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1,361 result(s) for "Das, Gaurav"
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Effect of gold nanoparticles on the structure and neuroprotective function of protein L-isoaspartyl methyltransferase (PIMT)
Fibrillation of peptides and proteins is implicated in various neurodegenerative diseases and is a global concern. Aging leads to the formation of abnormal isoaspartate (isoAsp) residues from isomerization of normal aspartates in proteins, triggering fibril formation that leads to neurodegenerative diseases. Protein L -isoaspartyl methyltransferase (PIMT) is a repair enzyme which recognizes and converts altered isoAsp residues back to normal aspartate. Here we report the effect of gold nanoparticles (AuNPs) of different sizes on the structure and function of PIMT. Spherical AuNPs, viz . AuNS5, AuNS50 and AuNS100 (the number indicating the diameter in nm) stabilize PIMT, with AuNS100 exhibiting the best efficacy, as evident from various biophysical experiments. Isothermal titration calorimetry (ITC) revealed endothermic, but entropy driven mode of binding of PIMT with all the three AuNSs. Methyltransferase activity assay showed enhanced activity of PIMT in presence of all AuNSs, the maximum being with AuNS100. The efficacy of PIMT in presence of AuNS100 was further demonstrated by the reduction of fibrillation of Aβ42, the peptide that is implicated in Alzheimer’s disease. The enhancement of anti-fibrillation activity of PIMT with AuNS100 was confirmed from cell survival assay with PC12 derived neuronal cells against Aβ42 induced neurotoxicity.
A study of Human Epidermal Growth factor receptor-2 HER-2 in Carcinoma Oesophagus Single Institutional Tertiary cancer centre study from North-East part of India
Background: Oesophageal cancer both squamous cell [SCC] and adenocarcinoma have poor outcomes with high morbidity and mortality. Our hospital-based registry for year 2017-2018 showed that oesophageal cancer constituted 22.7% of annual case load. The main objective of this study was to determine the presence of HER-2 receptors in patients with oesophageal carcinoma in our region. Methodology: From September 2018 to September 2019, data regarding expression of HER-2 receptors was analysed in 133 patients of oesophageal carcinoma. Data were statistically described as frequencies (number of cases) and percentages where appropriate. Chi-square and Fischer's exact test was used to find out the association between categorical variables. A P value less than 0.05 was considered as statistical significant at 95% confidence interval. The statistical analysis was performed using SSPS [statistical package for the social sciences] software version 17.0. Results: A total of 133 patients were taken into study. Majority of patients were males (96) with mean age of 52 years. Squamous cell carcinoma was predominant histology. HER-2 receptor positivity was seen in 6.01% of patients. Patients with HER-2 receptor positivity presented in advanced stage with poor functional status and poor grades of differentiation. Statistically significant correlation of Her-2 expression was seen with stage (p = 0.001) and pathology of tumour (p = 0.0001). Conclusion: Squamous cell carcinoma of oesophagus still predominates in North-eastern part of India. For studying the role of effective targeted therapies knowledge of frequency of HER-2 receptor positivity is of utmost importance in our population, and our study aims to answer this question. The present study shows low prevalence of HER-2 neu overexpression in our community, probably due to disproportionately high incidence of SCC compared to adenocarcinoma. Patients with HER-2 receptor positivity presented in advanced stage with poor functional status and poor grades of differentiation.
Diagnostic accuracy of Liver Imaging Reporting and Data System locoregional treatment response criteria: a systematic review and meta-analysis
Objective There is increasing adoption of Liver Imaging Reporting and Data System (LI-RADS) treatment response (LR-TR) criteria. However, there is still a relative lack of evidence evaluating the performance of these criteria. We performed this study to assess the diagnostic accuracy of LI-RADS LR-TR criteria. Methods A thorough search of PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials for studies reporting diagnostic accuracy of LI-RADS LR-TR criteria was conducted through 30 June 2020. The meta-analytic summary of sensitivity, specificity, and diagnostic odds ratio of LI-RADS LR-TR criteria was computed using explant histopathology as the reference standard. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results Four studies were found eligible for meta-analysis. The total number of LR-TR observations was 462 (240 patients, 82.5% males). Different locoregional therapies (LRTs), including bland embolization, chemoembolization, radiofrequency ablation, and microwave ablation, had been used. The mean time interval between LRT and liver transplantation ranged from 181 to 219 days. There was a moderate to good inter-reader agreement for LR-TR criteria. The pooled sensitivity and specificity of LR-TR criteria for viable disease were 62% (95% CI, 49–74%; I 2 = 69%) and 87% (95% CI, 76–93%; I 2 = 57%), respectively. The pooled diagnostic odds ratio and area under the curve were 9.83 (95% CI, 5.34–18.08; I 2 = 19%) and 0.80. Conclusions LI-RADS LR-TR criteria have acceptable diagnostic performance for the diagnosis of viable tumor after LRT. Well-designed prospective studies evaluating criteria of equivocal lesions and effect of different LRTs should be performed. Key Points • The pooled sensitivity and specificity of LI-RADS LR-TR criteria for the diagnosis of viable tumor were 62% and 87%, respectively. • The pooled diagnostic odds ratio and area under the curve were 9.83 and 0.80. • LR-TR criteria had a moderate to good inter-reader agreement.
