Median Level Research Articles

An Assessment of Drinking Water Quality in the Chief Albert Luthuli Local Municipality, South Africa: A Case Study of the Elukwatini Water Supply Scheme

This study analysed the water quality of 156 samples collected from 13 different points within the Chief Albert Luthuli Local Municipality between January and December 2021, focusing on compliance with the South African National Standard 241 (SANS 241). Microbiological assessments revealed widespread contamination, with heterotrophic plate counts (HPCs) exceeding the recommended range in nearly all samples. The median HPC levels were particularly concerning, with the untreated source (RE000) exhibiting a median of 2555 CFU/mL. Total coliforms and Escherichia coli were present at alarming levels, indicating significant faecal contamination; the highest total coliform count, 2420 CFU/100 mL, was recorded at RE000. Physically, while all samples complied with electrical conductivity standards (0–70 µS/cm), turbidity levels showed variability, with nine samples exceeding the acceptable threshold of 1 NTU. The highest turbidity, 7.55 NTU, was recorded at the untreated source (RE000). Chemically, pH levels fell within safe ranges (6.0–9.0), with all samples being compliant with standards. However, only one sample (E001) met the free chlorine standard of 0.3–0.6 mg/L, suggesting inadequate disinfection practices. The untreated source was classified as ‘Unsuitable for drinking’ (WQI = 207.27). These findings highlight the critical need for enhanced monitoring and remediation strategies to improve drinking water safety in the region.

Alkaline phosphatase is useful for predicting giant cell arthritis complications in patients with polymyalgia rheumatica.

This study determined whether alkaline phosphatase can be used to distinguish giant cell arthritis complications in patients with polymyalgia rheumatica. This retrospective study included patients diagnosed with polymyalgia rheumatica between January 2014 and October 2023 at our hospital. The predictive accuracy of biomarkers for diagnosing giant cell arthritis was evaluated. Logistic regression was performed to identify factors predicting giant cell arthritis complications. In total, 128 participants were included in this study and divided into two groups: isolated polymyalgia rheumatica (n = 111) and polymyalgia rheumatica with giant cell arthritis (n = 17). The median alkaline phosphatase level of polymyalgia rheumatica with giant cell arthritis group was significantly higher than that of the isolated polymyalgia rheumatica group (242.0 [interquartile range, 221.0-595.0] vs. 187.0 [interquartile range 97.5-254.5] U/L, P < 0.001). Setting a cut-off value of 214 U/L for alkaline phosphatase yielded a sensitivity and specificity of 0.88 and 0.55, respectively, for diagnosing giant cell arteritis. Multivariate analysis revealed that alkaline phosphatase was a significant independent variable in the complications of giant cell arteritis (odds ratio, 25.2; P = 0.032). Alkaline phosphatase can help distinguish giant cell arthritis complications in patients with polymyalgia rheumatica.

Ocular Pharmacodynamics of Intravitreal Faricimab in Patients With Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema.

Evaluate the ocular pharmacodynamics (PD) of intravitreal faricimab, a bispecific inhibitor of angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME). Aqueous humor (AH) samples (1025 free Ang-2 concentrations and 1345 free VEGF-A concentrations) were collected from approximately 300 faricimab-treated patients with nAMD or DME in phase2/3 trials. A population pharmacokinetic pharmacodynamic (popPKPD) model was developed to describe the dynamic effect of faricimab on free AH Ang-2 and VEGF-A. Mean baseline Ang-2 concentrations were 8.1 and 13.4pg/mL in patients with nAMD and DME, respectively. The corresponding mean baseline VEGF-A concentrations were 58 and 135pg/mL, respectively. Overall, approximately 79% of Ang-2 (84% within 8 weeks postdose and 55% beyond 12 weeks postdose) and 7% of VEGF-A postdose observations were below the lower limit of quantification. Model-derived Ang-2 and VEGF-A concentration-time profiles for patients on every 4-week/every 8-week dosing were predicted to maintain greater than 50% suppression of Ang-2 concentrations for the entire dosing period. Patients on every 12-week/16-week dosing were predicted to have greater than 50% Ang-2 suppression for 12 or more weeks, whereas 50% VEGF-A suppression was maintained for 9 to 10 weeks. At 8 weeks postdose, the median Ang-2 concentrations remained suppressed by approximately 80%. At 16 weeks postdose, the median VEGF-A concentrations returned to baseline, but median Ang-2 levels remained below baseline. A popPKPD analysis demonstrated faricimab's rapid and sustained suppression of AH Ang-2 and VEGF-A. A popPKPD analysis suggested that sustained suppression of ocular Ang-2 contributes to faricimab's extended durability, observed in clinical trials.

