English as their primary language, 3.6% spoke Spanish, and 5.0% spoke another non-English language. Patients with a non-English primary language were significantly less likely to undergo minimally invasive hysterectomy compared to patients who spoke English (OR 0.60, 95% CI 0.56–0.64, p <.001). This association remained significant following adjustments for age, race, insurance, median income, state, and fibroid, abnormal uterine bleeding, prolapse or endometriosis diagnosis (aOR 0.77, 95% CI 0.71–0.84). In a sensitivity analysis of English vs Spanish vs other non-English language, the association remained significant for other non-English languages (aOR 0.67, 95% CI 0.60–0.75) but not for Spanish (aOR 0.95, 95% CI 0.83–1.09). ConclusionPatients who are non-English speaking are significantly less likely to receive a minimally invasive hysterectomy. Addressing language disparities may improve access to a minimally invasive route of surgery, a possible surrogate for improved surgical outcomes, for our gynecologic patients.

Development and validation of a digital biopsy model to predict microvascular invasion in hepatocellular carcinoma.

Microvascular invasion is a major histopathological risk factor of postoperative recurrence in patients with hepatocellular carcinoma. This study aimed to develop and validate a digital biopsy model using imaging features to predict microvascular invasion before hepatectomy. A total of 217 consecutive patients who underwent hepatectomy for resectable hepatocellular carcinoma were enrolled at two tertiary-care reference centers. An imaging-based digital biopsy model was developed and internally validated using logistic regression analysis with adjustments for age, sex, etiology of disease, size and number of lesions. Three imaging features, i.e., non-smoothness of lesion margin (OR = 16.40), ill-defined pseudocapsula (OR = 4.93), and persistence of intratumoral internal artery (OR = 10.50), were independently associated with microvascular invasion and incorporated into a prediction model. A scoring system with 0 - 3 points was established for the prediction model. Internal validation confirmed an excellent calibration of the model. A cutoff of 2 points indicates a high risk of microvascular invasion (area under the curve 0.87). The overall survival and recurrence-free survival stratified by the risk model was significantly shorter in patients with high risk features of microvascular invasion compared to those patients with low risk of microvascular invasion (overall survival: median 35 vs. 75 months, P = 0.027; recurrence-free survival: median 17 vs. 38 months, P < 0.001)). A preoperative assessment of microvascular invasion by digital biopsy is reliable, easily applicable, and might facilitate personalized treatment strategies.

Assessing renal function with the use of cystatin C in a rural cohort of people living with HIV on highly active antiretroviral therapy within the Limpopo Province, South Africa

The kidneys in people living with HIV (PLWH) are constantly exposed to highly antiretroviral therapy (HAART) which may cause renal dysfunction. Cystatin C (CystC), a biomarker of renal function, is well associated with renal impairment in various populations, however, it is underexplored in the South African population of PLWH, as compared to creatinine-based measurements. Creatinine-based measurements for assessing kidney function in people with HIV can be limited due to the influence of muscle wasting, altered creatinine metabolism, and the potential for certain antiretroviral medications to impact creatinine secretion. Therefore, the current study aimed to explore the effect of HAART on renal function among PLWH with the use of Cyst C-based measures. We conducted a cross-sectional study of 111 adults PLWH, 84 on HAART, and 27 on HAART-naïve. The cluster of differentiation 4 (CD4 +) count, plasma CystC, as well as the estimated glomerular filtration rate (eGFR) using the chronic kidney disease-epidemiology collaboration (CKD-EPI) formula, were determined. In the present study, no significant differences were observed between HAART-treated and HAART-naïve groups in terms of plasma CystC and eGFRCystC. Participants who were on HAART for > 5 years were significantly associated with eGFRCystC < 90 mL/min/1.73 m2, as indicated by substantial odds ratio of 4.39 (confidence interval: 1.60–12.02, p = 0.004) in the unadjusted analysis and even after adjustment for age, sex and smoking status, with odds ratio of 4.10 (confidence interval: 1.41–11.86, p = 0.009). Advanced World Health Organization (WHO) clinical stage significantly associated with eGFRCystC < 90 mL/min/1.73 m2 as indicated by odds ratio of 11.73 (confidence interval: 2.27–60.75, p = 0.003) in the unadjusted analysis. Even after adjusting for confounders which included age, sex, and smoking status, the association persisted, with an odds ratio of 16.71 (confidence interval: 2.57–108.75, p = 0.003). In conclusion, CystC and eGFRCystC levels were not different between PLWH on HAART and not on HAART but prolonged HAART use for over five years and advanced HIV disease were associated with reduced renal function in this population of PLWH on HAART, as assessed using CystC-based measures. These findings may suggest that HAART had initial beneficial effects and long-term adverse effects. The future risk of progressive eGFR decline may be increased in this HIV population on HAART due to the cumulative effect of prolonged tenofovir disoproxil fumarate (TDF) use. These findings remain important to guide future research with larger populations on the management of conditions related to renal function decline in PLWH.Highlights.

