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The severe acute respiratory distress syndrome-associated coronavirus-2 infection can activate innate and adaptive immune responses which may lead to harmful tissue damage, both locally and systemically. C3, a member of complement system of serum proteins, is a major component of innate immune and inflammatory responses. This study is aimed to assess serum C3 as a marker of COVID-19 severity and a predictor of disease progression. A total of 150 COVID-19 patients, confirmed by RT-PCR, and 50 healthy controls were recruited. Serum C3 levels were determined by using direct colorimetric method. Median levels of serum C3 in total cases and controls were 157.8 and 165.7 mg/dL respectively. Serum C3 although not significantly decreased, they were lower in cases when compared to controls. Similarly, significant differences were found between the groups, with severe group (140.6 mg/dL) having low levels of serum C3 protein when compared to mild (161.0 mg/dL) and moderate group (167.1 mg/dL). Interestingly, during hospitalization, significant difference between baseline (admission) and follow-up (discharge) was observed only in patients with moderate disease. Based on our results, lower levels of C3, with an increase in IL-6 and d-dimer levels, are associated with higher odds of mortality. Therefore, we would like to emphasize that measuring serum C3 levels along with other inflammatory markers might give an added advantage in early identification of patients who are prone to having a severe disease course and can help in a more effective follow-up of disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01148-x.
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Objective: Early diagnosis of sepsis is crucial to institute appropriate therapy and then to avert a possible negative outcome. We planned this study to evaluate the diagnostic value of presepsin, its sensitivity and specificity for diagnosing sepsis in critically ill patients, and its ability to prognosticate the outcome of sepsis. Methods: In this prospective observational study, adult patients admitted to the intensive care unit (ICU) at our institute were screened, and those with features suggestive of sepsis were recruited into the study. Procalcitonin (PCT) and presepsin were assessed on the day of admission and day 7 of the ICU stay, apart from routine investigations. Patients were followed for outcome in terms of mortality till 28 days. Results: The study comprised 82 patients who satisfied the inclusion criteria. Presepsin sensitivity for sepsis diagnosis was determined to be 78%, while that of PCT was determined to be 69%. This gave a combined sensitivity of presepsin and PCT of 93% when used in parallel for the diagnosis of sepsis. Conclusion: A combination of PCT and presepsin provides higher sensitivity and can be used to screen for sepsis in the ICU. How to cite this article: Roy S, Kothari N, Sharma A, Goyal S, Sankanagoudar S, Bhatia PK, et al. Comparison of Diagnostic Accuracy of Presepsin and Procalcitonin for Sepsis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2023;27(4):289-293.
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Background: On reviewing our teaching methods through students' feedback, we realized they were dissatisfied with the present teaching methodology of lectures in terms of knowledge retention and problem-solving. This issue was addressed using student-centred and cooperative learning methodology, i.e. process-oriented guided inquiry learning (POGIL) where pre-designed questions guide students to enquire concepts, with reflection writing exercise helping students to strengthen their concepts. This study analysed the effectiveness and perceptions of POGIL sessions conducted after lectures. Methods: The study was approved by the institutional ethical committee. A total of 42 (7 groups; each group with 6 members of high, low and average achievers) consented and POGIL-sensitized MBBS phase I students were part of the study. One-hour POGIL sessions were conducted a week after lecturing with reading material. Pre-, post- and retention test multiple-choice questions (MCQs) were administered for assessment of effectiveness and a close-ended questionnaire for recording perception. Results: Post-test and retention test MCQ scores were statistically higher than pre-test scores both in all participants and low achievers (p<0.05). Around 60% of the students felt that the POGIL activities and working in teams helped them to understand concepts. Reflection analysis revealed the best and least understood concept and students came up with memory aids to remember complex metabolic regulation. Conclusion: POGIL might be a promising reinforcement strategy to lectures in biochemistry and preferred tool to address the issue of low achievers in the class.
