Early Marker Research Articles

MiR-145a-5p/SIK1/cAMP-dependent alteration of synaptic structural plasticity drives cognitive impairment induced by coke oven emissions

Exposure to fine particulate matter (PM) is associated with the neurodegenerative diseases. Coke oven emissions (COEs) in occupational environment are important sources of PM. However, its neurotoxicity is still unclear. Therefore, evaluating the toxicological effects of COE on the nervous system is necessary. In the present study, we constructed mouse models of COE exposure by tracheal instillation. Mice exposed to COE showed signs of cognitive impairment. This was accompanied by a decrease in miR-145a-5p and an increase in SIK1 expression in the hippocampus, along with synaptic structural damage. Our results demonstrated that COE-induced miR-145a-5p downregulation could increase the expression of SIK1 and phosphorylated SIK1, inhibiting the cAMP/PKA/CREB pathway by activating PDE4D, which was associated with reduced synaptic structural plasticity. Furthermore, restoring of miR-145a-5p expression based on COE exposure in HT22 cells could partially reversed the negative effects of COE exposure through the SIK1/PDE4D/cAMP axis. Collectively, our findings link epigenetic regulation with COE-induced neurotoxicity and imply that miR-145a-5p could be an early diagnostic marker for neurological diseases in patients with COE occupational exposure.

Effect of curcumin-containing nanofibrous gelatin-hydroxyapatite scaffold on proliferation and early osteogenic differentiation of dental pulp stem cells.

In recent years, the electrospinning method has received attention because of its usage in producing a mimetic nanocomposite scaffold for tissue regeneration. Hydroxyapatite and gelatin are suitable materials for producing scaffolds, and curcumin has the osteogenesis induction effect. This study aimed to evaluate the toxicity and early osteogenic differentiation stimulation of nanofibrous gelatin-hydroxyapatite scaffold containing curcumin on dental pulp stem cells (DPSCs). The objective of the present investigation was the evaluation of the proliferative effect and primary osteogenic stimulation of DPSCs with a nanofibrous gelatin-hydroxyapatite scaffold containing curcumin. Hydroxyapatite and gelatin were used as suitable and biocompatible materials to make a scaffold suitable for stimulating osteogenesis. Curcumin was added to the scaffold as an osteogenic differentiation-enhancing agent. The effect of nano-scaffold on the proliferation of DPSCs was evaluated. The activity of alkaline phosphatase (ALP) as the early osteogenic marker was considered to assess primary osteogenesis stimulation in DPSCs. The nanofibrous gelatin-hydroxyapatite scaffold containing curcumin significantly increased the proliferation and the ALP activity of DPSCs (P<0.05). The proliferative effect was insignificant in the first 2 days, but the scaffold increased cell proliferation by more than 40% in the fourth and sixth days. The prepared scaffold increased the activity of the ALP of DPSCs by 60% compared with the control after 14 days (P<0.05). The produced nanofibrous gelatin-hydroxyapatite scaffold containing curcumin can be utilized as a potential candidate in tissue engineering and regeneration of bone and tooth. The prepared scaffold in the present study could be a beneficial biomaterial for tissue engineering and the regeneration of bone and tooth soon.

Neutrophil lymphocyte ratio and heart type fatty acid binding protein as a prognostic marker in Myocardial infarction within 48h of admission.

The neutrophil to lymphocyte ratio (NLR) is a measure of systemic inflammation, whereas Heart type fatty acid protein (HFABP) is a cytosolic protein released early after acute coronary syndrome (ACS). The aim of this research study is to determine whether NLR and H-FAB are useful in predicting the prognosis in patients with ST segment elevation myocardial infarction (STEMI) 48h after admission. This is a prospective observational study conducted on 97 patients who had been admitted to emergency room with ST-elevation myocardial infarction in their ECG in a tertiary care centre of south India. The neutrophil-lymphocyte ratio was measured at the time of admission, 24th hour and 48th hour, and then compared with the outcome. To determine their significance in the MI episode, troponin-I and H-FABP were also measured. A significant correlation was found in the final outcomes of patients and the NLR at the time of admission and at 48h (p = 0.01). Additionally, a substantial correlation between NLR and various degrees of LV dysfunction was also observed (p = 0.01). H-FABP was found to be positive in all 97 of the patients examined, whereas Troponin-I was only found to be positive in 56.7%. The study's findings, indicated strong correlations between NLR and LVEF, indicated that NLR might serve as an early predictor of cardiac events which could be either poor prognosis or higher mortality. This research found that H-FABP may serve as an early MI diagnostic marker.

