Elevated Values Research Articles

Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial.

Fostamatinib, a spleen tyrosine kinase inhibitor, has been reported to improve outcomes of COVID-19. To evaluate the efficacy and safety of fostamatinib in adults hospitalized with COVID-19 and hypoxemia. This multicenter, phase 3, placebo-controlled, double-blinded randomized clinical trial was conducted at 41 US sites and 21 international sites between November 17, 2021, and September 27, 2023; the last follow-up visit was December 31, 2023. Participants were adults aged 18 years or older hospitalized with acute SARS-CoV-2 infection and hypoxemia. Data were analyzed between January 10 and March 8, 2024. Fostamatinib, 150 mg orally twice daily for 14 days, or placebo. The primary outcome was oxygen-free days, an ordinal outcome classifying a participant's status at day 28 based on mortality and duration of supplemental oxygen use. An adjusted odds ratio (AOR) greater than 1.0 was considered to indicate superiority of fostamatinib over placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included elevated transaminase values, neutropenia, and hypertension. Of the 400 participants randomized (median age, 67 years [IQR, 58-76 years]; 210 [52.5%] men), 199 received fostamatinib and 201 received placebo. The mean (SD) number of oxygen-free days was 13.4 (12.4) in the fostamatinib group and 14.2 (12.1) in the placebo group (unadjusted mean difference, -1.26 days [95% CI, -3.52 to 1.00 days]; AOR, 0.82 [95% credible interval (CrI), 0.58-1.17]). Mortality at 28 days occurred in 22 of 195 patients (11.3%) in the fostamatinib group and 16 of 197 (8.1%) in the placebo group (AOR, 1.44; 95% CrI, 0.72-2.90). Aspartate aminotransferase elevation occurred more commonly in the fostamatinib group (23 [11.6%]) than in the placebo group (11 [5.5%]; AOR, 2.28; 95% CrI, 1.07-4.84). Other safety outcomes were similar between groups. In this randomized clinical trial of adults hospitalized with COVID-19 and hypoxemia, fostamatinib did not increase the number of oxygen-free days compared with placebo. These results do not support the hypothesis that fostamatinib improves outcomes among adults hospitalized with hypoxemia during the Omicron era. ClinicalTrials.gov Identifier: NCT04924660.

Expansion of Pleioblastus amarus in tea plantations significantly enhances the appearance and nutritional composition of bamboo shoots but adversely affects palatability

The expansion of Pleioblastus amarus into tea plantations introduces environmental heterogeneity, significantly influencing the growth and quality of bamboo shoots. This study examined the effects of bamboo expansion on the appearance, nutrition, and palatability of bamboo shoots, utilizing partial least squares structural equation modeling (PLS-SEM) to identify key influencing factors. Results revealed that bamboo expansion increased shoot diameter, length, and fresh weight, enhancing overall size and edibility, particularly in the tea-bamboo mixed forest center zone (TBC), where appearance quality peaked. Nutritional analysis revealed substantial increases in protein, fat, starch, and vitamin C content after bamboo expansion, along with the improvements in amino acid score (AAS), essential amino acid index (EAAI), and nutritional index (NI), indicating elevated nutritional value. However, despite the rise in soluble sugars and flavor-enhancing amino acids, higher levels of total acids, oxalic acid, tannins, and cellulose diminished the palatability, notably in TBC site. PLS-SEM further indicated that while bamboo expansion positively influenced shoot appearance and nutrition, soil factors predominantly drove these changes and concurrently detracted from overall palatability. These findings provide a framework for enhancing bamboo shoot quality and optimizing management practices in tea plantation ecosystems.

Design of a novel complex 99mTc-Nilutamide as a tracer for prostate cancer disorder detection in mice

Abstract Male prostate cancer (PCa) is considered among the most fatal illnesses. Despite the recent decrease in prostate cancer incidence attributed to advancements in early detection and therapy, these reductions have not effectively mitigated the elevated fatality rate linked to this disease. The drug Nilutamide was effectively radiolabeled with technetium-99m, producing a radiochemical yield of 96 ± 0.14 % under optimal conditions. In our study, two cohorts of mice were utilized, namely the control group and the group with prostate cancer. Various biochemical parameters, including PSA levels in serum, were assessed, revealing a significantly elevated value in the group with prostate cancer, indicating potential tumor development. Furthermore, the activities of antioxidant enzymes (CAT, SOD) were notably lower in the group with prostate cancer compared to the healthy control group, while the oxidative activity reflected by MDA levels, the final product of lipid peroxidation, was higher in the prostate cancer group than in the healthy control group. The biodistribution analysis showed rapid localization of 99mTc-Nilutamide in prostate cancer tissue after 2 h post-injection, with a substantial value of 11.4 ± 1.1 % I. D/g tissue. Consequently, it was deduced that radiolabeled 99mTc-Nilutamide can serve as an effective imaging tool for prostate cancer.