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Evaluación Educacional , Aprendizaje , Curriculum , Humanos , Percepción , EstudiantesRESUMEN
Background & objectives: Earlier reports have shown hypocholesterolaemia in cancer patients and high number of lipid rafts in cancer cells. The primary objective of this study was to compare the intracellular cholesterol turnover in non-cancerous (benign) prostatic hyperplasia (BPH) and carcinoma prostate (CAP) with normal prostate cells obtained from patients undergoing radical cystectomy for carcinoma bladder (sham control). Methods: ELISA-based estimation of prostate-specific antigen (PSA), evaluation of expression of low-density lipoprotein receptor (LDLR), peripheral-type benzodiazepine receptor (PBR) and cyclin E, immunohistochemistry and confocal microscopy, measurement of integrated optical density of the diaminobenzidine (DAB)-stained immunohistograms, isolation of nucleus and cell cytoplasm from prostate tissue by ultracentrifugation followed by estimation of cholesterol spectrophotometrically in isolated nuclear and cytoplasmic fractions were performed. Results: Seventy five individuals, 25 for each group (BPH n=25; CAP n=25 and sham control n=25), were included in the study. Cholesterol was increased in the cytoplasm and nucleus of the prostate cancer cells along with elevated expression of LDLR. Increased cholesterol concentration in the cell nucleus was found comparable with the increased expression of cholesterol transporter viz. PBR in the prostate tumour tissues as compared to its expression in normal prostate cells obtained from individuals undergoing radical cystectomy for carcinoma bladder. Cell cycle protein cyclin E was also highly expressed in cancer tissues. Interpretation & conclusions: The present findings along with increased expression of cell cycle protein cyclin E in the cell nucleus of the tumour tissue suggested the possibility of an intriguing role of cholesterol in the mechanism of cell cycle process of prostate cell proliferation.
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Carcinoma/genética , Colesterol/genética , Hiperplasia Prostática/genética , Neoplasias de la Próstata/genética , Carcinoma/sangre , Carcinoma/patología , Ciclo Celular/genética , Proteínas de Ciclo Celular/sangre , Colesterol/sangre , Cistectomía , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/sangre , Hiperplasia Prostática/patología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Receptores de GABA/genética , Receptores de LDL/sangreRESUMEN
BACKGROUND: Cancer stem cells (CSCs) have been implicated in prostate cancer (PCA) progression and therapeutic resistance. This study aimed to compare the expression levels of CSC CD (CD 44, CD 133, and CD 24) markers in treatment-naive patients with metastatic PCA before and after treatment. METHODS: The study included 60 treatment-naïve patients with metastatic PCA who received androgen deprivation therapy (ADT) alone (nâ¯=â¯30) and ADT plus chemotherapy (nâ¯=â¯30). The level of CD44, CD133, and CD24 were obtained by flow cytometric analysis before and after treatment. Baseline characteristics were also assessed, including age, pretreatment testosterone levels, and pretreatment prostate-specific antigen (PSA) levels. RESULTS: The baseline characteristics analysis showed no significant difference in pre-treatment testosterone levels between the ADT+ chemotherapy and ADT-alone groups. In the flow cytometric analysis, no significant difference was observed in pre-treatment CD44+ and CD133+ levels between the 2 treatment groups, although a trend towards higher pretreatment CD24- levels was observed in the ADT+ chemotherapy group. After treatment, significant reductions in testosterone and PSA levels were observed in both treatment arms. The ADT+ chemotherapy group showed a greater reduction in CD44+ and CD133+ levels compared to the ADT-alone group. Bioinformatic analysis using the UALCAN TCGA database also showed a similar trend of CD 44, CD 24, and CD 133 gene expression patterns. CONCLUSION: Combination therapy involving chemotherapy and ADT appears to have a greater impact on suppressing CSCs compared to ADT alone. These findings highlight the potential of targeting CSCs as a prognostic and predictive marker therapeutic strategy in metastatic PCA.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Antígeno Prostático Específico/uso terapéutico , Antagonistas de Andrógenos/efectos adversos , Testosterona/uso terapéutico , Células Madre/patologíaRESUMEN