Differential contributions of the gut microbiota and metabolome to pathomechanisms in ulcerative colitis: an in vitro analysis

ABSTRACT The gut microbiota has been implicated in onset and progression of ulcerative colitis (UC). Here, we assess potential causal involvement of the microbiota and -associated fecal water (FW) metabolome in altering key functional parameters of the colonic epithelium. Fecal samples were collected from N = 51 healthy controls (HC), N = 36 patients with active UC (UC-A), and N = 41 subjects in remission N = 41 (UC-R). Using in vitro incubation experiments, the FW metabolome’s impact on butyrate oxidation rates/gene expression and cell death (cytotoxicity) of HT-29 cells, cytokine production by PBMC, and barrier integrity of Caco2 monolayers was evaluated. The FW metabolome from patients and individuals hosting the Bacteroides 2 (Bact2) enterotype (69% of UC-A, 31% of UC-R, 3% of HC), characterized by lower levels of median- and short-chain fatty acids and furan compounds, left butyrate oxidation rates unaltered but affected associated gene expression profiles. UC patients/Bact2-carriers’ FW lowered PBMC IL-8 production and increased IL-1β production. Patients’ FW increased cytotoxicity, associated with sulfide compound levels. Bact2 carriers’ FW, displaying higher levels of bile acids, lowered barrier function upon incubation of monolayers. The FW metabolome of patients and individuals hosting a dysbiotic microbiota could contribute to the disruption of functional processes of the colonic epithelium as observed in UC.

Correlation Between Vitamin D Deficiency and Calcium, Phosphorus, Alkaline Phosphatase in Preterm Libyan Infants: Case-Control study

Vitamin D plays a vital role in regulating calcium and phosphorus levels and in bone mineralization. Vitamin D deficiency is a widespread issue contributing to metabolic bone disease in preterm infants. This study aimed to evaluate the biochemical parameters associated with varying levels of vitamin D deficiency. Serum samples were collected from preterm infants at the Neonatal Intensive Care Unit of Althawra Hospital Center, Al Beyda, Libya, from Feb-July 2019. The study included two groups: 62 preterm infants and a control group of 34 full-term infants. Serum levels of calcium, phosphorus, alkaline phosphatase, and 25OH-Vitamin D were measured using enzyme immunoassays and standard method. The study involved 62 preterm neonates, with a median gestational age of 32 weeks (range 28-36) and median birth weight of 1960 gm (range 900-2800 gm). The median levels recorded were calcium at 8.7 mg/dl (p=0.000), phosphorus at 4.1 mg/dl (p=0.584), ALP at 458 U/L (p=0.008), and vitamin D at 13.6 ng/ml. The prevalence of varying degrees of vitamin D deficiency was noted: very severe (9.7% &lt; 5 ng/ml), severe (19.4% 5-10 ng/ml), and overall deficiency (45% 10-20 ng/ml), and suboptimal (25.8% 20-30 ng/ml). Comparing preterm infants to the control group revealed statistically significant differences across all parameters (Vitamin D p=0.000, Ca p=0.007, PO4 p=0.036, and ALP p=0.000). All preterm infants exhibited inadequate vitamin D levels, and there was an inverse relationship between the biochemical parameters and vitamin D deficiency. Notably, the elevated ALP level could serve as a crucial marker for diagnosing vitamin D deficiency in clinical settings.

Cytokine correlations in childhood-onset rheumatic diseases with pulmonary involvement