Cardiovascular autonomic failure in hereditary transthyretin amyloidosis and TTR carriers is an early and progressive disease marker.

The cardiomyopathic and neuropathic phenotype of hereditary transthyretin amyloidosis are well recognized. Cardiovascular autonomic dysfunction is less systematically and objectively assessed. Autonomic and clinical features, quantitative cardiovascular autonomic function, and potential autonomic prognostic markers of disease progression were recorded in a cohort of individuals with hereditary transthyretin amyloidosis and in asymptomatic carriers of TTR variants at disease onset (T0) and at the time of the first quantitative autonomic assessment (T1). The severity of peripheral neuropathy and its progression was stratified with the polyneuropathy disability score. A total of 124 individuals were included (111 with a confirmed diagnosis of hereditary transthyretin amyloidosis, and 13 asymptomatic carriers of TTR variants). Symptoms of autonomic dysfunction were reported by 27% individuals at T0. Disease duration was 4.5 ± 4.0years [mean ± standard deviation (SD)] at autonomic testing (T1). Symptoms of autonomic dysfunction were reported by 78% individuals at T1. Cardiovascular autonomic failure was detected by functional testing in 75% individuals and in 64% of TTR carriers. Progression rate from polyneuropathy disability stages I/II to III/IV seemed to be shorter for individuals with autonomic symptoms at onset [2.33 ± 0.56 versus 4.00 ± 0.69years (mean ± SD)]. Cardiovascular autonomic dysfunction occurs early and frequently in individuals with hereditary transthyretin amyloidosis within 4.5years from disease onset. Cardiovascular autonomic failure can be subclinical in individuals and asymptomatic carriers, and only detected with autonomic function testing, which should be considered a potential biomarker for early diagnosis and disease progression.

Spatially distinct epithelial and mesenchymal cell subsets along progressive lineage restriction in the branching embryonic mammary gland.

How cells coordinate morphogenetic cues and fate specification during development remains a fundamental question in organogenesis. The mammary gland arises from multipotent stem cells (MaSCs), which are progressively replaced by unipotent progenitors by birth. However, the lack of specific markers for early fate specification has prevented the delineation of the features and spatial localization of MaSC-derived lineage-committed progenitors. Here, using single-cell RNA sequencing from E13.5 to birth, we produced an atlas of matched mouse mammary epithelium and mesenchyme and reconstructed the differentiation trajectories of MaSCs toward basal and luminal fate. We show that murine MaSCs exhibit lineage commitment just prior to the first sprouting events of mammary branching morphogenesis at E15.5. We identify early molecular markers for committed and multipotent MaSCs and define their spatial distribution within the developing tissue. Furthermore, we show that the mammary embryonic mesenchyme is composed of two spatially restricted cell populations, and that dermal mesenchyme-produced FGF10 is essential for embryonic mammary branching morphogenesis. Altogether, our data elucidate the spatiotemporal signals underlying lineage specification of multipotent MaSCs, and uncover the signals from mesenchymal cells that guide mammary branching morphogenesis.

Left Atrial Mechanics Following Preeclamptic Pregnancy.

