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Some gene polymorphisms can lead to monogenic diseases, whereas other polymorphisms may confer beneficial traits. A well-characterized example is congenital erythrocytosis-the non-pathogenic hyper-production of red blood cells-that is caused by a truncated erythropoietin receptor. Here we show that Cas9-mediated genome editing in CD34+ human haematopoietic stem and progenitor cells (HSPCs) can recreate the truncated form of the erythropoietin receptor, leading to substantial increases in erythropoietic output. We also show that combining the expression of the cDNA of a truncated erythropoietin receptor with a previously reported genome-editing strategy to fully replace the HBA1 gene with an HBB transgene in HSPCs (to restore normal haemoglobin production in cells with a β-thalassaemia phenotype) gives the edited HSPCs and the healthy red blood cell phenotype a proliferative advantage. Combining knowledge of human genetics with precise genome editing to insert natural human variants into therapeutic cells may facilitate safer and more effective genome-editing therapies for patients with genetic diseases.

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).

The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (∼E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo. Guided by the arterial origins of blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic progenitors within 10 days. hPSC-derived hematopoietic progenitors generate T, B, NK, erythroid, and myeloid cells in vitro and, critically, express hallmark HSC transcription factors HLF and HOXA5-HOXA10, which were previously challenging to upregulate. We differentiated hPSCs into highly enriched HLF+ HOXA+ hematopoietic progenitors with near-stoichiometric efficiency by blocking formation of unwanted lineages at each differentiation step. hPSC-derived HLF+ HOXA+ hematopoietic progenitors could avail both basic research and cellular therapies.

Treatment of youth concussion during the acute phase continues to evolve, and this has led to the emergence of guidelines to direct care. While symptoms after concussion typically resolve in 14-28 days, a portion (∼20%) of adolescents endorse persistent post-concussive symptoms (PPCS) beyond normal resolution. This report outlines a study implemented in response to the National Institute of Neurological Diseases and Stroke call for the development and initial clinical validation of objective biological measures to predict risk of PPCS in adolescents. We describe our plans for recruitment of a Development cohort of 11- to 17-year-old youth with concussion, and collection of autonomic, neurocognitive, biofluid, and imaging biomarkers. The most promising of these measures will then be validated in a separate Validation cohort of youth with concussion, and a final, clinically useful algorithm will be developed and disseminated. Upon completion of this study, we will have generated a battery of measures predictive of high risk for PPCS, which will allow for identification and testing of interventions to prevent PPCS in the most high-risk youth.

Platelets are the terminal progeny of megakaryocytes, primarily produced in the bone marrow, and play critical roles in blood homeostasis, clotting, and wound healing. Traditionally, megakaryocytes and platelets are thought to arise from multipotent hematopoietic stem cells (HSCs) via multiple discrete progenitor populations with successive, lineage-restricting differentiation steps. However, this view has recently been challenged by studies suggesting that (1) some HSC clones are biased and/or restricted to the platelet lineage, (2) not all platelet generation follows the "canonical" megakaryocytic differentiation path of hematopoiesis, and (3) platelet output is the default program of steady-state hematopoiesis. Here, we specifically investigate the evidence that in vivo lineage tracing studies provide for the route(s) of platelet generation and investigate the involvement of various intermediate progenitor cell populations. We further identify the challenges that need to be overcome that are required to determine the presence, role, and kinetics of these possible alternate pathways.

Background: Physiological and psychosocial changes experienced by women during the perinatal period may put them at risk for postpartum mental health disturbances. Accumulating evidence suggests that dietary patterns may influence mental health through the modulation of the gut microbiota and its effects on host immune activity. Thus, targeting the gut microbiota via dietary intake could serve as both a preventative and therapeutic strategy in improving perinatal mental health. Objectives: Here, we present a protocol for a prospective cohort study that primarily aims to determine if diet quality during pregnancy is protective against postpartum depression severity. Secondary objectives will examine if microbiota- and blood-based inflammatory markers may be associated with the relationship between prenatal diet quality and postpartum depression severity, as well as with associations between additional dietary and mental health outcomes. Methods and Analysis: Dietary patterns and mental health symptoms will be documented in 100 pregnant women at 4 time points during pregnancy and postpartum. Participants will also provide stool and blood samples at the same time points to determine microbiota composition and predicted function and inflammatory factors, respectively. Stool microbiota will be analyzed using 16S ribosomal RNA gene sequencing and bioinformatics tools (QIIME 2/PICRUSt2). Inflammatory factors will be determined using high-sensitivity antibody-based immunoassays. Statistical analyses will include linear mixed models and hierarchical linear mixed effect models. Ethics: The study was approved by the Research Ethics Boards of the Royal Ottawa Health Care Group (#2022002) and of the University of Ottawa (#H-06-22-8013). Informed consent will be obtained from all participants before their enrollment. Discussion: Findings from this study will help develop evidence-based dietary recommendations and potential interventions for women susceptible to or suffering from postpartum mental health issues that are accessible, noninvasive, and have potential to play a role in prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: Prematurity-related brain injury is a common and serious complication that has long-term effects on the survival and development of affected infants. Currently, the roles of certain biomarkers such as the protein hydrolysis product SBDP145, melatonin, soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), high mobility group box 1 protein (HMGB1), and hypoxia-inducible factor 1-alpha (HIF-1α) in prematurity-related brain injury remain not fully elucidated. Our study aims to assess the significance of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in preterm infants with brain injury. Methods: 135 preterm infants admitted to our hospital from January 2020 to February 2022 were selected and divided into 78 cases in a prematurity-associated brain injury group, and 57 cases in another group of preterm infants without brain injury or other diseases according to the magnetic resonance imaging results. The levels of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in the two groups were analyzed. The serum concentrations of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in newborns with different severity of ventricular hemorrhage were observed, and the levels of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in those with different severity of white matter brain injury were compared. Results: The levels of SBDP145, sLOX-1, HMGB1 and HIF-1α were significantly higher in the preterm combined brain injury group than in the preterm group, and melatonin levels were significantly lower than in the preterm group(P < 0.05). The levels of SBDP145, sLOX-1, HMGB1 and HIF-1α were higher in the moderate to severe group and melatonin levels were lower in the mild group of newborns with ventricular hemorrhage (P < 0.05). The levels of SBDP145, sLOX-1, HMGB1 and HIF-1α were higher in the moderate-severe group and melatonin levels were lower in the mild group in newborns with cerebral white matter injury (P < 0.05). The independent variables were SBDP145, melatonin, sLOX-1, HMGB1, HIF-1α, and the dependent variable was the prognosis of neonates with brain injury. Univariate logistic regression analysis and multivariate logistic regression analysis were performed. The results showed that the influencing factors of newborns with brain injury were SBDP145, melatonin, sLOX-1, HMGB1, HIF-1α. Conclusion: The levels of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α were highly expressed in preterm newborns with brain injury, and the levels were higher when the condition of the newborns was more severe. These findings suggest the potential clinical utility of these biomarkers in predicting and monitoring brain injury in preterm infants, which could aid in early intervention and improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: The triglyceride-glucose (TyG) index is recognized as a robust indicator for evaluating insulin resistance (IR). Despite the well-documented anti-aging biological functions of Klotho protein, its correlation with the TyG index remains unexplored. Methods: A cross-sectional analysis was conducted involving participants from the National Health and Nutrition Examination Surveys (NHANES) 2007–2016. The TyG index was computed using laboratory data, while serum Klotho concentrations was determined using ELISA kit. After adjusting potential confounding variables, multivariate regression models were employed to evaluate the association between the TyG index and Klotho protein levels among middle-aged and elderly females and males separately. Additionally, smooth curve fitting and segmented regression model were applied to investigate potential threshold effects and identify the inflection point. Results: A total of 6,573 adults qualified for inclusion, comprising 3,147 (47.88%) males and 3,426 (52.12%) females. Multivariate regression analysis revealed that females with a higher TyG index exhibited significantly lower serum Klotho concentrations (β=-83.41, 95% CI: -124.23 to -42.60, P < 0.0001). This association was not statistically significant in males (β = 15.40, 95% CI: -19.16 to 49.95, P = 0.3827). Subgroup analyses revealed a significant interaction effect by diabetes status in females (P-interaction = 0.0121), where non-diabetic females showed a stronger negative association between TyG index and serum Klotho levels compared to diabetic females. In the female group, when TyG index was divided into quartiles, individuals in the highest quartile of TyG index exhibited reduced levels of Klotho protein (Q4: -88.77 pg/ml) compared to those in the lowest quartile (Q1) after full adjustment (P = 0.0041). Segmented regression analysis indicated a turning point value of 9.4 in females. Notably, a 1-unit increase in TyG index was significantly associated with a decrease in Klotho levels by -111.43 pg/ml (95% CI: -157.34 to -65.52, P < 0.0001) when TyG index was below 9.4, while above this threshold, the association was not significant (Log likelihood ratio test: 0.009). Conclusions: The findings highlight a non-linear correlation between the TyG index and serum Klotho concentrations among females, indicative of a saturation effect. This relationship was particularly pronounced in non-diabetic women. In contrast, no statistically significant association was observed in male participants. [ABSTRACT FROM AUTHOR]