BackgroundThere was less research about cytokines in lung involvement of childhood-onset rheumatic diseases (RD) patients.ObjectiveIn this investigation, blood levels of 12 cytokines were tested in order to explore their associations with lung involvement in newly diagnosed childhood-onset RD patients.MethodsHigh-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) were performed on 53 newly diagnosed RD patients without any treatment in our department between July 2021 and December 2023. Patients were separated into groups based on whether their lungs were involved or not according to abnormalities found on HRCT or PFTs. We examined the serum cytokines with 41 healthy, age and gender-matched controls.ResultsThe majority of serum cytokine levels were statistically different between the RD group with lung involvement and the control group. The RD group with lung involvement had considerably higher serum IL-6 and IFN-γ levels than the RD group without lung involvement or control group. The median serum IL-6 levels were 19 pg/ml [interquartile range (IQR) 6.9, 27.6], 4.4 pg/ml (IQR 2.0, 10.5), and 2.0 pg/ml (IQR 2.0, 2.0) in RD group with lung involvement, RD group without lung involvement, and control group, respectively. Similarly, the median serum IFN-γ levels were 6.0 pg/ml (IQR 5.0, 15), 5.0 pg/ml (IQR 5.0, 5.0), and 5.0 pg/ml (IQR 5.0, 5.0) in RD group with lung involvement, RD group without lung involvement, and control group, respectively. The receiver operating characteristic (ROC) curve study showed that IL-6 and IFN-γ had area under the curve (AUC) values of 0.782 and 0.742, respectively, indicating their significant diagnostic potential for lung involvement in RD patients.ConclusionOur findings imply that IL-6 and IFN-γ may be associated with the development of lung illnesses and may be involved in the pathophysiology of RD. Thus, in individuals with RD, elevated levels of IFN-γ over 5.42 pg/ml or IL-6 above 6.25 pg/ml may warrant suspicion of lung involvement.

Postnatal levels of glycated albumin and glycated hemoglobin A1c in mothers of large-for-gestational-age newborns

BackgroundGestational diabetes mellitus (GDM) is an important cause of macrosomia. The value of glycated albumin (GlyA) has been demonstrated to be a useful marker of glycemic control in pregnancy and a predictor of adverse perinatal outcomes. The aim of this study was to investigate the relationship between the postnatal levels of GlyA and glycated hemoglobin A1c (HbA1c) regarding the prenatal diagnosis of GDM in mothers of large-for-gestational-age (LGA) newborns.MethodsThe study included mothers and their LGA newborns born between July 2017 and September 2019. The mothers were grouped according to the prenatal diagnosis of GDM, and measurements of GlyA and HbA1c levels in their serum were performed on the first day after delivery of a LGA newborn.ResultsA total of 61 LGA newborns and their mothers were enrolled in the study. The median GlyA level was higher, at 16.4% (81.0 µmol/L), whereas the HbA1c level was lower in the group without a prenatal diagnosis of GDM; the differences between groups regarding the GlyA and HbA1c levels were not significant (p &amp;gt; 0.05). The postnatal level of maternal GlyA was positively correlated with birth weight (β = 0.022, p = 0.007), but no correlation with the presence of other adverse perinatal outcomes was found.ConclusionMothers of LGA newborns who were not diagnosed with GDM during pregnancy had higher median levels of GlyA and lower HbA1c levels than mothers with prenatal diagnosis of GDM. Values of GlyA in mothers were positively correlated with the birth weight of their newborns but no correlation with other adverse perinatal outcomes was found. Our results indicate the potential value of GlyA for screening of GDM in the last trimester of pregnancy.

Abstract 4119595: Impact of Environmental Noise and Sleep Health on Pediatric Hypertension Incidence: The ABCD Study

Background: Pediatric hypertension is linked to environmental factors like neighborhood noise disrupting sleep, which is crucial for health. The specific interaction between noise and sleep health in causing hypertension still needs to be explored. Research Question: How does the interaction between neighborhood environmental noise and sleep health affect the incidence of pediatric hypertension? Aims: To estimate the incidence of hypertension in American adolescents and to investigate the individual and joint effects of exposure to neighborhood environmental noise and sleep health on its incidence. Methods: Our analysis involved 3,320 individuals from the Adolescent Brain Cognitive Development (ABCD) study across 21 US cities, followed prospectively from 2018-2020 (T0) to 2020-2022 (T1). We included only those with complete data: Fitbit-tracked sleep, blood pressure, height, neighborhood noise, and relevant covariates (biological sex, ethnicity, pubertal stage, waist circumference). Hypertension was defined as average blood pressure at or above the 95th percentile for age, sex, and height, based on American Academy of Pediatrics guidelines. Sleep health was classified based on daily duration into three categories: healthy (9-12 hours), moderately healthy (1 hour below or above optimal), and low (more than 1-hour deviation). Neighborhood noise exposure was quantified using median anthropogenic noise levels at night, linked to participants’ zip codes. We estimated hypertension incidence and its relative risks (RR, 95% CI), examining the effect (individual and joint) of sleep health and environmental noise on hypertension risk. Results: At Time 1 (T1), the mean age was 13.9 years; 47.6% were girls, and 52.9% were White. Hypertension prevalence in 2018-2020 was 1.7% (CI95% 1.4; 2.1), and the incidence after two years was 2.9% (CI95% 2.4; 3.6). Night noise was 58.4 decibels, 29.9% healthy sleep time (T0); 20.3% healthy sleep time (T1). Adolescents with more favorable healthy sleep showed a lower risk of developing hypertension RR= 0.63 (CI 95% 0.25 to 0.82). We found no association between noisy neighborhoods and no joint effects (neighborhood noise + sleep health) with hypertension incidence. Conclusions: Adequate sleep is associated with a lower risk of hypertension in adolescents. However, no significant link was found between neighborhood noise and pediatric hypertension. This highlights the need for public health efforts to improve sleep quality in youth.

