Higher Serum Research Articles

Oxidative stress drives endometrial fibrosis via TGF-β1/MAPK signaling pathway in breast cancer.

Breast cancer patients have high serum reactive oxygen species (ROS) levels, which exert toxicity on the ovary. However, it is still unclear whether tumor-derived ROS play a role in endometrial development and function in breast cancer. Breast cancer patients and healthy controls were recruited and endometrial thickness was measured by transvaginal ultrasound (TVUS). Xenograft tumors of the breast cancer cell line MDA-MB-231 in a female BALB/c nude mice model were established, and the therapeutic mechanism of vitamin C (VC) was investigated on uterine pathology invivo and the contribution of co-culture of breast cancer cell and endometrial epithelial cell on this process was examined invitro. Median thickness in endometria was lower in breast cancer patients and tumor-bearing mice compared to controls. A gene signature of uteri in tumor-bearing mice demonstrated differential expression of genes (DEGs) regulating extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT), and activation of TGF-β and MAPK signaling pathways. In addition, ROS, EMT- and ECM-related protein levels were enhanced in uteri in tumor-bearing mice, as well as in Ishikawa cells which were co-cultured with MDA-MB-231 cells compared to controls. Supplementation with VC reduced endometrial damage, inhibited the EMT process and collagen deposition, and maintained better histologic architecture of uteri in tumor-bearing mice via inactivation of the TGF-β1/p38MAPK pathway. In women with breast cancer oxidative stress in the endometrium results in a fibrotic response as a consequence of EMT. VC could alleviate endometrial fibrosis via TGF-β1/p38MAPK pathway and provide new predictive and therapeutic targets for fertility preservation in younger breast cancer patients.

Evaluation of Proteinuria in Diabetic Patients Attending Gitwe District Hospital

Background: Proteinuria is a serious condition in which body proteins leak into urine due to kidney dysfunction nearly always caused by elevated serum glucose due to prolonged diabetes. Proteinuria occurs and affects individuals with diabetes, approximately 25% of diabetic patients may have proteinuria. Aim: The aim of this study is to assess the levels of serum glucose and proteins in urine and their association in diabetic patients attending Gitwe District Hospital. Methodology: The study population mainly comprised of diabetic patients, 110 study participants were included. Blood was drawn from finger for testing serum glucose using glucometer and urine samples were collected from diabetic patients and samples were analyzed in parasitology service using urine chemistry strips for proteins in urine testing. Results: During data analysis, SPSS version 22 was used, the majority were female with 66.4% while 33.6% were male. The highest frequency of participants presented in this study were 27(24.6%) found in [43-52] years old. The mean age was 53 years ± 13.882 SD (ranged from 23 to 86 years). 53.7% had normal serum glucose level while 46.3% had high serum glucose level. However, 63.6% had no proteinuria while 20.0% had trace, 11.8% had mild and 4.6% had moderate proteinuria levels. Association between serum glucose and proteinuria was analyzed for statistical significance with Chi-square test and it was statistically significant as their p values were below 0.05(P-value of 0.000). Conclusion: The study found that high serum glucose level leads to the presence of proteins in the urine. This study recommends regular monitoring of serum glucose levels, as well as routine urine tests to detect proteinuria as essential components of diabetes management and other researchers to study the effects of proteinuria in diabetic patients. Keywords: Proteinuria, serum glucose, proteins, diabetic patients