Preterm preeclampsia is a pregnancy complication associated with myocardial dysfunction and premature cardiovascular disease morbidity and mortality. Left atrial (LA) strain is a noninvasive index of left ventricular end diastolic pressure and an early marker of heart failure risk. This study aimed to evaluate LA strain during the postpartum period in participants with and without preterm preeclampsia and to assess whether this varied in the presence of hypertension and/or cardiac dysfunction. In this longitudinal cohort study, 321 women from 28 hospitals with preterm preeclampsia (cases) underwent cardiovascular assessment 6 months postpartum. This is a secondary analysis of the PHOEBE study (ISRCTN01879376). An uncomplicated pregnancy control group (n=30) was recruited from a single center for comparison. A full cross-sectional transthoracic echocardiogram was performed, and from these images, the myocardial strain of the left atrium, including reservoir, conduit, and contractile strain, as well as LA stiffness, were calculated. At 6 months postpartum, compared with controls, prior preeclampsia was associated with a significantly attenuated LA reservoir, conduit, and contractile strain, as well as increased LA stiffness (all P<0.001). LA strain was further reduced in preeclamptic women who had and had not developed hypertension, systolic, or diastolic dysfunction at 6 months postpartum (all P<0.05). LA mechanics were significantly attenuated at 6 months postpartum in participants with preterm preeclampsia, whether or not they remained hypertensive or had evidence of ventricular dysfunction. Further studies are needed to determine whether postnatal LA strain may identify women at greater risk for future cardiovascular disease.

WHEN AND WHERE DOES A CARRIER OF HEREDITARY TRANSTHYRETIN AMYLOIDOSIS (ILE88LEU) SHOW THE FIRST SIGNS OF THE DISEASE? DIAGNOSTIC CHALLENGES OF A NOT ONLY CARDIOGENIC MUTATION

Abstract We present the case of a 58–year–old man with a familiar history (mother affected) positive for ATTR–v (Ile88Leu) amyloidosis. The mother initially had a pure cardiac phenotype and was firstly treated with tafamidis, but progression of the disease to the nervous system warranted a switch to patisiran. Our patient carried the Ile88Leu mutation and had a medical history notable for surgically treated left carpal tunnel syndrome (CTS) and untreated right CTS. Furthermore, he was affected by systemic arterial hypertension and was a habitual smoker. He has been followed at our Institution since 2018. His first echocardiogram showed normal left ventricular ejection fraction (LVEF 65%), mild hypertrophy (anterior septum: 12 mm), and borderline values of GLS (– 16%) without any specific pattern. Further exams were executed: Bone scintigraphy (BS): negative (Perugini score 0); Coronary artery ct scan: moderate stenosis of proximal LAD; Neurologic evaluation: no signs of peripheral neuropathy. The clinical picture remained unaltered in 2020 and 2021. However, during November 2022 the patient developed atrial fibrillation (AF) and presented to the ED for dyspnea and palpitations. Electrical cardioversion was performed with success but subsequent recurrences warranted AF ablation in April 2023. At that moment, the patient was re–evaluated. Basal ECG did not show any significant alteration (FIg.1)This time, echocardiogram showed mild worsening of hypertrophy (13 mm septum), GLS – 16% with apical sparing pattern, no other major variations (Fig.2). BS was repeated and revealed grade 1 Perugini score (Fig.3). Hence, a series of clinical question arose: Should we begin a specific treatment or is the disease in an excessively early stage that does not warrant treatment? Is AF linked to concomitant arterial hypertension or might it be an early marker of disease? We questioned the usefulness of endomyocardial biopsy in this specific setting. In this case, we repeated electromyography that showed mild axonal sensitive–motor polyneuropathy. Finally, we concluded for initial signs of systemic amyloidosis ATTR–v (Ile88Leu) type with mixed phenotype (neurological+cardiac). The neurological involvement allowed us to start a gene–silencer (Patisiran). In conclusion, a periodic neurological evaluation is necessary and has crucial therapeutic implications in all genotypes. Indeed, there is increasing evidence that Ile88Leu is a not only cardiogenic mutation.