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase mainly found in the focal adhesion regions of the plasma membrane and it has a crucial role in migration and the remodeling of cellular morphology. FAK is also linked to several aspects of cancer biology, from cytokine production to angiogenesis, drug resistance, invasion, and metastasis, as well as epithelial-to-mesenchymal transition. The gene locus of FAK is frequently amplified in several human tumors, thus causing FAK overexpression in several cancers. Furthermore, FAK can influence extracellular matrix production and exosome secretion through cancer-associated fibroblasts, thus it has an important role in tumor microenvironment regulation. Although the role of FAK in solid tumors is well known, its importance in onco-hematological diseases remains poorly explored. This review collects studies related to FAK significance in onco-hematological diseases and their microenvironments. Overall, the importance of FAK in blood tumors is increasingly evident, but further research is required to confirm it as a new therapeutic target in hematological contexts. [ABSTRACT FROM AUTHOR]

Background: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. Methods: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. Results: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). Conclusion: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring. [ABSTRACT FROM AUTHOR]

Background: The burgeoning field of regenerative medicine has significantly advanced with recent findings on biotherapies using human platelet lysates (HPLs), derived from clinical-grade platelet concentrates (PCs), for treating brain disorders. These developments have opened new translational research avenues to explore the neuroprotective effects of platelet-extracellular vesicles (PEVs). Their potential in managing neurodegenerative conditions like traumatic brain injury (TBI) and Parkinson's disease (PD) warrants further exploration. We aimed here to characterize the composition of a PEV preparation isolated from platelet concentrate (PC) supernatant, and determine its neuroprotective potential and neurorestorative effects in cellular and animal models of TBI and PD. Methods: We isolated PEVs from the supernatant of clinical-grade PC collected from healthy blood donors utilizing high-speed centrifugation. PEVs were characterized by biophysical, biochemical, microscopic, and LC–MS/MS proteomics methods to unveil biological functions. Their functionality was assessed in vitro using SH-SY5Y neuronal cells, LUHMES dopaminergic neurons, and BV-2 microglial cells, and in vivo by intranasal administration in a controlled cortical impact (CCI)-TBI model using 8-weeks-old male C57/BL6 mice, and in a PD model induced by MPTP in 5-month-old male C57/BL6 mice. Results: PEVs varied in size from 50 to 350 nm, predominantly around 200 nm, with concentrations ranging between 1010 and 1011/mL. They expressed specific platelet membrane markers, exhibited a lipid bilayer by cryo-electron microscopy and, importantly, showed low expression of pro-coagulant phosphatidylserine. LC–MS/MS indicated a rich composition of trophic factors, including neurotrophins, anti-inflammatory agents, neurotransmitters, and antioxidants, unveiling their multifaceted biological functions. PEVs aided in the restoration of neuronal functions in SH-SY5Y cells and demonstrated remarkable neuroprotective capabilities against erastin-induced ferroptosis in dopaminergic neurons. In microglial cells, they promoted anti-inflammatory responses, particularly under inflammatory conditions. In vivo, intranasally delivered PEVs showed strong anti-inflammatory effects in a TBI mouse model and conserved tyrosine hydroxylase expression of dopaminergic neurons of the substantia nigra in a PD model, leading to improved motor function. Conclusions: The potential of PEV-based therapies in neuroprotection opens new therapeutic avenues for neurodegenerative disorders. The study advocates for clinical trials to establish the efficacy of PEV-based biotherapies in neuroregenerative medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cachexia is a complex metabolic condition that is often overlooked and recognized in a late irreversible phase. There is a continuing effort to discover and define a biochemical biomarker of the condition. In this study, we have chosen interleukin-13 (IL-13) and transforming growth factor beta (TGF-β), i.e., two cytokines with presumed roles in the development of cancer cachexia, and we measured their concentrations in the serum and saliva of cachectic patients with metastatic solid tumors, non-cachectic patients with metastatic solid tumors, and healthy individuals. We have demonstrated the role of saliva cytokine measurement as a potential sample for cachexia investigations as opposed to the standard approach to biomarker research, which is serum measurement. We have also found that the salivary IL-13 and TGF-ß are independent risk factors and thus could serve as potential biomarkers of the condition, a fact that warrants further research and confirmation. Cancer cachexia is a syndrome characterized by weight and muscle loss and functional impairment, strongly influencing survival in cancer patients. In this study, we aimed to establish the role of saliva cytokine measurement in cancer cachexia investigation and define two potential independent salivary biomarkers of the condition. Methods: serum and saliva specimens were obtained from 78 patients. Forty-six patients were non-cachectic, and 32 patients were cachectic (per SCRINIO group criteria), all with metastatic solid tumors. Commercial ELISA kits were used to determine the salivary and serum concentrations of interleukin 13 (IL-13) and transforming growth factor beta (TGF-β) in two patient groups and healthy controls. Laboratory values were obtained from the hospital information system, and weight and height were measured at the time of sampling. Results: A statistically significant difference was observed between the groups in saliva IL-13 concentrations but no difference in serum concentrations. Statistically significant differences were also observed between the groups in saliva and serum concentrations of TGF-β. Logistic regression analysis has identified salivary IL-13 and TGF-β as independent factors for cancer cachexia. Conclusions: We demonstrated saliva as a valuable specimen for cachexia investigation and established IL-13 and TGF-β as potential cancer cachexia biomarkers. Further research is needed to evaluate these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: The Fas/Fas ligand (FasL) system is an apoptosis-regulating pathway that holds a key role in tumor immune surveillance and metastasis. Although this pathway has been extensively investigated in pre-clinical models and in primary tumor tissues, however its role in the periphery is largely unexplored. To this end, the expression of Fas/FasL was for the first time assessed on circulating tumor cells (CTCs) and matched peripheral blood mononuclear cells (PBMCs) in the peripheral blood of patients with metastatic breast cancer (BC). The results show that Fas and FasL are frequently expressed on BC patients' CTCs, with Fas/FasL-co-expressing CTCs emerging as a poor prognostic marker predicting a high risk for disease progression. On the other hand, Fas and FasL were also frequently expressed on BC patients' PBMCs, and Fas/FasL co-expression on PBMCs emerged as a favorable prognostic marker associated with a low risk for death. These results show that the assessment of Fas/FasL expression on CTCs and PBMCs can provide valuable prognostic information for patients with metastatic BC, and highlight their potential role in the peripheral immune response and metastatic progression of BC. The Fas/Fas ligand (FasL) system is a major apoptosis-regulating pathway with a key role in tumor immune surveillance and metastasis. The expression of Fas/FasL on mammary tumor tissues holds prognostic value for breast cancer (BC) patients. We herein assessed Fas/FasL expression on circulating tumor cells (CTCs) and matched peripheral blood mononuclear cells (PBMCs) from 98 patients with metastatic BC receiving first-line treatment. Fas+, FasL+, and Fas+/FasL+ CTCs were identified in 88.5%, 92.3%, and 84.6% of CTC-positive patients, respectively. In addition, Fas+/FasL+, Fas-/FasL+, and Fas-/FasL- PBMCs were identified in 70.3%, 24.2%, and 5.5% of patients, respectively. A reduced progression-free survival (PFS) was revealed among CTC-positive patients (median PFS: 9.5 versus 13.4 months; p = 0.004), and specifically among those harboring Fas+/FasL+ CTCs (median PFS: 9.5 vs. 13.4 months; p = 0.009). On the other hand, an increased overall survival (OS) was demonstrated among patients with Fas+/FasL+ PBMCs rather than those with Fas-/FasL+ and Fas-/FasL- PBMCs (median OS: 35.7 vs. 25.9 vs. 14.4 months, respectively; p = 0.008). These data provide for the first time evidence on Fas/FasL expression on CTCs and PBMCs with significant prognostic value for patients with metastatic BC, thus highlighting the role of the Fas/FasL system in the peripheral immune response and metastatic progression of BC. [ABSTRACT FROM AUTHOR]