Association between relatively low blood lead levels and urinary δ-aminolevulinic acid concentrations among male workers at a Japanese battery factory.

Whether the known positive association between blood lead (PbB) levels and urinary δ-aminolevulinic acid (ALAU) also exists at relatively low PbB levels (<40μg/dL) remains unclear. We aimed to investigate this association at lower PbB levels. We analyzed data from biannual medical examinations of workers at a Japanese factory from August 2013 to August 2023. We excluded records from female workers and those with missing data, resulting in a dataset consisting of 1396 records from 155 male workers. We employed mixed-effect linear regression models with a random intercept for workers and additional adjustments for age and smoking status. The median PbB level across all the analyzed records was 8μg/dL (range: 1, 31μg/dL). Significant positive associations were observed between PbB and ALAU, with a one-unit increase in natural logarithm-transformed PbB corresponding to a 10.0% increase in ALAU (95% CI: 2.7, 17.9%). Categorized PbB analyses showed a 23.8% increase in ALAU (95% CI: 2.7, 49.2%) for PbB levels at 20-24μg/dL and an 83.1% increase (95% CI: 30.1, 157.7%) for PbB levels ≥25μg/dL, compared to those <5μg/dL. The exposure-response curve analysis indicated a plateau followed by an increasing trend. A positive and non-linear association between PbB and ALAU levels was observed at relatively low PbB levels.

Investigation of the relationship between adiponectin gene polymorphism (ADIPOQ SNP rs-266729) and obesity Patients / Basra-Iraqi

Adiponectin is one of the most important hormones secreted by adipose tissue and plays a major role in the development of obesity. A variant-specific ADIPOQ single nucleotide polymorphism (SNP rs-266729) with a C to G missense mutation can be strongly associated with obesity. Therefore, this study aims to evaluate the association of single nucleotide polymorphisms (SNP rs-266729) of the ADIPOQ gene with obesity and some biochemical markers in these patients. The case-control study included 186 participants (106 patients and 80 healthy control). DNA was extracted from whole blood and then the Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP-PCR) technique was used to limit the genotype of the ADIPOQ gene (rs266729) polymorphism. Also, the lipid profile, glycated hemoglobin (HbA1C), fasting blood glucose (FBG), insulin, and adiponectin were measured by standard methods. Results: The allele G in the ADIPOQ-gene polymorphism (rs266729) was a significantly higher frequency of 23 (21.6%) in the obese patients (P_Value = 0.039) compared with the control subject of 10 (12.5%). It significantly increased the risk in the additive model and allele frequency (P = 0.0139 and 0.0133), respectively. The rs266729 SNP showed a significant association with increased BMI, insulin, HOMO-IR, TG, VLDL, and lower adiponectin at a p-value of 0.001 for all, after adjustments for age and sex. Lower levels of high-density lipoprotein (HDL) were observed in the CG and GG genotypes compared to the ADIPOQ rs266729 SNP C.C genotype (p = 0.032). In obese individuals, there was no significant relationship between rs266729 SNP and HbA1C, FBS, TC, and LDL. In conclusion, the single nucleotide polymorphism (rs266729) of the ADIPOQ gene has a significant difference with BMI, insulin, TG, VLDL, and HOMO-IR in obese patients, which might be the cause of obesity.