Associated factors with non[sbnd]operative management failure in bowel obstruction

BackgroundBowel obstruction caused by adhesion syndrome is a prevalent condition in emergency departments, presenting significant economic and morbidity challenges. While nonsurgical approaches succeed in 70–90% of cases, surgery becomes necessary for nonresponsive patients. This study aims to identify predictors of non-operative management failure in patients with bowel obstruction upon emergency room admission. MethodsA retrospective cross-sectional analytical study was conducted from 2015 to 2022 at Hospital Militar Central, focusing on patients with bowel obstruction secondary to adhesion syndrome. Comparative analysis of medical and surgical histories and admission laboratory values aimed to identify possibles factors associated with non-operative management failure and subsequent surgical intervention. ResultsAmong 354 patients with bowel obstruction, 130 met inclusion criteria, of whom 98 responded to non-operative treatment and 32 experienced treatment failure. Significant differences were found between groups, including age (p: 0.035), history of two or more abdominal surgeries (10.2% vs. 25%, p: 0.01), appendectomy (17% vs. 37%, p: 0.01), previous surgical intervention for bowel obstruction (22.5% vs. 9.38%, p: 0.008), and hospital stay duration (4.26 vs. 13.2 days, p: 0.001). In multivariate analysis using Poisson regression, age had a prevalence ratio (PR) of 1.01 [95% CI (1.00; 1.02), p < 0.04] for non-operative management failure, the history of peritonitis had a PR of 3.83 [95% CI (2.34; 6.26), p < 0.001], while each unit increase in lactate showed a PR increase of 1.24 [95% CI (0.99; 1.57), p 0.05]. ConclusionAge, history of peritonitis, and elevated lactate values upon emergency room admission are predictive factors for non-operative management failure in bowel obstruction in the population studied.

The influence of water conservancy project on microplastics distribution in river ecosystem: A case study of Lhasa River Basin in Qinghai-Tibet Plateau

Water conservancy projects affect the migration, suspension, and deposition of microplastic (MP). However, its impact on MP pollution of river ecosystem remains elusive. Herein, we investigated the MP characteristics and the influence of water conservancy projects on MPs in the Lhasa River Basin of the Qinghai-Tibet Plateau, China. The results demonstrated that the MPs concentration in surface water decreased from upstream to downstream, as more MPs in surface water were settling down and stored in reservoir sediments in the midstream. It is postulated that reservoir sedimentation of MPs occurs at a greater rate due to the barrier effect of reservoirs, steady hydrodynamics, and weak salinity-induced buoyancy. To evaluate the ecological risk of the Lhasa River Basin, the pollution load index, the polymer hazard index, and the potential ecological risk index were analyzed. The upstream exhibits elevated polymer hazard index values (>100), and the potential ecological risk index values in the Lhasa River Basin showed ecological risk similar to those of pollution load index values. This research represents the initial exploration of MP distribution within the entire Lhasa River basin, providing a foundational framework for investigating the impact of water conservancy projects on MP migration.

Correlation between Immune Microenvironment and Clinicopathological Characteristics and Prognosis of Primary Large B-cell Lymphoma of Immune-Privileged Sites

ObjectivesTo explore the correlation between tumor-associated macrophages (TAMs), tumor-infiltrating lymphocytes (TILs), and tumor-associated angiogenesis (TAA) in the tumor microenvironment with the clinicopathological characteristics and prognosis of primary large B-cell lymphoma of immune-privileged sites (LBCL-IP).MethodsA total of 46 cases of LBCL-IP from the Department of Pathology, the Third Affiliated Hospital of Xinjiang Medical University, from January 2010 to February 2024, were collected, along with clinical and follow-up data of LBCL-IP patients. Immunohistochemistry and triple immunofluorescence were used to detect related proteins of TAMs, TILs, and TAA, and to analyze the correlation between TAMs, TILs, TAA, and the polarization of TAMs with the clinical and prognostic factors of LBCL-IP patients.ResultsThere are 30 cases (65.2%) showed high expression of CD68 proteins, 32 cases (69.6%) showed high expression of CD163 proteins, 19 cases (41.3%) showed high expression of CD4 proteins, 34 cases (73.9%) showed high expression of CD8 proteins, and 25 cases (54.3%) showed high expression of CD34 proteins. A total of 27 cases (58.7%) showed CD68+CD163+/CD68+CD86+≥1. The chi-square tests showed that high expression of CD163 proteins was positively correlated with elevated LDH and BMG values, and the count of CD68+CD163+/CD68+CD86+≥1 was positively correlated with ECOG scores ≥2, Ann Arbor staging III-IV, and increased BMG value. High expression of CD8 proteins was positively correlated with a Ki-67 proliferation index ≥70%, and high MVD values were positively correlated with Ann Arbor staging III-IV. The Kaplan-Meier estimator analysis showed that LBCL-IP patients with low expression of CD68 proteins, high expression of CD163 proteins, CD68+CD163+/CD68+CD86+≥1, low expression of CD8 proteins, high MVD values, ECOG scores ≥2, Ann Arbor staging III-IV, LDH ≥250U/L, BMG ≥2.2mg/L, and IPI scores ≥2 had shorter survival times. Multivariate Cox regression analysis showed that low expression of CD8 proteins, CD68+CD163+/CD68+CD86+≥1, LDH ≥250U/L, and ECOG scores ≥2 are independent risk factors affecting the survival of LBCL-IP patients.ConclusionM2-polarized TAMs and low infiltration of CD8+ TILs were more strongly correlated with poor clinical pathological indicators and worse prognosis, and MVD values may serve as an aiding means for the diagnosis and prognostic prediction of LBCL-IP disease.

