Biological Profile Research Articles

Comparing Nutritional Values and Bioactivity of Kefir from Different Types of Animal Milk.

The growing interest in fermented dairy products is due to their health-promoting properties. The use of milk kefir grains as a starter culture made it possible to obtain a product with a better nutritional and biological profile depending on the type of milk. Cow, buffalo, camel, donkey, goat, and sheep milk kefirs were prepared, and the changes in sugar, protein, and phenol content, fatty acid composition, including conjugated linoleic acids (CLAs), as well as antioxidant activity, determined by ABTS and FRAP assays, were evaluated and compared. The protein content of cow, buffalo, donkey, and sheep milk increased after 24 h of fermentation. The fatty acid profile showed a better concentration of saturated and unsaturated lipids in all fermented milks, except buffalo milk. The highest content of beneficial fatty acids, such as oleic, linoleic, and C18:2 conjugated linoleic acid, was found in the cow and sheep samples. All samples showed a better antioxidant capacity, goat milk having the highest value, with no correlation to the total phenolic content, which was highest in the buffalo sample (260.40 ± 5.50 μg GAE/mL). These findings suggested that microorganisms living symbiotically in kefir grains utilize nutrients from different types of milk with varying efficiency.

Chromatographic descriptors in QSAR examination of the N, N-disubstituted chloroacetamides’ bioactivity

The main goal of this study was the assessment of the N, N-disubstituted-2-chloroacetamides’ biological profile by chromatographic and in silico approach. Preliminary, their drug-like as well as lead-like properties and the bioactivity scores were analyzed. By applying reversed phase thin-layer chromatography as the simulator of compound’s distribution across biological membranes, the assumed bioactivity descriptors of the studied chloroacetamides were obtained. The compliance between obtained chromatographic parameters (R M,0 m) and relevant software lipophilicity/pharmacokinetic/ecotoxicity predictors of studied derivatives were examined by linear regression and additionally supported by more detailed relations established by multivariate methods. Also, it was confirmed that the studied bioactivity properties of the given chloroacetamides are conditioned by the type of the present hydrocarbon substituents (number, arrangement and binding of C atoms).

Deep mapping of the cytokine release syndrome inflammatory continuum: Comprehensive grade-specific profiling and differentiation from sepsis in patients receiving immune checkpoint therapy.

12129 Background: The delineation of cytokine release syndrome (irCRS) from sepsis and its transition to compensatory anti-inflammatory response syndrome (irCARS) is crucial during ICI therapy for personalized care. Methods: We conducted an extensive biological and immune profiling on PBMC and serum from 38 oncology patients with various irCRS grades, including immune-related hemophagocytic lymphohistiocytosis irHLH (n=9) and sepsis during ICI treatment (n=8). Results: Our results show a dominant Th1 response in irCRS. Early markers of irCRS increased progressively with clinical severity in different grades, especially CXCL9, CXCL10 and IFN-γ levels. Starting with low-grade (G) (G1 and 2), a concomitant irCARS response was detected, characterized by an initial increase in IL-1RA and a significant upregulation of IL-10 specifically in G4. 3 subclusters with different overall survival (OS) and cytokine profiles were identified using routine biomarkers. Cluster 1 (C1, n=7) and Cluster 2 (C2, n=17) showed a 2-year OS of 100% and 48.49%, respectively (HR=4.025 [95% CI = 1.052-15.39], p=0.0419) and differed with higher levels of CCL3/11, CXCL10 and Il-1RA. Cluster 3 (C3, n=3) had the lowest OS, 6-month OS of 0%, and a distinct biological profile with highest levels of CXCL8/12/13, IL1-RA, IL-6, IL-21, HGF, significantly different from C1 (HR=111.4 [95% CI=6.63-1871], p=0.0011) and C2 (HR=30.04 [95% CI=2.686-335.9], p=0.0256). In 12 patients with severe irCRS (G3 and 4) and refractory to steroids, treatment with tocilizumab (TCZ) resulted in 100% resolution. In irHLH patients (n=9), the clusters retained their prognostic impact. Similarly, in irHLH with poor prognosis (irHLH cluster 3, n=3), high levels of CXCL8/12/13, IL-6 and IL-21 were identified. 13 patients with sepsis-like symptoms (irHLH, n=8; or sepsis during ICI, n=5) showed distinct cytokine and immune cell profiles. irHLH showed elevated IL-1-RA, IL-10, IL-18, IFN-γ, CXCL9/10, CCL2/3/4 while sepsis was characterized by increased IL-7. In irHLH, higher HLA-DR+/CD38+ populations were seen in T cells, monocytes, DCs and NK cells. There was significant CD62L downregulation in neutrophils during sepsis. Our decision tree using ferritin, EGF, IL-6 and leukocytes effectively discriminated irHLH from sepsis and G3 irCRS. High CXCL-9 levels predicted the diagnosis and severity of irHLH more accurately than the conventional HScore. Conclusions: We've identified a panel of biomarkers associated with OS. CXCL9 emerges as a superior marker, outperforming HScore. The successful treatment with TCZ underscores the importance of targeted interventions. Our decision tree enhances diagnostic accuracy for sepsis-like symptoms, aiding in the differentiation between irCRS, irHLH, and sepsis. This supports the optimal implementation of personalized strategies.