Phase angle is inversely related to the consumption of ultra-processed foods and positively related to the consumption of minimally processed foods by university students: a cross-sectional study.

Ultra-processed foods (UPF) and minimally processed foods (MPF) consumption are differentially connected to adiposity and possibly body composition. Phase angle (PhA) originates from bioelectrical impedance analysis (BIA) and is connected to cellular health. This study is the first to investigate associations between UPF/MPF consumption and PhA. A cross-sectional study was conducted. Anthropometrical and BIA were performed. The Hellenic Physical Activity Questionnaire was used for physical activity evaluation, while a validated FFQ was used for dietary assessment. UPF and MPF intake (% energy) were determined according to the NOVA system. Partial correlation coefficients of PhA and dietary variables were assessed after multi-adjustment. Students were recruited (n 151, 114 women). University. Median and interquartile range (IQR) of PhA were 5·5° (5·1-6·4°) in the total sample, 6·8° (6·1-7·3°) in men and 5·3° (5·1-5·9°) in women (P < 0·001). The median and IQR for UPF consumption was 13·7 (8·1-33·4) % in the total sample, 23·8 (8·1-70·5) % in men and 12·9 (8·1-27·5) % in women (P < 0·001). The mean (sd) of MPF consumption was 60·2 (sd 15·7) % for the total sample, 59·1 (sd 16·4) % for men and 60·5 (sd 15·6) % for women (P = 0·720). The consumption of UPF was negatively (rho = -0·267, P = 0·002), while the consumption of MPF was positively (rho = 0·218, P = 0·010) associated with the PhA, after adjustment for age, sex, BMI and physical activity. PhA relates inversely to UPF and positively to MPF consumption. The observed associations possibly reflect the effects of diet on cellular health and in turn PhA.

The relationship between HbA1c and the activities of daily living in complex chronic patients with and without intracerebral hemorrhage

BackgroundAssociations between HbA1c and adverse outcomes in ischemic and hemorrhagic stroke have been confirmed. It is still unclear whether HbA1c is related to the activities of daily living (ADL) score in complex chronic patients (CCP) with and without intracerebral hemorrhage (ICH).AimThe associations between HbA1c and ADL (Barthel score) in CCP with ICH and without ICH were evaluated, respectively.MethodsWe have analyzed data from a previous cohort study involving in 3594 CCPs without a ICH history at baseline, who were followed up for 5 years to assess ICH episode.ResultsOne hundred sixty-one ICH case were detected in a total of 3594 patients during the period of follow up for 5 years. Our nonlinear analysis suggested positive trends on the association between HBA1c and Barthel score in ICH and non-ICH patients, respectively. The multivariate linear regression analysis showed that elevated HbA1c was positively associated with a higher Barthel score among all study population (β = 1.25, 95% CI: 0.92, 1.59; P < 0.0001) with adjusted age and sex. Among non-ICH patients, increased HbA1c was still positively associated with an increased Barthel score (β = 1.24, 95% CI: 0.90, 1.58; P < 0.001). However, HbA1c appeared to have no any relationship with Barthel score in ICH patients (β = 1.87, 95% CI: -0.07, 3.82; P = 0.0613) after adjustment for age and sex. By additionally using sensitivity analysis, we still observed that the strong relationship was still existed in non-ICH patients (β = 0.90, 95% CI: 0.56, 1.24; P < 0.001) but not in ICH patients (β = 1.88, 95% CI: -0.10, 3.86; P = 0.0649).ConclusionWe observed for the first time that elevated HbA1c is associated with better ADL in CCPs without ICH but not in those with ICH. This interesting discovery contradicts the traditional adverse effects of elevated HbA1c.