Precocious Puberty in Boys with NR0B1 Variants

Precocious puberty (PP) requires appropriate management to prevent short adult height, psychosocial issues, and other adverse outcomes. Genetic diagnosis potentially improves the management of PP. Pathogenic NR0B1 variants, which typically cause X-linked adrenal hypoplasia congenita, can also affect gonadal function. While boys with NR0B1 variants usually exhibit hypogonadotropic hypogonadism during adolescence, previous reports have suggested that minipuberty, a physiological transient activation of the hypothalamic–pituitary–gonadal axis during infancy, occurs in these patients and can persist beyond a typical duration. In rare cases, NR0B1 variants cause PP. PP associated with NR0B1 variants has unique features such as early onset and high serum testosterone levels that are often disproportionate to testicular size. Three underlying mechanisms have been proposed for the association between PP and NR0B1 variants: (1) adrenocorticotropic hormone (ACTH)-dependent, (2) gonadotropin-dependent, and (3) ACTH- and gonadotropin-independent mechanisms. The factors contributing to PP vary among cases. Determining the underlying mechanisms is crucial for adopting appropriate therapeutic strategies to control PP. However, as the detailed molecular networks mediating these mechanisms are largely unclear, further research is needed to pave the way for a more effective and personalized management of patients with PP associated with NR0B1 variants.

Serum urea concentration and risk of 16 site-specific cancers, overall cancer, and cancer mortality in individuals with metabolic syndrome: a cohort study.

The relationship between serum urea concentration and cancer in patients with metabolic syndrome (MetS) remains unclear. This study aimed to investigate the association between serum urea concentration and 16 site-specific cancers, overall cancer incidence, and cancer mortality in individuals with MetS. We analysed the data of 108,284 individuals with MetS obtained from the UK Biobank. The Cox proportional hazards model was used to determine the association between serum urea concentration at recruitment and cancer. The Benjamini-Hochberg correction was used to account for multiple comparisons. Over the median follow-up period of 11.86years, 18,548 new incident cases of cancer were documented. There were inverse associations of urea concentration with overall cancer incidence, and the incidence of oesophageal and lung cancers, with respective hazard ratios (95% confidence intervals) [HR (95% CI)] for the highest (Q4) vs lowest (Q1) urea quartiles of 0.95 (0.91-0.99), 0.68 (0.50-0.92), and 0.76 (0.64-0.90). However, high serum urea concentrations increased the male prostate cancer risk (HR 1.15; 95% CI 1.02-1.30). Although the Cox model indicated a protective effect of higher urea levels against stomach (HR 0.67; 95% CI 0.45-0.98; p = 0.040; FDR 0.120) and colorectal cancer (HR 0.86; 95% CI 0.74-0.99; p = 0.048; FDR 0.123), no strong evidence of association was found after applying the Benjamin-Hochberg correction. Moreover, across the median follow-up period of 13.77years for cancer mortality outcome, 5034 cancer deaths were detected. An "L-shaped" nonlinear dose-response relationship between urea concentration and cancer mortality was discovered (p-nonlinear < 0.001), and the HR (95% CI) for urea concentration Q4 vs Q1 was 0.83 (0.77-0.91). Serum urea concentration can be considered as a valuable biomarker for evaluating cancer risk in individuals with MetS, potentially contributing to personalised cancer screening and management strategies.

Relationship of serum calcium concentration with chronic kidney disease and mortality in type 2 diabetes mellitus patients: evidence from the NHANES 1999-2018.

This study aims to explore the relationship of serum calcium (Ca) concentration with diabetic kidney disease (DKD) and all-cause mortality among type 2 diabetes mellitus (T2DM) patients using National Health and Nutrition Examination Surveys (NHANES). Data of T2DM patients aged ≥ 40 years were screened from the NHANES database from 1999 to 2018. The outcomes were the risk of DKD diagnosed by urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and the risk of all-cause mortality ascertained by linkage to National Death Index (NDI) records through 31 December 2019. The weighted univariate and multivariate logistic regression model and cox proportional hazard model were utilized to explore the relationships of serum Ca concentration with DKD and all-cause mortality, respectively, with odds ratios (ORs), hazard ratios (HRs) and 95% confidence interval. The relationships were further explored stratified by age, gender, body mass index (BMI), the duration of T2DM, and the history of cardiovascular disease (CVD), cancer and DKD. Totally, 6595 T2DM patients were included. Of these patients, 2441 (37.01%) had DKD and 1868 (28.32%) deaths occurred over a mean follow-up of 104.50 (± 1.61) months. In fully adjusted model, we observed high serum Ca concentration was associated with high risk of DKD (OR = 1.45, 95% CI 1.18-1.77) and high all-cause mortality risk (HR = 1.33, 95% CI 1.16-1.52). These relationships remained significant after performing subgroup analyses. The Restricted cubic spline curves shown that linear correlations were observed between serum Ca concentration and DKD as well as all-cause mortality (P < 0.05). Elevated serum Ca concentration may predict the high risk of DKD and poor prognosis in T2DM patients, and future large-scale and well-designed prospective cohort study is needed to explore the association of serum Ca concentration and DKD and prognosis in T2DM patients.