Abstract 4113942: Validation of Changes in the Cutoff Values of Achilles Tendon Thickness on Radiography in the Clinical Criteria of Heterozygous Familial Hypercholesterolemia in Japan

Background: To increase sensitivity and maintain specificity, the 2022 Japan Atherosclerosis Society familial hypercholesterolemia (FH) clinical criteria was modified. In particular, the cutoff value of Achilles tendon thickness (ATT) on radiography was changed from ≥9 mm in both men and women to ≥8.0 mm in men and ≥7.5 mm in women. The current study aimed to validate the efficacy of this modification in independent samples. Methods: Patients with FH were retrospectively reviewed. The proportions of patients with pathogenic FH mutation who had an ATT of &lt;7.5/8.0 mm (group 1), ≥7.5/8.0 and &lt;9.0 mm (group 2), and ≥9 mm (group 3) were assessed. Results: In total, 492 patients were included in group 1, 102 in group 2, and 263 in group 3. Approximately 14.0%, 55.9%, and 79.8% of patients in groups 1, 2, and 3, respectively, exhibited FH mutation. Further, 37.3%, 77.3%, and 86.5% of patients with a low-density lipoprotein cholesterol level of ≥180 mg/dL in groups 1, 2, and 3, respectively, harbored FH mutation. Moreover, the median low-density lipoprotein cholesterol levels (157, 182, and 253 mg/dL, respectively) and the proportion of patients with protein-truncating mutation (3.8%, 16.7%, and 53.2%, respectively) had a significant trend. Conclusions: There was a substantial number of patients with FH who had an ATT of ≥7.5/8.0 and &lt;9.0 mm. These patients previously had a deferred diagnosis of FH. However, they were diagnosed with FH based on the new clinical guideline.

Impact of Environmental Noise and Sleep Health on Pediatric Hypertension Incidence: ABCD Study.

Pediatric hypertension is linked to environmental factors like neighborhood noise disrupting sleep, which is crucial for health. The specific interaction between noise and sleep health in causing hypertension still needs to be explored. We analyzed data from 3320 participants of the ABCD (Adolescent Brain Cognitive Development) study, recruited across 21 US cities and monitored from 2018 to 2020 through 2020 to 2022. Participants with complete data on Fitbit-tracked sleep, blood pressure, height, neighborhood noise, and covariates (biological sex, race and ethnicity, pubertal stage, waist circumference) were included. Hypertension was defined as average blood pressure ≥95th percentile for age, sex, and height. Sleep health was categorized on the basis of daily duration: healthy (9-12 hours), moderately healthy (±1 hour from optimal), and low (≥1 hour deviation). Noise exposure was measured as median nighttime anthropogenic noise levels by zip code. The incidence of hypertension increased from 1.7% (95% CI, 1.4-2.1) in 2018 to 2020 to 2.9% (95% CI, 2.4-3.6) in 2020 to 2022. Adolescents with healthier sleep had a lower risk of developing hypertension (relative risk, 0.63 [95% CI, 0.25-0.82]), while no significant effects were found for neighborhood noise alone or in combination with sleep health. Adequate sleep significantly reduces the risk of hypertension in adolescents, independent of environmental noise exposure. These findings underscore the importance of promoting good sleep hygiene among youth to mitigate hypertension risk.

Associations of Circulating Platelet Endothelial Cell Adhesion Molecule-1 Levels With Progression of Cerebral Small-Vessel Disease, Cognitive Decline, and Incident Dementia.