Globally, Triple-negative breast cancer (TNBC) is an unsurpassed variant of breast cancer (BC) with a very high fatality rate, and disease burden. Nevertheless, the deficit of diagnostic markers and focused treatment are major hurdles for potent therapeutics. They are also the reason for bad outcomes and causes of a worse prognosis and a high rate of flare up in patients with TNBC diagnosis. Long non-coding RNAs (lncRNA) are a new class of molecules that have recently gained interest in healthcare management due to their potential as biomarkers for human diseases especially cancers. The growing interest in lncRNA in clinical practice has created an unmet need for developing assays to test lncRNA quickly and accurately for early diagnostics. These lncRNA modulate multiple stages of tumor development, including growth, proliferation, invasion, angiogenesis, and metastases, by controlling several genes and changing metabolic networks. Highly invasive phenotype and chemo resistance are prominent characteristics of TNBC subtypes that require accurate diagnostic and prognostic instruments involving lncRNA. This review focusses on the evolving purpose and coalition of lncRNAs in TNBC and accentuates their capable effects in diagnosis and treatment of cancer. Moreover, the extensive literature analysis of our review creates an opportunity in the translational application concerning the TNBC lncRNAs described until now. The depiction of lncRNAs enrolled in TNBC is comprehensive, and sufficient substantiation studies are the need of the hour to authenticate the current outcomes and create imminent upcoming of elemental research setting into clinical practice.
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ARN Largo no Codificante , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Carcinogénesis/metabolismo , Pronóstico , Transformación Celular Neoplásica/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Background: Growth differentiation factor-15 (GDF-15) is involved in insulin resistance and diabetes. In this study, we determine the associations of GDF-15 with miR-181b-5p, miR-330-3p, mothers against decapentaplegic homolog 7 (SMAD7), and insulin resistance in visceral adipose tissue (VAT) and peripheral blood mononuclear cells (PBMCs) in type 2 diabetes mellitus (T2DM) patients. Methods: Sixty patients, equally divided into those with T2DM and non-diabetic controls, were recruited for gene expression analysis. Protein-protein interaction (STRING), target prediction (miRNet), and functional enrichment were conducted accordingly. Results: Our study showed that VAT and PBMCs had similar expression profiles, where GDF-15 and miR-181b-5p were upregulated, whereas SMAD7 and miR-330-3p were downregulated. Serum GDF-15 could differentiate between T2DM and non-diabetic patients (P<0.001). Target prediction revealed a microRNA (miRNA)-messenger RNA regulatory network, transcription factors, and functional enrichment for the miRNA that suggested involvement in T2DM pathogenesis. Conclusion: VAT GDF-15 is associated with insulin resistance and is possibly regulated by miR-181b-5p, miR-330-3p, and SMAD7 in T2DM.
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BACKGROUND: MicroRNAs are small, non-coding RNA molecules that regulate important cellular processes such as tumorigenesis, cell proliferation, and apoptosis. Cancer stem cells are a subset of cells that control metastasis and cell proliferation. In this study, we focus on the roles of miR-10b, miR-21 and correlate with cancer stem cells through the apoptotic pathway in different stages of prostate cancer (PCa). METHODS: In total, 45 patients, each group with Benign prostatic hyperplasia (BPH), localised PCa, and metastatic PCa, were recruited. MicroRNA and gene expression were estimated through quantitative polymerase chain reaction. Flow cytometry was used to characterise prostate cancer stem cells (PCSCs), estimate reactive oxygen species (ROS), apoptosis and chemiluminescent immunoassay was used to estimate interleukin 6 (IL-6), tumour necrosis factor (TNF-α), prostate-specific antigen (PSA), and testosterone. RESULTS: The fold change mean expressions of miR-21, miR-10b, Cytochrome C, and B-cell lymphoma 2 (BCL-2) were significantly upregulated in localised and metastatic PCa compared with BPH. In contrast, the mean fold change expressions of Bcl-2-associated X protein (BAX), Caspase-3, Caspase-9, and Second mitochondria-derived activator of caspase (SMAC) were lower in localised and metastatic PCa compared to BPH. The levels of IL-6, TNF-α, ROS, PSA and testosterone also showed a significant increase while apoptosis was decreased in both localized PCa and metastatic PCa as compared with BPH. In bioinformatics analyses, we found a similar pattern of miRNAs and gene expression in PCa databases. Our study also found a high expression of CD44+/CD24- and CD44+/CD133+ in localised and metastatic PCa compared with BPH. CONCLUSION: Our findings suggest miR-10b and miR-21 promote PCSCs and may target apoptotic genes involved in PCa pathogenesis; these miRNAs could be used as diagnosis biomarkers of PCa. In PCa pathogenesis and PCSCs regulation, the interaction between these two players is crucial and will help develop new PCa therapeutic targets.
