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Objective Chronic subdural hematoma (CSDH) is a common neurological problem with significant recurrence after surgery. Risk considerations can vary, ranging from patient-related factors to those related to the surgical procedure. This study explores the association between preoperative eosinophil count and systemic immune inflammation (SII) with CSDH recurrence. Materials and Methods We conducted a prospective analysis of 105 patients with equal numbers of CSDHs who underwent surgery for CSDH between January 2023 and January 2024. The preoperative eosinophil counts, along with other differential leukocyte counts, were measured. The SII index was calculated using the standard formula (SII = neutrophil count × platelet count/lymphocyte count). Multivariate and univariate regression analyses were performed to assess the association between risk factors and CSDH recurrence. Results The preoperative eosinophil count showed a significant correlation with recurrence (p < 0.001). The SII index was significantly higher in patients with recurrent CSDH (p = 0.003). Neutrophils were found to be significantly associated with CSDH recurrence (p = 0.038). Age (p < 0.001) and SII (p = 0.005) were found to be independent predictors of CSDH recurrence, whereas hematoma volume (p < 0.001) and the antiplatelet regimen were a significant predictor of CSDH recurrence (p = 0.047). Variables like male gender, diabetes mellitus, anticoagulants, and hematoma volume were associated with eosinophil-rich or eosinophil-poor status. Conclusion Preoperative eosinophil count, neutrophils, and the SII index may serve as potential predictors of CSDH recurrence. Further studies with larger sample sizes are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a significant public health challenge globally, affecting millions of individuals. Despite numerous pharmacological treatments, lifestyle interventions remain a cornerstone of hypertension management. Methods: This study was a randomized controlled trial conducted at a primary care clinic with a sample size of 200 patients diagnosed with hypertension. Participants were randomly assigned to one of two groups: dietary modification and increased physical activity, or standard care. The study duration was 12 months. Results: Both interventions resulted in statistically significant reductions in systolic and diastolic blood pressure. However, the group receiving combined dietary and physical activity interventions showed a more significant reduction compared to the standard care group. Conclusion: Lifestyle interventions, specifically a combination of dietary changes and increased physical activity, are effective in managing hypertension in a primary care setting and offer a viable alternative to medication for some patients. [ABSTRACT FROM AUTHOR]

In India, drug-resistant tuberculosis (DR-TB) is a major public health issue and a significant challenge to stop TB program. An estimated 27% of new TB cases and 44% of previously treated TB cases are resistant to at least one anti-TB drug. The conventional methods for DR-TB diagnosis are time-consuming and have limitations, leading to delays in treatment initiation and the spread of the disease. Next-generation sequencing (NGS) based approaches have emerged as a promising tool for diagnosing DR-TB, simultaneously offering rapid and accurate detection of resistance mutations in multiple genes. NGS-based approaches generate a large amount of data, which requires efficient and reliable bioinformatics pipelines for data analysis. TBProfiler and Mykrobe are the bioinformatics pipelines that have been created to analyze NGS data for the diagnosis of DR-TB. These pipelines use reference-based and machine-learning approaches to detect resistance mutations and predict drug susceptibility, enabling clinicians to make informed treatment decisions. Implementing NGS-based approaches and bioinformatics pipelines for DR-TB diagnosis can potentially improve patient outcomes by facilitating early detection of drug resistance and guiding personalized treatment regimens. However, the widespread adoption of these approaches in India faces several challenges, including high costs, limited infrastructure, and a lack of trained personnel. Addressing these challenges requires concerted effort to ensure equitable access to and effective implementation of these innovative technologies. [ABSTRACT FROM AUTHOR]

Modern agriculture practices heavily depend on the application of chemical fertilizers and continuous application disturbs the soil quality and health. Fluorescent Pseudomonas are the well characterized group of bacteria proficient in plant growth promotion and have excellent phosphate solubilizing abilities and solubilize insoluble phosphate to plants available form via secretion of organic acids. This study focused on the phosphate solubilization ability of Pseudomonas, arouse of Aloin-A molecule, gluconic acid production, as well as biometric parameters of key medicinal plant, the Aloe vera (Aloe barbadensis). Two strains (P. putida and Pseudomonas sp.) were found very effective PSBs and solubilized 236.73 and 153.73 mg L−1 phosphate, respectively. High-performance liquid chromatography analysis (HPLC) showed the production of gluconic acid (GA). P. putida and P. sp. produced 23970 ± 231 and 21538 ± 129 mg L−1 GA, respectively. Inoculation of the plants with consortium of P. putida and Pseudomonas sp. enhanced the plant growth, soil available P and phosphate uptake in plants than individual inoculation. An increase in aloin-A content (18.15 and 28.71 fold) was recorded in A. barbadensis treated with a PSB consortium in a soil amended without and with TCP (tricalcium phosphate), respectively. P-uptake ultimately enhances the aloin-A synthesis and biomass of plant. Therefore, agronomic attributes of Aloe vera plants can be improved for used as a medicinal plant through application of potent Fluorescent Pseudomonas. [ABSTRACT FROM AUTHOR]