High Serum Irisin Concentration Is Associated with More Disturbed Behavioural Eating Pattern in Adolescent Rhythmic Gymnasts

Background/Objectives: There are strict demands on body weight and shape in highly trained adolescent female athletes, and they are in the highest risk group for the development of eating disorders. This study aims to compare the behavioural eating patterns between highly trained female adolescent athletes and untrained controls (UCs), and to describe the associations between behavioural eating patterns and different energy homeostasis hormones. Methods: A total of 33 rhythmic gymnasts (RGs), 20 swimmers (SWs), and 20 UCs (n = 20) that were 14 to 18 years old participated in this investigation. Anthropometric measurements, body composition, training volume, 3-consecutive-day energy intake, and different energy homeostasis hormones were measured. For the evaluation of the individual behavioural eating pattern, an eating disorders assessment scale (EDAS) questionnaire with different subscales was used. Results: The mean EDAS subscale of restrained eating score was significantly higher in the RG group compared to the UC group (17.2 ± 7.4 vs. 11.5 ± 5.8; p &lt; 0.05). The EDAS total score (r = 0.380) and the subscale score of preoccupation with body image and body weight (r = 0.371) were both positively correlated (p &lt; 0.05) with serum irisin concentrations in the RG group. Conclusions: In conclusion, female rhythmic gymnasts reported a more often restrained eating pattern than untrained controls, and their more disturbed behavioural eating pattern was associated with a higher serum irisin concentration.

Abstract 4125587: Vasomotor function and its regulation by perivascular adipose tissue in metabolic syndrome vary depending on severity and combination of metabolic parameters

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. Because perivascular adipose tissue (PVAT) regulates arterial tone by releasing vasorelaxing/vasocontracting factors, the effects of PVAT on vasomotor function have been heterogeneously reported. Various PVAT functions can result from the severity or combination of metabolic parameters in MetS. Therefore, we compared the effects of mesenteric arterial PVAT on the nitric oxide-dependent vasorelaxation response among the three metabolic syndrome (MetS) model strains. We compared male OLETF, Zucker fatty (ZF), and SHRSPZF (SPZF) rats aged 20 weeks to lean controls, LETO, ZF +/+ , and Wistar-Kyoto (WKY) rats. To determine the effects of PVAT on vasodilators, we used organ bath techniques to assay nitroprusside-induced relaxation of isolated mesenteric arterial ring preparations with intact or removed PVAT. The waist circumference to length ratio in OLETF and ZF rats was higher than that in SPZF rats, and the systolic blood pressure was higher in SPZF rats than in the other groups. In the serum, there was no significant difference in triglyceride levels. Still, glucose and thiobarbituric acid reactive substance levels were higher in OLETF and SPZF rats than in ZF rats. Relaxation in ZF rats did not change compared to that in ZF +/+ rats and the presence of PVAT. In contrast, relaxation in OLETF rats was lower than in LETO rats, and there was no difference between the presence and absence of PVAT. However, relaxation in SPZF rats was lower than in WKY rats, and relaxation increased to the same level as in WKY rats in the presence of PVAT. This study unveils novel insights, suggesting that high serum glucose and oxidative stress cause arterial dysfunction, whereas high blood pressure induces PVAT functional changes. These findings underscore the complex interplay between metabolic disorders and vascular health, potentially paving the way for more targeted interventions in patients with MetS.

