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Methodological Considerations in Blood Pressure Variability Assessment for Branch Atheromatous Disease
(WILEY, 2025) Aker, Mücahit; Kalçık, Macit; Bekar, Lütfü
Dear Editor, The recent multicenter study examining the relationship between systolic blood pressure variability (BPV) and 90-day functional outcomes in branch atheromatous disease (BAD) provides valuable data on a clinically challenging stroke subtype [1].
Comments on the relationship between microRNA-155-5p and postoperative inflammatory markers in children with acute suppurative appendicitis, and its role in predicting postoperative complications
(TURKISH J PEDIATRICS, 2025) Coşkun, Nurcan
Dear Editor, I read with interest the study by Dr. Duan et al.1 titled “The relationship between microRNA-155-5p and postoperative inflammatory markers in children with acute suppurative appendicitis and its role in predicting postoperative complications” published in The Turkish Journal of Pediatrics.
A scoping review of the health effects of fermented foods in specific human populations and their potential role in precision nutrition: current knowledge and gaps
(FRONTIERS MEDIA SA, 2025) Humblot, Christele; Alvanoudi, Panagiota; Alves, Emilia; Assuncao, Ricardo; Belovic, Miona; Bulmuş Tüccar, Tuğçe; Karagöz, Mustafa Fevzi
Background: Diets and specific foods have a significant impact on health, and individual responses to nutritional factors vary. This variability among humans can be considered a basis for developing personalized or precision nutrition. Fermented foods (FF) contain a wide range of macro- and micronutrients, bioactive compounds, and live or dead microorganisms. FF represent a diverse range of products and have garnered significant interest due to their potential health benefits. However, consistent evidence remains limited, possibly due to heterogeneity in individual responses. Objectives: The objective of this review is to assess and compile existing evidence on the variable responses of populations to FF and to determine whether FF could be integrated into a precision nutrition strategy. Design: Interventional and observational human studies were systematically collected. The publication identified the main factors likely to contribute to variable responses to FF across all health outcomes. The question was systematically addressed to assess the available evidence and identify knowledge gaps, guiding future research. A pragmatic approach was employed, following EFSA health claim guidelines, which require an assessment of food characteristics and mechanisms of action, as well as conducting a systematic search of human interventional studies. A similar approach was used to analyze data extracted from observational studies. The population included all humans (healthy and non-healthy, of all ages), encompassing both observational and interventional studies. The intervention consisted of the ingestion of any FF, while the control was defined as the absence or lower consumption of FF or consumption of a corresponding non-FF. Outcomes included all markers of the population's health status. Results: The main factors contributing to variable responses to FF across all health outcomes were related to initial phenotypic characteristics (biological sex, geographical origin, hormonal status, and age), baseline health status [metabolic syndrome [MetS], chronic metabolic pathologies, cancer, and psychological disorders], and genetic background. Additionally, since the gut microbiota is person-specific and influences metabolic responses, particular attention was paid to its functions and role in the variability of population responses to FF. Conclusion: Collectively, this review represents a first step toward evaluating the feasibility of using FF in tailored nutritional strategies. Systematic review registration: https://osf.io/69d3f/overview.
Long-Term Cardiac Outcomes Following Renal Denervation: A Need for Imaging-Based Evidence
(WILEY, 2025) Çelik, Muhammet Cihat; Çelik, Ömer Burak; Kalçık, Macit
Dear Editor, We read with interest the article by Sesa-Ashton et al., which examined electrocardiographic changes in left ventricular mass index (LVMI) and atrial fibrillation (AF) incidence over more than 8 years of follow-up after renal denervation (RDN) [1].