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MicroARNs , Hiperplasia Prostática , Neoplasias de la Próstata , Humanos , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Interleucina-6/genética , MicroARNs/genética , MicroARNs/metabolismo , Antígeno Prostático Específico/metabolismo , Hiperplasia Prostática/patología , Neoplasias de la Próstata/patología , Especies Reactivas de Oxígeno/metabolismo , Testosterona , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
The deficiencies of trace elements and infectious diseases often coexist and exhibit complex interactions. Several trace elements such as zinc (Zn), copper (Cu) and magnesium (Mg) have immunomodulatory functions and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of trace metals in association with severity and mortality in SARS-CoV-2 patients. A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate and severe) and outcome (discharged or deceased). Serum Zn, Mg and Cu levels were analysed by direct colourimetric method. Both serum Cu and Zn levels were significantly decreased in cases when compared to those in controls (p < 0.005 and p < 0.0001). Serum magnesium levels although not significant were found to be slightly decreased in controls. On comparing the trace elements between the deceased and discharged cases, a significant difference was found between serum copper and zinc levels, but for magnesium, both groups have similar levels. The receiver operating characteristic (ROC) curve results indicate that a serum Cu/Zn ratio along with the age of patient provides some reliable information on COVID-19 course and survival odds by yielding an AUC of 95.1% with a sensitivity of 93.8% and specificity of 89.8%. Therefore, we would like to emphasize that measuring the serum copper and zinc along with their ratio can be used as routine investigations for COVID-19 patients in proper identification and management of severe cases in upcoming new waves of COVID-19.
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COVID-19 , Oligoelementos , Humanos , Cobre , Magnesio , SARS-CoV-2 , ZincRESUMEN
BACKGROUND AND AIMS: LDL-cholesterol (LDL-C), being the primary predictor of cardiovascular disease in Type 2 diabetes (T2D), is associated with cardiovascular risk stratification and requires to be estimated with better accuracy with minimal bias. Different formulae have been devised to calculate the LDL-C from the measured lipid profile parameters. METHODS: In this analytical cross-sectional study, a total of 150 patients with T2D were studied, and blood samples were subjected for lipid profile analysis at the Central Biochemistry laboratory. Different formulae assessed calculated LDL-C. RESULTS: We observed that all formulae, except Ahmadi, underestimated the LDL-C compared to direct assay. A significant difference was observed between all calculated LDL-C and directly measured LDL-C. On linear regression analysis, the newer formula Martin's has a better approximation with direct assay (slope: 0.9708) than Friedewald (slope: 0.9477). Similarly, Martin's formula exhibited lesser bias (-13.56) in calculating LDL-C in patients with T2D compared with Friedewald's formula. CONCLUSIONS: The study demonstrated that in patients with T2D, all formulae except Ahmadi significantly underestimated the LDL-C when compared with the direct assay. The newer Martin's formula appeared to more precisely calculate LDL-C in T2D when compared with the traditional Friedewald's formula.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , LDL-Colesterol , Estudios Transversales , Humanos , TriglicéridosRESUMEN
BACKGROUND AND AIMS: Over the past few years, branched-chain amino acids (BCAAs) are increasingly being linked to insulin resistance and type 2 diabetes mellitus (T2DM), but their relevance for metabolic dyslipidaemia in T2DM is unclear. This study aims to determine the plasma and urinary BCAAs and their association with insulin resistance, lipid profile and glycated haemoglobin in patients with T2DM among Indian adults. METHODS: In this analytical cross-sectional study, a total of eighty subjects were recruited, 40 T2DM cases and 40 healthy controls. Blood samples collected were subjected to fasting blood sugar (FBS), lipid profile, HbA1c, insulin and BCAAs analysis and urine samples were assessed for BCAAs. All associations were assessed using Spearman Rank Correlation. RESULTS: The plasma levels of BCAAs were significantly higher (p < 0.05) in subjects with T2DM than in control subjects. Spearman Rank Correlation analyses revealed a non-significant (p = 0.21) but positive association between BCAAs and homeostasis model assessment of insulin resistance (HOMA-IR) in patients with T2DM (Rho: 