SCARY ECG IN TAKOTSUBO CARDIOMYOPATHY

Abstract Takotsubo cardiomyopathy (TTC) is characterized by a transient ventricular wall motion abnormality and shares common features with acute coronary syndrome (ACS) with a wide spectrum of triggers, such as both emotional or physical, activating common toxic catecholamines–mediated pathways. TTC might be associated with severe clinical complications. We report a case of a 74–year female patient with circulatory shock with mixed phenotype, distributive due to sepsis and cardiogenic due to TTC. The patient presented to the emergency department with severe hypotension, pathological qSOFA score and clinical and laboratory findings consistent with severe sepsis. ECG showed diffuse lambda ST–segment elevation, also called “shark fin”(fig.1). According to hemodynamically unstable scenario and ECG pattern, emergency coronary angiography was performed, showing absence of coronary artery disease(fig. 2). Echocardiography revealed severe LV systolic disfunction (EF 20–25%) with apical ballooning and severe systolic anterior motion (SAM) of the anterior mitral leaflet eliciting dynamic LVOTO with peak gradient greater than 90 mmHg; fig. 3) and severe MR. Patient was treated with cautious fluid administration, hemotrasfusion and empiric large spectrum antibiotic therapy. According to TTC working diagnosis, even if septic state was thought to contribute to cardiogenic shock, norepinephrine was not administered due to concerns for LVOTO and SAM. After overcoming of dramatic first phase and after hemodynamic steadiness was achieved, beta blockade and ACEi were progressively administered. Seriate transthoracic echocardiogram revealed progressive improvement of LV systolic function, regression of apical ballooning, SAM and LVOTO. ECG monitoring showed regression of ischemic ST elevation. ST elevation has been described in about 56% of TTC cases, however with amplitude tipically lower than in STEMI. Lambda–wave ST elevation has been rarely reported. Vasospasm, local intermittent microvascular constriction, catecholamine–induced metabolic toxicity, transmural systolic wall tension and its the mechano–electric feedback can explain scaring ECG–pattern. Despite its rare prevalence in TTC “shark fin” pattern appears to relate to adverse outcome and it should be used as an early marker of potential further clinical deterioration, suggesting more intensive monitoring to avoid delays in possible therapy escalation.

Exploring early life social and executive function development in infants and risk for autism: a prospective cohort study protocol of NICU graduates and infants at risk for cerebral palsy

BackgroundDelays in early social and executive function are predictive of later developmental delays and eventual neurodevelopmental diagnoses. There is limited research examining such markers in the first year of life. High-risk infant groups commonly present with a range of neurodevelopmental challenges, including social and executive function delays, and show higher rates of autism diagnoses later in life. For example, it has been estimated that up to 30% of infants diagnosed with cerebral palsy (CP) will go on to be diagnosed with autism later in life.MethodsThis article presents a protocol of a prospective longitudinal study. The primary aim of this study is to identify early life markers of delay in social and executive function in high-risk infants at the earliest point in time, and to explore how these markers may relate to the increased risk for social and executive delay, and risk of autism, later in life. High-risk infants will include Neonatal Intensive Care Unit (NICU) graduates, who are most commonly admitted for premature birth and/or cardiovascular problems. In addition, we will include infants with, or at risk for, CP. This prospective study will recruit 100 high-risk infants at the age of 3–12 months old and will track social and executive function across the first 2 years of their life, when infants are 3–7, 8–12, 18 and 24 months old. A multi-modal approach will be adopted by tracking the early development of social and executive function using behavioural, neurobiological, and caregiver-reported everyday functioning markers. Data will be analysed to assess the relationship between the early markers, measured from as early as 3–7 months of age, and the social and executive function as well as the autism outcomes measured at 24 months.DiscussionThis study has the potential to promote the earliest detection and intervention opportunities for social and executive function difficulties as well as risk for autism in NICU graduates and/or infants with, or at risk for, CP. The findings of this study will also expand our understanding of the early emergence of autism across a wider range of at-risk groups.

Activin A: a marker of mineral bone disorder in children with chronic kidney disease?

Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease(CKD-MBD) and its relationship with other markers has not been studied in children with CKD. A cross sectional study was conducted among 40 children aged 2 to 18years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant. The mean age of children with CKD was 9.30 ± 3.64years. Mean levels of activin A in cases were 485.55pg/ml compared to 76.19pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18pg/ml while in controls it was 6.93pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001). Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children.