Ultrafiltration pattern in automated peritoneal dialysis
(OXFORD UNIV PRESS, 2025) Sayarlıoğlu, Hayriye; Türkmen, Ercan; Doğan, İbrahim; Çınar, Ersin; Uçar, Emel
Real-world outcomes and prognostic factors in primary mediastinal B-cell lymphoma: a multicenter study of 157 patients
(SPRINGER, 2025) Küçükyurt, Selin; Koca, Oğuzhan; Demirsoy, Esra Terzi; Akın, Serkan; Doğan, Ali; Yıldız, Abdülkerim
Primary mediastinal B-cell lymphoma (PMBCL) is a rare and distinct subtype of non-Hodgkin lymphoma. No consensus exists on optimal frontline treatment, and the use of R-CHOP +/- radiotherapy (RT) and DA-EPOCH-R +/- RT remains common, yet comparative real-world data are limited. In our multicenter retrospective study, we analyzed PMBCL patients, stratified by the first-line therapy (R-CHOP-21 +/- RT or DA-EPOCH-R +/- RT). Primary outcomes were complete response (CR) rate, progression-free survival (PFS), and overall survival (OS), alongside assessment of treatment-related toxicities and prognostic factors for PFS and OS. We included 157 patients [R-CHOP +/- RT group (n = 80) and DA-EPOCH-R +/- RT group (n = 77)] with a median age of 31 years, of whom 68.2% were female. CR rates were similar for R-CHOP +/- RT (75%) and DA-EPOCH-R +/- RT (76.6%). RT use was higher in the R-CHOP group (41.2% vs. 19.5%, p = 0.002). DA-EPOCH-R had significantly higher toxicity (29.9% vs. 16.2%, p = 0.033). The median follow-up of the entire cohort was 29 months with 2-year PFS and OS rates of 73.9% and 83.6%, respectively. Also, PFS and OS did not differ between regimens. In patients achieving CR with R-CHOP, RT omission did not impact survival. Multivariate analysis identified older age, poor performance status, superior vena cava syndrome and splenic involvement as independent OS predictors, while pericardial effusion, splenic involvement and hemoglobin < 10.5 g/dL were linked to inferior PFS. R-CHOP-21 +/- RT and DA-EPOCH-R +/- RT provide comparable efficacy in PMBCL. Due to the higher toxicity of DA-EPOCH-R, for those achieving CR following R-CHOP, selective RT omission may be a reasonable alternative. Established and disease-specific prognostic factors should guide individualized treatment strategies.
Impact of the COVID-19 Pandemic on CLABSI Rates and Antibiotic Resistance: A Multicenter Study in Türkiye
(DOC DESIGN INFORMATICS CO LTD, 2025) Sargın Altınok, Elif; Keşke, Şiran; Batırel, Ayşe; Bilgin, Hüseyin; Akdoğan, Özlem
Objective: The COVID-19 pandemic significantly disrupted infection control practices in healthcare settings. Previous studies have reported increased rates of central line-associated bloodstream infections (CLABSI), particularly during the early stages and peak periods of the pandemic. This multicenter study aimed to evaluate the impact of the COVID-19 pandemic on CLABSI rates in T & uuml;rkiye over a four-year period from 2019 to 2022. Materials and Methods: We conducted a retrospective analysis of prospectively collected CLABSI data from hospitals across various regions of T & uuml;rkiye between 2019 and 2022. The study period was divided into three phases: pre-pandemic, early pandemic, and late pandemic. Demographic and clinical characteristics, mortality rates, and microbiological data were analyzed. Pathogen distribution and antibiotic resistance patterns were compared between the pre-pandemic and pandemic periods. Results: A total of 25 hospitals participated in the study. The CLABSI rates per 1000 catheter days were 4.26 in 2019, 4.13 in 2020, 3.68 in 2021, and 3.53 in 2022. Across all periods, 3238 pathogens were identified. Gram-negative bacteria predominated both before and during the pandemic, with Acinetobacter baumannii (18.6%) and Klebsiella pneumoniae (17.8%) being the most common. Notably, an increase in carbapenem and colistin resistance in K. pneumonia was observed during the pandemic compared to the pre-pandemic period. Conclusions: In T & uuml;rkiye, the predominant causative agents of CLABSI did not change during the pandemic, with Klebsiella spp. and A. baumannii being most frequently isolated. However, the rise in CLABSI-associated mortality during the pandemic highlights the broader impact of healthcare system disruptions.