0.27). Among lipid profile parameters, only triglycerides had a significant positive correlation to plasma BCAAs in cases (Rho: 0.5971) but not in control subjects. Findings also revealed a significant positive (p < 0.05) association between plasma BCAAs and HbA1c in patients with T2DM (Rho: 0.5325). Urinary BCAAs levels had a non-significant increase in T2DM subjects and did not show any significant correlation with other parameters assessed. CONCLUSION: Elevated levels of plasma BCAAs are positively associated with triglyceride and HbA1c. They could serve as an effective marker for the assessment of metabolic dyslipidaemia in subjects with T2DM. Further, large scale studies are needed for confirmation of the same.
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Diabetes Mellitus Tipo 2 , Dislipidemias , Resistencia a la Insulina , Adulto , Aminoácidos de Cadena Ramificada/metabolismo , Glucemia/análisis , Estudios Transversales , Hemoglobina Glucada/análisis , Humanos , TriglicéridosRESUMEN
Background Hypothyroidism is one among the many factors that predisposes one to coronary artery disease. As low-density lipoprotein-cholesterol (LDL-C) is associated with cardiovascular risk, calculated LDL-C should have good accuracy with minimal bias. Hypothyroidism alters the lipid composition of lipoproteins by the secretion of triglyceride-rich lipoproteins, which affects the calculation of LDL-C. The present study aimed to compare 13 different formulae for the calculation of LDL-C including the newly derived Martin's formula by direct assay in patients of hypothyroidism. Method In this analytical cross-sectional study, a total of 105 patients with laboratory evidence of hypothyroidism, from January to June 2019, were studied, and blood samples were subjected for lipid profile analysis at central biochemistry laboratory. Calculated LDL-C was assessed by different formulae. Result We observed that calculated LDL-C by Friedewald's, Cordova's, Anandaraja's, Hattori's, and Chen's formulae has bias less than ± 5 compared with direct LDL-C, with Anandaraja's formula having the lowest bias (2.744) and Cordova's formula having lowest bias percentage (-1.077) among them. According to the Bland-Altman plots, the bias in Friedewald's and Anandraja's were equally distributed below and above the reference line of direct LDL-C. Conclusion This is the first study comparing different formulae for LDL-C calculation in patients with hypothyroidism. Anandaraja's formula was as equally effective as Friedewald's formula when used as an alternative cost-effective tool to evaluate LDL-C in hypothyroid patients. The recently proposed Martin's formula for calculated LDL-C had a higher bias when compared with Friedewald's and Anandaraja's formulae in patients with hypothyroidism.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) is an ever-growing epidemic in India and poses significant morbidity, mortality, and socioeconomic burden. INTRODUCTION: Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine, increased in T2DM patients compared to control subjects without the disease. We aimed to assess whether serum GDF15 and adipose tissue GDF15 expression can differentiate between obese pre-diabetes and T2DM and control populations. METHODOLOGY: We recruited 156 individuals including 73 type 2 diabetes, 30 pre-diabetes, and 53 healthy controls. Clinical history, anthropometric measurements and biochemical profiling were taken. Insulin resistance indices were calculated following HOMA models. Serum GDF15 was measured by sandwich ELISA. Visceral adipose tissue (VAT) expression of GDF15 was observed in 17 T2DM patients and 29 controls using SYBR Green chemistry in RT-PCR using GAPDH as the housekeeping gene. The data were analyzed on R programming platform using RStudio. RESULTS: Serum GDF15 was significantly higher (p<0.001) in T2DM subjects (median 1445.47 pg/mL) compared to pre-diabetes (627.85 pg/mL) and healthy controls (609.01 pg/mL). Using the ΔΔCt method, the VAT GDF15 expression was 1.54 fold and 1.57 fold upregulated in T2DM (n=17) compared to control subjects (n=29), and obese (n=12) compared to non-obese (n=34)subjects, respectively. The optimal cut-off point following Youden's index method was found to be 868.09 pg/mL. ROC curve analysis revealed that serum GDF15 had a sensitivity, specificity, and area under the curve (AUC) of 90.41%, 79.52%, and 0.892 respectively. GDF15 levels were significantly associated with age, BMI, HbA1c, fasting blood sugar, and insulin resistance indices. CONCLUSION: Hence, serum GDF15 is a biomarker for T2DM patients in our study population from Western India. However, larger prospective cohorts are necessary to validate this claim.