Association between patient tumour characteristics and five-year survival in Nigerian patients with breast cancer.

e13504 Background: Breast cancer is a heterogeneous disease. The sociodemographic features and biological profile of breast cancer differ globally, especially in women of African descent. In Nigeria, limited studies explore the impact of these breast cancer-related factors on survival. This study evaluated the association between patients' tumour characteristics and survival in breast cancer patients in three regional tertiary cancer treatment centres across Nigeria. Methods: Data were extracted from patients' case files with a histopathologic diagnosis of breast cancer from January 1, 2005 - January 1, 2019. Patients' sociodemographic and clinical features were presented, and survival probabilities were reported; the Log-rank test was used to determine the association between time to death and categorical variables. Results: The study included 1020 patients across the three centres. Five-year survival probability was 0.65; 95% C.I: 0.60- 0.69. Most patients were between ages 30 and 49, and 49% presented with left-sided breast cancer. Patients aged>70 had significantly better survival. Only 40% had Immunohistochemistry (IHC) done, out of which HR+ breast cancer accounted for 43% while triple-negative breast cancer was 30%. Patients who received Herceptin and had molecular subtyping (immunohistochemistry) done had a higher survival probability. Conclusions: Most breast cancer patients in Nigeria present at earlier ages with advanced disease. Regardless of patient tumour characteristics, 5-year survival rates are lower than global rates. Only a few patients have access to optimal breast cancer management, molecular subtyping and targeted treatment inclusive. There is an urgent need to fund the National Cancer Control program to aid in implementing its strategic framework for breast cancer screening and management to improve access to cancer care in Nigeria.

Biological alterations associated with the orthodontic treatment with conventional appliances and aligners: A systematic review of clinical and preclinical evidence

Background&objectivesMechanical forces applied during an orthodontic tooth movement (OTM) propel several biochemical and molecular responses in the periodontal ligament and alveolar bone. Here, we compile the existing clinical and preclinical evidence on these biological changes, aiming to provide a comprehensive discussion on the influence of the mechanical parameters of the OTM in the biological profile of the periodontium. Material and methodsThis systematic integrative review was conducted according to PICOS strategy and PRISMA guidelines. A bibliographic search was performed in three electronic databases (PubMed, Scopus, and Web of Science) to find research articles published until 2023 and written in English. This search resulted in a total of 2279 publications, which were independently assessed by two evaluators using appropriate tools. ResultsForty-six studies were selected for this review. These revealed that compression, and stretching of the periodontal ligament fibers and cells are observed in the initial phase of the OTM. Specifically, on the tension side, high levels of IL-1β, OPG, and TIMPs are identified. On the compression side, an increase of RANKL, RANK, and MMPs levels predominate. ConclusionThis paper describes the release profile of common biomarkers according to the orthodontic protocol, suggesting the most appropriate parameters to keep the teeth and their supporting structures healthy. Overall, this manuscript provides a better understanding of the OTM-associated biological phenomena, also highlighting the importance of early evaluation of oral health, and thus it contributes as a fundamental basis for the development of more effective and safe orthodontic treatments with conventional appliances and aligners.

NPYR modulation: Potential for the next major advance in obesity and type 2 diabetes management?