Hepatic parenchymal resection with waterjet in the malignant setting – Results of an Initial Foray
Background : Liver resections for malignant disease are often complicated by significant intraoperative bleeding due to the liver’s rich vascularity. The waterjet device offers a tissue-selective dissection technique aimed at reducing blood loss and preserve vital intrahepatic structures. This study evaluates the efficacy and safety of hydrodissection in liver resections performed for malignant indications. Methods : This retrospective analysis included 27 patients who underwent hepatic resections using the ERBE ® waterjet device between April 2023 and June 2024 at a tertiary oncology center in North East India. Procedures included radical cholecystectomy ( n  = 16), metastasectomy ( n  = 7), left lateral sectionectomy ( n  = 2), right anterior sectionectomy ( n  = 1), and wedge resection ( n  = 1). Intraoperative parameters (blood loss, duration, need for inflow occlusion) and postoperative outcomes (bile leak, transaminase elevation, transfusion requirement) were assessed. Results : Median transection time was 36 min (range: 20–150), with a median blood loss of 150 mL (range: 80–350). Only one patient (3.7%) required the Pringle maneuver. Bile leak occurred in two patients (7.4%), resolving without intervention. Postoperative transaminase elevation (>3× ULN) was observed in 9 patients (33.3%), and 15 patients (59.3%) required blood transfusions. Median hospital stay was 4 days (range: 2–8). No reoperations or 30-day readmissions occurred. Conclusions : Waterjet-assisted liver resection appears to be a safe and hemostatically effective technique in malignant hepatic surgery, especially in limited resections. It minimizes blood loss, reduces reliance on vascular inflow occlusion, and preserves key vascular and biliary structures. These findings support the utility of hydrodissection in oncological liver surgery, warranting further prospective studies for broader validation.
Postoperative pancreatic fistulas after pancreaticoduodenectomy for malignancy: A Northeast Indian tertiary cancer center study
Background and Aim Postoperative pancreatic fistula (POPF) is an important cause of major morbidity and mortality after pancreaticoduodenectomy. We intend to estimate the incidence and study the risk factors and outcomes of patients who developed this dreaded complication. Methods This is a retrospective observational study. We included all patients who underwent pancreaticoduodenectomy at a specialized surgical unit of a single tertiary care cancer center in Northeast India. The period of study was from 23 April 2012 to 27 December 2019. The 2016 update on the definition of POPF by the International Study Group for Pancreatic Fistula was used to define the complication. Chi‐square test and Fischer's exact test were applied to categorical variables. t‐test was used to quantify mean difference among continuous variables. P value <0.05 was considered statistically significant at 95% confidence interval. Results A total of 59 patients underwent pancreaticoduodenectomy during the study period with almost equal distribution among males and females (29 and 30 patients respectively). The mean age of the patients was 54.0 years (range 20–72). Grade A, B, and C pancreatic fistulas were seen in five (8.5%), three (5.1%), and two (3.4%) patients, respectively. Preoperative hyperbilirubinemia, pancreatic duct size ≤3 mm, hypoalbuminemia, preoperative biliary decompression, and prolonged duration of surgery were identified as risk factors for POPF. POPF also resulted in increased 90‐day mortality (20%). Conclusion POPF remains a potentially life‐threatening complication of pancreaticoduodenectomies. The knowledge and management of modifiable risk factors for this condition may help in mitigating this problem. Postoperative pancreatic fistula remains a potentially life‐threatening complication of pancreaticoduodenectomies. Preoperative hyperbilirubinemia, pancreatic duct size less than or equal to 3 mm, hypoalbuminemia, preoperative biliary decompression, and prolonged duration of surgery were identified as risk factors for POPF. POPF also resulted in increased 90‐day mortality (20%).The knowledge and management of modifiable risk factors for this condition may help in mitigating this problem.
Forequarter Amputation for Malignant Tumours: Tale of Sustained Relevance or Telltale Sign of Doom?