Background: Allergen-specific immunotherapy, a unique inducer of tolerance, may result in T cell exhaution. Aims: To investigate how the duration of house dust mite (HDM) subcutaneous immunotherapy (SCIT) affects the expression of major immune checkpoint (ICP) molecules on the surface of CD4+ T-helper and regulatory T (Treg) cells. Study Design: Cross-sectional study. Methods: We enrolled 28 children with HDM-induced allergic rhinitis (AR) and six controls. The study participants were divided into six groups: one group each of patients in their first, second, and third years of HDM-SCIT; one group each comprising those in the first year following HDM-SCIT and those on pharmacotherapy; and the control group. The expression of ICPs on CD4+ T and Treg cells was determined using flow cytometry, and plasma levels of soluble ICPs were estimated by ELISA. Results: Our results revealed a significant increase in the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3) on CD4+ T cells during the second and third years of SCIT, respectively. Additionally, a strong correlation was observed between the expression of CTLA-4 and T cell immunoglobulin and mucin domain containing molecule-3 in CD4+ T cells. Furthermore, we observed a significant correlation between the expressions of programmed cell death protein-1, CTLA-4, T cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif domain, and LAG-3 on both CD4+ T and Treg cells. A robust correlation was observed between the plasma levels of soluble ICPs. Conclusion: HDM-SCIT induces CD4+ T cell exhaution, which may contribute to tolerance induction in children with AR. [ABSTRACT FROM AUTHOR]

Background: In India, 25%–65% of neonatal deaths are due to sepsis. Since it produces nonspecific symptoms, it is difficult to diagnose and manage. The present study assessed the value of brain natriuretic peptide (BNP) and C-reactive protein (CRP) to predict sepsis along with blood culture. Materials and Methods: Samples were collected from 90 neonates with suspected sepsis, submitted for blood culture, CRP by latex agglutination kit, and BNP by ELISA. Results: Of the 90 cases, blood culture was positive in 25 (28%) cases, BNP in 45 (50%) cases, and CRP in 36 (40%) cases. BNP was positive among 25 (100%) blood culture-positive cases. CRP, BNP, and blood culture were positive in 16 (18%) cases. Conclusion: Although BNP is an equally good marker in predicting sepsis, it is not widely available. Hence, screening by serial CRP along with blood culture alone reinforces the diagnosis. [ABSTRACT FROM AUTHOR]

Copyright of Cirugía y Cirujanos is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Exercise offers significant health benefits, promoting normal body system functioning, healthy growth, development, and overall well-being. Aims and Objectives: Therefore, the objective of the present study was to determine the effect of short-term high-intensity exercise (HIE) on hematological biomarkers and acute responses in athletes, as well as changes in these biomarkers immediately after 10 and 20 min of HIE. Materials and Methods: This cross-sectional study was carried out in the Department of Physical Education, Banaras Hindu University, Varanasi (UP). A total of 20 healthy male athletes with an age range of 22 to 26 years were randomly selected. All participants performed HIE for 5 min with maximal effort. Blood samples for selected hematological biomarkers were collected before exercise, immediately after exercise, and 10 and 20 min after the HIE. Results: A repeated measures analysis of variance with a Greenhouse-Geisser correction revealed that red blood corpuscles (F = 58.447; P < 0.05.), white blood cells (F = 59.778; P < 0.05), platelets (F = 23.794; P < 0.05), and hemoglobin (F = 46.853; P < 0.05) responses differed statistically significantly between time points. Post hoc analysis with a Bonferroni adjustment revealed that their response was significantly increased immediately after the HIE, reduced 10 min after the exercise, and closely returned to baseline levels after 20 min of exercise. Conclusion: HIE causes an inflammatory response in the blood by elevating the hematological biomarkers. These findings can be taken into consideration to develop high-intensity training programs for athletes. [ABSTRACT FROM AUTHOR]

Copyright of Namık Kemal Tıp Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Blood culture is crucial for accurate and timely bacteremia diagnosis and guide antibiotic therapy. However, during culture sampling, contamination can occur, resulting in misdiagnosis, unnecessary antibiotic exposure, and prolonged hospitalization. This before-and-after intervention study aimed to evaluate the effectiveness of a multimodal intervention in preventing blood culture contamination. The study was conducted in a 170-bed hospital in Portugal and included a total of 23,566 blood cultures. Contamination rates were assessed in two phases: Phase 1 (before intervention, month 0) included 10,928 cultures, and Phase 2 (after intervention, month 6) included 12,638 cultures. During the study period, a multimodal intervention targeting the nursing staff was implemented, consisting of training actions, guideline updates, regular data monitoring and feedback, and introduction of a blood culture pack. Following the intervention, blood culture contamination decreased from 6.8% (Phase 1) to 3.9% (Phase 2). A comparative analysis revealed that the risk of contamination before the intervention was nearly four times higher in first culture, OR = 3.97 (CI 2.86–5.49). Our findings suggest that the multimodal intervention enhanced nurses' adherence to recommended practices, resulting in a reduced risk of blood culture contamination, earlier identification of infectious agents, and improved accuracy of antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormone is the key endocrine regulator of growth, development, metabolism, and other bodily functions. α-Klotho has been involved in the aging process and acts as an endocrine factor involved in the regulation of various metabolic processes in humans. However, the relationship between α-Klotho and thyroid profile has not been uniformly recognize. Objective: To determine the relationship between α-Klotho and thyroid profile in adult individuals. Methods: Population data of 4614 adult individuals were obtained from the NHANES database during the period of 2007–2012. Weighted multivariable regression analysis was performed using a general linear model with serum α-Klotho as the independent variable and thyroid profile as the dependent variables, respectively. The generalized additive model was used for smoothing curve fitting and threshold effect analysis. Results: α-Klotho was associated with a slightly higher FT3, TT3 and TT4 level in unadjusted and adjusted regression models. However, a higher α-Klotho level was associated with a lower TSH level. After α-Klotho was grouped as quantiles with reference (Q1), α-Klotho still showed a statistically significant positive correlation with FT3 and TT3 levels in Q2, Q3 and Q4. In addition, α-Klotho was positively corrected with TT4, but negatively associated with TSH in Q4. Conclusions: Serum soluble α-Klotho was positively associated with FT3, TT3 and TT4, but negatively correlated with TSH. The significant effect of α-Klotho on thyroid profile suggests its potential as a predictive marker of thyroid functions, indicating its possible involvement in the regulation of thyroid hormone secretion. [ABSTRACT FROM AUTHOR]