Temporal Statistical Analysis and Retrospective Assessment of Mortality Rate in the United States from 1999 to 2018

Objectives: To retrospectively examine the mortality trend in the USA from 1999 to 2018 using a basic statistical model while examining multiple variables. The inferential and descriptive statistical tools will be prioritized to elucidate the mortality of both years in simple terms. Methods: We conducted a retrospective observational descriptive analysis of data on the 10 leading causes of death in the United States by age, race, and sex over 2 decades (1999 to 2018). The data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia. The causes of death are classified by the International Classification of Diseases, 10th Revision (ICD–10), which is ranked according to the number of deaths (Cause-of-death statistics are based on the underlying cause of death). This report supplements “Deaths: Final Data for 2020,” the National Center for Health Statistics’ annual report of final mortality statistics. SPSS (statistical package for social sciences) version 29 Software in Excel sheet was used to analyze the generated datasets. Descriptive and inferential (parametric and non-parametric) analyses were used. The statistically significant relationships and assumptions were made using the chi-square/t-test, Kruskal-Wallis, and Fischer's exact tests with the significance level set at p ≤ 0.05. The analysis and determination of the level of agreement between the initial diagnosis and findings from the new analysis done. Results: The proportion of age-adjusted death rates of the heart (such as coronary artery disease) account for the highest proportion of 24%, while Malignant neoplasms (cancers) represent 23%, Chronic lower respiratory diseases contribute 6%, Unintentional injuries (accidents) also play a significant role, accounting for 5% of deaths. The regression analysis reveals a strong and statistically significant relationship between the number of causes in females and males. There was a high death rate of around 60 years in 1999 and a consistent decline over the years, reaching below 40 by 2018, with a 15/100,000 death fluctuation mark. Asian or Pacific Islander has the lowest age adjustment value of 8762.4, American Indian or Alaska Native, Hispanic, or Latino(11673.2), Black or African American, Hispanic, or Latino (12992.1), White, not Hispanic or Latino(15457.1), Black or African American (15708.2), Hispanic or Latino(19624.1), American Indian or Alaska Native, not Hispanic or Latino (16287.9).Asian or Pacific Islander, not Hispanic or Latino( 8791.3), and 99.2% of the variability in the dependent variable and standard error of 6.7240. Conclusions: Cardiovascular death remains the most common cause of death, with a significant decrease in the death rate from 1999 to 2018 due to improved health care and the provision of measures to improve health care. The regression analysis reveals a strong and statistically significant relationship between the number of causes in females and males. Therefore, based on the results, the number of causes in females strongly predicts the number of causes in males.

Thyroid autoimmunity is associated with dietary fat consumption.

Dietary factors are crucial in the onset and development of autoimmune thyroid disease (AITD), but the relationship between specific fatty acids and AITD remains unexplored. We analyzed the US National Health and Nutrition Examination Survey (NHANES) 2007-2012 data on 3949 men and 3964 women aged 20 years and over with valid data on TPOAb, TgAb and details of fat intake, using multivariable regression models to examine the relationship of fat intake and specific fatty acid intake with thyroid autoimmunity. Of the 7913 participants, 7.5% had TgAb seropositivity and 11.9% had TPOAb seropositivity. The seropositivity of TgAb and TPOAb was more common in low-fat intake participants. In the overall population and men, fats were associated with thyroid autoimmunity before and after full adjustment for age, ethnicity, body mass index, smoking status and urine iodine concentration (total fat: OR=0.64, 95% CI 0.49 to 0.83; SFA: OR=0.65, 95% CI 0.51 to 0.84; MUFA: OR=0.65, 95% CI 0.50 to 0.85; PUFA: OR=0.76, 95% CI 0.57 to 0.995, after full adjustment in men). Some specific fatty acids followed a similar pattern. The association between fats and TgAb seropositivity was significant in the overall population and men. The association between fats and TPOAb seropositivity was only found in the overall population. We found a strong association between fat consumption and thyroid autoimmunity in the overall population and men from the nationally representative population-based survey. Fat and fatty acid consumption may be of benefit to individuals with thyroid autoimmunity.

Does Periodontitis Increase the Risk for Future Cardiovascular Events? Long-Term Follow-Up of the PAROKRANK Study.