Assisting the Diagnosis of Cirrhosis in Chronic Hepatitis C Patients Based on Machine Learning Algorithms: A Novel Non-Invasive Approach
(WILEY, 2025) Dirican, Emre; Bal, Tayibe; Önlen, Yusuf; Sarıgül, Figen; Baykam, Nurcan
Aim: This study aimed to determine the important features and cut-off values after demonstrating the detectability of cirrhosis using routine laboratory test results of chronic hepatitis C (CHC) patients in machine learning (ML) algorithms. Methods: This retrospective multicenter (37 referral centers) study included the data obtained from the Hepatitis C Turkey registry of 1164 patients with biopsy-proven CHC. Three different ML algorithms were used to classify the presence/absence of cirrhosis with the determined features. Results: The highest performance in the prediction of cirrhosis (Accuracy = 0.89, AUC = 0.87) was obtained from the Random Forest (RF) method. The five most important features that contributed to the classification were platelet, alpha lpha-feto protein (AFP), age, gamma-glutamyl transferase (GGT), and prothrombin time (PT). The cut-off values of these features were obtained as platelet < 182.000/mm3, AFP > 5.49 ng/mL, age > 52 years, GGT > 39.9 U/L, and PT > 12.35 s. Using cut-off values, the risk coefficients were AOR = 4.82 for platelet, AOR = 3.49 for AFP, AOR = 4.32 for age, AOR = 3.04 for GGT, and AOR = 2.20 for PT. Conclusion: These findings indicated that the RF-based ML algorithm could classify cirrhosis with high accuracy. Thus, crucial features and cut-off values for physicians in the detection of cirrhosis were determined. In addition, although AFP is not included in non-invasive indexes, it had a remarkable contribution in predicting cirrhosis. Trial Registration: Clinicaltrials.gov identifier: NCT03145844
Renal Function and Atrial Remodeling: Interpreting Voltage-Mapping Limitations
(WILEY, 2025) Aker, Mücahit; Kalçık, Macit; Bekar, Lütfü
To the Editor, We read with interest the recent article by Deng et al., hichexplored the association between renal function and left atriallow-voltage area (LVA) burden in patients with atrial fibrillation(Deng et al. 2025).
Critical Appraisal of Circadian Blood Pressure Patterns as Predictors of Mortality in the Intensive Care Setting
(WILEY, 2025) Kalçık, Macit; Bayam, Emrah
To the Editor, We have recently, with great interest, read the recent article byZhao et al., “Association of 24-h Blood Pressure Pattern withMortality in ICU Patients: A Retrospective Cohort Study” [1].
Integrating Sleep Disruption, Dietary Changes, and Therapy in Assessing the Effects of Ramadan Fasting on Blood Pressure
(WILEY, 2025) Yetim, Mücahit; Sarıhan, Abdullah; Kalçık, Macit
Kayaca, a new vertebrate locality from the Upper Miocene of Türkiye and its importance for the Turolian biogeography of the eastern peri-Mediterranean region
(SPRINGER HEIDELBERG, 2025) Konidaris, GE; Aytek, Aİ; Kostopoulos, DS; Yavuz, AY; Tarhan, E; Alçiçek, MC; Uyar, N; Harvati, K
We present here a new Upper Miocene vertebrate locality, Kayaca, from the Beya & gbreve;a & ccedil; Basin in southwestern T & uuml;rkiye that was discovered after surface survey and was subsequently systematically excavated. The locality yielded a diverse and rich vertebrate fauna notably including several complete cranial specimens. In this article we provide the first results on the taxonomy of the large mammal assemblage, and we discuss the biochronological implications. The Kayaca large mammal assemblage is dominated by hipparionine horses (Hipparion dietrichi morphotype, Cremohipparion sp.) and bovids (Gazella cf. ancyrensis, Sporadotragus parvidens, Tragoportax sp., Palaeoryx pallasi and the rare Gangraia), but includes also rhinocerotids (Miodiceros neumayri, Diceros sp.), suids (Hippopotamodon major), giraffids (Palaeotragus rouenii, Samotherium major), hystricids (Hystrix sp.), orycteropodids (Amphiorycteropus gaudryi), proboscideans (Deinotherium sp., Elephantimorpha indet.) and carnivorans. The latter are identified by some well-preserved specimens belonging to ictitheres (Protictitherium sp.), hyaenids (Adcrocuta eximia), felids (Pontosmilus sp. and a medium-sized felid) but also to the rare mustelid Parataxidea maraghana. The preliminary comparison with already known and well-studied faunal assemblages of T & uuml;rkiye and the wider region, particularly the neighboring localities of Samos in Greece, suggest an age of ca. 7.4, close to the transition of early/middle Turolian (MN 11/12). Located at the western corner of Asia, Kayaca comprises a key location linking the vertebrate faunas of Asia and Europe and offers valuable insights into the Late Miocene terrestrial ecosystems of the eastern peri-Mediterranean region.