Differentially expressed genes associated with high metabolic tumor volume served as diagnostic markers and potential therapeutic targets for pancreatic cancer

BackgroundThe lack of distinct biomarkers for pancreatic cancer is a major cause of early-stage detection difficulty. The pancreatic cancer patient group with high metabolic tumor volume (MTV), one of the values measured from positron emission tomography—a confirmatory method and standard care for pancreatic cancer, showed a poorer prognosis than those with low MTV. Therefore, MTV-associated differentially expressed genes (DEGs) may be candidates for distinctive markers for pancreatic cancer. This study aimed to evaluate the possibility of MTV-related DEGs as markers or therapeutic targets for pancreatic cancer.MethodsTumor tissues and their normal counterparts were obtained from patients undergoing preoperative 18F-FDG PET/CT. The tissues were classified into MTV-low and MTV-high groups (7 for each) based on the MTV2.5 value of 4.5 (MTV-low: MTV2.5 < 4.5, MTV-high: MTV2.5 ≥ 4.5). Gene expression fold change was first calculated in cancer tissue compared to its normal counter and then compared between low and high MTV groups to obtain significant DEGs. To assess the suitability of the DEGs for clinical application, the correlation of the DEGs with tumor grades and clinical outcomes was analyzed in TCGA-PAAD, a large dataset without MTV information.ResultsTotal RNA-sequencing (MTV RNA-Seq) revealed that 44 genes were upregulated and 56 were downregulated in the high MTV group. We selected the 29 genes matching MTV RNA-seq patterns in the TCGA-PAAD dataset, a large clinical dataset without MTV information, as MTV-associated genes (MAGs). In the analysis with the TCGA dataset, MAGs were significantly associated with patient survival, treatment outcomes, TCGA-PAAD-suggested markers, and CEACAM family proteins. Some MAGs showed an inverse correlation with miRNAs and were confirmed to be differentially expressed between normal and cancerous pancreatic tissues. Overexpression of KIF11 and RCC1 and underexpression of ADCY1 and SDK1 were detected in ~ 60% of grade 2 pancreatic cancer patients and associated with ~ 60% mortality in stages I and II.ConclusionsMAGs may serve as diagnostic markers and miRNA therapeutic targets for pancreatic cancer. Among the MAGs, KIF11, RCC1, ADCY, and SDK1 may be early diagnostic markers.

Sensitivity of miRNA-181a, miRNA-23b and miRNA-16 in the Late-Onset Neonatal Sepsis: A Diagnostic Study

Abstract Objective The study aimed to evaluate the expression and diagnostic value of levels of the microRNAs (miRNAs), miRNA-181a, miRNA-23b, and miRNA-16, in late-onset neonatal sepsis (LOS) and compare them with the diagnostic utility of C-reactive protein (CRP) levels. Methods This was a prospective diagnostic study conducted between January 2021 and March 2023 at a tertiary care center (Sri Ramachandra Hospital) in India. Quantitative real-time polymerase chain reaction was performed to determine miRNA-181a, miRNA-23b, and miRNA-16 expression levels, and CRP was measured by nephelometry. The diagnostic value of miRNA and CRP levels were analyzed using receiver operating characteristic (ROC) curves. ROC curves were utilized to determine optimal cutoff points, and Mann–Whitney tests were performed using SPSS to ascertain P values, with statistical significance defined as &lt;0.05. Results This study included 100 samples, with 50 cases of culture-proven LOS (27 female, 23 male) and 50 healthy controls (31 female, 19 male). In LOS, miRNA-181a and miRNA-23b expression levels were significantly downregulated (P &lt; 0.001), with area under the curve (AUC) values of 0.83 and 0.92, respectively, whereas those of miRNA-16 were significantly upregulated (P &lt; 0.001; AUC = 0.97). In comparison, CRP levels had an AUC value of 0.831 (P &lt; 0.001). Further, miRNA-23b showed the highest sensitivity (98%) of markers tested, whereas miRNA-16 exhibited the highest specificity (96%). Conclusion MiRNA, especially miRNA-16, shows diagnostic potential for neonatal sepsis compared with traditional biomarkers like CRP and procalcitonin, suggesting its use as an early marker for LOS. However, further cohort studies are needed before practical application.

Vasoactive intestinal peptide exerts an osteoinductive effect in human mesenchymal stem cells.

