11 research outputs found
Microstructure and mechanical properties of nickel coated multi walled carbon nanotube reinforced stainless steel 316L matrix composites by laser sintering process
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Evaluation of the Central Effects of Systemic Lentiviral-Mediated Leptin Delivery in Streptozotocin-Induced Diabetic Rats
No full textType 1 diabetes (T1D) is characterized by hyperphagia, hyperglycemia and activation of the hypothalamic–pituitary–adrenal (HPA) axis. We have reported previously that daily leptin injections help to alleviate these symptoms. Therefore, we hypothesized that leptin gene therapy could help to normalize the neuroendocrine dysfunction seen in T1D. Adult male Sprague Dawley rats were injected i.v. with a lentiviral vector containing the leptin gene or green fluorescent protein. Ten days later, they were injected with the vehicle or streptozotocin (STZ). HPA function was assessed by measuring norepinephrine (NE) levels in the paraventricular nucleus (PVN) and serum corticosterone (CS). Treatment with the leptin lentiviral vector (Lepvv) increased leptin and insulin levels in non-diabetic rats, but not in diabetic animals. There was a significant reduction in blood glucose levels in diabetic rats due to Lepvv treatment. Both NE levels in the PVN and serum CS were reduced in diabetic rats treated with Lepvv. Results from this study provide evidence that leptin gene therapy in STZ-induced diabetic rats was able to partially normalize some of the neuroendocrine abnormalities, but studies with higher doses of the Lepvv are needed to develop this into a viable option for treating T1D
Responsiveness of hypothalamo-pituitary-adrenal axis to leptin is impaired in diet-induced obese rats
No full textThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Background/objectives:
Diet-induced obese (DIO) rats have altered stress (HPA) axis activity compared to diet-resistant (DR) rats when chronically exposed to a high-fat (HF) diet. Since stress axis is tightly regulated by leptin, an adipocyte-secreted hormone that is important for controlling body weight, we hypothesized that leptin action is impaired in DIO rats leading to alterations in HPA axis activity.
Subjects/methods:
We intraperitoneally injected selectively bred DIO and DR rats with either saline or recombinant rat leptin. HPA axis activity was assessed by measuring norepinephrine (NE) in the paraventricular nucleus (PVN), corticotropin-releasing hormone (CRH) in the median eminence, and serum corticosterone (CORT). To test if HF exposure duration and the corresponding increase in leptin differentially affects HPA axis activity, we placed animals on a chow or HF diet for 1 or 6 weeks.
Results:
Leptin injection significantly increased serum leptin levels in both DIO and DR animals. It also reduced PVN NE in both groups, indicating that noradrenergic neurons in both groups remain responsive to leptin. HF diet duration-dependently increased serum leptin only in DIO animals whereas PVN NE increased in both groups. While DR rats responded to HF diet by increasing CRH and CORT at both time-points, responses in DIO rats varied, suggesting that they have altered HPA axis activity that may be dependent on HF-induced leptin levels and/or signaling. To understand the underlying mechanisms, we measured pSTAT-3, a marker of leptin signaling, in brainstem noradrenergic neurons and found reduced pSTAT-3 in A1 region of HF-fed DIO rats. We also found higher serum free fatty acids (FFAs) and a pro-inflammatory cytokine, IL-1β.
Conclusions:
Collectively, these findings reveal that DIO rats have inherent neuroendocrine impairment in NE-HPA axis circuitry that worsens with the extent of HF diet exposure, possibly due to brainstem leptin resistance and/or elevated circulating FFAs and IL-1β
Correlating the differences in the receptor binding domain of SARS-CoV-2 spike variants on their interactions with human ACE2 receptor
No full textAbstract Spike glycoprotein of SARS-CoV-2 variants plays a critical role in infection and transmission through its interaction with human angiotensin converting enzyme 2 (hACE2) receptors. Prior findings using molecular docking and biomolecular studies reported varied findings on the difference in the interactions among the spike variants with the hACE2 receptors. Hence, it is a prerequisite to understand these interactions in a more precise manner. To this end, firstly, we performed ELISA with trimeric spike glycoproteins of SARS-CoV-2 variants including Wuhan Hu-1(Wild), Delta, C.1.2 and Omicron. Further, to study the interactions in a more specific manner by mimicking the natural infection, we developed hACE2 receptors expressing HEK-293T cell line, evaluated their binding efficiencies and competitive binding of spike variants with D614G spike pseudotyped virus. In line with the existing findings, we observed that Omicron had higher binding efficiency compared to Delta in both ELISA and Cellular models. Intriguingly, we found that cellular models could differentiate the subtle differences between the closely related C.1.2 and Delta in their binding to hACE2 receptors. Our study using the cellular model provides a precise method to evaluate the binding interactions between spike sub-lineages to hACE2 receptors
Missed opportunities for detection of hypertension in public health facilities of 18 districts in India, 2022