Biomolecular nuclear magnetic resonance (NMR) spectroscopy and artificial intelligence (AI) have a burgeoning synergy. Deep learning-based structural predictors have forever changed structural biology, yet these tools currently face limitations in accurately characterizing protein dynamics, allostery, and conformational heterogeneity. We begin by highlighting the unique abilities of biomolecular NMR spectroscopy to complement AI-based structural predictions toward addressing these knowledge gaps. We then highlight the direct integration of deep learning approaches into biomolecular NMR methods. AI-based tools can dramatically improve the acquisition and analysis of NMR spectra, enhancing the accuracy and reliability of NMR measurements, thus streamlining experimental processes. Additionally, deep learning enables the development of novel types of NMR experiments that were previously unattainable, expanding the scope and potential of biomolecular NMR spectroscopy. Ultimately, a combination of AI and NMR promises to further revolutionize structural biology on several levels, advance our understanding of complex biomolecular systems, and accelerate drug discovery efforts. [Display omitted] In their review, Shukla et al. explore the evolving synergy of artificial intelligence (AI) and biomolecular nuclear magnetic resonance spectroscopy (NMR). AI tools excel in predicting protein conformations but lacks dynamics insight. NMR complements AI, bridging these gaps. Integrating deep learning into NMR enhances analysis, experimental design, and biophysical insight. [ABSTRACT FROM AUTHOR]

Enzymes are known to sample various conformations, many of which are critical for their biological function. However, structural characterizations of enzymes predominantly focus on the most populated conformation. As a result, single-point mutations often produce structures that are similar or essentially identical to those of the wild-type enzyme despite large changes in enzymatic activity. Here, we show for mutants of a histone deacetylase enzyme (HDAC8) that reduced enzymatic activities, reduced inhibitor affinities, and reduced residence times are all captured by the rate constants between intrinsically sampled conformations that, in turn, can be obtained independently by solution NMR spectroscopy. Thus, for the HDAC8 enzyme, the dynamic sampling of conformations dictates both enzymatic activity and inhibitor potency. Our analysis also dissects the functional role of the conformations sampled, where specific conformations distinct from those in available structures are responsible for substrate and inhibitor binding, catalysis, and product dissociation. Precise structures alone often do not adequately explain the effect of missense mutations on enzymatic activity and drug potency. Our findings not only assign functional roles to several conformational states of HDAC8 but they also underscore the paramount role of dynamics, which will have general implications for characterizing missense mutations and designing inhibitors. [ABSTRACT FROM AUTHOR]

Background: Valine is an important amino acid and its deficiency may result in reduced growth and immunity. However, studies in turkeys are limited. Hence a study was conducted to assess the effect of supplemental L-valine (L-val) on growth performance, immunocompetence traits, carcass quality and meat composition of turkey poults. Methods: Day old turkey poults (n=96) were distributed into four dietary treatment groups: T1-basal diet, T2-T1+0.04% L-val, T3- T1+0.08% L-val, T4- T1+0.12% L-val, having three replicates of 8 birds each. Result: No significance difference observed in average weekly body weight (BW), body weight gain (BWG) and feed conversion ratio (FCR) of birds throughout experimental period except at 7th week where T2 and T3 poults had a significantly higher (P<0.05) BW, BWG and significantly better (P<0.05) FCR. HA titre was significantly higher (P<0.05) in T3. Per cent breast weight was significantly higher (P<0.05) in T3. Percent crude protein level in breast muscle of turkey poults was significantly higher (P<0.05) in T3. Thus, supplementation of L-val @ 0.08% in turkey poults resulted in significantly better humoral immune response, higher percent breast yield and higher percent crude protein in breast meat. [ABSTRACT FROM AUTHOR]