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Diabetes Mellitus Tipo 2 , Estado Prediabético , Biomarcadores , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Obesidad/complicaciones , Estado Prediabético/complicaciones , Estado Prediabético/diagnóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Nutritional deficiency is associated with weaken immune system and increased susceptibility to infection. Among other nutrients, several trace elements have been shown to regulate immune responses. Iron is one of the most abundant trace elements present in our body, which is required in various biological processes. Iron has an immunomodulatory function and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of different iron-related biomarkers in association to severity and mortality in SARS-CoV-2 patients. MATERIALS AND METHODS: A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate, and severe) and outcome (discharged or deceased). Serum iron, TIBC, ferritin, transferrin, transferrin saturation levels were analyzed by the direct colourimetric method. RESULTS: In cases the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 29 µg/dL, 132.53 µg/dL, 106.3 mg/dL, 17.74 % and 702.9 ng/dL respectively. Similarly, in controls the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 53 µg/dL, 391.88 µg/dL, 313.51 mg/dL, 12.81 % and 13.52 ng/dL respectively. On comparing the cases with the controls, a significant lower level of iron, TIBC, and transferrin were found in the cases along with the significant higher levels of ferritin and transferrin saturation. On comparing the Receiver operating characteristic (ROC) curves of Iron, Ferritin, Transferrin, Transferrin sat % and TIBC in relation to survival in COVID-19 patients it was found that iron, followed by transferrin and ferritin has the highest area under the curve (AUC) with 74 %, 63 % and 61 % respectively. Further, in pairwise analysis of ROC curve, a significant difference was found between the Iron-transferrin (p < 0.01), iron-TIBC (p < 0.001) and transferrin-ferritin (P < 0.01). The multiple regression model based on Iron and transferrin outperformed any other combination of variables via stepwise AIC selection with an AUC of 98.2 %. The cutoff point according to Youden's J index is characterized with a sensitivity of 98 % and a specificity of 96.8 %, indicating that iron along with transferrin can be a useful marker that may contribute to a better assessment of survival chances in COVID-19. CONCLUSION: Our study demonstrated a significantly decreased levels of iron, TIBC, & transferrin and a significantly increased levels of ferritin and transferrin saturation in COVID-19 patients when compared with controls. Further, Iron and transferrin were observed to be a good predictor of mortality in patients with COVID-19. From the above analysis we confirm that iron-related biomarkers play an important role in the development of oxidative stress and further lead to activation of the cytokine storm. So, continuous monitoring of these parameters could be helpful in the early detection of individuals developing the severe disease and can be used to decrease mortality in upcoming new waves of COVID-19.