Background: Coagulopathies can manifest on a spectrum, from minor mucosal bleeding to life-threatening hemorrhage. Minor cases can be discovered in the setting of known risk factors, such as malignancy, old age, immunosuppression. However, acquired hemophilia A diagnosed after a snake bite is of lesser-known incidence and can present in a more acute, potentially life- or limb-threatening fashion. To properly diagnose this coagulopathy, one must be familiar with the related signs, symptoms, and laboratory findings so that swift diagnosis can follow. Diagnosis is key for early proper management, as displayed in the following case. Case Report: Our case report details a male patient presenting with diffuse bruising after a snake bite. Initially, on presentation to outside facilities, the diagnosis of acquired hemophilia A was not found. However, upon worsening of bruising in the setting of previous treatments initiated for the patient, he presented to our facility, where he subsequently received a diagnosis with acquired hemophilia A. He developed compartment syndrome due to excessive bleeding, requiring surgical intervention. With proper diagnosis, his bleeding diathesis was corrected with multiple rounds of repletion of factors and immunosuppression. His follow-up laboratory test results and examinations have shown continued resolution of his symptoms. Conclusions: As acquired hemophilia A is less often linked with snake bites, this case highlights the importance of considering this disease process as a differential in patients with bleeding diathesis after a snake bite. The coagulation dysfunction can be severe, and, as such, early identification of this diagnosis leads to more targeted and effective therapy [ABSTRACT FROM AUTHOR]

Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with many adverse health outcomes. However, further research is required to understand the critical genes and pathways relevant to CHIP subtypes, evaluate how CHIP clones evolve with time, and further advance functional characterisation and therapeutic studies. Large epidemiological studies are well placed to address these questions but often collect saliva rather than blood from participants. Paired saliva- and blood-derived DNA samples from 94 study participants were sequenced using a targeted CHIP-gene panel. The ten genes most frequently identified to carry CHIP-associated variants were analysed. Fourteen unique variants associated with CHIP, ten in DNMT3A, two in TP53 and two in TET2, were identified with a variant allele fraction (VAF) between 0.02 and 0.2 and variant depth ≥ 5 reads. Eleven of these CHIP-associated variants were detected in both the blood- and saliva-derived DNA sample. Three variants were detected in blood with a VAF > 0.02 but fell below this threshold in the paired saliva sample (VAF 0.008—0.013). Saliva-derived DNA is suitable for detecting CHIP-associated variants. Saliva can offer a cost-effective biospecimen that could both advance CHIP research and facilitate clinical translation into settings such as risk prediction, precision prevention, and treatment monitoring. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in the treatment of acute lymphoblastic leukemia (ALL) have led to a marked improvement in the survival rate of patients. Nevertheless, these patients may develop adverse effects during and after treatment, such as bone abnormalities and vitamin D deficiency. Bone remodeling allows for bone volume and structure to be maintained, which is controlled by the receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system-determining pathway in the balance between bone formation and resorption. Some reports have explored the role of corticosteroids in modulating the RANKL and OPG levels and RANKL/OPG ratio in pediatric patients. Nevertheless, studies evaluating the role of RANKL and OPG in the bone health of pediatric ALL patients during treatment are limited. During remission, we observed an increase in the RANKL/OPG ratio, increased RANKL levels, and decreased OPG levels in ALL patients. These changes may predispose such patients to the development of bone health disorders in their adult lives. Background: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption, and disruptions in this complex can affect bone metabolism. Methods: This study analyzes the changes in RANKL, OPG, and 25(OH)D levels; the RANKL/OPG ratio; and other bone turnover markers (BTMs) from diagnosis to complete remission in children with acute lymphoblastic leukemia (ALL). This is a prospective observational cohort study, carried out at the Instituto Mexicano del Seguro Social, Mexico City, including 33 patients (4–17 years) with newly diagnosed B-cell ALL. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A peripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. Results: Increased RANKL (p = 0.001) and osteocalcin (p < 0.001) levels and RANKL/OPG ratio (<0.001) and a decreased OPG level (p = 0.005) were observed at remission, predominantly in the high-risk (HR) relapse and vitamin D deficiency groups. A negative association between RANKL and OPG (r = −0.454, p = 0.008) was observed. Conclusions: we suggest that the RANKL/OPG ratio could serve as a bone remodeling marker in ALL patients. [ABSTRACT FROM AUTHOR]

Neurological disorders, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), may be associated with alterations in blood cell composition and phenotype. Here, we focused our attention on circulating mucosal-associated invariant T (MAIT) cells, a CD8+ T cell memory population expressing the invariant Va7.2 region in the T cell receptor and high surface levels of the CD161 marker. Transcriptomics data relative to peripheral blood mononuclear cells (PBMC) highlighted downregulation of CD161 and other MAIT-associated markers in progressive MS and not relapsing remitting (RR)-MS when gene expressions relative to each disease course were compared to those from healthy controls. Multiparametric flow cytometry of freshly isolated PBMC samples from untreated RR-MS, primary or secondary progressive MS (PP-or SP-MS), ALS and age-and sex-matched healthy controls revealed specific loss of circulating CD8+ MAIT cells in PP-MS and no other MS courses or another neurological disorder such as ALS. Overall, these observations point to the existence of immunological changes in blood specific for the primary progressive course of MS that may support clinical definition of disease. [ABSTRACT FROM AUTHOR]

Autophagy is a biological phenomenon whereby components of cells can self-degrade using autophagosomes. During this process, cells can clear dysfunctional organelles or unwanted elements. Autophagy can recycle unnecessary biomolecules into new components or sometimes, even destroy the cells themselves. This cellular process was first observed in 1962 by Keith R. Porter et al. Since then, autophagy has been studied for over 60 years, and much has been learned on the topic. Nevertheless, the process is still not fully understood. It has been proven, for example, that autophagy can be a positive force for maintaining good health by removing older or damaged cells. By contrast, autophagy is also involved in the onset and progression of various conditions caused by pathogenic infections. These diseases generally involve several important organs in the human body, including the liver, kidney, heart, and central nervous system. The regulation of the defects of autophagy defects may potentially be used to treat some diseases. This review comprehensively discusses recent research frontiers and topics of interest regarding autophagy-related diseases. [ABSTRACT FROM AUTHOR]

Even low levels of lead in children’s blood are associated with developmental delays, difficulty learning, and behavioral issues. Adults are also vulnerable to the detrimental health effects of lead exposure. The New York City (NYC) Department of Health and Mental Hygiene receives blood lead test results for NYC residents and conducts investigations of lead poisoning cases. Blood lead testing of a child aged 4 years in 2012 led to the discovery of blood lead levels above the CDC blood lead reference value of 3.5 μg/dL in the child as well as four other family members over a period of 11 years, including the child’s mother and three younger siblings born during 2012–2016. The only potential source of lead exposure identified for all cases was the use of surma, a traditional eye cosmetic, which was found to contain 390,000 ppm lead. The cases in this report highlight the challenges of risk communication when deeply ingrained cultural practices, such as the use of surma, persist despite health warnings. Moreover, they highlight the intergenerational nature of such practices and the need for comprehensive family follow-up once a member is identified as being at risk. These products continue to be available globally, even in places such as the United States where sales are prohibited. Multistakeholder efforts involving local and global engagement could promote reformulation of these products at the countries of origin to eliminate lead as an ingredient. [ABSTRACT FROM AUTHOR]

Background: The significance of tumor-secreted cytokines in tumor development has gained substantial attention. Nevertheless, the precise role of tumor-related inflammatory cytokines in prostate cancer (PCa) remains ambiguous. Objectives: To gain deeper insights into the inflammatory response in the process of PCa. Methods: A total of 233 cases were collected, including 80 cases of prostate hyperplasia as disease control, 65 cases of postoperative prostate cancer and 36 cases of prostate cancer as PCa group. Additionally, 52 patients undergoing physical examinations during the same period were collected as the healthy control. The levels of 12 inflammatory cytokines in peripheral blood samples were analyzed using flow cytometric bead array technology. The levels of total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) in peripheral blood samples were analyzed using electrochemiluminescence technology. Results: Our findings revealed significant increases in serum IL-8 levels in PCa group compared to the healthy control group. Additionally, IL-6, IL-10, IFN-γ and IL-12p70 levels were markedly elevated in the PCa group compared to the disease control group (all p < 0.05). Conversely, the level of IL-4, TNF-α, IL-1β, IL-17A and IFN-α were lower in the PCa group compared to those in control group. Following surgery, the concentration of IL-6 decreased; whereas, the concentrations of IL-4, TNF-α, IL-17A, IL-1β, IL-12p70, and IFN-α increased, demonstrating significant differences (p < 0.05). The differential upregulation of IL-6 or downregulation of IL-17A in peripheral blood exhibited diagnostic efficacy in PCa patients. Moreover, we observed a significant increase in IL-17A levels, accompanied by decreased of IL-2, IL-4, IL-10, TNF-a, IFN-γ, IL-1β, and IL-12P70 in patients with distant metastasis. Conclusion: The peripheral blood cytokines are closely associated with the occurrence and development of prostate cancer, especially the serum levels of IL-6 and IL-17A may be useful as potential predictors of PCa diagnosis. [ABSTRACT FROM AUTHOR]