Serum Calcium, Phosphate and Parathormone Levels in Thalassemic Children with High Ferritin Level

Background: In thalassemic children with high ferritin level due to iron accumulation in parathyroid gland may developed hypoparathyroidism leading to impaired homeostasis of calcium &amp; phosphate. Parathyroid dysfunctions may not be evident clinically in early state. So the parathyroid status should be evaluated at regular interval. Objective: To find out the association of serum calcium, phosphate and parathormone levels in thalassemic children with high serum ferritin level. Materials and methods: The study was a cross-sectional study carried out in Department of Paeditarics, Dhaka Medical College Hospital, Dhaka, Bangladesh during January, 2019 to December, 2019. Total 70 thalassemia patients both male &amp;female were included in this study between the age ranged from 5 to 12 years with serum ferritin level &gt;1000 ng/ml irrespective of chelation therapy. All study subjects were fully evaluated clinically, thoroughly investigated and properly treated as per protocol. Results: Total 70 patients were included in our study. Male were 39 (55.7%) and female were 31(44.3%). S. Calcium level was decrease in 22(31.4%) patient, S PO4 level increased in 44 (62.9%) patients &amp; parathyroid level was low in 16 (22.9%) patients. Conclusion: Based on result it could be concluded that thalassemic children age ranged from 5 years to 12 years, presenting with high ferritin level are likely to have low calcium, high phosphate &amp; low parathormone level.

Association between serum antibodies to oral microorganisms and nonalcoholic fatty liver disease in adults

BackgroundAlterations in the bacteria, such as the periodontal bacteria, might be considered potential risk factors for nonalcoholic fatty liver disease (NAFLD). Most studies analyzing this association have focused mainly on a specific periodontal bacteria (Porphyromonas gingivalis) and have involved relatively small study populations (tens or hundreds of individuals). To address this gap, a sizable, nationally representative adult population was utilized to investigate the association between the incidence of NAFLD and high serum IgG antibodies for 19 periodontal bacteria.MethodsTo explore this association, data from the Third National Health and Nutrition Examination Survey (NHANES III)—which provides a cross-sectional representation of the noninstitutionalized U.S. population, encompassing 33,994 individuals—were analyzed. Participants aged 40 years and above with data on NAFLD—determined by the gold standard of ultrasound examination (USON)—as well as comprehensive records of serum IgG antibodies against periodontal bacteria, were included, resulting in a final analysis subset of 6,330 individuals.ResultsUsing a cluster analysis based on the Socransky classification scheme for oral microorganisms, antibody titers for the 19 bacteria were grouped into four clusters—Red-Green, Orange-Blue, Yellow-Orange, and Orange-Red. When these clusters, as well as individual antibody relationships with NAFLD, were examined, the adjusted odds ratios (ORs) ranged from 0.958 [95% confidence interval (CI): 0.916, 1.003] to 1.021 [95% CI: 0.987, 1.055]. This indicated that no statistically significant associations were found (P > 0.05), underscoring the absence of a meaningful link.ConclusionsIn summary, it was discovered that there is currently no evidence to correlate serum antibodies to periodontal pathogens with NAFLD in the nationally representative NHANES III.Clinical trial numberNot applicable.

Sex-Specific Impact of Serum Calcium Levels on Acute Coronary Syndrome Risk: A 19-Year Cohort Study in Korea.

Background: This study aims to investigate the association between serum calcium levels and acute coronary syndrome (ACS) risk, examining whether this relationship differs by sex, given the known differences in calcium metabolism and hormonal influences between males and females. Methods: Utilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were serum calcium level and sex. The incidence of ACS served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. An interaction analysis was conducted to assess the interaction effect of calcium level and sex on ACS incidence. Results: After adjusting for confounding variables, high calcium intake did not significantly increase ACS incidence, with a hazard ratio (HR) of 1.07 (95% CI: 0.90-1.26). There was also no significant difference in ACS risk between females and males (HR: 0.81, 95% CI: 0.61-1.04). However, interaction effect analysis revealed that higher calcium levels were associated with an increased risk of ACS only in females (HR: 1.24, 95% CI: 1.07-1.58), whereas the association in males was not statistically significant (HR: 0.90, 95% CI: 0.71-1.15). Conclusion: Our study results indicate that elevated serum calcium levels alone did not independently increase the risk of ACS; however, high serum calcium levels were associated with an increased risk of ACS in females but not in males, underscoring the importance of sex-specific factors in assessing and managing ACS risk and highlighting the necessity for personalized medical approaches to improve cardiovascular health outcomes for women.