Ultrasound Utilization in Hospitalized Kidney Transplant Recipients: Useful or Overused?

Kidney transplant ultrasonography is an important diagnostic tool in the care of transplant recipients. This modality of nonradiation-based imaging allows for precise and expedient reporting of allograft architecture, which can inform clinical decision-making. However, as with any diagnostic tool, overuse may lead to unnecessary interventions and costs on the healthcare system. To better understand the use of ultrasonography in hospitalized kidney transplant recipients and outcomes of subsequent interventions, we conducted a single-center retrospective study at a large transplant program in Ontario, Canada. We noted that over 30% of admissions resulted in a ultrasonographic survey within the first 24 h of presentation; however, most of these did not change clinical management or lead to a subsequent procedural intervention. Using multivariable logistic regression, we identified predictors for receiving an ultrasound, including time from transplantation, elevated serum creatinine and infectious diagnosis. Procedural interventions (e.g., drain or biopsy) resulted from less than 20% of all ultrasound investigations, with patients closer to the time of index transplant or with elevated serum creatinine values more likely to receive an intervention. In conducting a cost analysis, we estimated that approximately $80000 CAD per year could be saved with more selective decisions on ultrasound requisitions. Overall, our results indicate that despite being an informative tool, the broad use of ultrasonography in the kidney transplant population may not yield significant changes to transplant care.

The effects of sample preparation on the interpretation of pyrolysis-based organic matter analysis in immature oil shale

Oil shale as well as shale oil and shale gas are significant energy resources with huge reserves present in different parts of the world. Various geochemical proxies have been applied to assess the petroleum potential of oil shales with samples pre-treated in various ways, e.g. as whole rock or demineralized sample or as solvent extracted rock/kerogen. In this respect, it is important to understand and quantify, how achieved geochemical parameters are influenced by pre-treatment. In this study, a systematic comparison is presented based on a study on i) whole rock, ii) extracted whole rock, iii) kerogen concentrate, and iv) extracted kerogen concentrate obtained after solvent extraction of demineralized shales. In total, seven immature, organic matter-rich samples from the Miocene lacustrine sediments of the Nördlinger Ries impact crater, Germany, were pretreated in this way leading to overall 28 samples. A set of elemental analysis (C, H, N), Rock-Eval pyrolysis, and Curie Point-pyrolysis–gas chromatography–mass spectrometry measurements were performed on these pretreated samples. Mineral matter removal leads to significant increase of total organic carbon, but also thermally evaporable and pyrolytically cracked organic matter (Rock-Eval S1 and S2 peaks). To some extent, labile organic matter represented in the original S2 peak can be destructed by mineral removal with hydrochloric and hydrofluoric acid, as shown by elevated values of PI [S1/(S1 + S2)] after demineralization. The organic matter type tends to be more petroleum-prone with raised hydrogen index (HI) and aliphaticity values after demineralization, while Rock-Eval Tmax values commonly applied as parameters for thermal maturity tend to decrease, though not for all samples.Reduced TOC, S1, S2 and PI values of extracted samples suggest that both thermally evaporable and additionally some non-evaporable but soluble organic matter hidden in the original S2 peak can be lost after solvent extraction. Increased values of HI, H/C and N/C of extracted samples indicate more oil-prone organic matter types than unextracted samples. Typical maturity-related parameters such as aliphaticity and Rock-Eval Tmax decrease. Smectite and zeolites, which are abundant in the samples, are suggested to protect organic matter to some extent against solvent extraction, influencing a variety of geochemical proxies and the occurrence of metal cation-containing minerals. Zeolite invigorates the protection effect.

