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Background Chronic kidney disease (CKD) is characterized by progressive loss of kidney function. Tumor necrosis factor-alpha (TNF-α) is a cytokine implicated in inflammatory processes, including those affecting the kidneys. Although this association is not yet comprehensible, a tie-up between renal disease and markers of inflammation - interleukin-6 (IL-6), preceded by TNF-α - is eminent. However, a pause in research is evident concerning the TNF-α gene with kidney disease in the inhabitants of India. So, this study investigates the association between TNF-α rs1800629 polymorphism and CKD. Methodology A prospective case-control study was conducted in Andhra Pradesh for over three years. A total of 579 patients participated in the study. These were divided into premature, late-stage CKD, and control groups. The amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) was used, and biochemical investigations and genotyping were carried out for the study participants. Hardy-Weinberg expected frequencies (HWE) with chi-square test was used for detecting allele and genotype frequencies. The association between TNF-α (-308 G/A, rs1800629) and CKD was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). Results We found a higher prevalence of CKD among males (n = 301, 52%) compared to females (n = 278, 48%). Both male and female participants diagnosed with CKD exhibited significantly elevated blood urea and serum creatinine levels compared to the control group, indicating impaired kidney function. Furthermore, these markers were generally higher in the late-stage CKD group compared to the early-stage group, suggesting a progressive decline in kidney function as the disease worsens. The homozygous genotype GG was more prevalent in late-stage CKD patients compared to both early-stage CKD patients and controls. Further, the heterozygous genotype GA was more frequent in the early-stage CKD group compared to the late-stage group. The homozygous genotype AA also showed a higher prevalence in the early-stage CKD group compared to the late-stage group. The G/G genotype and the G allele (rs1800629) were significantly associated with susceptibility to CKD (P<0.005). Conclusions Our study reported the TNF-α rs1800629 polymorphism and CKD risk in a South Indian population. G/G genotype and the G allele (rs1800629) were significantly associated with the risk of CKD. However, further research with larger sample sizes is warranted to confirm these observations and elucidate the underlying mechanisms by which TNF-α might influence CKD risk.
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Background The MTHFD1 G1958A polymorphism is a common variation in the gene encoding methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), an enzyme crucial for folate metabolism. This study investigated the association between the MTHFD1 G1958A polymorphism, which is involved in folate metabolism, and gestational diabetes mellitus (GDM) risk. Methods A case-control study was conducted and 304 pregnant women (152 with gestational diabetes as cases and 152 healthy pregnant as controls) participated in the study. The polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) techniques were used to determine the MTHFD1 1958G>A polymorphism genotypes. Results Analysis of genotype frequencies revealed a statistically significant difference (p-value < 0.05) between the GDM group and the control group, suggesting a potential association between this gene variant and the development of GDM. Interestingly, while allele frequencies alone did not show a significant association with GDM risk, analysis in a recessive model (both severe and mild forms) demonstrated a strong link between the homozygous AA genotype and increased susceptibility to GDM. Conclusion This study provides the first evidence linking the MTHFD1 G1958A polymorphism and GDM risk in an Indian setting. These findings warrant further investigation into the functional impact of the MTHFD1 G1958A polymorphism and its potential role in the pathogenesis of GDM.
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Pediatric iron deficiency anemia (IDA) is often treated with oral iron supplementation as the first-line therapy despite poor adherence. This single-institution retrospective chart review of pediatric patients was conducted to assess the safety, efficacy, and adherence of intravenous (IV) iron infusions compared to oral iron therapy in patients who had failed a trial of oral iron supplementation. We reviewed medical records of patients aged 1-21 with IDA who received at least one IV iron infusion at Cooper University Hospital between 2016 and 2021. Paired t-tests compared pre-infusion and post-infusion hematologic indices of hemoglobin (Hgb), mean corpuscular volume, red blood cell count, red cell distribution width, ferritin, total iron binding capacity, iron stores, and iron saturation. We compared adherence and adverse reactions to both oral iron supplementation and IV iron infusions using McNemar's test. A total of 107 subjects were included (mean age of 12.7 years). Hgb, ferritin, iron, and iron saturation between pre-infusion and post-final infusion significantly improved (p < 0.001). Hgb, ferritin, and iron improved when subcategorizing by race and etiology of IDA. Adherence to IV iron infusions (70.1%) was significantly greater than adherence to oral iron therapy (43.0%). There were also significantly fewer adverse effects with IV iron infusions (3.7%) compared to oral iron (77.9%). We demonstrated the safety, efficacy, and improved adherence of IV iron infusions compared to oral iron supplementation for treatment of pediatric IDA in patients who were unable to tolerate oral iron supplementation. Future studies could compare adherence to multiple doses of IV iron infusions in contrast with other single-dosing IV iron formulations.