Elevated serum sodium is linked to increased amyloid-dependent tau pathology, neurodegeneration, and cognitive impairment in Alzheimer's disease.

Vascular dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). While sodium is essential for maintaining vascular function, its role in AD pathology remains unclear. We included 353 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), assessing serum sodium levels, cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, magnetic resonance imaging (MRI), and cognitive function. An independent sample (N = 471) with available CSF sodium-related proteins and AD biomarkers was also included. Associations between serum sodium levels and AD pathology, neurodegeneration, and cognition were evaluated using linear regression models. Spearman's correlation analyses assessed the relationships between CSF sodium-related proteins and AD biomarkers. Higher serum sodium levels were associated with increased AD pathology, reduced hippocampal volume, and greater cognitive decline (all p < 0.05). The relationship between serum sodium and amyloid PET was evident in several AD-susceptible brain regions, including the neocortex and limbic system. Individuals with high serum sodium exhibited higher tau pathology, lower hippocampal volume, and more severe cognitive decline per unit increase in amyloid PET compared to those with low serum sodium (all p < 0.05). Among the 14 CSF sodium-related proteins, which were inter-correlated, six were significantly correlated with CSF AD pathology and amyloid PET, while two were correlated with hippocampal volume and cognitive function, with sodium channel subunit beta-2 (SCN2B) and sodium channel subunit beta-3 (SCN3B) showing the strongest correlations. These findings underscore the crucial role of serum sodium in AD progression, highlighting a potential network of sodium dysregulation involved in AD pathology. Targeting sodium may offer a novel therapeutic approach to slowing AD progression, particularly by impeding the progression of amyloid-related downstream events.

Evaluation of Infectivity, Length of Infection, and Immune Response of Avian Reovirus Variants in Egg-laying Hens.

ABSTRACTWe conducted research studies on avian reovirus (ARV) infectivity in egg-laying hens, focusing on three variants (δC genotypes 2, 3, and 5) detected in layer chickens in Pennsylvania to date. Day-old chicks (Hy-Line North America, LLC, PA), raised at the Poultry Education and Research Center of Penn State University Park campus, showed healthy growth and normal egg production after 20 weeks of age. ARV variants were propagated in LMH cell cultures, with concentrations measured at TCID50/mL. Each group of 10 hens received a 1.0 mL dose containing 103 to 104 TCID50/mL of one ARV variant through oral, nasal, and ocular routes. Infected hens showed normal egg production, with minimal symptoms of watery droppings in the first-week post-inoculation (pi). Cloacal and oral pharyngeal swabs were collected daily in the first week pi and every other day in the second-week pi to monitor virus shedding. Virus shedding began 24 hours pi through feces, peaked at 2 to 4 days pi, decreased by 5 to 7 days pi, and ceased after 12 to 14 days pi. A few birds' oral pharyngeal swabs were weakly positive for 1 to 3 days pi, then all turned negative. Infected hens developed high serum and egg yolk antibody titers at 2 to 3 weeks pi, showing 100% protection against subsequent infections with the same variant strain, demonstrating a 100% protection rate.

Serum CYFRA 21-1 as a Prognostic Marker in Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.