Several neuropeptides present in bone tissues, produced by nerve fibers and bone cells, have been reported to play a role in regulating the fine-tuning of osteoblast and osteoclast functions to maintain bone homeostasis. This study aims to characterize the influence of the neuropeptide vasoactive intestinal peptide (VIP) on the differentiation process of human mesenchymal stem cells (MSCs) into osteoblasts and on their anabolic function. We describe the mRNA and protein expression profile of VIP and its receptors in MSCs as they differentiate into osteoblasts, suggesting the presence of an autocrine signaling pathway in these cells. Our findings reveal that VIP enhances the expression of early osteoblast markers in MSCs under osteogenic differentiation and favors both bone matrix formation and proper cytoskeletal reorganization. Finally, our data suggest that VIP could be exerting a direct modulatory role on the osteoblast to osteoclast signaling by downregulating the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio. These results highlight the potential of VIP as an osteoinductive differentiation factor, emerging as a key molecule in the maintenance of human bone homeostasis.

The Development of Socially Directed Attention: An Functional Magnetic Resonance Imaging Study in Infant Monkeys.

Socially guided visual attention, such as gaze following and joint attention, represents the building block of higher-level social cognition in primates, although their neurodevelopmental processes are still poorly understood. Atypical development of these social skills has served as early marker of autism spectrum disorder and Williams syndrome. In this study, we trace the developmental trajectories of four neural networks underlying visual and attentional social engagement in the translational rhesus monkey model. Resting-state fMRI (rs-fMRI) data and gaze following skills were collected in infant rhesus macaques from birth through 6 months of age. Developmental trajectories from subjects with both resting-state fMRI and eye-tracking data were used to explore brain-behavior relationships. Our findings indicate robust increases in functional connectivity (FC) between primary visual areas (primary visual cortex [V1] - extrastriate area 3 [V3] and V3 - middle temporal area, ventral motion areas middle temporal area - AST, as well as between TE and amygdala (AMY) as infants mature. Significant FC decreases were found in more rostral areas of the pathways, such as areas temporal area occipital part - TE in the ventral object pathway, V3 - lateral intraparietal (LIP) of the dorsal visual attention pathway and V3 - temporo-parietal area of the ventral attention pathway. No changes in FC were found between cortical areas LIP-FEF and temporo-parietal area - Area 12 of the dorsal and ventral attention pathways or between AST-AMY and AMY-insula. Developmental trajectory of gaze following revealed a period of dynamic changes with gradual increases from 1 to 2 months, followed by slight decreases from 3 to 6 months. Exploratory association findings across the 6-month period showed that infants with higher gaze following had lower FC between primary visual areas V1-V3, but higher FC in the dorsal attention areas V3-LIP, both in the right hemisphere. Together, the first 6 months of life in rhesus macaques represent a critical period for the emergence of gaze following skills associated with maturational changes in FC of socially guided attention pathways.

Protein expression of the amino acid transporter SLC7A5 in tumor tissue is prognostic in early-stage colorectal cancer

Proteins overexpressed in early-stage cancers may serve as early diagnosis and prognosis markers as well as targets for cancer therapies. In this study, we examined the expression of an essential amino acid carrier SLC7A5 (LAT1, CD98, or 4F2 light chain) in cancer tissue from two well-annotated cohorts of 575 cases of early-stage and 106 cases of late-stage colorectal cancer patients. Immunohistochemistry showed SLC7A5 overexpression in 72.0% of early-stage and 56.6% of late-stage cases. SLC7A5 expression was not influenced by patient gender, age, location, or mismatch repair status, although it appeared to be slightly less prevalent in tumors of mucinous differentiation or with lymphovascular invasion. Statistical analyses revealed a positive correlation between SLC7A5 overexpression and both overall survival and disease-free survival in early-stage but not late-stage cancers. Co-expression analyses of the TCGA and CPTAC colorectal cancer cohorts identified a network of gene transcripts positively related to SLC7A5, with its heterodimer partner SLC3A2 having the highest co-expression score. Network analysis uncovered the SLC7A network to be significantly associated with ncRNA such as tRNA processing and the mitotic cell cycle. Since SLC7A5 is also a marker of activated lymphocytes such as NK, T, and B lymphocytes, SLC7A5 overexpression in early colorectal cancers might trigger a strong anti-tumor immune response which could results in better clinical outcome. Overall, our study provides clear evidence of differential SLC7A5 expression and its prognostic value for early-stage colorectal cancer, although the understanding of its functions in colorectal tumorigenesis and cancer immunity is currently rather limited and awaits further characterization.