The approval of the glucagon-like peptide 1 (GLP-1) mimetics semaglutide and liraglutide for management of obesity, independent of type 2 diabetes (T2DM), has initiated a resurgence of interest in gut-hormone derived peptide therapies for the management of metabolic diseases, but side-effect profile is a concern for these medicines. However, the recent approval of tirzepatide for obesity and T2DM, a glucose-dependent insulinotropic polypeptide (GIP), GLP-1 receptor co-agonist peptide therapy, may provide a somewhat more tolerable option. Despite this, an increasing number of non-incretin alternative peptides are in development for obesity, and it stands to reason that other hormones will take to the limelight in the coming years, such as peptides from the neuropeptide Y family. This narrative review outlines the therapeutic promise of the neuropeptide Y family of peptides, comprising of the 36 amino acid polypeptides neuropeptide Y (NPY), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP), as well as their derivatives. This family of peptides exerts a number of metabolically relevant effects such as appetite regulation and can influence pancreatic beta-cell survival. Although some of these actions still require full translation to the human setting, potential therapeutic application in obesity and type 2 diabetes is conceivable. However, like GLP-1 and GIP, the endogenous NPY, PYY and PP peptide forms are subject to rapid in vivo degradation and inactivation by the serine peptidase, dipeptidyl-peptidase 4 (DPP-4), and hence require structural modification to prolong circulating half-life. Numerous protective modification strategies are discussed in this regard herein, alongside related impact on biological activity profile and therapeutic promise.

Associations between mosaic loss of sex chromosomes and incident hospitalization for atrial fibrillation in the United Kingdom.

Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear. We estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190,613 men and 224,853 women with genotyping data from the UK Biobank. Among these participants, we analyzed 37,037 men with mLOY and 13,978 women with mLOX detected using Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization (MR) was conducted to estimate causal associations. Among men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR=1.06, 95%CI:1.03-1.11). The associations were apparent in both never-smokers (HR=1.07, 95%:1.01-1.14) and ever-smokers (HR=1.05, 95%CI:1.01-1.11) as well as men > and ≤60 years of age. MR analyses supported causal associations between mLOY and atrial fibrillation (HRMR-PRESSO=1.15, 95%CI:1.13-1.18). Among post-menopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR=0.90, 95%CI:0.83-0.98). However, associations with mLOY and mLOX were not found for other heart diseases. Our findings suggest that mLOY and mLOX reflect sex-specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization.

Biological profile of secondary hyperparathyroidism in chronic renal failure patients

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease, especially in hemodialysis patients. It is characterized by overproduction of parathyroid hormone in response to chronic deterioration of renal function. The aim of this retrospective study was to determine the average time to develop secondary hyperparathyroidism, analyze the initial phosphocalcic profiles, and evaluate the evolution of these profiles in hemodialysis patients, following the recommendations of the KDOQI 2003 and KDIGO 2009 groups. The study included 134 hemodialysis patients from two private dialysis centers. Data were collected from patients' medical records and analyzed using SPSS software. The results showed that the average time to develop secondary hyperparathyroidism was 3.15 years according to KDOQI recommendations and 4.64 years according to KDIGO recommendations based on parathyroid hormone levels. The initial assessment revealed an imbalance in phosphocalcic metabolism in approximately 20.1% to 22.5% of patients, a proportion that increased to 27.5% during follow-up, according to both sets of recommendations. In conclusion, secondary hyperparathyroidism is an inevitable complication of chronic kidney disease, affecting the vital and functional prognosis of hemodialysis patients. Diagnosis primarily relies on parathyroid hormone levels, associated with phosphocalcemia, vitamin D, and PAL analyses. Treatment aims mainly to maintain blood levels of calcium, phosphorus, and vitamin D within recommended limits and to reduce parathyroid response to phosphocalcic disturbances.

Epidemiological, clinical and biological profile of COVID-19 in patients hospitalized at the Avicenne Military Hospital in Marrakech