Assessing Dexmedetomidin's Efficacy in Traumatic Brain Injury Treatment Using a Rat Experimental Model
(TURKISH NEUROSURGICAL SOC, 2025) Öztürk, Y; Bozkurt, İ; Mammadkhanli, O; Güvenç, Y; Şentürk, S; Güney, G; Ramírez, MDE; Gülbahar, O
AIM: To elucidate the effects of nasal and intraperitoneal dexmedetomidine (DexN and DexP, respectively) administration in an animal model, and to explore the underlying action mechanisms on the treatment of traumatic brain injury (TBI). MATERIAL and METHODS: A total of 31 Wistar albino rats served as a weight-drop model to induce experimental TBI. The two treatment groups received DexN and DexP on the day of the trauma and then after 5 days. The Garcia test was performed for the neurological evaluation along with histopathological and biochemical analyses. RESULTS: The rats in the treatment group displayed better neurological outcomes, as evidenced by a higher Garcia test score (p<0.001). DexP group presented with increased anti-inflammatory and neuroprotective effects in comparison to DexN (p<0.001). DexN group demonstrated a reduction in the neuron specific enolase (NSE) levels (p=0.023), indicating that it inhibited the neuronal destruction. CONCLUSION: The present study support the hypothesis that a psychoactive drug, Dex, which has been conventionally used for sleep disorders and is also known for its cognitive-enhancing properties, may have beneficial effects after TBI owing to its antiinflammatory, anti-oxidative, and neuroprotective properties.
Treatment and Follow-up of Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency in Childhood and Adolescence
(GALENOS PUBL HOUSE, 2025) Kendirci, HNP; Ünal, E; Dündar, I; Buluş, AD; Güneş, SO; Sıklar, Z
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease caused by the deficiency of one of the enzymes involved in cortisol synthesis. More than 95% of the cases occur as a result of defects in the gene encoding 21-hydroxylase (CYP21A2). 21-hydroxylase deficiency has been divided into classical and non-classical forms. In the treatment of classical CAH, it is necessary to replace both glucocorticoid (GC) and mineralocorticoid hormones to prevent salt wasting crisis and reduce excessive corticotropin. In addition to biochemical measurements to evaluate the adequacy of GC and mineralocorticoid treatment; growth rate, body weight, blood pressure and physical examination should be evaluated regularly. There is insufficient data regarding the use of continuous slow-release or modified-release hydrocortisone (HC) preparations and continuous subcutaneous HC infusion, additional/alternative treatment approaches, and cell-based therapies and gene editing technology in children with CAH. GC therapy is recommended in children with inappropriately early onset and rapidly progressing pubarche or accelerated bone age progression, and in adolescents with non-classical CAH (NCCAH) who have overt virilization. In patients with NCCAH, stress doses of HC is recommended for major surgery, trauma, or childbirth but only if the patient has a suboptimal cortisol response to the adrenocorticotropic hormone test. Here, members of the 'Adrenal Working Group' of 'The Turkish Society for Pediatric Endocrinology and Diabetes' present an evidence-based review with good practice points and recommendations for optimize treatment, and follow-up of children with CAH due to 21-hydroxylase deficiency in the light of the most recent evidence.