Forequarter amputation (interscapulothoracic amputation) includes surgical removal of an upper limb and the shoulder girdle, including the scapula and a portion of the clavicle. We aim to report about our recent experience of having to resort to this mutilating surgery and the clinicopathological variables in that context. The study was done at a cancer centre in Northeast India. It was an ambispective study design, where the patient cohort who underwent FQA was identified retrospectively from the operative register of major surgeries for the time period 1st June 2020 to 31st May 2022 (24 months), and these patients were followed up prospectively from 1st June 2022 to 31st May 2023 (1 year). The study variables were obtained from the electronic medical records (EMR), the physical case files and the hospital-based cancer registry (HBCR). There were 7 patients who underwent forequarter amputation (FQA) during the two years, and in the same period, 15 patients underwent limb salvage surgery for tumours around the shoulder girdle. This translates to a FQA rate of 31.8%. The male:female ratio of the patients was 3:4. The median age of the patients was 32 years (range 19 to 59 years). The histologies included osteosarcoma (2), chondrosarcoma (2), Ewing’s sarcoma (2) and hidradenocarcinoma (1). None of these patients had any distant metastatic disease. Four patients had local disease progression on neoadjuvant chemotherapy. Three of the patients had emergency surgery as a life-saving procedure on account of bleeding from their ulcerated tumours. Two patients had disease which was recurrent and unsalvageable due to the encasement of the neurovascular bundle. The median follow-up was 8 months (range 4 to 18 months). Five patients had distant recurrence with pulmonary metastases (100%) and bone secondaries (14.3%) within a range of 3 to 8 months. None of the patients had any local recurrence. Two patients are on follow-up without any evidence of disease (17 and 18 months respectively). Forequarter amputation is the surgical option when tumours around the shoulder girdle are not amenable to limb-sparing procedures by virtue of their disease extent. These cancers are usually aggressive leading to early distant metastasis.
Layered reward signalling through octopamine and dopamine in Drosophila
Dopamine is synonymous with reward in mammals but associated with aversive reinforcement in insects, where reward seems to be signalled by octopamine; here it is shown that flies have discrete populations of dopamine neurons representing positive or negative values that are coordinately regulated by octopamine. Shared neuronal reward signals The neurotransmitter dopamine has been synonymous with reward in mammals, but is associated with aversive reinforcement in insects. In insects, it was thought, reward was signalled by octopamine. Now Scott Waddell and colleagues show that flies have discrete 'negative' and 'positive' populations of dopamine neurons, which are coordinately regulated by octopamine. This work reconciles previous findings with octopamine and dopamine, and suggests that reinforcement systems in flies are more like those in mammals than previously thought. Dopamine is synonymous with reward and motivation in mammals 1 , 2 . However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies 3 , 4 . Instead, octopamine has historically been considered to be the signal for reward in insects 5 , 6 , 7 . Here we show, using temporal control of neural function in Drosophila , that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the α-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the β-adrenergic-like OCTβ2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought.
Best non-contrast magnetic resonance imaging sequence and role of intravenous contrast administration in evaluation of perianal fistula with surgical correlation
PurposeTo evaluate the best non-contrast magnetic resonance imaging (MRI) sequence and role of intravenous contrast administration in preoperative characterization and classification of perianal fistulae, keeping surgery as gold standard.MethodsThis prospective study comprised of forty-five consecutive patients with actively draining external perianal opening. MRI was performed on a 1.5 T scanner using non-contrast and contrast enhanced sequences in multiple planes. St. James’s University Hospital MRI based classification system was used to classify the fistulae into five grades. Taking surgery as gold standard, association between surgical and MRI findings was statistically analysed.ResultsOf the 45 patients recruited, forty were deemed eligible for inclusion. Mean age was 39.7 ± 11.7 years with male preponderance (M: F = 8:1). Commonest type was Grade 1 (40%). The best sequences in terms of overall accuracy were axial & coronal planes of contrast enhanced fat suppressed (FS) T1W turbo spin echo (TSE) (95.7%) followed by FS T2W TSE (94.1%) while sagittal T2W TSE sequence with or without fat suppression had the lowest accuracy (90.13%). The difference in overall diagnostic accuracy of FS T2W TSE and contrast enhanced FS T1W TSE sequence for evaluating perianal fistula was not statistically significant (p = 0.52). However, contrast study had a better accuracy in detecting internal openings and secondary tract of recurrent/ post-operative cases.ConclusionBest non-contrast MRI sequence is FS T2W TSE (axial and coronal). Non-contrast MRI is equally efficient to contrast study while evaluating primary/previously unoperated cases thereby eliminating the role of contrast in such cases. However, intravenous contrast should be administered for evaluating post-operative cases with recurrence.
Outcomes of Patients Undergoing Major Surgery for Cancer with COVID-19 in the Postoperative Period
The aim of our study was to report about the clinical outcomes of patients who underwent major surgery for cancer and developed COVID-19 in the postoperative period. A retrospective and observational study was done in the Surgical Oncology Division of a tertiary care cancer hospital in North-East India. The study period was from 1 st April 2020 to 31 st December 2021. Patients with a confirmed diagnosis of cancer who underwent a major surgery and developed COVID-19 in the postoperative period, within the same hospital stay were included in the study. Data was obtained from a prospectively maintained database and case records. Descriptive statistics were used to state the results in median values, range and percentages. A total of 22 patients developed COVID-19 in the postoperative period during the study period out of a total of 1402 patients operated during that time period (1.57%). The have been followed up for a median period of 16 months (range 2 to 18 months). The median age at presentation was 50 years (range 25 to 74 years). The incidence of co-morbidities was 27.3%. The median duration of ICU stay was 3 days (range 0 to 9 days) and median duration of hospital stay was 22 days (range 9 to 55 days).. The postoperative mortality rate was 18.2%. COVID-19 in the postoperative period in patients undergoing major abdominal and thoracic surgeries for cancer caused high postoperative mortality and prolonged hospital stay.