In late December 2019, a series of cases of viral pneumonia caused by a novel coronavirus emerged in Wuhan, China, and quickly spread to all continents. This coronavirus, identified in respiratory tract samples, was named SARS-CoV-2 for Severe Acute Respiratory Syndrome Coronavirus-2 by the ICTV (International Committee on Taxonomy of Viruses). The disease it causes was designated COVID-19 for Coronavirus Disease 2019 by the Word Health Organization. Most often, SARS-CoV-2 infection is responsible for a mild or moderate form, with the most typical clinical presentation being that of a febrile respiratory infection with dry cough, dyspnea, fatigue, and myalgia. Approximately 10-15% of cases are severe, and 5% are critical. Cases of reinfection have been described. Treatment for COVID-19 is currently symptomatic, relying on supportive care. The present study aims to investigate the demographic, clinical, and diagnostic aspects, as well as the study of risk factors associated with SARS-CoV-2 infection among 318 patients admitted to the Avicenne Military Hospital in Marrakech during the first wave of the pandemic. This is a retrospective descriptive and analytical study involving 318 cases of SARS-CoV-2 infection, diagnosed at the microbiology-virology department, and followed up in various non-intensive care units of the Avicenna Military Hospital in Marrakech, during the period of the first wave of the epidemic in Morocco, schematically between March 22, 2020, and July 19, 2020. For patients who developed pneumonia, 20% were diabetic and 13.3% were hypertensive. A quarter of patients with pneumonia experienced desaturation upon admission. In the multivariate logistic regression model, risk factors associated with the development of pneumonia and the various disease outcomes included advanced age and absence of a history of contact with a confirmed case. In the univariate analysis, hyperleukocytosis, neutrophilia, lymphopenia, eosinopenia, anaemia, hyperferritinaemia with elevated aspartate aminotransferase, hyponatraemia and fasting hyperglycaemia were significantly associated with a higher risk of an unfavourable outcome. Patients who presented with pneumonia on admission had an unfavourable outcome during their hospitalisation compared with patients who did not develop pneumonia. The statistically significant risk factors associated with an unfavourable outcome were advanced age (>60 years) with p <0. 001: OR=1.194; 95%IC= [1.114-1.278], absence of contact with a confirmed case (p <0.001 : OR= 43.138; 95%IC= [8.893-209.263]), presence of comorbidity (P<0.001 : OR=11. 503; 95%CI= [3,306-40,028]), mainly diabetes (P<0.001: OR=16,971; 95%CI= [4,267-67,504]) and arterial hypertension (P<0.001: OR=18,812; 95%CI= [3,977-88,954]). The study of the epidemiological, clinical and biological characteristics of COVID 19 at the Avicenne military hospital in Marrakech has enabled us to gain a better understanding of the profile of our patients with SARS-CoV-2 infection, and then to detect shortcomings in terms of prophylaxis, diagnosis and management, in order to be able to provide the necessary solutions aimed at further improving the quality of care for this population.

Spindle architecture constrains karyotype in budding yeast.

The eukaryotic cell division machinery must rapidly and reproducibly duplicate and partition the cell's chromosomes in a carefully coordinated process. However, chromosome number varies dramatically between genomes, even on short evolutionary timescales. We sought to understand how the mitotic machinery senses and responds to karyotypic changes by using a series of budding yeast strains in which the native chromosomes have been successively fused. Using a combination of cell biological profiling, genetic engineering, and experimental evolution, we show that chromosome fusions are well tolerated up until a critical point. Cells with fewer than five centromeres lack the necessary number of kinetochore-microtubule attachments needed to counter outward forces in the metaphase spindle, triggering the spindle assembly checkpoint and prolonging metaphase. Our findings demonstrate that spindle architecture is a constraining factor for karyotype evolution.

The oncologic burden of residual disease in incidental gallbladder cancer: An elastic net regression model to profile high-risk features

IntroductionIncidental Gallbladder Cancer (IGBC) following cholecystectomy constitutes a significant portion of gallbladder cancer diagnoses. Re-exploration is advocated to optimize disease clearance and enhance survival rates. The consistent association of residual disease (RD) with inferior oncologic outcomes prompts a critical examination of re-resection's role as a modifying factor in the natural history of IGBC. MethodsAll patients diagnosed with gallbladder cancer between 2012 and 2022 were included. An elastic net regularized regression model was employed to profile high-risk predictors of RD within the IGBC group. Survival outcomes were assessed based on resection margins and RD. ResultsAmong the 181 patients undergoing re-exploration for IGBC, 133 (73.5 %) harbored RD, while 48 (26.5 %) showed no evidence. The elastic net model, utilizing a selected λ = 0.029, identified six coefficients associated with the risk of RD: aspiration from cholecystectomy (0.141), hepatic tumor origin (1.852), time to re-exploration >8 weeks (1.879), positive margin status (2.575), higher T stage (1.473), and poorly differentiated tumors (2.241). Furthermore, the study revealed a median overall survival of 44 months (CI 38–60) for IGBC patients with no evidence of RD, compared to 31 months (23–42) for those with RD (p < 0.001). ConclusionRe-resection revealed a high incidence of RD (73.5 %), significantly correlating with poorer survival outcomes. The preoperative identification of high-risk features provides a reliable biological disease profile. This aids in strategic preselection of patients who may benefit from re-resection, underscoring the need to consolidate outcomes with tailored chemotherapy for those with unfavorable characteristics.