Background: A prognostic marker in patients with non-small-cell lung cancer (NSCLC) treated with anti-PD-1/PD-L1 antibodies must be established. This study explored serum cytokeratin fraction 21-1 (CYFRA 21-1), which represents a squamous cell histology, as a prognostic factor in anti-PD-1/PD-L1 antibody treatment, stratifying by histology and treatment regimen. Methods: This study retrospectively evaluated patients with advanced NSCLC without driver mutations receiving anti-PD-1/PD-L1 antibodies between November 2015 and March 2023. Cutoff values for CYFRA 21-1 and carcinoembryonic antigen (CEA) were 3.5 and 5.0 ng/mL, respectively. The Kaplan-Meier method and a log-rank test were conducted. The Cox proportional hazards model was utilized for univariate and multivariate analyses. Results: This study included 258 patients. The squamous NSCLC group demonstrated a shorter overall survival (OS) than the non-squamous NSCLC group (median, 17.8 vs. 23.7 months, p = 0.141). Patients with high serum CYFRA 21-1 and CEA levels exhibited a significantly shorter OS than those with normal levels (median, 11.7 vs. 32.7 months, p < 0.005; 15.8 vs. 29.7 months, p < 0.005). The multivariate analysis identified a performance status (PS) of ≥2, a PD-L1 expression of ≥50%, and a serum CYFRA 21-1 of >3.5 ng/mL as independent prognostic factors. Patients with high serum CYFRA 21-1 levels exhibited a significantly shorter OS even focusing on non-squamous NSCLC, anti-PD-1/PD-L1 antibody and chemotherapy combination therapy, or anti-CTLA-4 antibody combination therapy. Conclusion: Serum CYFRA 21-1 is a poor prognostic marker for patients with NSCLC receiving anti-PD-1/PD-L1 antibody treatment even when stratifying by histology or treatment regimen.

Prognostic role of serum procalcitonin in neonatal sepsis at a tertiary care hospital.

Objective: To analyze the prognostic role of serum procalcitonin in neonatal sepsis at a tertiary care hospital. Study Design: Cross-sectional study. Setting: Department of Pediatric, Dr. Ziauddin University Hospital, Kemari, Karachi, Pakistan. Period: October 2023 to March 2024. Methods: Neonates of both genders aged between 1 to 28 days having confirmed neonatal sepsis were included. At baseline, demographic characteristics were noted and necessary laboratory investigations were performed. At baseline, serum procalcitonin levels were evaluated in all neonates. The prognostic value of baseline PCT was assessed by comparing its association with the mortality. Other outcome variables like need for non-invasive ventilation, mechanical ventilation, need for inotropics, and acute kidney injury were also documented. Results: In a total of 131 neonates, 76 (58.0%) were male. The median age was 2.00 days (IQR=1-7 days). The median baseline procalcitonin level was 3.17 ng/ml (IQR=0.55 to 10.34 ng/ml). Need for non-invasive ventilation, and mechanical ventilation was noted in 93 (71.0%), and 19 (14.5%) neonates, respectively. Need for inotropics was documented in 23 (17.6%) neonates. The median duration of NICU stay was 3.00 (2.00-5.00 days). Among neonates who died, procalcitonin levels were significantly higher than those who survived (p=0.015). Mortality was found to have significant association with need for mechanical ventilation (p&lt;0.001), and need for inotropics (p&lt;0.001). Conclusion: High serum procalcitonin was found to be a significant predictor of mortality in neonatal sepsis. Mortality was significantly associated with need for mechanical ventilation, and need for inotropics.

Sjögren's syndrome positive for isolated anti-Ro52/SS-A antibody and anti-centromere antibody.

This current case report describes a Japanese woman in her 80s with xerostomia who presented with salivary gland dysfunction. She was positive for isolated anti-Ro52/SS-A antibody as determined by a chemiluminescent enzyme immunoassay and positive on a fluorescence enzyme immunoassay that recognizes both Ro52 and Ro60 antigens. A high serum concentration of anti-Ro52/SS-A antibody was determined by an enzyme-linked immunosorbent assay. A high anti-centromere antibodies (ACA) titre was also observed. Although Raynaud's phenomenon or a high serum immunoglobulin G concentration were not observed, Masson-trichrome staining of the patient's labial salivary glands showed considerable fibrosis. Her serum type I and type II interferon concentrations were normal. The present patient is the first with Sjögren's syndrome (SS) to exhibit isolated anti-Ro52/SS-A antibody and ACA without anti-Ro60/SS-A antibody. This current case report presents her case together with those of four other SS patients who were positive for isolated anti-Ro52/SS-A antibody. The SS literature also includes cases positive for ACA and describes clinical characteristics. The other four SS patients with isolated anti-Ro52/SS-A antibody described here had no ACA; interstitial pneumonia and polyneuropathy were observed in these cases, although there was no consistent tendency regarding types I and II interferon.