Therapeutic efficacy of CRISPR RNA nanoparticles on cervical cancer disease using ultrasound elastography imaging

This work aimed to evaluate the therapeutic efficacy of clustered regularly interspaced short palindromic repeats (CRISPR) ribonucleic acid (RNA) nanoparticles (NPs) in the therapy of cervical cancer (CC) using ultrasound elastography imaging. Using poly(β-amino esters) (PBAE), CRISPR RNA NPs encapsulating Human Papillomavirus 16 (HPV16) E7, namely Poly(β-amino ester) (PBAE)/CRISPR16E7-GFP and PBAE/shRNA-16E7, were prepared. The characterization of these NPs was conducted using transmission electron microscopy (TEM) and laser diffraction particle size analysis. The cytotoxicity of PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 NPs on CC cell lines SiHa, HeLa, and CaSki was assessed using the cell counting kit-8 (CCK-8) assay. Sixty female Sprague Dawley (SD) rats were rolled into six groups randomlyas follows: the blank Ctrl group (Group A, no treatment), the model group (Group B, CC model), the pSpCas9-GFP plasmid group (Group C, CC model + pSpCas9-GFP), the PBAE/CRISPR-16E7 group (Group D, CC model + PBAE/CRISPR-16E7), the pSIREN-U6-shRNA-CMV-iRFP plasmid group (Group E, CC model + pSIREN-U6-shRNA-CMV-iRFP), and the PBAE/shRNA-16E7 group (Group F, CC model + PBAE/shRNA-16E7), each consisting of 10 rats. The impact of NPs on the expression levels (ELs) of HPV16E7 and RB1 proteins in tumor tissues was assessed using Western Blot (WB) analysis. Additionally, ultrasound elastography imaging was employed to analyze the strain ratio (SR) and shear wave velocity (SWV) in lesions of various rat groups. The results indicated that the PBAE/CRISPR16E7-GFP NPs exhibited a particle size of 125.64 ± 7.8 nm, a zeta potential of 19.17 ± 3.61 mV, and a polydispersity index (PDI) of 0.281 ± 0.03. These NPs demonstrated a regular spherical structure with a compact morphology. The PBAE/shRNA-16E7 NPs displayed a particle size of 112.93 ± 9.1 nm, a zeta potential of 13.54 ± 1.39 mV, and a PDI of 0.185 ± 0.03. They exhibited a uniform distribution of spherical shape with regularity in size. The plasmids within PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 NPs exhibited distinct trends of burst and sustained release. The viability of SiHa, HeLa, and CaSki cells remained unaffected by PBAE/CRISPR16E7-GFP NPs. At various mass ratios, neglectable differences (P > 0.05) were observed in cell viability of SiHa, HeLa, and CaSki cells treated with PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 NPs relative to Ctrl group. Relative to Group B, both Groups C and E exhibited a drastic decrease in tumor volume, tumor mass, and HPV16E7 protein ELs (P < 0.05), whereas Groups D and F showed a notably greater reduction in tumor volume, tumor mass, and HPV16E7 protein ELs (P < 0.01). The HPV16E7 protein ELs, SR, and SWV values greatly increased (P < 0.001) in tumors of Group B rats while the EL of RB1 protein notably decreased (P < 0.001) versus Group A. Groups C and E demonstrated elevated HPV16E7 ELs, SR, and SWV values (P < 0.05), with a marked decrease in RB1 protein EL (P < 0.001). Group F exhibited a notable reduction in HPV16E7 protein levels, SR, and SWV values (P < 0.001).The CRISPRRNA NPs composed of PBAE encapsulating HPV16 E7, namely PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 plasmids, demonstrated a significant role in CC therapy. These NPs hold potential application value in the treatment of HPV-related CC, indicating their importance in addressing this particular disease.

INCIDENCE OF PULMONARY THROMBOEMBOLISM IN PATIENTS SUBJECTED TO COMPUTERIZED TOMOGRAPHY AND PULMONARY ANGIOGRAPHY AT THE UNIVERSITY CLINICAL HOSPITAL MOSTAR

Introduction: Pulmonary embolism is a serious medical problem with high mortality if not recognized in time. CT pulmonary angiography is a key method for diagnosing pulmonary embolism in patients with nonspecific symptoms such as shortness of breath, chest pain, and elevated D-dimer values. Objective: To determine the incidence of pulmonary embolism in patients undergoing CT pulmonary angiography at the University Clinical Hospital Mostar. Subjects and methods: A retrospective study included 300 patients with suspected pulmonary embolism who underwent CT pulmonary angiography. Technical imaging parameters included a low-dose protocol with intravenous iodine contrast. The results were analyzed by descriptive statistics, with an assessment of the frequency of pulmonary embolism, thrombus localization and incidental findings. Results: Pulmonary embolism was diagnosed in 27% of patients, with the most frequent involvement of the lobar arteries (43%). Massive emboli were recorded in 33% of cases. The average age of the respondents was 64 years, with an almost equal gender distribution. Elevated D-dimers were not sufficient to confirm the diagnosis in most patients. Incidental findings included pleural effusions, pneumonia, and tumors. Conclusion: CT pulmonary angiography is necessary for accurate diagnosis of pulmonary embolism, especially in patients with nonspecific symptoms. The results highlight the need to combine clinical and imaging methods, as well as adapt diagnostic protocols to reduce radiation exposure and optimize treatment outcomes. In the local context, these guidelines can improve diagnosis and treatment.