#1096 Improving the diagnostic accuracy of absorptive hypercalciuria: a comparative analysis of calcium load tests at 2-hour and 4-hour intervals

Abstract Background and Aims A calcium load test (CLT) has been developed by Pak et al in 1974 to better discriminate absorptive, resorptive and renal hypercalciuria, leading to a tailored treatment approaches for patients. Originally, Calcium load was a 4-hours (4 h) test with a timepoint at 2-hours (2 h) defining an absorptive hypercalciuria (AH) by an increase of the difference between urinary calcium on creatininuria ratio (ΔUCa/Cr) of more than 0.5 mmol/mmol. In clinical practice and in more recent studies, CLT is only a 2 h test using this 0.5 or sometime 0.6 mmol/mmol cut-off. We hypothesized that a 2-hours timepoint is not sufficient to diagnose all AH and that the 4-hours timepoint as initially described is more efficient to improve accuracy of AH diagnosis. Method We report a single-centre, retrospective study including all patients who underwent CLT between January 2015 and September 2020. These tests were carried out in patients with hypercalciuria or in patients with elevated parathyroid hormone (PTH, standard 15-65 ng/L, Elecsys PTH) with normocalcemia, with or without kidney stones history. After a low-calcium diet for 3 days and a 12-hours fast, 24-hours urine were collected and blood and urinary samples were done at arrival. Two hours and 4 h after ingestion of one gram of calcium per os, blood and urinary samples were collected. AH was diagnosed by a ΔUCa/Cr at baseline and 2 h or 4 h timepoints of more than 0.5 mmol/mmol. We compared the number of AH diagnosed after 2 h and 4 h of testing using a 0.5 mmol/mmol delta at each timepoint. We also analysed clinical and biological profile of early and late AH. Results A total of 328 patients were included, 48 ± 14.8 years old, mean glomerular filtration rate of 92.8 ± 22.1 mL/min/1.73 m², 52.8% of women. At baseline, ionized calcemia (iCa2+) was 1.2 ± 0.1 mmol/L with a significant increase at 2 h (1.3 ± 0.1 mmol/L, p &amp;lt; 0.001) and a stabilisation at 4 h (1.3 ± 0.1 mmol/L, p = ns). Simultaneously, PTH showed a significant drop between baseline and 2-hours (60 ± 26.1 ng/L versus 35.3 ± 19.7 ng/L, p &amp;lt; 0.001) follows by a significant increase between 2 and 4 h (35.3 ± 19.7 ng/L versus 39.5 ± 21.4 ng/L, p &amp;lt; 0.01). Mean 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D3 were respectively 67.4 ± 24.7 ng/mL and 154.6 ± 54pg/mL. Baseline UCa/Cr ratio was 0.3 ± 0.2 mmol/mmol and increased significantly after 2 h (0.6 ± 0.3 mmol/mmol, p &amp;lt; 0.001) and 4 h (0.8 ± 0.4 mmol/mmol, p &amp;lt; 0.001) (Fig. 1a). ΔUCa/Cr was significantly different between baseline and 2 h and between baseline and 4 h (0.2 ± 0.2 versus 0.5 ± 0.4, p &amp;lt; 0.001) (Fig. 1b). AH was diagnosed in 35 (10.7%) patients after 2 h, 84 (25.6%) more were diagnosed at 4 h (p &amp;lt; 0.001) for a total of 119 (36.3%) AH diagnosed. Between early and late AH, we found no significant differences in 1,25-Dihydroxyvitamin D3, phosphatemia or phosphaturia, but 25-Hydroxyvitamin D which (67.3 ± 21 ng/mL in late AH versus 59.2 ± 18.3 ng/mL, p = 0.039). In comparison to the rest of the cohort, AH have a higher 1,25-Dihydroxyvitamin D3 level, a lower PTH at 2 h and 4 h, a lower phosphaturia at 2 h and 4 h and a higher magnesiuria at 4 h. Conclusion This study shows that performing the 4 h CLT improves the diagnosis of AH with more than fifty percent of AH diagnosed within 4 h of calcium ingestion. It seems that there are AH of later diagnosis with a similar clinical and biological profile depending of enteral absorption.