Rodents are considered good models for investigating genotoxic damage and mutagenic alterations caused by xenobiotic agents, due to their occupation of a wide variety of habitats. However, relatively few in situ studies have focused on DNA damage in wild rodents associated with environmental exposure. In this review, we investigate trends in the application of the micronucleus test and comet assay in in situ studies of wild rodents. A total of 33 papers were identified, distributed across 14 different countries. Brazil and Spain had the most published studies (six each), followed by Bulgaria (n = 5), Mexico (n = 4) and Italy (n = 3). Only 24 of the 2,652 recognized rodent species have been the subject of in situ studies, which have most frequently focus on species of the genus Mus. The protocols used for the micronucleus test and comet assay varied widely, although blood and bone marrow were the primary types of tissue used. Given the paucity of studies on wild rodents, we recommend further research, particularly focusing on the use of this group as bioindicators of environmental quality and the standardization of protocols. [ABSTRACT FROM AUTHOR]

Objective of the study was to find the association of vitamin D receptor (VDR) polymorphisms (Fokl, Taql and Apal) with vitamin D levels in diabetic foot ulcer (DFU) patients in South India. In this case–control study, plasma vitamin D levels and VDR genotype frequencies of 70 cases (DFU patients) were compared with 70 diabetic (diabetes mellitus [DM] [non‐DFU]) patients and 70 apparently healthy controls (HC) from South India. Plasma vitamin D levels were measured using the ELISA technique, and genotyping of VDR polymorphisms was carried out using real‐time polymerase chain reaction. Logistic regression was used to find the association between DFU versus HC and DFU versus DM traits. Association analysis was performed based on additive, dominant and recessive models with age and gender as covariates. A 45.7% of DFU patients have sufficient vitamin D levels than 48.6% and 40% of DM patients and HC, respectively. Linkage disequilibrium analysis for DFU versus HC and DFU versus DM traits shows that single nucleotide polymorphisms (SNPs) Taq1 (rs731236) and Apal (rs7975232) are in strong linkage disequilibrium in DFU patients. The alleles and genotype frequencies were similar in all three groups. Although the additive model does not show statistical significance, age and sex correlate with the three SNPs (Fokl, Taql and Apal). No association was found between VDR gene polymorphisms and vitamin D levels in DFU patients in Southern India. On the other hand, age and sex correlate with the three SNPs. [ABSTRACT FROM AUTHOR]

Background: Blood donation is an essential and most important part of the health care system across the world. It becomes necessary to know the root cause of individuals who are willing to donate the blood but deferred on some grounds. Aim and Objectives: The aim of this study is analysis of such deferrals so as to promote voluntary blood donation practice in our health-care system. The objectives of this study are to promote voluntary blood donation, provide safe blood and blood components/products to the recipients, ensure the safety and well-being of blood donors and make strategies to retain already motivated but deferred donors. Materials and Methods: A prospective observational study was done during the period January 2021-December 2021 at blood center of S.B.K.S. MI & RC, Dhiraj Hospital, Vadodara. All individuals willing for whole blood donation were subjected to detailed history taking and general physical examination and were either accepted or denied for blood donation using the standard blood donor guidelines. Pre-donation deferred individuals and their data were then thoroughly analyzed. Results: A total of 2168 individuals reported at blood center for whole blood donation out of which 311 donors (14.34%) were deferred. Of all deferred donors, male-to-female ratio of deferral found out to be 4.02:1. Two hundred and forty-nine deferrals (80.06%) were males while 62 deferrals (19.94%) were females. Two hundred and seventy-two deferrals (12.54%) were deferred temporarily while 39 deferrals (1.79%) were permanent. Youngest deferred donor was aged 18 years while the eldest was 59 years. Low hemoglobin cases were 134 making it 43.09% of all reasons of deferring a pre-donation whole blood donor. Conclusion: Low hemoglobin (<12.5 gm%) was the leading cause of deferrals accounting for 43.09%. The majority of the deferrals were temporary where the cause can be treated or eliminated. Such donors need to be remotivated and bring them back to the donor pool so that maximum blood donation which indeed is a life-saving measure can be promoted. Furthermore, the analysis done by doing such study can help to promote the blood donation on a large scale and not only saving many lives but also create awareness among the society. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to investigate the diagnostic value of cerebrospinal fluid (CSF) and serum levels of the soluble form of triggering receptor-1 expressed on myeloid cells (sTREM-1) in neonatal meningitis. Methods: Serum sTREM-1 levels were measured in all neonatal sepsis patients at the start of antibiotic therapy and the 48th hour of treatment. At the beginning of antibiotic therapy, CSF samples were collected for sTREM-1 measurements. Control CSF samples were also collected from the patients with meningitis at the 48th hour of treatment. Results: A total of 77 preterm (50) and term (27) patients with neonatal sepsis were included in the study. There was no significant difference between the CSF sTREM-1 levels of patients with and without meningitis. The CSF sTREM-1 levels of preterm infants with meningitis decreased significantly after treatment (p = 0.038). Although the CSF/serum sTREM-1 ratios tended to increase in babies with meningitis, no significant difference was found between the groups. CSF/serum sTREM-1 ratios (mean ± SD) were 1.42 ± 0.91 and 1.14 ± 0.85 in preterm babies with and without meningitis and 1.15 ± 0.97 and 0.97 ± 0.55 in term babies with and without meningitis, respectively. Conclusions: Serum and CSF sTREM-1 levels increase in patients with neonatal sepsis. CSF s-TREM-1 levels decrease after treatment in preterm infants with meningitis. [ABSTRACT FROM AUTHOR]

Blood transfusion is a common therapeutic intervention in hospitalized patients. There are numerous indications for transfusion, including anemia and coagulopathy with deficiency of single or multiple coagulation components such as platelets or coagulation factors. Nevertheless, the practice of transfusion in critically ill patients has been controversial mainly due to a lack of evidence and the need to consider the appropriate clinical context for transfusion. Further, transfusion carries many risk factors that must be balanced with benefits. Therefore, transfusion practice in ICU patients has constantly evolved, and we endeavor to present a contemporary review of transfusion practices in this population guided by clinical trials and expert guidelines. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is one of the most common gynaecological diseases, yet it lacks efficient biomarkers for early detection and unravels disease mechanisms. Proteomic profiling has revealed diverse patterns of protein changes in various clinical samples. Integrating and systematically analysing proteomics data can facilitate the development of biomarkers, expediting diagnosis and providing insights for potential clinical and therapeutic applications. Hence, this systematic review and meta-analysis aimed to explore potential non-invasive diagnostic biomarkers in various biological samples and therapeutic targets for endometriosis. Methods: Online databases, including Scopus, PubMed, Web of Science, MEDLINE, Embase via Ovid, and Google Scholar, were searched using MeSH terms. Two independent authors screened the articles, extracted the data, and assessed the methodological quality of the included studies. GO and KEGG analyses were performed to identify the pathways that were significantly enriched. Protein‑protein interaction and hub gene selection analyses were also conducted to identify biomarker networks for endometriosis. Results: Twenty-six observational studies with a total of 2,486 participants were included. A total of 644 differentially expressed proteins (180 upregulated and 464 downregulated) were identified from 9 studies. Proteins in peripheral blood exhibited a sensitivity and specificity of 38-100% and 59-99%, respectively, for detecting endometriosis, while proteins in urine had a sensitivity of 58-91% and specificity of 76-93%. Alpha-1-antitrypsin, albumin, and vitamin D binding proteins were significantly DEPs in both serum and urine. Complement C3 is commonly expressed in serum, menstrual blood, and cervical mucus. Additionally, S100-A8 is commonly expressed in both menstrual blood and cervical mucus. Haptoglobin is commonly detected in both serum and plasma, whereas cathepsin G is found in urine, serum, and plasma. GO and KEGG enrichment analyses revealed that proteoglycans in cancer pathways, which regulate cell-to-cell interactions, modulate the extracellular matrix, and promote the proliferation and invasion of endometrial cells, are commonly enriched in serum and urine. Conclusion: This comprehensive study revealed potential proteomes that were significantly differentially expressed in women with endometriosis utilizing various non-invasive clinical samples. Exploring common differentially expressed proteins in various biological samples provides insights into the diagnosis and pathophysiology of endometriosis, as well as potential clinical and therapeutic applications. [ABSTRACT FROM AUTHOR]