The study 'Periodontitis and Its Relation to Coronary Artery Disease' (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow-up study aims to test the hypothesis that those with PD-compared to periodontally healthy individuals-are at increased risk for cardiovascular (CV) events and death. A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%-66%) or severe (<66%). A composite CV event (first of all-cause death, non-fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow-up period of 9.9 years (range 0.2-12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan-Meier method and Cox regression. The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01-1.57; p = 0.038), following adjustment for age, smoking and diabetes. The PAROKRANK follow-up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease.

Postoperative epidural analgesia and outcomes following pediatric bilateral lung and heart-lung transplantation: a retrospective observational study

BackgroundThe value of epidural analgesia in pediatric patients having heart and lung transplant surgery is unknown. We aimed to characterize various quality outcomes in patients who did and did not...

Anatomic changes in asymptomatic pachychoroid spectrum diseases after cataract surgery

Pachychoroid spectrum disease (PSD) involves various chorioretinal pathologies associated with increased choroidal blood flow. Theoretically, PSD could worsen after cataract surgery since the choroidal thickness tends to increase after surgery. Therefore, we evaluated the prevalence of asymptomatic PSD in patients who underwent cataract surgery and compared the clinical characteristics according to the presence of PSD. The subretinal fluid (SRF) development risk was evaluated using the Cox proportional hazard model. Of 924 eyes, 184 (19.9%) showed asymptomatic PSD. Patients with asymptomatic PSD were older, predominantly male, hyperopic, and showed thicker choroid (P < 0.001, 0.001, < 0.001, and < 0.001). Seven (3.8%) of 184 eyes with asymptomatic PSD developed SRF. The Cox proportional hazard model showed that the flat, irregular pigment epithelial detect (FI-PED; HR 37.337, 95% CI 3.880–359.9300, P = 0.002) was the sole indicator for the SRF development after adjustment of age, sex, and axial length. The SRF-developed PSD group experienced a profound and prolonged increase in the choroidal thickness (P = 0.001, 0.002, and 0.002 at 1, 3, and 12 months). Meticulous preoperative evaluation for FI-PED and postoperative monitoring for choroidal thickness would predict SRF development after cataract surgery in eyes with asymptomatic PSD.

Preserved ratio impaired spirometry and severity of obstructive sleep apnea: An observational cross-sectional study

Background and objectiveLung function abnormality of obstructive sleep apnea (OSA) has not been explored well. Preserved ratio impaired spirometry (PRISm) is known for its association with obesity and cardiovascular morbidity, which are also characteristic features of OSA. This study aims to investigate whether the prevalence of PRISm increases according to apnea–hypopnea index levels among subjects with OSA. MethodsConducted as an observational cross-sectional study, the study included 372 patients ≥40 years of age with definitive diagnoses of OSA and pulmonary function assessment from 2000 to 2004. Study subjects were classified based on OSA severity (mild/moderate versus severe). The prevalence of PRISm was estimated and compared between mild/moderate and severe OSA groups. ResultsThe prevalence of PRISm was 9.4 % in study subjects, with a higher prevalence in the severe OSA group than the mild/moderate group (12.9 % and 6.2 %, respectively, P = 0.04). The positive association between severe OSA and PRISm remained robust after multivariable adjustment for age, gender, and obesity (multivariable-adjusted odds ratio 2.29 (95 % confidence intervals 1.08–4.86), P = 0.03). ConclusionSevere OSA is an independent risk factor for PRISm, highlighting the need for comprehensive management of OSA that addresses the potential risk of PRISm.

Neural EGFL like 1 as a novel gene for Trabecular Bone Score in older adults: The Bushehr Elderly Health (BEH) program.