#2099 Long term outcomes in chronic kidney disease patients with heart failure with preserved ejection fraction

Abstract Background and Aims Heart failure (HF) is frequent in chronic kidney disease (CKD) and leads to high morbidity and mortality in this patient category. The aim of our study is to assess the clinical and biological profile, and outcomes in CKD patients with preserved left ventricular ejection fraction (LVEF). Method We prospectively enrolled CKD patients (pts) in pre-dialysis, stratified in two groups by the presence of heart failure symptoms: pts with NYHA class 1-2 (asymptomatic HF) versus pts with NYHA class 3-4 (symptomatic HF). Demographics, clinical history, co-morbidities, physical exam, ambulatory blood pressure monitoring, extensive blood chemistry, systemic inflammation and mineral bone disease parameters were recorded. Cardiac structure and systolic and diastolic function were assessed by echocardiography. Carotid Doppler ultrasound assessed intima media thickness (IMT). Al patients were followed until death of loss from records; patients with less than 6 months of surveillance were excluded. Primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality, a composite cardiac endpoint composite cardiac endpoint comprising coronary heart disease, heart failure hospitalization and new-onset arrhythmia, and reaching the end stage of renal disease (ESRD). Results We included 76 CKD patients (2 pts CKD stage 1, 9 pts CKD stage 2, 19 pts CKD stage 3a, 28 pts CKD stage 3b, 18 pts CKD stage 4) with LVEF ≥ 50%. Mean age 64.7 ± 11.4 years (yrs), men = 56 (73.7%). Mean follow up period was 86 ± 46.4 months (range 6-156 months). Patients with symptomatic HF (54 pts, 71.1%) were older (68 ± 9 vs 56 ± 12 yrs), hypertensive (98.1% vs 86.4%, p &amp;lt; 0.05), more frequent coronary artery disease (66.7% vs 27.3%, p &amp;lt; 0.05), had worse baseline biological profile: lower eGFR (36.9 ± 12.9 vs 55.5 ± 22.7 ml/min/1.73 m2, p &amp;lt; 0.05), lower serum albumin (4.1 ± 0.5 vs 4.4 ± 0.4 g/dl, p &amp;lt; 0.05), as well as higher levels of osteoprotegerin and fetuin A (p &amp;lt; 0.05). Also, symptomatic HF pts had more severe endothelial disease (higher IMT 0.81 ± 0.14 vs 0.63 ± 0.11 mm, p &amp;lt; 0.05), more severe subclinical LV dysfunction revealed by less negative global longitudinal strain GLS (−16.7 ± 2.66 vs −19.2 ± 2.95, p &amp;lt; 0.05) and higher ratio of mitral velocity to early diastolic velocity of the mitral annulus E/E` (12.64 ± 3.63 vs 9.68 ± 2.73, p &amp;lt; 0.05), as well as higher LV mass index (121.5 ± 31 vs 104.9 ± 22.7 g/m2, p &amp;lt; 0.05) and higher left atrial volume index LAVI (42.8 ± 16.8 vs 31.8 ± 11.3 ml/m2, p &amp;lt; 0.05) All-cause mortality was 17.1% (13 events), while cardiovascular mortality was 6.6% (5 events). All deaths were recorded in the symptomatic HF group. Also, a higher percent of pts from symptomatic HF group reached the composite cardiac endpoint (44.4% vs 22.7%) and ESRD (33.3% vs 18.2%) compared to asymptomatic HF group. Kaplan-Meier survival analysis showed significantly higher all-cause mortality (log rang = 0.008) and lower ESRD-free survival (log rank= 0.045) in symptomatic HF group. All-cause mortality was significantly correlated with NYHA class (p &amp;lt; 0.0001), etiology of CKD (p = 0.038), eGFR (p &amp;lt; 0.0001), proteinuria (p = 0.001), intact PTH (p = 0.008), osteocalcin (p = 0.012), osteopontin (p = 0.029), FGF23 (p = 0.044), IL6 (p = 0.037), GLS (p = 0.023), E/E` (p = 0.009). Cardiovascular mortality was significantly correlated with NYHA class (p = 0.019), etiology of CKD (p = 0.008), eGFR (p = 0.011), proteinuria (p = 0.001), intact PTH (p = 0.008), osteocalcin (p = 0.011), osteopontin (p = 0.006), FGF23 (p = 0.006). Cox regression analysis identified NYHA class (p = 0.004), FGF23 (p = 0.009) and IL6 (p = 0.025) as predictors for all-cause mortality, while E/E` (p = 0.032) and intact PTH (p-0.042) were predictors for cardiovascular mortality. Conclusion In our study, CKD pts with symptomatic HF carry a significant burden of morbidity and mortality, even in the case of preserved LV ejection fraction. This emphasizes the need for more comprehensive regular assessments of subclinical cardiac dysfunction in CKD pts. This approach might support targeted interventions, better symptom control, and improved long term outcomes.