Introduction: Blood culture is the gold standard for diagnosing bacteremia and direct the physicians to select appropriate antimicrobials. In hospitals, blood culture contamination (BCC) is a common problem that has a detrimental effect on patient outcomes. Hence, we implemented strategies in our tertiary care setup, for training phlebotomists and nurses in proper blood sampling techniques, and assessed their effectiveness in reducing BCC rates. Methods: This interventional study was conducted at the Indus Hospital, Karachi, Pakistan from 1st January 2021 to 30th June 2023. All blood cultures received from different departments of the hospital were included. The 2.5-year study period was divided into pre-intervention and intervention periods, with monthly monitoring of BCC. The BCC data between 1st January 2021 and 31st December 2021 was taken as the baseline pre-intervention period and the next 1.5 years comprised the intervention period (1st January 2022-30th June 2023). To improve compliance, various strategies were implemented, such as regular training sessions, didactic sessions, and re-competencies. Results: A total of 86 774 Blood cultures were received from all departments of the hospital, out of which n = 30 672 were received in the pre-intervention period whereas, n = 56 102 were received in the intervention period. Mean BCC rate in the pre-intervention period was found to be 4.6%. However, after the implementation of different measures to reduce BCC, the contamination rate decreased to a mean of 3.1% by the end of the intervention period. Emergency department accounted for the highest proportion of BCC in the pre-intervention and intervention periods. Conclusion: We decreased BCC in our tertiary care setup by implementing a simple and inexpensive collaborative intervention, and came to the conclusion that the higher incidence of BCC was probably caused by factors unique to the emergency department and provided measures to successfully address them. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aimed to investigate the effect of dexmedetomidine on brain-derived neurotrophic factor (BDNF) levels in individuals undergoing various medical procedures. We systematically searched electronic databases and manually identified relevant articles to assess the impact of dexmedetomidine on BDNF levels in surgical patients. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Embase, and Web of Science databases with no language restrictions. Studies that examined the effects of dexmedetomidine administration on BDNF levels in surgical patients were included. Results: The overall analysis revealed a statistically significant increase in BDNF levels in individuals receiving dexmedetomidine compared to controls (Standardized Mean Difference SMD = 1.65, 95% CI: 1.02 to 2.28; I2: 89%). Subgroup analyses based on the anesthesia method (p < 0.01), and the type of surgery (p < 0.01) showed significant between-group differences (Fig. 3). The results of the sensitivity analyses indicated that individual studies did not significantly affect the overall results. Conclusion: This meta-analysis indicates that dexmedetomidine administration is associated with a significant increase in BDNF levels in individuals undergoing surgical procedures. These findings highlight the potential role of dexmedetomidine in modulating BDNF levels, which may have implications for optimizing perioperative neuroprotective strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: In the available literature, levels of BDNF and CRP have been reported to correlate with suicide in depressive patients but there are inconsistencies in the results. We aimed to evaluate and compare BDNF and CRP concentrations in MDD patients with(MDD + SA) and without suicide attempts (MDD-SA) and healthy controls. Methods: 30 (MDD + SA) patients, 30 (MDD-SA) patients, and 26 healthy controls were enrolled in the study. Age, sex, and BMI of patients were recorded. Blood sample was obtained for measurement of BDNF and CRP. Smoking and drug history, family history of suicide, and history of self-harm were also documented. Data were analyzed with SPSS version 22 and R version 4.1.1. Results: 86 patients in three groups were evaluated (mean age: 28.45 ± 9.27 years, 56.71% female). Baseline and demographic parameters except for self-harm (40%, 3.3%, and 0% for MDD + SA, MDD-SA, and healthy controls, respectively, p = 0.001) did not differ between groups. CRP level was not significantly different between groups. BDNF showed a significant difference between groups (17.35, 16.45, and 19.43 for three groups, respectively, p < 0.001). An increase in BDNF decreased the odds of both depression and suicide. Roc curve showed excellent power for BDNF in discriminating MDD groups With healthy group.Roc can notdicrimiate MDD + SA and MDD-SA. Conclusion: In our study, the concentration of BDNF differed significantly between depressed patients with/without suicide attempts and healthy controls which shows the association of BDNF with depression development and not suicide attempts. We could not find any association between CRP level and suicide attempt but still larger cohorts are needed for a definite conclusion. [ABSTRACT FROM AUTHOR]

Background: Infective endocarditis poses many clinical and diagnostic challenge. The diagnosis of infective endocarditis is made by high index of clinical suspicion based on the American Heart Association modified Duke's criteria, and the main imaging modality of choice is echocardiography. Case presentation: Here, we reported a case of recurrent infective endocarditis revealed by FDG PET/CT study despite completion of antibiotics and negative on echocardiography. A 38-year-old female with history of double-valve replacement for aortic stenosis presented with 1-week history of chest pain, dyspnea and intermittent fever. She was treated with 5 weeks of antibiotic with IV Cephalexin for prosthetic valve endocarditis. The repeated blood culture after IV antibiotic was negative for infection. She represented again with episodes of palpitation. Post-treatment blood investigation showed normal leukocyte level with increasing CRP and Troponin T level. The repeated blood culture and transesophageal echo was negative. The F-18 FDG PET/CT showed a mild hypermetabolic focus at the inferior basal myocardial wall adjacent to the prosthetic valve, however not involving the paraaortic region which is likely secondary to ongoing inflamed myocardium. As the fear of another relapse of endocarditis, oral suppression antibiotic therapy was continued for another 6 months. Conclusions: This case report illustrates a patient with a prosthetic valve replacement detected by F-18 FDG PET/CT, which one could have overlooked an endocarditis if one had relied on transesophageal echo (TEE) alone. F-18 FDG PET/CT is a promising adjunctive tool in the diagnostic workup of patients with suspected IE, particularly prosthetic device endocarditis where the TEE sensitivity is lower. In our patient, the positive F-18 FDG PET/CT governs the subsequent therapeutic consequences which include adjustment of antibiotic and length of treatment, and it prevents unnecessary intervention. [ABSTRACT FROM AUTHOR]

In the ancient times, the Kazakhstan population were considered as nomadic people, where a cult of all types of cattle breeding had a leading position. However, currently the processing approaches of livestock slaughter wastes and secondary meat raw materials are weakly developed. The presented review of waste-free technologies considers the utilization processes of following: carcasses, skins, bones, meat scraps, blood, adipose tissue, horns, feet, hooves, and internal organs. These substances are an important source of animal protein, collagen, bioactive peptides, blood plasma, minerals, and fats that can be applied in various industries: food, feed, medical, and technological. When slaughtering livestock, meat on bones makes up almost half of the total weight of livestock, yet the remaining half contains offal and inedible raw materials. Blood consists of: erythrocytes, leukocytes, platelets, and plasma. Animal bones have mostly proteins (30-50%) and lipids (13-20%) from bone tissues. Tendons, bones and skins contain a large amount of collagen. Animal fat and adipose tissue have 54.9% saturated acids, 40.9% unsaturated fatty acids and 4.2% polyunsaturated fatty acids. Bioactive peptides from collagen derivatives contain from 2 to 20 amino acids and have various biological (antihypertensive, antioxidant, and antimicrobial) activity. This review considers a world current status, modern prospects and opportunities in the slaughter wastes and themeat by-products recycling technologies. Overview of existing approaches for waste processing with the subsequent use of the final product in the food industry, the production of feed, medicines and technical products is considered. The complete processing within the slaughtering livestock and the secondary meat raw materials allows to expand the wide-range products with a low prime cost, thereby promoting to the sustainable development of agroecology by applying the waste hierarchy: Reducing, Reusing, and Recycling. [ABSTRACT FROM AUTHOR]