Alkalothermophilic Iron-Reducing Bacteria of the Goryachinsk Thermal Water Basin

A study of iron-reducing prokaryotes that use the poorly crystalline mineral ferrihydrite as an electron acceptor revealed their widespread occurrence on the planet. However, the ability of iron reducers to develop under polyextreme conditions (at elevated values of pH and temperature) has not been previously demonstrated. To confirm the existence of alkalothermophilic iron reducers, we studied the water and sediment samples from the Goryachinsk nitrogen-rich thermal water basin. These springs are associated with young tectonic fractures in the Baikal rift zone; their water is characterized by low salinity, alkaline pH (8.8‒9.2) and temperature of 53‒55°C. Enrichment cultures reducing synthesized ferrihydrite were obtained by adding this mineral to the water and sediment samples from the Goryachinsk thermal springs, followed by anaerobic incubation at 50 and 55°C. The 16S rRNA gene profiling of the water and sediment samples and of the primary enrichment cultures revealed high taxonomic diversity, almost exclusively represented by bacterial taxa. Subsequent transfers with ferrihydrite and organic acids or hydrogen as electron donors resulted in stable enrichment cultures of organo- and lithotrophic alkalothermophilic iron reducers. Members of the genus Parvivirga, one of the first cultured representatives of the OPB41 group (now the order Anaerosomatales, phylum Actinomycetota), constituted 30 to 50% of the total abundance.

In Silico Design of Peptide Inhibitors Targeting HER2 for Lung Cancer Therapy

Background/Objectives: Human epidermal growth factor receptor 2 (HER2) is overexpressed in several malignancies, such as breast, gastric, ovarian, and lung cancers, where it promotes aggressive tumor proliferation and unfavorable prognosis. Targeting HER2 has thus emerged as a crucial therapeutic strategy, particularly for HER2-positive malignancies. The present study focusses on the design and optimization of peptide inhibitors targeting HER2, utilizing machine learning to identify and enhance peptide candidates with elevated binding affinities. The aim is to provide novel therapeutic options for malignancies linked to HER2 overexpression. Methods: This study started with the extraction and structural examination of the HER2 protein, succeeded by designing the peptide sequences derived from essential interaction residues. A machine learning technique (XGBRegressor model) was employed to predict binding affinities, identifying the top 20 peptide possibilities. The candidates underwent further screening via the FreeSASA methodology and binding free energy calculations, resulting in the selection of four primary candidates (pep-17, pep-7, pep-2, and pep-15). Density functional theory (DFT) calculations were utilized to evaluate molecular and reactivity characteristics, while molecular dynamics simulations were performed to investigate inhibitory mechanisms and selectivity effects. Advanced computational methods, such as QM/MM simulations, offered more understanding of peptide–protein interactions. Results: Among the four principal peptides, pep-7 exhibited the most elevated DFT values (−3386.93 kcal/mol) and the maximum dipole moment (10,761.58 Debye), whereas pep-17 had the lowest DFT value (−5788.49 kcal/mol) and the minimal dipole moment (2654.25 Debye). Molecular dynamics simulations indicated that pep-7 had a steady binding free energy of −12.88 kcal/mol and consistently bound inside the HER2 pocket during a 300 ns simulation. The QM/MM simulations showed that the overall total energy of the system, which combines both QM and MM contributions, remained around −79,000 ± 400 kcal/mol, suggesting that the entire protein–peptide complex was in a stable state, with pep-7 maintaining a strong, well-integrated binding. Conclusions: Pep-7 emerged as the most promising therapeutic peptide, displaying strong binding stability, favorable binding free energy, and molecular stability in HER2-overexpressing cancer models. These findings suggest pep-7 as a viable therapeutic candidate for HER2-positive cancers, offering a potential novel treatment strategy against HER2-driven malignancies.

The effect of seaweed fertilisation on sulfur isotope ratios (δ34S) and grain size in barley: implications for agronomy and archaeological research