Prognostic utility of point-of-care measured bioadrenomedullin in patients presenting with acute heart failure at the emergency department

Abstract Funding Acknowledgements None. Background Acute heart failure (AHF) is a severe condition that is frequently encountered in the emergency department (ED). We aimed to investigate the role of bioadrenomedullin (bio-ADM)- a molecule previously shown to be associated with clinical congestion- as an early prognostic marker for short-term outcomes in patients presenting with AHF in the ED. Methods Seventy-six AHF patients were prospectively enrolled upon ED presentation. Clinical, echocardiography, standard laboratory and cardiac biomarker assessments were performed. Bio-ADM was measured from whole blood sample using a commercially available point-of-care immunoassay. We examined prognostic utility of bio-ADM for predicting 30-day mortality. Results Study group consisted of 61% males, of mean(±SD) age 71±13years, systolic blood pressure (SBP) 140±41mmHg, categorized according to AHF clinical phenotypes as 15(20%) pulmonary edema, 53(70%) decompensated chronic HF and 8(10%) cardiogenic shock. Median (IQR) creatinine, NTproBNP, hsTroponinT and bio-ADM were: 1.15(0.90-1.83)mg/dl, 5094(2836-12816)pg/ml, 38(24-91)pg/ml and 52.3(45-113)pg/ml, respectively. Levels of bio-ADM were higher in patients with cardiogenic shock compared to acute pulmonary edema and decompensated chronic HF [median (IQR): 266.8(101.9-500)pg/ml, 49.8(45-67.5)pg/ml and 47.4(45-97.5)pg/ml, respectively], (p=0.019). Log(bio-ADM) was significantly correlated with SBP (Spearman rho= -0.387, p=0.003), logCreatinine (rho=0.430, p&amp;lt;0.001), log(NTproBNP) (rho=0.430, p=0.003) and log(hsTroponinT) (rho= 0.386, p=0.003). During 30-days follow-up, 15 patients died. In ROC analysis, a bio-ADM cutoff of 64.8pg/ml predicted 30-day mortality with 75% sensitivity and 65% specificity (AUC 0.763, p=0.017). In a multivariable Cox proportional hazards model that included log(bio-ADM), log(NTproBNP) and logCreatinine and adjusted for AHF phenotype, only log(bio-ADM) seemed to be independently prognostic of 30-day mortality (HR,95%CI: 5.80, 0.97-34.66, p=0.054). Conclusions In a broad AHF population, point-of-care bio-ADM measured upon presentation at the ED is associated with worse clinical and biochemical AHF profiles and may provide independent prognostic information for 30-day mortality.30-day mortality by bio-ADM ≥ vs &amp;lt;64.8

Neutrophil gelatinase-associated lipocalin (NGAL) levels for early prediction and ruling out future contrast nephropathy in patients undergoing primary coronary intervention

Abstract Funding Acknowledgements None. Background Neutrophil gelatinase-associated lipocalin (NGAL), is an early marker of acute kidney injury(AKI) . We aimed to investigate the diagnostic utility of sequential NGAL measurements for both prediction and ruling out of contrast induced AKI (CI-AKI) among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). Methods We included 133 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (NGAL 0) and 24 hours after PCI (NGAL 24). Optimal threshold for the development of CI-AKI were determined using receiver operating characteristic curves (ROC). Patients were also assessed for the dynamics between NGAL 0 and NGAL 24 levels. Results Mean age was 62 ±13 years and 78% were men, and a total of 20 (15%) developed CI-AKI . Patients with CI-AKI demonstrated higher plasma NGAL 0 levels (164 ± 42 vs. 95 ± 30 ng/mL; p &amp;lt; 0.001) as well as NGAL 24 levels (142 ± 41 vs. 93 ± 36 ng/mL; p &amp;lt; 0.001). There were no significant changes between NGAL 0 &amp; 24 hours within the 2 groups( figure 1). According to the ROC curve analysis (figure 2), the optimal NGAL 0 level for CI-AKI prediction was &amp;gt;125 ng/mL (AUC 0.841, 95% CI 0.801–0.961, p &amp;lt; 0.001), with a sensitivity of and specificity of 70% and 84% respectively, while the negative predictive value of NGAL 0&amp;lt;125 ng/mL was 94%. Conclusions Among STEMI patients, NGAL levels before primary PCI may be utilized both for ruling out and for the prediction of CI-AKI.NGAL 0 vs 24 according to CI-AKINGAL AUC