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COVID-19 , Oligoelementos , Biomarcadores , Ferritinas , Humanos , Hierro/metabolismo , SARS-CoV-2 , TransferrinaRESUMEN
INTRODUCTION: The presence of rheumatism is well recognized in primary hypothyroidism. Dehydroepiandrstenedione sulphate (DHEAS) is associated with rheumatological diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study aims to explore relationship between joint pains and DHEAS levels in primary hypothyroidism. METHODS: Retrospective study of 78 subjects with subclinical hypothyroidism, with TSH within reference range. The joint pains were evaluated by European Union League against rheumatism (EULAR-CSA) score and compared with serum DHEAS, RA factor, Anti-TPO antibody, highly sensitive C-recative protein (hsCRP), vitamin D levels. RESULT: DHEAS levels <43.6 mcg/dl significantly predicted clinical features of pre RA as assessed by EULAR CSA criteria with acceptable specificity (82%). EULAR CSA score is fairly valid in assessing imminent RA in primary hypothyroidism. CONCLUSION: Lower DHEAS predicts clinical features of imminent RA in subjects with primary hypothyroidism. This is akin to low DHEAS seen in many rheumatological disease with possibly similar mechanism. Another possibility is low DHEAS alters hepato-hypothalamo pituitary adrenal axis in presense of cytokines and induces a hitherto unrecognized state of pre rheumatoid arthritis like syndrome. Future studies on primary hypothyroidism should focus on role of lower DHEAS levels in inducing symptoms of fatigue and joint pains.
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Artritis Reumatoide/complicaciones , Artritis Reumatoide/metabolismo , Deshidroepiandrosterona/metabolismo , Hipotiroidismo/complicaciones , Anciano , Femenino , Humanos , Masculino , Estudios Retrospectivos , RiesgoRESUMEN
BACKGROUND: Diabetes Mellitus is a multifactorial disease encompassing various pathogenic pathways. To avoid morbidity and mortality related to diabetic complications, early detection of disease complications as well as targeted therapeutic strategies are essential. INTRODUCTION: MicroRNAs (miRs) are short non-coding RNA molecules that regulate eukaryotic posttranscriptional gene expression. MicroRNA-21 has diverse gene regulatory functions and plays a significant role in various complications of Type 2 diabetes mellitus (T2DM). METHODS: The study included electronic database searches on Pubmed, Embase, and Web of Science with the search items MicroRNA21 and each of the diabetic complications. The search was carried out up to November, 2019. RESULTS: MicroRNA-21 modulates diabetic cardiomyopathy by affecting vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. At the renal tubules, miR-21 can regulate the mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria and fibrotic and inflammatory gene expression related to diabetic nephropathy. Overexpression of miR-21 has been seen to play a pivotal role in the pathogenesis of diabetic retinopathy by contributing to diabetes-induced endothelial dysfunction as well as low-grade inflammation. CONCLUSION: Considering the raised levels of miR-21 in various diabetic complications, it may prove to be a candidate biomarker for diabetic complications. Further, miR-21 antagonists have shown great potential in the treatment of diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy related complications in the future. The current review is the first of its kind encompassing the roles miR-21 plays in various diabetic complications, with a critical discussion of its future potential role as a biomarker and therapeutic target.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Retinopatía Diabética , MicroARNs , Albuminuria , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/genética , Retinopatía Diabética/genética , Humanos , MicroARNs/genéticaRESUMEN
INTRODUCTION: COVID-19 has similarities to the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, as severe patients and non-survivors have frequently shown abnormal coagulation profiles. Immune-mediated pathology is a key player in this disease; hence, the role of the complement system needs assessment. The complement system and the coagulation cascade share an intricate network, where multiple mediators maintain a balance between both pathways. Coagulopathy in COVID-19, showing mixed features of complement-mediated and consumption coagulopathy, creates a dilemma in diagnosis and management. AREAS COVERED: Pathophysiology of coagulopathy in COVID-19 patients, with a particular focus on D-dimer and its role in predicting the severity of COVID-19 has been discussed. A comprehensive search of the medical literature on PubMed was done till May 30th, 2020 with the keywords 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Coagulopathy', and 'D-dimer'. Twenty-two studies were taken for weighted pooled analysis of D-dimer. EXPERT OPINION: A tailored anticoagulant regimen, including intensification of standard prophylactic regimens with low-molecular-weight heparin is advisable for COVID-19 patients. Atypical manifestations and varying D-dimer levels seen in different populations bring forth the futility of uniform recommendations for anticoagulant therapy. Further, direct thrombin inhibitors and platelet inhibitors in a patient-specific manner should also be considered.