IntroductionStable sulfur isotope ratios (δ34S) in bone collagen are often employed to study the consumption of marine and freshwater fish, wetland grazing, marine foraging patterns, and the possible geographic origins of food sources. However, a recent small-scale crop experiment showed that biofertilisation with seaweed can elevate δ34S in Celtic beans by ca. 10 ‰. Consumption of this food could erroneously suggest a marine diet and therefore has important implications for the reconstruction of past diets and dietary origins. However, limited research has so far been undertaken on cereals.MethodsTo address this issue, a large-scale field trial was undertaken on the Orkney Islands, whereby bere barley (a Scottish landrace, Hordeum vulgare L.) was biofertilised with seaweed at different dosages (25 t/ha, 50 t/ha), with a mineral NPK fertiliser, and left unfertilised as a control.ResultsThe total barley biomass yield was higher and barley grains were enlarged following all fertilisation treatments compared to the control barley. Barley grain and straw from seaweed-fertilised crops had more elevated δ34S values by around 2–3 ‰ compared to unfertilised plants, while the NPK-fertilised grains and plants had δ34S values 1 ‰ lower.DiscussionThese results confirm previous hypotheses that seaweed fertilisation can elevate cereal δ34S values. The comparatively small δ34S difference between control and seaweed fertilised crops in this field trial is likely due to background elevated δ34S values in the soil (+12.7 ‰), which in turn may be due to long-term exposure to oceanic-influenced rain and sea spray and/or possible historical application of seaweed, or the underlying bedrock composition. The results of this study show that seaweed fertilisation can increase barley grain sizes and δ34S values, and thus should be considered when reconstructing land management and dietary practices in the archaeological record.

Comparative study of micro ESR with CRP and blood culture sensitivity

Background: Neonatal sepsis is one of the leading causes of morbidity and mortality among neonates in India. Indian association of paediatrics has developed sepsis screen which is useful for early diagnosis. To test the reliability of micro ESR as bedside tool in early diagnosis of neonatal sepsis we conducted this study. Comparison of Micro-erythrocyte sedimentation rate (micro ESR) with C-reactive protein (CRP) and blood culture sensitivity in neonatal sepsis. To establish a relation between severity of sepsis and Micro-erythrocyte sedimentation rate. Methods: This is a cross sectional study done at neonatal intensive care unit (NICU), at our institute over a period of six months. Fifty neonates with risk factors for sepsis and who had a positive sepsis screen were enrolled prospectively into the study. Results: Out of 50 samples collected, micro ESR (&gt;15 mm/hour) was positive in 12 cases (24%) and CRP was positive in 18 cases (36%). After procuring the blood culture report, 48 cases had neonatal sepsis (84%). Our study showed that micro-ESR as a bedside test had a positive correlation with mortality (p value &lt;0.001) when compared with CRP values (p value=0.546) in neonatal sepsis. As expected, elevated micro ESR and high CRP value had 100% correlation but was not statistically significant (p=0.319). In all the 12 cases with raised micro ESR had 100% blood culture positivity but significance could not be established. Conclusions: Micro-ESR had a significant correlation with mortality in neonatal sepsis.

Newborn Screening Program for Cystic Fibrosis in Türkiye: Experiences from False-Negative Tests and Requirement for Optimization.

Since January 2015, the Cystic Fibrosis National Newborn Bloodspot Screening (CF-NBS) program has been implemented in Turkey with two samples of immune reactive trypsinogen (IRT-1/IRT-2) testing. This study aimed to evaluate the Turkish national CF screening program, which included patients referred to a tertiary pediatric pulmonology center, to ascertain the optimal cut-off values for IRT-1/IRT-2 and to identify alternative strategies for mitigating the number of late-diagnosed false-negative patients (FNPs) who initially exhibited screen negative results but were diagnosed subsequently based on clinical suspicion. The study also compared NBS-positive patients to FNPs to determine the influence of delayed diagnosis. A retrospective cohort study. Screening for CF was conducted in accordance with the national CF-NBS program within 48-72 hours of birth by collecting a few drops of heel blood on Guthrie paper. A cut-off value of 90 μg/l was accepted for the first IRT, while 70 μg/l was accepted for the second sample. Infants with elevated IRT values in both samples were referred to the CF centers for a sweat test (ST). Based on the diagnosis, the NBS-positive infants referred to our CF center for ST analysis were divided into three groups: CF; cystic fibrosis-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID); and false-positive NBS. In addition, the study included NBS-negative patients who initially received negative screen results but were subsequently diagnosed with CF based on clinical suspicion. Of the 227 NBS-positive infants referred within the study period, 53 (23.34%) were diagnosed with CF (true-positive NBS), 11 were classified as CRMS/CFSPID (4.84%), and 163 were classified as falsepositive NBS (71.8%). CF was diagnosed in 66 infants, 53 (80.3%) of whom were confirmed using the NBS test, while the 13 (19.7%) patients who were missed on the NBS test were diagnosed based on clinical suspicion (FNP). The study findings indicate that the IRT/IRT approach exhibited a sensitivity of 80.3% and a positive predictive value (PPV) of 23.3%. The current study is the first to analyze the NBS program for CF using data from the Western Anatolian Region of Türkiye. Due to the low sensitivity and PPV of the IRT/IRT protocol and the high proportion of false-positive infants and FNPs, the current national program is not practicable for Türkiye. False-negative results significantly delay the diagnosis and invalidate the screening objectives. It is essential to establish optimal cut-off values for IRT-1/IRT-2 or revise existing strategies to reduce the number of FNPs missed by the screening program.