Recurrent bleeding in the synovial joint, such as the knee, can give rise to chronic synovitis and degenerative arthritis, which are major causes of morbidity. Whereas chronic arthropathy affects one-fifth of hemophiliacs, conditions such as rheumatoid arthritis (RA), periarticular and articular fractures, osteochondral autograft transplantation surgery, and anterior cruciate ligament (ACL) injury are also associated with joint bleeding. Synovial joint trauma is associated with inflammation, acute pain, bloody joint effusion, and knee instability. Clinically, some physicians have advocated for blood aspiration from the joint post-injury to mitigate the harmful effects of bleeding. Despite the significant potential clinical impact of joint bleeding, the mechanism(s) by which joint bleeding, acute or microbleeds, leads to deleterious changes to the synovial joint remains understudied. This review will address the impact of blood on synovial joint tissues observed from in vitro and in vivo studies. While the deleterious effects of blood on cartilage and synovium are well-described, there are much fewer reports describing the negative effects of blood on the meniscus, cruciate ligaments, and subchondral bone. Based on our studies of blood in co-culture with chondrocytes/cartilage, we raise the possibility that ferroptosis, an iron-dependent, nonapoptotic form of regulated cell death, plays a contributing role in mediating hemophilic arthropathy (HA) and may represent a therapeutic target in reducing the negative impact of joint bleeds. [ABSTRACT FROM AUTHOR]

Head-down bed rest (HDBR) is one of the models of the physiological effects of weightlessness used, among other things, to assess the effect of hypokinesia on the physiological systems of the human body and, first of all, on the cardiovascular system. The aim of the work was to study the effect of 21 days of HDBR factors on the cardiovascular system based on blood proteomic profile data. It was revealed that HDBR conditions led to an increase in the levels of proteins of the complement and the coagulation cascade systems, platelet degranulation, fibrinolysis, acute phase proteins, post-translational modification of proteins, retinol-binding protein 4 (RBP4), apolipoprotein B, which are associated with cardiovascular diseases, and other proteins that affect the functions of endothelial cells. Blood levels of proteins involved in cytoskeletal remodelling, oxygen transport, heme catabolism, etc. have been shown to decrease during HDBR. [ABSTRACT FROM AUTHOR]

cells, can be caused by blood loss, hemolysis, or impaired erythropoiesis. Types of anemia include iron-deficiency anemia and vitamin-deficiency anemia. Given their high iron and nutrient content, certain medicinal plants offer potential therapeutic benefits for anemia. This review aims to identify medicinal plants from Northwest Iran traditionally used for treating this condition. Methodology: To identify relevant literature, a comprehensive database search was conducted using keywords such as 'medicinal plants,' 'Iran,' 'anemia,' 'hematopoietic,' 'Urmia,' 'Tabriz,' 'Ardabil,' 'West Azerbaijan,' 'East Azerbaijan,' and 'ethnobotany. Databases such as Google Scholar, SID, Magiran, PubMed, and Scopus were used to search for relevant articles, particularly ethnobotanical studies related to the subject. Results: The review identified that medicinal plants such as Nasturtium sp., Salvia officinalis, Centaurea depressa, Centaurea virgate, Achillea biebersteinii, Cichorium intybus, Urtica dioica, Prunus cerasifera, Cichorium intybus, Saponaria officinalis, Foeniculum vulgare, Achillea millefolium, Berberis vulgaris, Capsella bursa-pastoris, Crataegus aronia, Adiantum capillus-Veneris, Anthemis cotula, Gandelia tourenfortii, Rheus ribes, Lactuca virosa, Hyssopus officinale, and Salix alba are used in traditional and ethnobotanical practices to treat anemia. Conclusion: Further research is recommended to conduct phytochemical analysis of these medicinal plants, identifying the active compounds that influence anemia and hematopoiesis. Additionally, clinical trials involving animal and human models could explore the potential of these plants as a basis for developing effective and affordable herbal combination drugs for the treatment of anemia. [ABSTRACT FROM AUTHOR]

Objective Crush syndrome (CS) remains a life-threatening condition. This research aims to investigate the changes of the macro- and microelement content in blood, liver and bone tissue in a rat model of CS. Methods Studies were conducted on 40 nonlinear mature white male rats. The left hind limb of the rat was subjected to the mechanical pressure for 4 hours. The compressed area was 4 cm2 with a compressive force of 4.25 kg/cm2 . Determination of total calcium, magnesium and inorganic phosphate contents in blood serum was performed on a semi-automatic biochemical analyser Humalyzer 2000 (Human, Germany) using standard reagent kits. The content of calcium, magnesium, copper and zinc in the liver and bone tissue was determined by atomic absorption spectrometry on a Selmi C-115 M spectrophotometer. Results It was found that serum content of calcium decreased on the 1st day of observation (by 10.1%), but increased on the 14th day (by 23.0%); the magnesium content progressively decreased during postcompression period, and the content of inorganic phosphate increased on the 14th day of observation by 36.6% (p<0.05) exeeded control data. The content of calcium in the liver tissue started to increase on the 3rd day of observation, and on 14th day by 25.9% (p<0.05) exceeded the control data. Magnesium content in the liver tissue was progressively decreasing during all days of observation. At the same time the content of zinc and copper in the liver tissue gradually increased during postcompression period. The content of calcium, magnesium, zinc and copper in the bone tissue significantly changed from the 3rd day of the postcompression period, in particular the content of bioelements vs. control group progressively decreased by 30.6%, 42.7%, 43.9% and 30.1% respectively on the 14th day of observation. Conclusion : The postcompression period in a rat model of CS is characterized by the pronounced imbalance of macro- and microelements content in blood, liver and bone tissues, which is important for the regulation of metabolic processes. These findings warrant further studies and can be used for developing new treatments that are efficient for dysmacro- and dysmicroelementosis that develop in case of experimental CS. [ABSTRACT FROM AUTHOR]

Objective: It was previously shown that the levels of several biomarkers increase due to acromegaly disease-related inflammation, and some markers are parallel to the disease's activity. The current study compared the possible relationship of growth differentiation factor-15 (GDF-15) with acromegaly disease activity in healthy subjects. Methods: This case-control study was conducted in a single center. It included 40 acromegaly patients (25 active/15 controlled) (47.7 ± 9.4 years, 20 female/20 male) and 24 healthy individuals (49.9 ± 10.1 years, 13 female/11 male) with age-sex-body mass index similar to the patient group. Demographic data, metabolic and hormonal parameters, and GDF-15 levels of the study population were studied. Results: The median GDF-15 levels were significantly higher in patients with acromegaly compared to healthy subjects (HS) (280.4 (Q1-Q3: 197.0-553.2) vs. 213.3 (Q1-Q3: 179.9-297.2) ng/L, P = .01). Serum GDF-15 levels of active and controlled acromegaly patients were comparable (P = .39). Interestingly, compared to HS, GDF-15 levels were significantly higher in controlled disease (P = .013), whereas GDF-15 levels tended to be higher in active disease but did not reach statistical significance (P = .06). Growth differentiation factor-15 levels were positively correlated with fasting plasma glucose (r = 0.304, P = .01) and HbA1c (r = 0.292, P = .02). When evaluated across the entire cohort, GDF-15 levels were found to be higher in diabetic patients compared to non-diabetic individuals (P = .04). Conclusion: Plasma GDF-15 levels were increased in the patients with acromegaly compared to healthy subjects. This increment may be due to accompanying diseases such as diabetes rather than a disease-specific effect. [ABSTRACT FROM AUTHOR]