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Trastornos de la Coagulación Sanguínea/etiología , COVID-19/complicaciones , Activación de Complemento , SARS-CoV-2 , Animales , Anticoagulantes/uso terapéutico , Biomarcadores , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/inmunología , Trastornos de la Coagulación Sanguínea/fisiopatología , Pruebas de Coagulación Sanguínea , COVID-19/sangre , COVID-19/inmunología , COVID-19/terapia , China/epidemiología , Comorbilidad , Infecciones por Coronavirus/sangre , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/epidemiología , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/fisiopatología , Ferritinas/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Predicción , Humanos , Inmunización Pasiva , Inflamación/etiología , Inflamación/fisiopatología , Quelantes del Hierro/uso terapéutico , Isquemia/sangre , Isquemia/etiología , Isquemia/fisiopatología , Ratones , Prevalencia , Síndrome Respiratorio Agudo Grave/sangre , Índice de Severidad de la Enfermedad , Trombofilia/tratamiento farmacológico , Trombofilia/etiología , Trombofilia/fisiopatología , Tromboembolia Venosa/sangre , Tromboembolia Venosa/etiología , Tromboembolia Venosa/fisiopatología , Sueroterapia para COVID-19RESUMEN
AIM: Specific amino acids have been linked to regulation of insulin secretion from pancreatic ß-cells; on the contrary, increased concentration of certain amino acids is associated with insulin resistance (IR) and development of type 2 diabetes mellitus (T2DM). Nowadays, urine as a biological sample has attracted more attention for diagnosis of disease for its special superiority; insufficient research in the study of urinary amino acid (UAA) pattern in patients with T2DM has led to the present study with the aim to determine the levels of UAAs, their excretory patterns and the association of UAA to plasma glucose and IR in patients with T2DM. METHODS: Quantification of total urinary amino acids was done spectrophotometrically and the patterns of amino acid excretion was elucidated by thin layer chromatography technique. Fasting blood samples were used for plasma glucose and insulin estimation by fully automated analyzer. RESULT: The levels of UAA in patients with T2DM in comparison to healthy controls were higher (p < 0.0001). The frequency of urinary phenylalanine, arginine, tryptophan, tyrosine and cysteine were significantly higher in patients with T2DM than controls. There was also a strong positive correlation of UAA levels with blood glucose levels and HOMA-IR in patients with T2DM. CONCLUSION: Our study has shown subtle abnormalities in UAA patterns in patients with T2DM. The measurement of UAA levels and excretory pattern can be used as an index of hyperglycemia and IR which could serve as an inexpensive and non-invasive marker for T2DM. More studies are required to confirm this association.
Asunto(s)
Aminoácidos/orina , Biomarcadores/orina , Diabetes Mellitus Tipo 2/orina , Resistencia a la Insulina , Centros de Atención Terciaria/estadística & datos numéricos , Adulto , Anciano , Glucemia/análisis , Estudios de Casos y Controles , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Prostate cancer (CaP) is a leading cause of cancer deaths in the worldwide with broad range of clinical manifestations ranging from relatively indolent to aggressive metastasis. Altered expression of many circulating long non-coding RNAs (lncRNAs), known to have role in tumorigenesis and metastasis, have already been reported in CaP patients. These lncRNAs modulate CaP pathogenesis by modulating multiple genes and thus altering metabolic pathways. Sustained androgen receptor (AR) signaling is one such key feature of castration-resistant prostate cancer, a CaP stage that has unmet need of accurate diagnostic and prognostic tools, that is affected by lncRNAs. In this review, we have discussed the emerging functions and associations of AR lncRNAs in CaP and highlighted their potential implications in cancer diagnostics and therapeutics. Further, extensive literature analysis in this article indicates that there is an immediate unmet need in the translational approach toward the hitherto identified AR lncRNAs. The characterization of AR lncRNAs involved in CaP is not exhaustive and adequate validation studies are still required to corroborate the present results that would be the impending future of basic research setting into clinical practice.