The association between platelet endothelial cell adhesion molecule-1 (PECAM-1) with cerebral small-vessel disease and cognition in dementia-free subjects remains uninvestigated. A prospective cohort of dementia-free subjects was recruited from memory clinics and followed up for 5 years. Annual neurocognitive assessments and twice-yearly brain magnetic resonance imaging scans were performed. Associations of baseline plasma PECAM-1 levels with cerebral small-vessel disease, cognitive decline (Montreal Cognitive Assessment scores and executive function Z scores), and incident dementia were evaluated. Of 213 subjects (aged 70.2±7.7 years, 51.2% men), median PECAM-1 levels were 0.790 (interquartile range, 0.645-0.955 ng/mL). Compared with the highest tertile, subjects within the lowest PECAM-1 tertile had greater cross-sectional white matter hyperintensity volume (β=4.84 [95% CI, 0.67-9.01]; P=0.023), age-related white matter change scores (β=1.39 [95% CI, 0.12-2.67]; P=0.033), and cerebral microbleeds (Adjusted risk ratio, 2.59 [95% CI, 1.19-5.62]; P=0.016). Of the 204 participants with follow-up data (median, 60.0 [interquartile range, 60.0-60.0] months), 24 (11.8%) developed incident dementia. Compared with the highest tertile, subjects within the lower tertiles of PECAM-1 had a higher risk of incident dementia (first tertile: adjusted hazard ratio [AHR], 4.52 [95% CI, 1.35-15.13]; P=0.024; second tertile: AHR, 3.28 [95% CI, 1.02-10.60]; P=0.047). The lowest PECAM-1 tertile was associated with greater progression of white matter hyperintensity volume (β=4.15 [95% CI, 0.06-8.24]; P=0.047), cerebral microbleeds (incident relative risk [IRR], 2.21 [95% CI, 1.05-4.65]; P=0.036), and decline in executive function (β=-0.45 [95% CI, -0.76 to -0.14]; P=0.004), and Montreal Cognitive Assessment (β=-1.32 [95% CI, -2.30 to -0.35]; P=0.008) scores. In dementia-free subjects, lower circulating PECAM-1 levels are associated with greater cerebral small-vessel disease progression and cognitive decline, thus warranting future study as a potential therapeutic target.

THE IMPACT OF ANTICOAGULANTS ON COAGULATION PARAMETERS IN THE TREATMENT OF PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA ASSOCIATED WITH COVID-19

The aim of the study was to evaluate the effect of anticoagulants on coagulation parameters in the treatment of patients with community-acquired pneumonia associated with coronavirus infection. Materials and methods. An open, prospective, observational study was conducted to achieve the research objectives. Between January 2021 and February 2022, 256 patients aged 40 to 65 years with community-acquired pneumonia were examined at the outpatient clinic of the Kherson City Clinical Hospital named after Athanasius and Olga Tropin of the Kherson City Council. Of these, 177 cases were associated with SARS-CoV-2, while 79 patients tested negative for coronavirus infection. Additionally, thirty-five healthy individuals were examined on an outpatient basis. After randomization, 143 hospitalized patients with severe community-acquired pneumonia associated with COVID-19 were divided into subgroups based on the anticoagulant used in their treatment regimen. The first subgroup consisted of 71 patients who received standard heparin infusions, while the second subgroup included 72 patients treated with enoxaparin. Results. The prothrombin time in the group of healthy volunteers was 12.60 [11.80; 13.30] seconds, and the median value was significantly higher by 13.5% compared to both the group of patients with community-acquired pneumonia associated with COVID-19 and the group without COVID-19 (p &lt; 0.05). The median fibrinogen level in patients with COVID-19 and community-acquired pneumonia was 4.80 [4.50; 5.40] g/L, which did not significantly differ from the 4.60 [4.30; 5.40] g/L in the non-COVID-19 pneumonia group (p &gt; 0.05). However, a significant difference was observed when compared to the healthy volunteer group, which had a fibrinogen level of 3.30 [2.50; 3.80] g/L (p &lt; 0.05). After 72 hours of treatment, prothrombin time was significantly higher in the first subgroup (12.00 [11.00; 13.00] seconds) compared to the second subgroup (11.30 [10.00; 12.30] seconds) (p &lt; 0.05). There was also a statistically significant difference in the international normalized ratio (INR) levels between the subgroups after 72 hours of treatment, with the first subgroup showing an INR of 1.20 [1.10; 1.30] U, versus 1.10 [1.00; 1.30] U in the second subgroup (p &lt; 0.05). After 14 days of treatment, fibrinogen levels showed a statistically significant difference: 4.30 [4.10; 4.60] g/L in the first subgroup compared to 4.50 [4.30; 4.90] g/L in the second subgroup (p &lt; 0.05). Conclusion. In patients with community-acquired pneumonia, blood coagulation parameters are disturbed, characterised by a decrease in prothrombin time and activated partial thromboplastin time, as well as an increase in total fibrinogen levels. After 72 hours, heparin demonstrated a more effective effect on prothrombin time and international normalised ratio compared to enoxaparin. When assessing the dynamics of coagulation parameters after 14 days, heparin was found as was more effective in reducing the level of total fibrinogen compared to enoxaparin.