No full textAbstract Background More than half of the individuals with hypertension remain undiagnosed in India. The National Non-Communicable Disease (NCD) program has implemented opportunistic screening to improve diagnoses. In the public health facilities across 18 districts in nine states of India, we estimated the missed opportunity for hypertension detection in routine program settings. Methods In each of the chosen districts, we conducted a cross-sectional study in one district hospital (DH), one community health centre (CHC), and three primary health centres (PHCs), selected randomly. We collected data from 706 consecutively enrolled eligible out-patient department (OPD) attendees in each facility type and abstracted the data regarding coverage and yield of opportunistic screening for hypertension from the available registers. We then derived the missed opportunity for hypertension detection. We also estimated the median time for Blood Pressure (BP) measurement through observation and derived the staff requirement for BP screening at each facility type. Results Of the 41,012 eligible OPD attendees, 32.1% [31.6%-32.5%]) were screened for hypertension. The yield for hypertension screening was 23.2% (3,050/13,157). Among the OPD attendees, the proportion of missed diagnoses for hypertension among the expected was 57.1% (1,962/3,437), 67.4% (1,860/2,758), and 79.3% (2,597/3,274) in PHCs, CHCs, and DHs, respectively. The minimum number of dedicated staff required for measuring BP was one at PHC/CHC and two at DH. Conclusions Sixteen out of every 100 eligible OPD attendees miss the opportunity to get diagnosed with hypertension due to inadequate screening coverage. Innovative measures like task-sharing and utilizing trainee nurses for BP measurement to overcome staff shortages can help improve screening coverage
Clinical triage of patients on kidney replacement therapy presenting with COVID-19: An ERACODA registry analysis
No full textBackground: Patients on kidney replacement therapy (KRT) are at very high risk of coronavirus disease 2019 (COVID-19). The triage pathway for KRT patients presenting to hospitals with varying severity of COVID-19 illness remains ill-defined. We studied the clinical characteristics of patients at initial and subsequent hospital presentations and the impact on patient outcomes. Methods: The European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or non-hospitalized at initial triage and those re-presenting a second time. Predictors of outcomes (hospitalization, 28-day mortality) were then determined for all those not hospitalized at initial triage. Results: Among 1423 KRT patients with COVID-19 [haemodialysis (HD), n = 1017; transplant, n = 406), 25% (n = 355) were not hospitalized at first presentation due to mild illness (30% HD, 13% transplant). Of the non-hospitalized patients, only 10% (n = 36) re-presented a second time, with a 5-day median interval between the two presentations (interquartile range 2-7 days). Patients who re-presented had worsening respiratory symptoms, a decrease in oxygen saturation (97% versus 90%) and an increase in C-reactive protein (26 versus 73 mg/L) and were older (72 vs 63 years) compared with those who did not return a second time. The 28-day mortality between early admission (at first presentation) and deferred admission (at second presentation) was not significantly different (29% versus 25%; P = 0.6). Older age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation were identified as risk predictors of mortality when re-presenting after discharge at initial triage. Conclusions: This study provides evidence that KRT patients with COVID-19 and mild illness can be managed effectively with supported outpatient care and with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19 to aid clinical triage and optimize resource utilization during the ongoing pandemic. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy
No full text\ua9 2022, The Author(s). In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk
Recovery of dialysis patients with COVID-19: health outcomes 3 months after diagnosis in ERACODA
No full text© The Author(s) 2022.Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8–6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis
Evaluation of the Potential for Valorization of Potato Waste as a Substrate for Biobutanol Production: A Critical Review
No full textilustraciones, diagramas, mapas, tablasEste proyecto de tesis tuvo como objetivo evaluar la potencialidad de aprovechamiento de residuos de papa como materia prima para la producción de biobutanol, específicamente de los tubérculos que no pueden comercializarse debido a que no cumplen con los parámetros de calidad. Para esto, se llevó a cabo una caracterización del material para determinar su composición, incluyendo contenido de humedad, lignina, hemicelulosa y celulosa. Posteriormente, se extrajo el almidón de los residuos, obteniendo un rendimiento del 14,96% p/p. Se realizó una hidrólisis enzimática usando amilasa y amiloglucosidasa sobre el almidón, y se maximizó mediante pruebas cinéticas, evaluando la producción de azúcares reductores con el método DNS, determinando así las condiciones óptimas de temperatura y pH. La glucosa alcanzó un rendimiento de 47,78% p/p, y fue cuantificada mediante HPLC-IR. Se realizó también un ensayo preliminar de fermentación ABE, monitoreando el crecimiento y el pH del medio. Finalmente, se realizó una revisión de literatura buscando identificar tendencias con respecto a la producción biológica de solventes, a fin de encontrar un marco de acción con el cual encauzar una posterior investigación experimental (Texto tomado de la fuente).This thesis project aimed to evaluate the potential of using potato waste as raw material to produce biobutanol, specifically from tubers that cannot be marketed due to not meeting quality standards. To achieve this, a characterization of the material was carried out to determine its composition, including moisture content, lignin, hemicellulose, and cellulose. Subsequently, starch was extracted from the waste, yielding 14,96% w/w on a wet basis. Enzymatic hydrolysis was performed using amylase and amyloglucosidase on the starch, and was maximized through kinetic tests, evaluating the production of reducing sugars with the DNS method, thereby determining the optimal temperature and pH conditions. Glucose reached a yield of 47,78% w/w and was quantified by HPLC-IR. A preliminary ABE fermentation assay was also conducted, monitoring the growth and pH of the medium. Finally, a literature review was carried out to identify trends in the biological production of solvents, to find a framework for guiding further experimental research.MaestríaMagíster en Ingeniería - Ingeniería AmbientalProcesos Sostenible