Neural EGFL like 1 (NELL-1), is a secreted glycoprotein and stimulates osteogenic cell differentiation and bone mineralization. This study aimed to explore the relationship between NELL-1 and Trabecular Bone Score (TBS) as a novel tool for the evaluation of osteoporosis in an elderly population-based cohort study in Iran. A single-locus analysis was performed on TBS using data from 2,071 participants in the Bushehr Elderly Health (BEH) Program. The study investigated 376 independent single nucleotide polymorphisms (SNPs) within the NELL-1 on chromosome 11p15.1. The association between SNPs and the mean TBS L1 to L4 was analyzed through an additive model. Significant variants in the additive model (PFDR<0.05) were further examined within dominant, recessive, over-dominant, and co-dominant models. Multiple linear regression was employed to assess the relationship between the genetic risk score (GRS) derived from significant SNPs and TBS. Three SNPs within the NELL-1 showed a statistically significant association with TBS after adjusting for age and sex. The associations for rs1901945 (β = 0.013, PFDR = 0.0007), rs1584851 (β = -0.011, PFDR = 0.0003), and rs58028601 (β = 0.011, PFDR = 0.0003) were significant in the additive model. Additionally, significant results were observed for rs1901945 and rs58028601 in the dominant model (P<0.05). The GRS showed a statistically significant relationship with TBS, considering adjustments for age, sex, Body Mass Index, type 2 diabetes, and smoking (β = 0.077, P = 1.7×10-5). This study highlights the association of NELL-1 with TBS, underscoring its potential as a candidate for further research and personalized medicine concerning the impact of this gene on bone quality.

Short- and long-term outcomes in isolated vs. hybrid thoracoscopic ablation in patients with atrial fibrillation: a systematic review and reconstructed individual patient data meta-analysis.

Both isolated thoracoscopic and hybrid thoracoscopic atrial fibrillation (AF) ablation techniques have demonstrated favourable outcomes in the management of patients with (long-standing) persistent AF, as compared with catheter ablation. However, it is currently unknown whether there is a difference in short- and long-term outcomes when comparing these two minimally invasive surgical AF ablation procedures. Therefore, a systematic review and meta-analysis were performed to investigate these two techniques, with a specific emphasis on long-term freedom from atrial tachyarrhythmias (ATAs). A systematic search through PubMed, EMBASE, and the Cochrane Library databases was performed. All studies reporting on short-term outcomes were included in the meta-analysis. A pooled analysis of long-term freedom from ATA was performed based on Kaplan-Meier (KM) curve-derived individual patient data. Reconstructed individual time-to-event data were analysed in a multivariable Cox frailty model with adjustments for age, sex, type of AF, duration of AF history, and study variable (frailty term in the frailty Cox model). In total, 53 studies were included in the meta-analysis, encompassing 4950 patients. There were no differences in major short-term outcomes (mortality or stroke) between isolated thoracoscopic and hybrid thoracoscopic ablation. A total of 18 studies reported KM curves for long-term freedom from ATA, comprising 2038 patients. Adjusted analysis revealed that hybrid ablation was significantly associated with greater freedom from ATA [adjusted hazard ratio (aHR) = 0.59, 95% confidence interval (CI): 0.43-0.83, P < 0.001] compared with isolated thoracoscopic ablation. Additionally, older age (aHR = 1.07, 95% CI: 1.03-1.12, P = 0.002) and a higher percentage of male patients (aHR = 1.02, 95% CI: 1.01-1.03, P < 0.001) were significantly associated with lower long-term freedom from ATA recurrence. Hybrid thoracoscopic AF ablation is associated with a greater long-term freedom from ATA when compared with isolated thoracoscopic ablation, without differences in complications.

Association of procalcitonin with voriconazole concentrations: a retrospective cohort study

Inflammation is a potential risk factor of voriconazole (VCZ) overdose, procalcitonin (PCT) is reported to act as a diagnostic marker for bacterial infections. However, the association of PCT with VCZ trough serum concentrations (VCZ-Cmin) is not fully clear. Our study aims to investigate the associations between PCT and VCZ-Cmin. In this retrospective cohort study, we collected the clinical data of 147 patients who received VCZ and monitored the VCZ concentration of them in our hospital from August 2017 to August 2021. All patients underwent routine clinical examinations on the day or the day before VCZ administration. General information and clinical symptoms of these patients were recorded. Multivariate liner analysis showed that PCT was significantly associated with VCZ-Cmin (p < 0.001). Overall, it was shown that VCZ-Cmin was significantly increased by 0.32 µg/mL for each fold increment in PCT in crude model. In the minor adjusted model (Model 1, adjustment for sex, age, albumin, direct bi1irubin, WBC) and fully adjusted model (Model 2, adjustment for sex, age, albumin, direct bilirubin, WBC, AST and ALT), VCZ-Cmin was significantly increased by 0.23 µg/mL and 0.21 µg/mL, respectively, for each fold increment in PCT. In conclusion, this research reveals the correlation between PCT and VCZ-Cmin, indicating that PCT has the potential to serve as a valuable biomarker for drug monitoring in the treatment of VCZ.