Effects of thyroid status on HbA1c

Introduction: Altered erythrocyte turnover may not adequately reflect the glycemic status in the glycated hemoglobin (HbA1c) levels. Hypothyroidism is one such condition that might cause reduced erythropoiesis and falsely high HbA1c values. The aim of the study is to evaluate the effect of thyroid hormone on HbA1c levels on non-diabetic hypothyroid individuals and also to evaluate HbA1c levels in hypothyroid individuals with diabetes and to compare them with normal healthy subjects. Methods: This prospective study was conducted on 210 individuals, of whom 70 were assigned to group I- hypothyroid individuals, 70 to group II- hypothyroid individuals with diabetes, and 70 to group III—Normal individuals. Following data regarding laboratory investigations were collected which included fasting blood sugar (FBS), postprandial blood sugar (PPBS), HbA1c, free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH). Data analysis was performed using SPSS version 16.0. Results: The median level of HbA1c was significantly higher in hypothyroid than in normal individuals (5.6 [5.5-5.7] % vs 5.2 [5-5.3] %, P≤0.001). The median level of TSH was significantly higher in hypothyroid than in normal individuals (11.13 [6.9-22.9] μIU/mL vs 2.15 (1.33-1.60) μIU/mL). The serum level of HbA1c was significantly positively correlated with TSH in hypothyroid individuals (r=0.281, P≤0.01). Conclusion: There is a positive correlation between HbA1c and TSH, and a negative correlation between HbA1c and fT4 levels. Serum HbA1c levels were significantly higher in hypothyroid individuals than the normal individuals. Therefore, our study suggests that we should proceed with caution while interpreting HbA1c levels in individuals with hypothyroidism.

A cross-sectional study of point-of-care lactate testing in integrated community care management (ICCM) for children with acute respiratory illness in rural uganda.

Integrated community case management (iCCM) programs leverage lay village health workers (VHWs) to carry out the initial evaluation of children with common conditions including malaria, pneumonia and diarrhea. Therefore, it is imperative that VHWs are able to identify children who are critically ill and require referral to a health facility. Elevated venous lactate levels have been associated with severe illness and adverse health outcomes, including death. However, lactic acidosis may not be recognized in rural settings because it is not routinely measured outside of hospitals and research studies. Point-of-care lactate tests may help identify patients in need of a higher level of care and improve VHWs' ability to make timely and appropriate referrals. The study was a cross-sectional evaluation of children aged <5 y presenting to VHWs in rural southwestern Uganda with complaints of fever and cough. Demographics, clinical presentation, evaluation, management and disposition were recorded. VHWs were trained and instructed to perform lactate testing using a point-of-care assay in eligible participants. During the study period, 238 children were enrolled and completed an initial assessment. Of the 204 participants included in the analysis, 113 (55.4%) were female, and the median (IQR) age was 23 (9-36) months. Most participants, 139/200 (69.5%), had negative results on the malaria rapid diagnostic test. The median lactate level was 2.1mmol/L; 12% (24/204) had a lactate ≥3.5 mmol/L and only nine participants (4.4%) had a lactate ≥5mmol/L. Having a lactate level above either cut-off was not associated with the presence of danger signs at presentation. Few children presenting with fever and cough to VHWs in western Uganda had elevated lactate levels. However, most of the children with elevated lactate levels did not otherwise satisfy established iCCM criteria based on physical examination findings for referral to a health facility. Therefore, while elevated lactate was not associated with danger signs in this small study, it is possible that there is under-recognition of severe illness using current iCCM guidelines.

Case-control study of otoconia proteins otolin-1 and otoconin-90 in patients with Meniere’s disease

Backgrounds Otolin-1 and otoconin-90, the main otoconia matrix protein, can pass through the labyrinth-blood barrier and are detectable in the peripheral blood. Previous studies have shown that serum levels of these proteins well reflect otolith status, but none of concerning Meniere’s disease (MD). Objectives This study aimed to evaluate the serum levels of otolin-1 and otoconin-90 in patients with MD. Material and Methods Patients with MD confirmed during an acute episode, and age- and sex-matched controls were recruited. Their demographic and clinical data were recorded. The serum levels of otolin-1 and otoconin-90 were measured and compared. Results A total of 33 patients with MD and 176 healthy controls were recruited. In patients with MD, the median otolin-1 level was 284.96 pg/mL (interquartile range [IQR] 208.65–331.49 pg/mL) and the median otoconin-90 level was 60.50 ng/mL (IQR 40.61–85.62 ng/mL), which were significantly higher than those in the control group (p < 0.0001 and p = 0.005, respectively). Among patients with MD, serum otoconin-90 levels were correlated with the MD clinical grade (ρ = 0.487, p = 0.04), whereas serum otoconin-1 levels were not (ρ = 0.327, p = 0.063). Conclusions Serum levels of otolin-1 and otoconin-90 may serve as biomarkers of otolith lesions in patients with MD.