2023 Society for Academic Emergency Medicine Consensus Conference on Precision Emergency Medicine: Development of a policy-relevant, patient-centered research agenda.

Precision medicine is data-driven health care tailored to individual patients based on their unique attributes, including biologic profiles, disease expressions, local environments, and socioeconomic conditions. Emergency medicine (EM) has been peripheral to the precision medicine discourse, lacking both a unified definition of precision medicine and a clear research agenda. We convened a national consensus conference to build a shared mental model and develop a research agenda for precision EM. We held a conference to (1) define precision EM, (2) develop an evidence-based research agenda, and (3) identify educational gaps for current and future EM clinicians. Nine preconference workgroups (biomedical ethics, data science, health professions education, health care delivery and access, informatics, omics, population health, sex and gender, and technology and digital tools), comprising 84 individuals, garnered expert opinion, reviewed relevant literature, engaged with patients, and developed key research questions. During the conference, each workgroup shared how they defined precision EM within their domain, presented relevant conceptual frameworks, and engaged a broad set of stakeholders to refine precision EM research questions using a multistage consensus-building process. A total of 217 individuals participated in this initiative, of whom 115 were conference-day attendees. Consensus-building activities yielded a definition of precision EM and key research questions that comprised a new 10-year precision EM research agenda. The consensus process revealed three themes: (1) preeminence of data, (2) interconnectedness of research questions across domains, and (3) promises and pitfalls of advances in health technology and data science/artificial intelligence. The Health Professions Education Workgroup identified educational gaps in precision EM and discussed a training roadmap for the specialty. A research agenda for precision EM, developed with extensive stakeholder input, recognizes the potential and challenges of precision EM. Comprehensive clinician training in this field is essential to advance EM in this domain.

Optimizing nutritional value and biological profile of non-conventional forages for animal feeding by utilizing sodium hydroxide

Increasing quality and decreasing quantity represent global trends in the forage processing for animal feed. Consequently, various techniques are applied to achieve these objectives. This study aims to evaluate the internal quality and biological attributes of leaves in animal reproduction by applying sodium hydroxide (NaOH) concentrations (control, 2, 4, 6, and 8%) and utilizing leaves from four non-conventional plants, namely Hedychium gardnerianum (HG), Pittosporum undulatum (PU), Arundo donax (AD), and Acacia melanoxylon (AM), while also examining their interactions simultaneously. NaOH doses did not affect the organic matter digestibility. A 2% NaOH concentration positively affected both acid detergent fibre and neutral detergent fibre. Notably, 6% NaOH significantly impacted dry matter, while ash content and dry matter digestibility peaked under treatment with 8% NaOH. The Arundo donax variety recorded the best values in ash and organic matter digestibility, while the leaves of Acacia melanoxylon significantly (P ≤ 0.05) influenced dry matter, acid detergent fibre, acid detergent lignin, and crude protein. The co-application of 2% NaOH with plant varieties demonstrated the most significant effectiveness on the observed characteristics, followed by 4% NaOH showing a subsequent impact. The findings of this study propose that utilizing NaOH concentrations with these plants represents a promising approach for including these forages in animal feeds.

Investigating neonatal health risk variables through cell-type specific methylome-wide association studies

Adverse neonatal outcomes are a prevailing risk factor for both short- and long-term mortality and morbidity in infants. Given the importance of these outcomes, refining their assessment is paramount for improving prevention and care. Here we aim to enhance the assessment of these often correlated and multifaceted neonatal outcomes. To achieve this, we employ factor analysis to identify common and unique effects and further confirm these effects using criterion-related validity testing. This validation leverages methylome-wide profiles from neonatal blood. Specifically, we investigate nine neonatal health risk variables, including gestational age, Apgar score, three indicators of body size, jaundice, birth diagnosis, maternal preeclampsia, and maternal age. The methylomic profiles used for this research capture data from nearly all 28 million methylation sites in human blood, derived from the blood spot collected from 333 neonates, within 72 h post-birth. Our factor analysis revealed two common factors, size factor, that captured the shared effects of weight, head size, height, and gestational age and disease factor capturing the orthogonal shared effects of gestational age, combined with jaundice and birth diagnosis. To minimize false positives in the validation studies, validation was limited to variables with significant cumulative association as estimated through an in-sample replication procedure. This screening resulted in that the two common factors and the unique effects for gestational age, jaundice and Apgar were further investigated with full-scale cell-type specific methylome-wide association analyses. Highly significant, cell-type specific, associations were detected for both common effect factors and for Apgar. Gene Ontology analyses revealed multiple significant biologically relevant terms for the five fully investigated neonatal health risk variables. Given the established links between adverse neonatal outcomes and both immediate and long-term health, the distinct factor effects (representing the common and unique effects of the risk variables) and their biological profiles confirmed in our work, suggest their potential role as clinical biomarkers for assessing health risks and enhancing personalized care.