The relationship between brain structure volumes, depressive symptoms and body composition in obese/overweight and normal-/underweight women

Depressive symptoms are highly prevalent and heterogeneous in women. Different brain structures might be associated with depressive symptoms and body composition in women with obesity/overweight and normal-/underweight, although the data is limited. The analysis included 265 women from Bialystok PLUS population study, untreated with antidepressive or antipsychotic medications. The subjects underwent brain magnetic resonance imaging and body composition analysis. Beck Depression Inventory (BDI) score was inversely associated with nucleus accumbens volume (β = −0.217, p = 0.008) in women with BMI ≥ 25 kg/m2, but with insula volume (β = −0.147, p = 0.027) in women with BMI < 25 kg/m2 after adjustment for age and estimated intracranial volume (eTIV). In women with BMI ≥ 25 kg/m2, nucleus accumbens volume was inversely associated with the percentage of visceral fat and BDI score (β = −0.236, p = 0.012, β = −0.192, p = 0.017) after adjustment for age and eTIV. In women with BMI < 25 kg/m2, insula volume was positively associated with total fat-free mass and negatively with the BDI score (β = 0.142, p = 0.030, β = −0.137, p = 0.037) after adjustment for age and eTIV. Depressive symptoms might be associated with nucleus accumbens volume in overweight/obese women, while in normal-/ underweight women—with alterations in insula volume.

Virulence gene polymorphisms in Shandong Helicobacter pylori strains and their relevance to gastric cancer.

Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease. The cagA and vacA genotypes of 87 H. pylori strains were determined by PCR and sequencing. The EPIYA and CM motif patterns were analyzed and related to clinical outcomes. We examined the associations between the virulence genes of H. pylori and gastrointestinal diseases in Shandong, and the results were analyzed via the chi-square test and logistic regression model. Overall, 76 (87.36%) of the strains carried the East Asian-type CagA, with the ABD types being the most prevalent (90.79%). However, no significant differences were observed among the different clinical outcomes. The analysis of CagA sequence types revealed 8 distinct types, encompassing 250 EPIYA motifs, including 4 types of EPIYA or EPIYA-like sequences. Additionally, 28 CM motifs were identified, with the most prevalent patterns being E (66.67%), D (16.09%), and W-W (5.75%). Notably, a significant association was discovered between strains with GC and the CM motif pattern D (P < 0.01). With respect to the vacA genotypes, the strains were identified as s1, s2, m1, m2, i1, i2, d1, d2, c1, and c2 in 87 (100%), 0 (0), 26 (29.89%), 61 (70.11%), 73 (83.91%), 14 (16.09%), 76 (87.36%), 11 (12.64%), 18 (20.69%), and 69 (79.31%), respectively. Specifically, the vacA m1 and c1 genotypes presented a significantly greater prevalence in strains from GC compared to CG (P < 0.05). Following adjustment for age and sex, the vacA c1 genotype demonstrated a notable association with GC (OR = 5.174; 95% CI, 1.402-20.810; P = 0.012). This association was both independent of and more pronounced than the correlations between vacA m1 and GC. CagA proteins possessing CM motif pattern D were more frequently observed in patients with GC (P < 0.01), implying a potentially higher virulence of CM motif pattern D than the other CM motif patterns. Moreover, a strong positive association was identified between the vacA c1 genotype and GC, indicating that the vacA c1 genotype is a robust risk indicator for GC among male patients aged ≥55 years in Shandong.