Biochemical recurrence after open radical prostatectomy in a single-center cohort with a minimum follow-up of 10 years

Purpose: To investigate the long-term oncological outcomes and report biochemical recurrence (BCR)-free survival for men who underwent open radical prostatectomy at a single center. Materials and methods: A total of 360 patients who underwent open radical prostatectomy at our institution between 2003 and 2011 were included in this study. The BCR-free survival rates were calculated by Kaplan-Meier method and log-rank analysis. Multivariable Cox regression models were used to test the effect of other factors such as age, preoperative prostate-specific antigen (PSA), Gleason score, and surgical margins on BCR. Results: Median patient age was 65.4 years, with a median preoperative PSA level of 6.21 ng/ml. Operating time had a median duration of 155.1 minutes, ranging from 104 to 301 minutes. Nerve-sparing surgery was achievable in 48.1% of patients, including 34.2% undergoing bilateral procedures and 13.9% unilateral. In terms of surgical precision and outcomes, the overall rate of positive surgical margins was 23.6%, which decreased significantly to 11.1% in patients with localized prostate cancer. Lymph node involvement occurred in 3.6% of cases. Postoperative care statistics revealed a median catheterization duration of 9.1 days (range: 4–30 days) and a low rate of significant complications (4.4%). The early continence rate in a standardized pad test was 80.6%. At a median follow-up of 150.5 months, the 5-year and 10-year BCR-free survival rates for the entire cohort were 91.4% and 77.5%, respectively. The 10-year BCR-free survival rates were 84.8%, 81.5%, and 68.5% for low-, intermediate-, and high-risk patients, respectively. Furthermore, the 10-year BCR-free survival rates were 78.8% and 62.8% for localized and locally advanced prostate cancer, respectively. Preoperative PSA &gt;20 ng/ml, postoperative Gleason sum ≥3 + 4, and positive surgical margins were associated with increased risk of BCR on multivariable Cox regression analysis. Conclusion: Our long-term oncological results match or exceed those previously published in similar contemporary cohorts with long follow-up.

High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.

Mitochondrial DNA (mtDNA) rearrangements are recognised factors in mitochondrial disorders and ageing, but their involvement in neurodevelopmental disorders, particularly intellectual disability (ID) and autism spectrum disorder (ASD), remains poorly understood. Previous studies have reported mitochondrial dysfunction in individuals with both ID and ASD. The aim of this study was to investigate the prevalence of large-scale mtDNA rearrangements in ID and ID with comorbid ASD (ID-ASD). We used mtDNA-targeted next-generation sequencing and the MitoSAlt high-throughput computational pipeline in peripheral blood samples from 76 patients with ID (mean age 52.5years, 37% female), 59 patients with ID-ASD (mean age 41.3years, 46% female) and 32 healthy controls (mean age 42.4years, 47% female) from Catalonia. The study revealed a high frequency of mtDNA rearrangements in patients with ID, with 10/76 (13.2%) affected individuals. However, the prevalence was significantly lower in patients with ID-ASD 1/59 (1.7%) and in HC 1/32 (3.1%). Among the mtDNA rearrangements, six were identified as deletions (median size 6937bp and median heteroplasmy level 2.3%) and six as duplications (median size 10 455bp and median heteroplasmy level 1.9%). One of the duplications, MT-ATP6 m.8765-8793dup (29bp), was present in four individuals with ID with a median heteroplasmy level of 3.9%. Our results show that mtDNA rearrangements are frequent in patients with ID, but not in those with ID-ASD, when compared to HC. Additionally, MitoSAlt has demonstrated high sensitivity and accuracy in detecting mtDNA rearrangements, even at very low heteroplasmy levels in blood samples. While the high frequency of mtDNA rearrangements in ID is noteworthy, the role of these rearrangements is currently unclear and needs to be confirmed with further data, particularly in post-mitotic tissues and through age-matched control studies.