Effect of Inspiratory Muscle Training on Diaphragm and Abdominal Wall Muscle Thickness with Fatty Liver Density in Elderly Women: A Randomized Controlled Trial
(MDPI, 2025) Gökçelik, E; Yılmaz, C; Budak, C; Soylu, HH; Bayrakdaroğlu, S; Ceylan, Hİ; Muntean, RI; Küçük, H; Ceylan, L
Background and Objectives: Post-menopausal estrogen decline is considered a contributing factor to sarcopenia, and inspiratory muscle training (IMT) may provide benefits in this demographic. This study examined the impact of a four-week IMT program on diaphragm thickness, abdominal wall muscle thickness (AWMT; transversus abdominis, internal oblique, and external oblique), and liver fat percentage in healthy elderly women. Materials and Methods: Twenty-six women aged 60-80 years were randomly assigned to an IMT group (n = 13) or a control group (n = 13). The IMT group used the PowerBreathe (R) Classic device at 40% of maximal inspiratory pressure (MIP), with weekly increments of 10%. Training was performed twice daily, five days per week, with 30 breathing cycles per session (60 per day). The control group maintained their usual routines. AWMT, diaphragm thickness (DT), and fatty liver density (FLD) were measured by a radiologist before and after the intervention. Results: After four weeks, the IMT group showed significant improvements in all parameters compared to controls. Mid-diaphragm thickness (MDT) increased by 11.44% (effect size (ES) = 0.358, p < 0.001) versus 0.76% in controls (p = 0.271). Posterior diaphragm thickness (PDT) improved by 7.48% (ES = 0.282, p < 0.001) versus 0.38% (p = 0.564). Right AWMT increased by 12.7% (ES = 0.492, p < 0.001) compared to 0.10% (p = 0.872), and left AWMT increased by 9.93% (ES = 0.395, p < 0.001) versus 2.64% (p = 0.014). FLD improved by 11.79% (ES = 0.959, p < 0.001) in the IMT group, while the control group showed no meaningful change (-0.13%, p = 0.847). Conclusions: A short-term IMT protocol significantly enhanced diaphragm and AWMT and reduced liver fat in elderly women. These findings support the use of IMT as a simple, non-invasive intervention to preserve musculoskeletal and metabolic health in aging populations.
Maximizing performance in child footballers: chronotype and time of day study
(FRONTIERS MEDIA SA, 2025) Kaba, İ; Çelikel, BE; Adanur, O; Yılmaz, C; Sezer, SY; Tan, Ç; Durhan, TA; Özer, U; Ceylan, T
Background A limited number of studies have investigated the effects of circadian rhythm-based running exercise interventions on physical fitness in child athletes. This study aimed to investigate the effects of an eight-week morning and evening running program on lower extremity strength, agility and respiratory function in 10-12-year-old male footballers.Methods Participants visited the laboratory three times, with one-day intervals before and after the training program. The assessments included maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the FEV1/FVC ratio. Additionally, agility and functional performance tests (FPTs) were conducted for both the dominant and non-dominant legs.Results The findings indicated that morning running was more effective than evening running in enhancing respiratory function. Morning running also showed superior results in lower extremity strength tests, particularly in the single-leg (SL) and triple-leg (THD) crossover hop for distance tests (CHDs) and the 6-m timed-hop test (6 m THT). Furthermore, the agility performance of the morning running group was significantly better than that of the evening and control groups.Conclusion Consequently, morning running interventions had a positive impact on key physical fitness parameters, including respiratory muscle strength, respiratory function, agility, and lower extremity strength in child footballers.
Structural and Magnetic Characterization, Biomedical Applications, and Hyperfine Interactions of Quaternary Nanospinel Ferrites
(AMER CHEMICAL SOC, 2025) Aljameel, SS; Baykal, A; Almessiere, MA; Rehman, S; Çalışkan, S; Khan, FA; Amir, M; Shirsath, SE; Güngüneş, H; Slimani, Y