Synthesis of Fluorinated Nucleosides/Nucleotides and Their Antiviral Properties.

The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.

Sex Estimation With Three-Dimensional Analysis of the Maxillary Sinus From Computed Tomography Images.

Sex estimation from human skeletal relics is essential in creating an individual's biological profile. This study was performed to examine whether the dimensions and volume of the maxillary sinus can be used to estimate sex. The maxillary sinus's volume, length, width, and height were obtained on the paranasal computed tomography images of 232 adult subjects (116 males and 116 females). All parameters were significantly higher in males except for the right maxillary sinus length (P < 0.05). The highest precision for sex determination was the right maxillary sinus volume (68.1%). The ability of the maxillary sinus parameters to define sex was 78.6% for males and 58.6% for females. The precision of sex estimation of the maxillary sinus parameters was 68.2%. The volume and dimensions of the maxillary sinus can be useful for sex estimation in forensic sciences with a relatively close accuracy rate to reference value (close to 70%). The volume and dimensions of the maxillary sinus can be used for sex estimation together with other bony structures in the skull in cases where the entire skeleton is not available.

Naphthyl‐Based Chalcone Derivatives: A Multifaceted Player in Medicinal Chemistry

AbstractResearch has placed a great deal of emphasis on molecule development and discovery with substantial biological profiling in recent years. Despite the significant side effects, medicinal chemists have long strived to synthesize drug molecules with the highest level of therapeutic activity and the lowest possible level of toxicity. The naphthyl‐based chalcone derivatives have drawn attention due to their simple structures and wide range of pharmacological effects. The main focus of this review is to outline the biologically active molecules based on naphthyl moiety‐substituted chalcone derivatives developed over the years. A synopsis of pharmacological screening, including relevant structure‐activity relationships, action mechanisms, and possible therapeutic applications, is provided in this article. It is true that prospective hybrids combining the naphthyl moiety with different chalcone pharmacophores are needed to address drug resistance and improve specificity. Therefore, this review may be useful in the development and design of new, highly successful therapeutic drugs based on previously reported methodologies.

Comparative Study of Sex Estimation by Mesiodistal width of Mandibular Canine and Mesiodistal width of Maxillary Canine in North Indian Population

Abbreviations: MD: Mesiodistal, SD: Standard deviation, mm: millimetres. Introduction: Various methods of identification such as anthropometry, stature estimation, dactylography, sex estimation, age estimation, DNA analysis, differentiation by blood groups and odontology are used in forensic medicine to create biological profile of an unknown individual. Estimation of sex is the first step towards identification of person. Determination of sex from skeletal remains is an essential task in medicolegal examination.Teeth are highly indestructible and reveal minimal turnover of natural substance hence teeth can be used for sex estimation. Mesiodistal parameter of mandibular and maxillary canine gave evidence of sex estimation due to sexual dimorphism. Aim: The aim of our study was to evaluate the sex estimation by mesiodistal width of mandibular canine and mesiodistal width of maxillary canine in north Indian population. Materials and Methods: The sample comprised of dental impression from 120 individuals (60 males and 60 females), all young adults between 20 and 35 years of age. Impressions of the teeth were made using irreversible hydrocolloid (alginate) material and casts poured in dental stone. Mesiodistal (MD) dimensions of mandibular and maxillary canine of both right and left side is measure by caliper. Results: Mean mandibular canine width of both right and left sidewere higher in male than female and were statistically significant whereas, mean maxillary canine width of both right and left side were slightly higher in male than female but were not statistically significant in young north Indian population. Left mandibular canine width (6%) was more sexually dimorphic than right mandibular canine width (5.1%). Whereas negligible sexual dimorphism shown by maxillary canine. Conclusion: The study confirmed that among maxillary and mandibular canine, mandibular canine can be used for sex estimation and shows significant sexual dimorphism.