Background: Surgical intervention has been shown to have good post-operative outcomes in patients with chronic pancreatitis with pain refractory to oral analgesics. We present our initial experience with robotic lateral pancreaticojejunostomy (LPJ) and modified Frey's procedure (MFP). Methodology: Patients with chronic calcific pancreatitis were evaluated with routine biochemical and radiological investigations. The indication of surgery was intractable pain which was recorded by an Intensity Frequency, Consequence (IFC) pain score. The patient was placed in a reverse Trendelenburg position with four 8-mm robotic ports and one 12-mm assistant port. Robotic ultrasound was utilized to identify the pancreatic duct. After retrieving all the calculi, which was confirmed by pancreatoscopy with the help of a video choledochoscope and performing the head coring in particular cases, the Roux-en-Y LPJ was performed. Results: Among five patients (4 males, one female), robotic LPJ was performed in 2 and MFP in 3 patients. The cohort's median age was 32 (interquartile range (IQR), 28, 40) years, and the median (IQR) pancreatic duct size was 9 (9, 13) mm. The median (IQR) duration of the procedure was 385 (380, 405) minutes, with a median (IQR) blood loss of 100 (50–100) ml, and the patients were discharged on median post-operative day 5. The patients continue to do well at a median follow-up of 3–30 months without the requirement of oral analgesics. Conclusion: Robotic LPJ and MFP are feasible in experienced hands with good post-operative outcomes and enhanced quality of life. Intra-operative pancreatoscopy with the help of a choledochoscope can be utilized to ascertain the complete clearance of pancreatic duct stones and the consequent pain relief. [ABSTRACT FROM AUTHOR]

Introduction: Post-operative chylothorax is a dreaded complication after esophagectomy; hence real-time identification of the thoracic duct (TD) may aid in avoiding its injury or promptly tackling injury when it occurs. We utilized intra-nodal injection of Indocyanine green (ICG) dye to delineate TD anatomy while performing esophagectomy for esophageal carcinoma.Method: Two ml of 1 mg/ml solution of ICG was injected into the inguinal lymph nodes under ultrasound guidance. TD was checked with the laparoscopic Karl Storz IMAGE1 STM or Robotic da Vinci Xi system. The thoracic esophagus, periesophageal tissue, and lymph nodes were dissected. The TD was visualized throughout the dissection using OverlayTM technology & Firefly mode™ and checked at the end to rule out any dye leak. TD was clipped if any dye leakage or TD injury (TDI) was noted using Near Infra-Red Spectroscopy.Results: Twenty one patients with M:F 13:8 underwent minimally invasive esophagectomy (MIE) [thoracoscopic assisted (n = 15) and robotic-assisted (n = 6)]. TD was visualized in all the cases after a median (IQR) time of 35 (30, 35) min. The median (IQR) duration of the thoracic phase was 150 (120,165) min. TDI occurred in 1 case, identified intra-operatively, and TD was successfully clipped. There were no post-operative chylothorax or adverse reactions from the ICG injection.Conclusion: Intra-nodal ICG injection before MIE helps to identify the TD in real-time and is a valuable intra-operative aid to prevent or successfully manage a TD injury. It may help to prevent the dreaded complication of post-operative chylothorax after esophagectomy. [ABSTRACT FROM AUTHOR]

'Katarni Rice' is a fine quality scented rice landrace of Bihar, India and has tremendous export potential and commercial value. This is a preferred rice in the state due to its flavour, palatability and popcorn like essence before and after cooking. But its area has been shrunken drastically in recent years due to its low yielding (25–30 Q/ha) ability caused due tall and week stature and lodging tendency at maturity. To overcome this problem, marker assisted introgression of semi-dwarfing (sd1) gene from semi-dwarf and high yielding rice varieties Rajendra Sweta and BPT5204 was attempted. Parental polymorphism was obtained through 109 SSR markers. The gene specific markers for fragrance and semi-dwarfing genes were used in the segregants to track their transfer. Recombinant selection was done for the donor genome segments flanking to the target gene i.e., sd1 followed by background selection through genome wide polymorphic SSR markers. More than 90% recurrent parent genome recovery was observed and the selected plants showed a reduction of plant height and flowering time in comparison to Katarni in the successive backcross generation along with the retention of aroma. The identified lines can be evaluated further in multilocation trials to release it as a sustainable high yielding aromatic genotype. [ABSTRACT FROM AUTHOR]

Introduction: Choledochal cyst (CDC) excision with bilio-enteric anastomosis has been reported by a laparoscopic approach. With the advent of robotic surgery, it is likely to simplify the performance of such complex procedures. Herein, we present our technique of total robotic CDC excision with intra-corporeal Roux-en-Y hepaticojejunostomy (RYHJ). Methods: The patient was placed in a reverse Trendelenburg position. The robotic ports were placed in a "C"-shaped manner, with the camera port placed ~2 cm below the umbilicus. A 12-mm assistant port was placed in between the camera and the left-sided robotic port. Robotic dissection and excision of extrahepatic part CDC were performed, and subsequently, intra-corporeal robotic RYHJ with jejunojejunostomy was completed. Intra-operatively, indocyanine green dye was used to delineate the biliary anatomy and to check the anastomotic integrity. Results: All three patients were female with a median age of 21 (18–34) years. Two patients had type IVa, and one had a mixed variant of type I(C) with type VI. The median operative time was 420 min, whereas docking and console time was 22 (20–25) min and 400 (360–450) min, respectively. The median blood loss and length of hospital stay were 50 (50–100) ml and 6 (5–6) days, respectively. One patient has mild acute pancreatitis in the post-operative period, which was managed conservatively. Conclusion: Robotic CDC excision and reconstruction seem to be a safe, feasible, and effective surgical option that provides the benefits of minimal access surgery but also greatly aids in complex dissection and reconstruction. [ABSTRACT FROM AUTHOR]