In this study, the following, Co0.25Ni0.25Mn0.25Zn0.25Fe2O4 (CoNiMnZn), Co0.25Ni0.25Mn0.25Cu0.25Fe2O4 (CoNiMnCu), Co0.25Ni0.25Zn0.25Cu0.25Fe2O4 (CoNiZnCu), Co0.25Mn0.25Zn0.25Cu0.25Fe2O4 (CoMnZnCu), and Ni0.25Mn0.25Zn0.25Cu0.25Fe2O4 (NiMnZnCu), nano spinel ferrites (NSFs) have been synthesized via a sol-gel auto combustion route. Their XRD analysis confirmed the formation of cubic crystalline nanoproducts without any impurity. The crystallite size of the products varied between 15 and 26 nm. EDX analysis confirmed the chemical composition of each product. According to Mossbauer results, Zn2+ ions occupy A sites. The s-electron density of Fe3+ ions at the A and B sites increased with the Zn2+ doping. The magnetic features of samples with various combinations of Co, Ni, Cu, Mn, and Zn were systematically investigated at room temperature (RT, 300 K) and 10 K. Key magnetic parameters M s (saturation magnetization), M r (remanent magnetization), H c (coercivity), squareness ratio, magnetic moment, and magnetocrystalline anisotropy field) are extracted to elucidate the influence of cationic doping and temperature on their magnetic response. Among all samples, CoNiMnCu displayed the highest magnetic hardness and anisotropy, while NiMnZnCu NSFs exhibited soft magnetic behavior with high M s and low H c. The results demonstrate significant improvements in magnetic ordering and anisotropy at 10 K across all samples, revealing the temperature-driven enhancement of ferrimagnetic coupling. These findings highlight the tunability of magnetic performance through cation engineering and provide guidance for designing spinel ferrites tailored to specific technological applications, such as permanent magnets, sensors, and magnetic devices. The breast cancer cell (MCF-7) biomedical application of all samples showed a significant decrease in cancer cells as revealed by the MTT assay. Among all samples, CoNiZnCu NSFs showed the highest anticancer activities, as the cell viability was 57.95%. We have also examined the treatment of NSFs on HEK-293, and we detected a reduction in cancer cell viability. However, treatment of NSFs showed more cytotoxicity to breast cancer cells than normal cells. The cells were also stained with DAPI staining. The treatment of CoNiZnCu NSFs produced significant cytotoxicity in breast cancer cells. Moreover, CoNiZnCu NSFs induced chromatin abridgment and apoptotic bodies' formation in the cancer cells. The antimicrobial potential of synthesized metal-based compounds was investigated against Enterococcus faecalis and Candida albicans. Five NSFs were tested at a 16 mg/mL concentration using the broth dilution method. E. faecalis showed strong susceptibility to all compounds except CoNiMnZn NSFs. C. albicans exhibited mild resistance, with only CoMnZnCu NSFs showing notable antifungal activity. The findings highlighted selective and promising antimicrobial effects based on the microbial structure.
Therapeutic Effects of tDCS on Calcium and Glutamate Excitotoxicity in a Cerebral Ischemia-Reperfusion Rat Model
(TURKISH NEUROSURGICAL SOC, 2025) Akçay, G; Demirdöğen, F; Kotan, D; Gül, T; Yılmaz, A; Ergül, YM; Çelik, C
AIM: To investigate the therapeutic effects of transcranial direct current stimulation (tDCS) on calcium and glutamate excitotoxicity caused by ischemia-reperfusion (IR). MATERIAL and METHODS: The IR model was generated by transient middle cerebral artery occlusion. tDCS treatment was applied at 1 mA for 30 min daily at the 2nd, 24th, and 48th h of IR. The motor and cognitive functions and the concentrations of Ca2+, glutamate, and N-methyl-D-aspartate receptor (NMDAR) in the hippocampus tissues were evaluated. RESULTS: Results showed a reduction in motor and cognitive functions in the IR group compared with that in the sham group, whereas these functions increased in the IR+tDCS group compared with those in the IR group. Ca2+, glutamate, and NMDAR concentrations were higher in the IR group than in the sham group but lower in the IR+tDCS group than in the IR group. CONCLUSION: These results suggest that tDCS treatment improves motor and cognitive dysfunctions after IR and exerts therapeutic effects on learning and memory through the regulation of Ca2+ and glutamate excitotoxicity.