Dynamics of the main parameters of carbohydrate metabolism and possible causes of its disorders in the autumn and winter periods in modern residents of the North

To assess the reserve capacity of the body from a physiological point of view, it is important to study the specific “northern” hormone metabolic profile of the body during critical (autumn and winter) periods in apparently healthy individuals born and living in the North.The aim of the work. To study the main parameters of carbohydrate metabolism, as well as possible causes of its disorders in the dynamics of autumn and winter periods in men living in the North.Materials and methods. The autumn (October) and winter (December) stages of the study included 45 men (mean age 40.0 ± 0.8 years) permanently residing in the Magadan Region. We used chemiluminescent immunoassay, enzymatic method and immunochromatographic assay.Results of the study. It was found that the average values of carbohydrate metabolism parameters in the examined male northern residents are comparable with the standard ranges with a shift towards higher values relative to the established limits and do not meet the main criteria of the “polar metabolic type”. “Polar metabolic type” is characterized by hypoglycemia and hypoinsulinemia against the background of elevated serum cortisol values. It is shown that during the critical period of the year from October to December (temperature transition through zero) against the background of relative “hypercortisolism”, activation of the insular apparatus of the pancreas is observed, accompanied by an increase in the insulin level, as well as the development of insulin resistance in the absence of compensatory secretion of β-cells of the pancreas. At the same time, the presence of signs of insulin resistance in northern male residents in the winter period may be determined by an imbalance towards greater dominance of the sympathetic nervous system, formed as a response to the critical period of the year.Conclusion. The obtained results indicate the formation of a transformed “northern” hormone metabolic profile of the body of a modern resident of the North, which should be considered as a certain adaptive response to the modern modification of the socio-economic lifestyle of northern residents (hypodynamia, overeating, etc.).

The Crop Succession Systems Under No-Tillage Alters the Surface Layer Soil Carbon Stock and Stability

The main challenge of the no-tillage system (NTS) is to reconcile productivity, the maintenance of surface residues, and the stabilization of soil organic matter (SOM). To address this challenge, particularly in tropical regions, various cover crops have been tested. The objective of this study was to test the effects of agricultural crop succession systems on the stock and stability of soil organic carbon in different surface layers of the soils. The research was carried out in the state of Goiás, Brazil, in an experiment set up in 2016, designed in randomized blocks with a split-plot scheme (treatments and soil layers), comprising four repetitions (blocks). The treatments (plots) consisted of crops grown in succession to soybean, which were as follows: T1—soybean/corn (Zea mays); T2—soybean/pearl millet (Pennisetum glaucum); T3—soybean/Urochloa ruziziensis (brachiaria); and T4—corn + Urochloa ruziziensis. The subplots represented the following soil layers: 0–5, 5–10, 10–20, and 20–40 cm. We evaluated the biomass dry mass and the soil parameters such as soil density, total porosity, and light organic matter across all layers. The organic carbon, grain size fractionation (mineral-associated organic carbon—MOC; sand-sized carbon—POC), and isotopic composition (δ13C) were determined in the 0–5 and 5–10 cm layers. The highest biomass dry production was observed in the soybean/pearl millet succession, which reduced the soil density and increased the total porosity in the surface layer. The soybean/pearl millet treatment produced high amounts of light organic matter, particularly in the 0–5 cm layer, a result also found for the soybean/brachiaria and soybean/corn + brachiaria systems. The crop successions did not alter the soil carbon stock or stability; however, the surface layer stored the highest amount of carbon, with elevated total organic carbon values and carbon stocks and stability (MOC and POC). Overall, in this study, replacing corn with other crops in succession with soybean did not affect the stock or stability of soil organic carbon. The species grown in succession with soybean contributed to the higher surface carbon stock and stability, promoting the formation of more stable and recalcitrant carbon.

Impacts of mesenchymal stem cells and hyaluronic acid on inflammatory indicators and antioxidant defense in experimental ankle osteoarthritis.