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Anemia Ferropénica , Hierro , Humanos , Estudios Retrospectivos , Femenino , Niño , Masculino , Hierro/administración & dosificación , Hierro/efectos adversos , Adolescente , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/sangre , Infusiones Intravenosas , Preescolar , Lactante , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION/OBJECTIVES: Diabetic Kidney Disease (DKD) is the leading cause of end-stage kidney disease. Despite optimal glycemic control and blood pressure management, progression to DKD cannot be halted in some patients. We aimed to find the association of modifiable and non-modifiable risk factors and comorbid conditions in patients with DKD. METHODS: Retrospective medical record review of adult patients with diabetes mellitus (DM) was performed who visited our internal medicine office between January 1, 2020 and December 31, 2020. RESULTS: Among 728 patients with DM, 471 (64.7%) patients had DKD, and 257 (35.3%) patients were without DKD. Among the group of patients with DKD, the majority were in CKD stage G1A2 (34.6%), followed equally by G2A2 and G3aA1 (16.8% each). Mean age of the patients with DKD was significantly greater than the patients without DKD (69.4 years vs 62.2 years; P < .001). For each unit increase in age, there was a 7.8% increase in the odds of DKD (95% CI 5.3-10.4; P < .001). Women had 2.32 times greater odds of DKD (95% CI, 1.41-3.81; P = .001). We found decreased odds of DKD for those who consumed alcohol moderately (OR 0.612, 95% CI 0.377-0.994; P < .05). Significantly higher frequencies of associations of several comorbid medical conditions were seen in patients with DKD compared to the patients without DKD, such as hypertension (91.9% vs 75.6%), hyperlipidemia (86.6% vs 78.2%), coronary artery disease (39.3% vs 16.8%), cerebrovascular accidents (13.4% vs 7.4%), congestive heart failure (12.9% vs 4.1%), carotid artery stenosis (11.3% vs 2.6%), aortic aneurysm (5.4% vs 2.0%), peripheral artery disease (10.8% vs 3.5%), gout (12.4% vs 5.5%), and osteoarthritis (41.4% vs 31.2%). CONCLUSIONS: In patients with diabetes, increasing age, female sex, and lack of moderate alcohol consumption were associated with increased odds of DKD. Higher frequencies of association of hypertension, hyperlipidemia, coronary artery disease, cerebrovascular accidents, congestive heart failure, carotid artery stenosis, aortic aneurysm, peripheral artery disease, gout, and osteoarthritis were also seen in patients with DKD.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Hipertensión , Anciano , Presión Sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: Biofabrication of skin tissue equivalents using 3D bioprinting technology has gained much attention in recent times due to the simplicity, the versatility of the technology and its ability in bioengineering biomimetic tissue histology. The key component being the bioink, several groups are actively working on the development of various bioink formulations for optimal skin tissue construction. METHODS: Here, we present alginate (ALG), gelatin (GEL) and diethylaminoethyl cellulose (DCEL) based bioink formulation and its application in bioprinting and biofabrication of skin tissue equivalents. Briefly, DEAE cellulose powder was dispersed in alginate solution with constant stirring at 60 °C to obtain a uniform distribution of cellulose fibers; this was then mixed with GEL solution to prepare the bioink. The formulation was systematically characterized for its morphological, physical, chemical, rheological, biodegradation and biocompatibility properties. The printability, shape fidelity and cell-laden printing were assessed using the CellInk bioprinter. RESULTS: The bioink proved to be a good printable, non-cytotoxic and stable hydrogel formulation. The primary human fibroblast and keratinocyte-loaded 3D bioprinted constructs showed excellent cell viability, collagen synthesis, skin-specific marker and biomimetic tissue histology. CONCLUSION: The results demonstrated the successful formulation of ALG-GEL-DCEL bioink and its application in the development of human skin tissue equivalents with distinct epidermal-dermal histological features.
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Alginatos/farmacología , DEAE-Celulosa/química , Gelatina/farmacología , Tinta , Microtecnología , Piel/efectos de los fármacos , Ingeniería de Tejidos , Andamios del Tejido/química , Adulto , Animales , Materiales Biocompatibles/química , Biomarcadores/metabolismo , Bioimpresión , Línea Celular , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Ratones , Impresión Tridimensional , Reología , Piel Artificial , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Layer-by-layer additive manufacturing process has evolved into three-dimensional (3D) "bio-printing" as a means of constructing cell-laden functional tissue equivalents. The process typically involves the mixing of cells of interest with an appropriate hydrogel, termed as "bioink", followed by printing and tissue maturation. An ideal bioink should have adequate mechanical, rheological, and biological features of the target tissues. However, native extracellular matrix (ECM) is made of an intricate milieu of soluble and non-soluble extracellular factors, and mimicking such a composition is challenging. To this end, here we report the formulation of a multi-component bioink composed of gelatin and alginate -based scaffolding material, as well as a platelet-rich plasma (PRP) suspension, which mimics the insoluble and soluble factors of native ECM respectively. Briefly, sodium alginate was subjected to controlled oxidation to yield alginate dialdehyde (ADA), and was mixed with gelatin and PRP in various volume ratios in the presence of borax. The formulation was systematically characterized for its gelation time, swelling, and water uptake, as well as its morphological, chemical, and rheological properties; furthermore, blood- and cytocompatibility were assessed as per ISO 10993 (International Organization for Standardization). Printability, shape fidelity, and cell-laden printing was evaluated using the RegenHU 3D Discovery bioprinter. The results indicated the successful development of ADA-gelatin-PRP based bioink for 3D bioprinting and biofabrication applications.