Effect of histidine and carnosine on haemoglobin recovery in anaemia induced-kidney damage and iron-loading mouse models
(SPRINGER WIEN, 2025) Vera-Aviles, M; Moreno-Fernandez, J; Kose, T; Hider, R; Latunde-Dada, GO
Histidine and carnosine can form complexes with divalent metal ions such as Fe2+, potentially providing stability to intracellular labile iron. Anaemia is a common comorbidity in the late stages of kidney disease, and patients are treated with erythropoiesis-stimulating agents (ESAs) and iron supplementation. However, iron supplementation is also associated with worse long-term outcomes. The purpose of this study is to investigate how histidine and carnosine supplementation can reduce symptoms of anaemia of chronic kidney disease (CKD) and the effects associated with iron-overloaded conditions. Adenine-induced chronic kidney disease mice were treated with histidine and carnosine by oral gavage for 10 days. Additionally, a model involving iron overload in mice was established, and these mice received concurrent treatment with histidine and carnosine. Haemoglobin, non-haem iron, malondialdehyde (MDA) and iron parameters were measured. Carnosine increased erythropoietin (EPO) levels (35.62 mu g/ml +/- 11.43) and resulted in haemoglobin repletion (16.7 g/dL +/- 3.4). When iron was supplemented alongside with histidine or carnosine, there were better effects on haemoglobin repletion (14.22 +/- 1.7 and 13.82 +/- 2.15 g/ dL respectively), ferritin (59.5 +/- 16.4, 52 +/- 29.5 mu g/ml) and non-haem iron (0.8 +/- 0.21, 0.7 +/- 0.38 nmol/mg), than the group receiving iron alone (p < 0.05). Furthermore, histidine and carnosine reduced non-haem iron and MDA, in iron-loaded conditions (p < 0.05). These positive effects observed in histidine and carnosine could be associated with reactive oxygen species (ROS) scavenging. EPO restoring levels in CKD model and the increment in haemoglobin and ferritin in carnosine treatments suggested the potential formation of a ternary complex with iron-glutathione. In conclusion, our results indicate the beneficial effect of histidine and carnosine in the context of iron supplementation for the correction of haemoglobin and protection against iron-loaded conditions.
Rapid, sensitive, and species-independent detection of Crimean Congo hemorrhagic fever virus nucleoprotein and GP38 antibodies
(ELSEVIER, 2025) Karaaslan, E; Chiang, CF; Kurutaş, GO; Barkay, O; Güler, NSC; Kalkan, MY; Parlayan, HNK; Akdoğan, O; Çelikbaş, AK; Aksoy, F; Binay, UD; Baykam, N; Yılmaz, G; Sajadi, MM; Pegan, SD; Klena, JD; Montgomery, JM; Karakeçili, F; Kalkan, A; Doymaz, MZ; Spiropoulou, CF; Bergerona, E
Background Crimean-Congo hemorrhagic fever virus (CCHFV), a zoonotic agent in the Nairoviridae family (genus Orthonairovirus), is a high-priority pathogen. CCHFV infection causes Crimean-Congo hemorrhagic fever (CCHF), a human disease with case fatality rates of up to 40%. Serological surveillance of CCHFV in animals and humans is crucial for ecological studies and public health. Methods We developed CCHFV mix-and-read assays utilizing split-NanoLuc technology (NanoBiT) to detect anti-CCHFV antibodies against the nucleoprotein (NP) stalk region and the GP38 glycoprotein. These species-and isotypeagnostic assays provide results in similar to 30 min. Using serum samples from RT-PCR-confirmed CCHF cases collected during and after hospitalization, we investigated anti-NP and anti-GP38 antibody development. The performance of the mix-and-read assays was compared to the NP-based IDScreen (R) CCHF commercial assay using human sera, and cross-reactivity potential was evaluated using a diverse panel of anti-orthonairovirus antisera raised in mice. Findings In human convalescent cases (n = 21), mix-and-read assay concordance between anti-GP38 and anti-NP antibody detection was 100%. Both mix-and-read assays and IDScreen (R) CCHF demonstrated identical sensitivity of 95.2% in convalescent patients. The specificity of the NP assay was 98.9%, and that of GP38 was 99.7%, both comparable to IDScreen (R) CCHF (specificity: 99.7%). Cross-reactivity against CCHF NP and GP38, regardless of assay type, was primarily observed in antisera raised against other orthonairoviruses within the Nairobi sheep disease genogroup. Interpretation The simplicity and robust performance of the CCHFV mix-and-read assays make them ideal tools for supporting serological surveillance in humans and animals. Furthermore, the inclusion of the GP38 antigen alongside NP enhances the precise identification of retrospective CCHF cases, further strengthening broad surveillance efforts. Funding CDC Emerging Infectious Disease Research Core Funds, funding for reagent, CDC personal, travel. Defence Threat Reduction Agency (HDTRA12210007): E.K. salary. Oak Ridge Institute for Science and Education (ORISE): E.K. salary and travel. National Institute of Allergy and Infectious Diseases (1R01AI180125-01A1): sample acquisition. Funding sources did not have a role in the writing or decision to submit the publication. Copyright Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

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