A kiloparsec-scale ordered magnetic field in a galaxy at z=5.6

Magnetic fields are widely observed in various astronomical contexts, yet much remains unknown about their significance across different systems and cosmic epochs. Our current knowledge of the evolution of magnetic fields is limited by scarce observations in the distant Universe, where galaxies have recently been found to be more evolved than most model predictions. To address this gap, we conducted rest-frame 131\,mu m full-polarisation observations of dust emission in a strongly lensed dusty star-forming galaxy, SPT0346$-$52, at $z=5.6$, when the Universe was only 1 Gyr old. Dust grains can become aligned with local magnetic fields, resulting in the emission of linearly polarised thermal infrared radiation. Our observations have revealed a median polarisation level of $0.9 percent with a variation of $ percent across the 3\,kiloparsecs extention, indicating the presence of large-scale ordered magnetic fields. The polarised dust emission is patchy, offset from the total dust emission and mostly overlaps with the C\ ii $. The bimodal distribution of field orientations, their spatial distribution, and the connection with the cold gas kinematics further emphasise the complexity of the magnetic environment in this galaxy and the potential role of mergers in shaping its magnetic fields. Such early formation of ordered galactic magnetic fields also suggests that both small-scale and large-scale dynamos could be efficient in early galaxies. Continued observations of magnetic fields in early galaxies, as well as expanding surveys to a wider galaxy population, are essential for a comprehensive understanding of the prevalence and impact of magnetic fields in the evolving Universe.

An analysis of vitamin K status in Chinese healthy children aged 0–18 years

BackgroundVitamin K (VK), an essential fat-soluble nutrient, exists in two primary forms, vitamin K1 (VK1), and vitamin K2 (VK2). VK1 plays an essential role in blood coagulation, while VK2 plays a crucial role in managing bone calcification, supporting bone strength and health. However, comprehensive epidemiological data on VK remains sparse, particularly in children. This study aims to evaluate the levels and characteristics of VK in children of Wenzhou area, China.MethodsA total of 3,342 children undergoing routine physical examinations in the outpatient department from December 2020 to August 2022 were recruited. The levels of VK (including VK1 and menaquinones (MK-4), a major form of VK2) and 25-hydroxy vitamin D (25(OH)D) in fasting serum samples from these children were measured using high-performance liquid chromatography-tandem mass spectrometry. The study analyzed the levels and distribution of VK and 25(OH)D across different sex, age, and weight groups, and explored their potential related factors.ResultsThe median serum levels of MK-4 and VK1 were 0.12 (0.07, 0.21) ng/ml and 0.33 (0.18, 0.57) ng/ml, respectively. The reference ranges of MK-4 and VK1 were 0.01–0.58 ng/ml and 0.03–1.48 ng/ml, respectively. The median serum 25(OH)D level was 21.26 (17.30, 25.35) ng/ml. Moreover, there were no significant variations in the levels of MK-4 and VK1 across different age and sex groups. The level of MK-4 in the underweight group was significantly higher than that in the normal weight group. MK-4 level reached its peak in summer, while the VK1 concentration was at its lowest. Furthermore, a very weak positive correlation was revealed between MK-4 and VK1 levels.ConclusionIn this study, we defined the median values and reference ranges of MK-4 and VK1 in a sample of Chinese children aged 0–18 years. MK-4 levels were higher in underweight children. Both MK-4 and VK1 levels exhibited seasonal variations. Further research is needed to explore the factors affecting MK-4 and VK1 levels.

Vanishing Bile Duct Syndrome in Pediatric Hodgkin Lymphoma: First Statistical Analysis of All Published Cases in Children and a Case Report.

Hodgkin lymphoma with vanishing bile duct syndrome is a rare paraneoplastic syndrome and has never been studied in the pediatric population. The objectives of this study were to determine the clinical characteristics of this rare condition in children through a literature review, and a descriptive analysis of all published cases with the index case report. All reported cases fulfilling the inclusion criteria were found through a literature search, and analyzed in descriptive statistics. A total of 10 cases were included in the study with a median age of 9.5 years and a male-to-female ratio of 9:1. The median duration of symptoms was 5.5 weeks with 3 cases having jaundice before the symptoms of lymphoma. The median bilirubin level was 8.4mg/dL. Seven cases received modified chemotherapy, and 5 used ursodeoxycholic acid. The survival rate was 50%. Normalization of liver functions after the lymphoma treatment was observed in 4 cases and was the only statistically significant factor (P=0.01) associated with the outcome. This is a rare entity in the pediatric population with a guarded prognosis comparable to the adult counterparts but a marked male predominance.