No effective treatment guarantees full recovery from osteoarthritis (OA), and few therapies have disadvantages. To determine if bone marrow mesenchymal stem cells (BMMSCs) and hyaluronic acid (HA) treat ankle OA in Wistar rats. BMMSCs were characterized using flow cytometry with detection of surface markers [cluster of differentiation 90 (CD90), CD105, CD34, and CD45]. Fifty male Wistar rats were divided into five groups of 10 rats each: Group I, saline into the right tibiotarsal joint for 2 days; Group II, monosodium iodate (MIA) into the same joint; Groups III, MIA + BMMSCs; Group IV, MIA + HA; and Group V, MIA + BMMSCs + HA. BMMSCs (1 × 106 cells/rat), HA (75 µg/rat), and BMMSCs (1 × 106 cells/rat) alongside HA (75 µg/rat) were injected intra-articularly into the tibiotarsal joint of the right hind leg at the end of weeks 2, 3, and 4 after the MIA injection. The elevated right hind leg circumference values in the paw and arthritis clinical score of osteoarthritic rats were significantly ameliorated at weeks 4, 5, and 6. Lipid peroxide significantly increased in the serum of osteoarthritic rats, whereas reduced serum glutathione and glutathione transferase levels were decreased. BMMSCs and HA significantly improved OA. The significantly elevated ankle matrix metalloproteinase 13 (MMP-13) mRNA and transforming growth factor beta 1 (TGF-β1) protein expression, and tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17) serum levels in osteoarthritic rats were significantly downregulated by BMMSCs and HA. The effects of BMMSCs and HA on serum TNF-α and IL-17 were more potent than their combination. The lowered serum IL-4 levels in osteoarthritic rats were significantly upregulated by BMMSCs and HA. Additionally, BMMSCs and HA caused a steady decrease in joint injury and cartilage degradation. BMMSCs and/or HA have anti-arthritic effects mediated by antioxidant and anti-inflammatory effects on MIA-induced OA. MMP-13 and TGF-β1 expression improves BMMSCs and/or HA effects on OA in Wistar rats.

Salivary Markers of Oxidative Stress and Their Relation to Periodontal and Dental Status Among Children With Down Syndrome.

The current body of literature on oral health in individuals with Down syndrome (SD) presents contradictory information. Individuals with DS often have distinct oral health difficulties that set them apart from the general population. This study aimed to measure malondialdehyde (MDA) and total oxidant status (TOS) levels in the saliva of children diagnosed with DS and explore their association with oral health status. A cross-sectional study enrolled 82 participants aged 7-12, comprising 40 children with DS and 42 controls matched based on age and gender. Diagnosing dental caries relied on the guidelines provided by the World Health Organization. Oral hygiene was examined with the plaque index, and gingival health was estimated using the gingival index (GI). To evaluate oxidative stress, unstimulated whole saliva samples were gathered to measure levels of MDA and TOS. The study data were analyzed using Statistical Package for the Social Sciences version 22 (IBM Corp., Armonk, NY). The p value for parametric variables was obtained using Pearson's chi-square test and Fisher's exact test. In this study, there were no significant differences between the two groups regarding periodontal health and dental decay. However, children with DS displayed significantly elevated GI values compared to the control group (p = 0.05).Children with DS demonstrated significantly higher MDA levels than the control group (p < 0.001). Furthermore, DS children demonstrated a higher prevalence of dental caries in their primary teeth than their permanent teeth. Children with DS have comparable rates of dental caries to non-DS childrenbut show elevated levels of GI values. Furthermore, children with DS exhibit high levels of saliva MDA compared to their peers without DS. Future research should include a wider age range, additional oxidative stress markers, and factors like diet, lifestyle, and antioxidant supplementation. Longitudinal studies and quality-of-life assessments could offer deeper insights into the oral health of individuals with DS.

Adolescent Blood Pressure and Early Age Stroke.

Underdiagnosis of relevant risk factors has contributed to the increasing stroke incidence in young adults. Blood pressure cut-off values for adolescents are neither sex specific nor based on cardiovascular outcomes. This nationwide, population-based, retrospective cohort study included all Israeli adolescents 16-19 years of age who were medically evaluated before compulsory military service from 1985 to 2013, including routine blood pressure measurements. The primary outcome was the first occurrence of a stroke (ischemic or hemorrhagic) at a young age (≤52 years), as documented in the Israeli National Stroke Registry. Cox proportional hazard models were stratified by sex and adjusted for birth year, sociodemographic variables, and adolescent body mass index. The cohort comprised 1,897,048 adolescents (42.4% women). During 11,355,476 person-years of follow-up, there were 1470 first stroke events at a young age. In men, an adolescent diastolic blood pressure value of ≥80 mmHg, compared with the reference group (diastolic blood pressure value of <70 mmHg), was associated with an increased risk of stroke (adjusted hazard ratio 1.28; 95% confidence interval [CI], 1.04 to 1.58), while a diastolic blood pressure value of 70-79 mmHg was not associated with an increased risk of stroke (adjusted hazard ratio 1.11; 95% CI 0.90 to 1.34). Among women, an adolescent diastolic blood pressure value of ≥80 mmHg, compared with the reference group (diastolic blood pressure value of <70 mmHg) was associated with an increased risk of stroke at a young age (adjusted hazard ratio 1.38; 95% CI 1.03 to 1.88), as was a diastolic blood pressure value of 70-79 mmHg (adjusted hazard ratio 1.41; 95% CI 1.09 to 1.81). Elevated adolescent systolic blood pressure values (≥120 mmHg) were not associated with an increased risk of stroke. Diastolic blood pressure values of ≥80 mmHg in adolescence were associated with an increased risk of stroke at a young age in both men and women. No similar association was observed for elevated systolic blood pressure.