In our study, blood concentrations of lead (Pb), arsenic (As), and cadmium (Cd) and urine concentrations of thallium (Tl) were measured together with related symptoms of heavy metal poisoning in cigarette smoking volunteers diagnosed with schizophrenia, in cigarette smokers not diagnosed with schizophrenia, and in the control group of non-smokers and not diagnosed with schizophrenia volunteers. Our study was performed on 171 volunteers divided into the following subgroups: patients diagnosed with schizophrenia with at least 1 year of continuous cigarette smoking experience (56 participants), cigarette smokers not diagnosed with schizophrenia with at least one year of continuous smoking experience (58), and control group (not diagnosed with schizophrenia and non-smoking volunteers) (57). Smoking durations of cigarette smokers diagnosed with schizophrenia and cigarette smokers not diagnosed with schizophrenia are not similar (p = 0.431). Blood Pb, As, and Cd concentrations and urine Tl concentrations were the highest in the subgroup of cigarette smokers not diagnosed with schizophrenia, followed by the subgroup of cigarette smokers diagnosed with schizophrenia, and the control group. Only blood Pb concentrations were significantly higher (probability value p < 0.05) in the group of cigarette smokers not diagnosed with schizophrenia (5.16 μg/dL), comparing to the group of cigarette smokers diagnosed with schizophrenia (3.83 μg/dL) and to the control group (3.43 μg/dL). Blood Cd and As concentrations and urine Tl concentrations were significantly higher (p < 0.05) in cigarette smokers not diagnosed with schizophrenia than in the control group. The results revealed a statistically significant positive correlation (p < 0.001) in the cigarette smokers in the schizophrenia diagnosed group between blood Pb, blood As, and urine Tl concentrations and the duration of cigarette smoking. [ABSTRACT FROM AUTHOR]

The acid resistance of erythrocytes of laboratory rats was studied under isolated and complex exposure to lead, cadmium, and zinc ions. It was shown that when exposed to heavy metal ions, there is a shift in erythrograms, an increase in the proportion of low-resistant erythrocytes, and a reduction in hemolysis time. The most significant changes in erythrocyte membranes are observed with the chronic action of Pb2+, Cd2+, Zn2+ ions, and a mixture of heavy metals. It was found that when Pb2+, Zn2+, and Cd2+ ions were exposed to laboratory rats for 30 days, the peak of erythrograms was 0.5, 1.0, and 1.5 minutes, respectively. The proportion of erythrocytes subjected to hemolysis at the peaks of erythrograms was significant and about 3 times higher than the control at prolonged exposure to Pb2+ and Zn2+ ions and almost corresponds to the control (36.0%) when exposed to Cd2+ ions. The hemolysis time was significantly reduced: 2.5 minutes at Pb2+ and Zn2+ ions, and 4.5 minutes at Cd2+ ions. It should be noted that by the 30th day of the experiment, all rats that received water with heavy metals had died. Thus, the results obtained indicate significant qualitative changes in the composition of the erythrocyte population of rats exposed to chronic exposure to heavy metal salts. [ABSTRACT FROM AUTHOR]

Simple Summary: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe hereditary skin disease characterized by skin and mucosa fragility. RDEB patients are predisposed to the development of life-threatening cutaneous squamous cell carcinoma (SCC). In this study, we investigated the immune profiles of SCCs occurring in a cohort of RDEB patients and compared them with clinical, histopathological and prognostic features. We describe two distinct clinical outcomes in RDEB patients with cutaneous SCCs. A majority of RDEB patients had local and not rapidly life-threatening SCC, while others developed early aggressive and metastatic SCCs. The high-risk primary RDEB-SCC was associated with a tumor microenvironment displaying a higher neutrophil-to-lymphocyte infiltration ratio. Increased levels of citrullinated histone H3, a marker of neutrophil extracellular traps (NET), were detected in tumoral skin and in the serum of RDEB patients with high-risk primary SCC. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs. [ABSTRACT FROM AUTHOR]

Simple Summary: From detection to monitoring therapeutic response, circulating tumor DNA has emerged at the forefront of numerous clinical applications in oncology. It provides a non-invasive, real-time window into the evolving tumor as the cancer progresses. Advances in liquid biopsies and circulating tumor DNA analysis are enhancing their diagnostic applicability with tools like liposomal nanoparticles and antibody priming agents by binding to cell-free DNA in circulation and aiding in evading clearance mechanisms. The development of highly sensitive techniques such as digital droplet PCR and next-generation sequencing-based technologies has enabled the detection of minute ctDNA fractions amid high background, increasing its potential for early detection and minimal residual disease. Circulating tumor DNA (ctDNA), a fragment of tumor DNA found in the bloodstream, has emerged as a revolutionary tool in cancer management. This review delves into the biology of ctDNA, examining release mechanisms, including necrosis, apoptosis, and active secretion, all of which offer information about the state and nature of the tumor. Comprehensive DNA profiling has been enabled by methods such as whole genome sequencing and methylation analysis. The low abundance of the ctDNA fraction makes alternative techniques, such as digital PCR and targeted next-generation exome sequencing, more valuable and accurate for mutation profiling and detection. There are numerous clinical applications for ctDNA analysis, including non-invasive liquid biopsies for minimal residual disease monitoring to detect cancer recurrence, personalized medicine by mutation profiling for targeted therapy identification, early cancer detection, and real-time evaluation of therapeutic response. Integrating ctDNA analysis into routine clinical practice creates promising avenues for successful and personalized cancer care, from diagnosis to treatment and follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer remains a burden for women worldwide. Among the factors that contribute to breast cancer development is estrogen exposure during one's lifetime, both endocrine and exocrine. Polymorphisms in KEAP1-NRF2 complex, the master regulator of oxidative stress metabolism, have been correlated with a poorer outcome. The aim of our study was to identify and correlate polymorphisms in this complex, in breast cancer tissue, benign surrounding tissue and in peripheral blood. We verified a tendency towards the loss of heterozygosity in the benign surrounding tissue when compared to blood and to tumour tissue. Correlating with clinical data, histologic grade 2 has a higher variability of genotypes. The results indicate a heterogeneous and active microenvironment. Therefore, clinical approaches would benefit from the evaluation of somatic mutations in this complex. Moreover, further studies should be developed in order to evaluate the predictive value of the histologic grades, taking into consideration the genetic profile. Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surrounding tissue (p-value = 0.023) and tumour/surrounding tissues (p-value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is the leading cause of cancer-related death. While sex and age impact outcomes in non-small cell lung cancer (NSCLC), it is not clearly understood how these factors affect tumor biology. We believe that sex and age influence the distribution of genomic alterations in NSCLC and evaluated for differences in predictive and/or prognostic alterations in individuals with advanced NSCLC. Our study is the largest, to our knowledge, to evaluate and confirm that the genomic landscape in advanced NSCLC differs by both sex and age. Genomic mutations impact non-small cell lung cancer (NSCLC) biology. The influence of sex and age on the distribution of these alterations is unclear. We analyzed circulating-tumor DNA from individuals with advanced NSCLC from March 2018 to October 2020. EGFR, KRAS, ALK, ROS1, BRAF, NTRK, ERBB2, RET, MET, PIK3CA, STK11, and TP53 alterations were assessed. We evaluated the differences by sex and age (<70 and ≥70) using Fisher's exact test. Of the 34,277 samples, 30,790 (89.83%) had a detectable mutation and 19,923 (58.12%) had an alteration of interest. The median age of the ctDNA positive population was 69 (18–102), 16,756 (54.42%) were female, and 28,835 (93.65%) had adenocarcinoma. Females had more alterations in all the assessed EGFR mutations, KRAS G12C, and ERBB2 ex20 ins. Males had higher numbers of MET amp and alterations in STK11 and TP53. Patients <70 years were more likely to have alterations in EGFR exon 19 del/exon 20 ins/T790M, KRAS G12C/D, ALK, ROS1, BRAF V600E, ERBB2 Ex20ins, MET amp, STK11, and TP53. Individuals ≥70 years were more likely to have alterations in EGFR L861Q, MET exon 14 skipping, and PIK3CA. We provided evidence of sex- and age-associated differences in the distribution of genomic alterations in individuals with advanced NSCLC. [ABSTRACT FROM AUTHOR]