Prognostic Factors Affecting Day+100 Survival in Patients Undergoing Allogeneic Haematopoietic Stem Cell Transplantation for Acute Leukaemia - A Single Centre Experience.

To determine the factors affecting the first 100 days of survival in acute leukaemia patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). Descriptive study. Place and Duration of the Study: Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from March 2016 to February 2022. Patients with acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) in complete remission (CR) undergoing Allo-HSCT were included. Data were collected on patient demographics, diagnosis, remission status, pre-transplant analysis, donor compatibility, conditioning regimen, GVHD prophylaxis, engraftment times, post-transplant complications, mortality causes, and overall survival (OS) at 100 days. Among 101 transplant recipients (mean age of 24 ± 11.05 years; n = 76 males, n = 25 females), 41 had AML and 60 had ALL. Ninety patients underwent matched sibling donor (MSD)-HSCT, while 11 had haplo-identical sibling-HSCT. Patients ≤13 years had higher survival rates than older patients (94.4% vs. 67.5%, p = 0.03). High pre-transplant serum ferritin levels (>2500 mg/dl) predicted lower OS (48.9% vs. 100% in ferritin <1000 mg/dl, p <0.01). AML patients had a survival advantage over ALL patients (82.9% vs. 65%, p = 0.05). Early neutrophil engraftment within 14 days correlated with better survival (96.4% vs. 54.3%, p <0.01). Lastly, severe mucositis also adversely affected survival (60% in Grade III vs. 9.5% in Grade IV, p <0.01). Identifying modifiable factors can improve long-term support and follow-up, enhancing the patient outcomes in underdeveloped nations. Haematopoietic stem cell transplant, Day + 100 survival, Acute leukaemia, Pakistan.

Low skeletal muscle density assessed by abdominal computerized tomography predicts outcome in children with chronic kidney disease.

Skeletal muscle loss and abnormal fat distribution are predictors of poor clinical outcomes in adults with chronic kidney disease (CKD). However, the relationship between body composition (muscle mass and adipose tissue) and prognosis in children with CKD has not been well elucidated. The retrospective single-center study enrolled children with CKD and healthy group who underwent an abdominal Computerized tomography (CT) examination and compared the body composition of the third lumbar spine (L3) between the two groups. We defined the primary outcome as hemodialysis, peritoneal dialysis, kidney transplantation, or death. Logistic regression analysis was applied to assess the connection between low skeletal muscle density (SMD) and clinical and demographic variables. Multivariate Cox regression analysis was used to evaluate the risk factors for progression to the primary outcome. Kaplan-Meier survival analysis was performed to compare the effect of different body composition on event-free survival rate. 32 patients with CKD [eGFR: 14.89(8.86, 29.88) (mL/min/1.73m2)] and 66 heathy subjects [eGFR: 135.72(121.70, 161.29) (mL/min/1.73m2)] were recruited in our study. From the assessment of body composition assessed by CT, skeletal muscle area, SMD and skeletal muscle index (SMI) in CKD group was lower than those in healthy group (P<0.05). On the other hand, visceral fat area and visceral fat index in CKD group were significantly higher than those in healthy group (P<0.05). In logistic regression analysis, triglyceride (OR: 8.635, 95%CI: 1.153-64.687) was independently associated with low SMD. After adjusting clinical data and body composition, high serum albumin (HR: 0.873, 95%CI: 0.798-0.955) and high SMD (HR: 0.895, 95%CI: 0.822-0.974) were protective factors for delaying renal failure. Based on the Kaplan-Meier analysis, only the group with low SMD had lower event-free survival in comparison to the reference group (P<0.05). These findings suggest that there is significant skeletal muscle loss and decrease in SMD in CKD children. Notably, low SMD is indicative of poor prognosis in CKD children.

High serum pesticide levels are associated with increased odds of inflammatory bowel disease in a nested case-control study.