Assessment of High Serum Cystatin C as an Early Marker of Renal Impairment in Pre Eclampsia

Introduction: Preeclampsia is the most common medical complication during pregnancy and one of the leading causes of maternal and perinatal morbidity and mortality in Bangladesh. Kidney has role in both adaptive physiology of normal pregnancy and in pathophysiology of preeclampsia. Among the new biomarkers, serum Cystatin C can reliably reflect the GFR in both healthy and hypertensive pregnant women. It is important to evaluate the diagnostic efficiency of Cystatin C as a marker of renal function in preeclampsia. Aim: To assess high serum Cystatin C level as an early marker of renal impairment in pre-eclamptic patients. Materials and Methods: From March, 2021 to February, 2022 (A total of 12 months) a cohort study was conducted among 66 pregnant women, aged 18 to 40 years with pre-eclampsia and normal serum creatinine (0.5-0.8mg/dl) at their 20-28 weeks of gestation attending the antenatal clinic and admitted in the Department of Feto maternal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, selected by non random purposive and convenient sampling. Results: Out of 66 respondents, final analysis was done with 62 patients. Among 62 study samples, 76% patients had “High Cystatin C” level that was greater than 0.84 and renal impairment developed in 15% pregnant women. Majority of the participants were in 25-30 age groups (46.8%). The mean serum creatinine level of the pregnant women increased throughout follow up and it was statistically significant (p&lt;0.05) in both cases. No significant difference was found between serum Cystatin C in renal impaired and normal renal function pre eclampsia patients at a cut off value of 0.84. ROC analysis of serum Cystatin C level for detection of renal impairment among Pre eclamptic patients found a cut-off value of ≥1.49 showed the highest Youden index of 0.721. The sensitivity, specificity, PPV, NPV and accuracy of serum Cystatin C were 77.78%, 94.34%, 70.00%, 96.15% and 91.94%. Conclusion: Higher Cystatin C level in pre-eclampsia reflected renal impairment at an early stage even before conventional marker like serum creatinine raise. The diagnostic efficiency of Cystatin C as a marker of renal function in pre eclampsia can be used to reduce maternal morbidity and mortality of Bangladesh. Medicine Today 2023 Vol.36 (1): 12-16

Identification of early coagulation changes associated with survival outcomes post severe burns from multiple perspectives

Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Young Children of Mothers with a History of Depression Show Attention Bias to Sad Faces: An Eye-tracking Study.

Maternal depression is a predictor of the emergence of depression in the offspring. Attention bias (AB) to negative emotional stimuli in children may serve as a risk factor for children of depressed parents. The present study aimed to examine the effect of maternal major depressive disorder (MDD) history on AB to emotional faces in children at age four, before the age of onset for full-blown psychiatric symptoms. The study also compared AB patterns between mothers and their offspring. Fifty-eight mothers and their four-year-old children participated in this study, of which 27 high-risk (HR) children had mothers with MDD during their children's lifetime. Attention to emotional faces was measured in both children and their mothers using an eye-tracking visual search task. HR children exhibited faster detection and longer dwell time toward the sad than happy target faces. The low-risk (LR) children also displayed a sad bias but to a lesser degree. Children across both groups showed AB towards angry target faces, likely reflecting a normative AB pattern. Our findings indicate that AB to sad faces may serve as an early marker of depression risk. However, we provided limited support for the mother-child association of AB. Future research is needed to examine the longitudinal intergenerational transmission of AB related to depression and possible mechanisms underlying the emergence of AB in offspring of depressed parents.