High serum pesticide levels are associated with increased odds of inflammatory bowel disease in a nested case-control study.

BDNF methylation associated with stress in women: Novel insights in epigenetics and inflammation

The brain-derived neurotrophic factor (BDNF) gene plays an important role in modulating the stress-response axis and inflammation, which can be regulated by epigenetic mechanisms. BNDF methylation has been associated with stress-related psychiatric disorders such as depression, anxiety and post-traumatic stress. Previous studies have reported that stressful events are involved with long-lasting alterations in DNA methylation (DNAm) of the BNDF exon IV promoter, suggesting that glucocorticoids and inflammatory cytokines can regulate this process. We previously found that perceived psychological stress is modulated by inflammatory cytokines, such as interleukin (IL)-6, IL-8 and IL-10, and IL-12p70, suggesting their role in mediating the stress response. However, the epigenetic mechanism mediating this response has yet to be fully understood. In this study, we propose that high perceived stress and high serum levels of inflammatory cytokines may correlate with specific methylation sites within the BNDF exon IV promoter. To address these questions, we conducted a cross-sectional study of 82 adult women teachers working in basic education in Brazil. The perceived stress scale was used to assess stress and blood samples were collected for the measurement of inflammatory markers and BNDF methylation through flow cytometry assay and DNA pyrosequencing, respectively. We detected differentially methylated CpG sites in the BNDF gene, where 5 CpG sites were directly correlated with high stress levels. However, 4 CpG sites showed inverse effects, indicating that changes in methylation levels in those sites could lead to a protective effect on perceived stress. About inflammatory markers, IL-6 and IL-8 were associated with high perceived stress. However, only IL-8 and IL-10 showed simultaneous modulation of perceived stress, while IL-10 and IL12p70 correlated with DNAm. We found that higher levels in IL-10 and IL-12p70 serum decrease methylation in CpG11. A direct relationship was also found to IL-12p70, where higher levels in serum increase methylation in CpG5 and 13, respectively. Taken as a whole, our findings reinforce the hypothesis regarding stress-sensitive regions within the BDNF gene, mainly for CpG5, 11, and 13. In addition to these results, CpG7 and 9 may be regarded as stress-protective regions. Our data suggest that BDNF DNAm in the blood may represent a novel biomarker for early detection of adverse effects of chronic exposure to stress in healthy individuals.

Admission albumin-globulin ratio associated with delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.

Despite the widespread use in ischemic stroke, cancer, and malnutrition, the predictive ability of serum albumin to globulin ratio (A/G) among patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) remains unknown. This study aimed to determine if serum A/G ratio is associated with the occurrence of delayed cerebral ischemia (DCI) after aSAH. We retrospectively viewed the medical records of aSAH patients from 08/2017 to 08/2022. Serum albumin and globulin laboratory test results were collected within 24 hours after admission. Serum A/G were dichotomized based on whether the DCI occurred. Logistic regression was used to determine the predictors of DCI. The relationship between serum A/G and the occurrence of DCI was analyzed with receiver operating characteristic(ROC) curve. A total of 363 eligible patients with aSAH were included in the study, among which DCI occurred in 87 patients(23.97%). Serum A/G[OR=2.720, 95%CI (1.190-6.270), P=0.018], non-surgical[OR=0.228, 95%CI (0.065-0.621), P=0.008], lactate dehydrogenase[OR=1.004, 95%CI (1.000-1.008), P=0.029], P[OR=0.354, 95%CI (0.130-0.926), P=0.038], plasma fibrinogen[OR=1.266, 95%CI (1.019-1.583), P=0.035] were associated with the occurrence of DCI. ROC showed that serum A/G, non-surgical, LDH, P, plasma fibrinogen could predict the occurrence of DCI in aSAH patients with values 0.575, 0.560, 0.602, 0.571 and 0.539 for serum A/G, non-surgical, LDH, P, plasma fibrinogen, respectively. In conclusion, serum A/G levels are correlated with DCI in individuals with aSAH, and high serum A/G levels on admission may be associated with the occurrence of DCI.