Background: Gastric conduit has emerged as the preferred treatment option for both esophageal bypass and replacement for corrosive stricture of the esophagus. There is a lack of consensus and a dearth of published literature regarding the short- and long-term complications of using a gastric conduit. This meta-analysis aims to evaluate the outcomes, morbidity, and complications associated with it. Methods: MEDLINE, Cochrane Library, and Google Scholar (January 1960 to May 2020) were systematically searched for all studies reporting short- and/or long-term outcomes and complications following the use of a gastric conduit for corrosive esophageal stricture. Results: Seven observational studies involving 489 patients (53.2% males, mean age ranging from 22.1 to 41 years) who had ingested a corrosive substance (acid in 74.8%, alkali in 20.7%, and unknown in the rest) were analyzed. Gastric pull-up was performed in 56.03% (274/489) of patients. Median blood loss in the procedure was 187.5 ml with a mean operative duration of 298.75 ± 55.73 min. The overall pooled prevalence rate of anastomotic leak was 14.4% [95% CI (6.2–24.0); p < 0.05, I2 = 67.38], and anastomotic stricture was 27.2% [95% CI (13–42.8); p < 0.001, I2 = 80.11]. Recurrent dysphagia according to pooled prevalence estimates occurred in 14.4% patients [95% CI (5.4–25.1); p < 0.05, I2 = 69.1] and 90-day mortality in 4.8% patients [95% CI (1.5–9.1%); I2 = 31.1, p = 0.202]. The dreaded complication of conduit necrosis had a pooled prevalence of 1.3% [95% CI (0.1–3.4%); I2 = 0, p = 0.734]. Conclusion: The stomach can be safely used as the conduit of choice in corrosive strictures with an acceptable rate of complications, postoperative morbidity, and mortality. [ABSTRACT FROM AUTHOR]

In this article, we present a novel Carleman estimate for ultrahyperbolic operators, in R t m × R x n. Then, we use a special case of this estimate to obtain improved observability results for wave equations with time-dependent lower order terms. The key improvements are: (1) we obtain smaller observation regions when compared with standard Carleman estimate results, and (2) we also address the case when observability is centered around a point inside the domain. Finally, as a corollary of the observability result, we obtain improved interior controllability for wave equations with same features. [ABSTRACT FROM AUTHOR]

A 14-year-old boy who had been complaining of double vision for the previous month was referred for neuro-ophthalmological evaluation. He was carrying a diagnosis of a cavernous sinus haemangioma causing a right VIth nerve palsy, based on imaging elsewhere. He reported having a boil at the angle of his mouth, which was associated with left-sided facial cellulitis, two weeks before the onset of the diplopia. His blood investigations showed a leukocytosis with elevated inflammatory markers. Re-evaluation of the magnetic resonance imaging suggested a sac-like out-pouching in the intracavernous part of the right internal carotid artery with differential intensity suggestive of turbulent flow. On the basis of the clinico-radiological findings, a diagnosis of mycotic aneurysm of the cavernous sinus part of internal carotid artery was made. A high index of suspicion is required to detect this rare clinical entity, which is associated with a potentially catastrophic clinical course. [ABSTRACT FROM AUTHOR]

The surface of proteins is covered by side chains of polar amino acids that are imperative for modulating protein functionality through the formation of noncovalent intermolecular interactions. However, despite their tremendous importance, the unique structures of protein side chains require tailored approaches for investigation by nuclear magnetic resonance spectroscopy and so have traditionally been understudied compared with the protein backbone. Here, we review substantial recent methodological advancements within nuclear magnetic resonance spectroscopy to address this issue. Specifically, we consider advancements that provide new insight into methyl-bearing side chains, show the potential of using non-natural amino acids and reveal the actions of charged side chains. Combined, the new methods promise unprecedented characterisations of side chains that will further elucidate protein function. [ABSTRACT FROM AUTHOR]

Objective: Dilated common bile duct (CBD) (8–15 mm) with normal liver function tests is seen not infrequently, while management of such patients is ambiguous. We propose a treatment algorithm for this cohort of patients after observing them over a period of 8 years. Methods: Seventy-eight such patients were managed from 2009 to 2017 and categorized as: Group A—dilated CBD with post-cholecystectomy status (n = 15); B—dilated CBD with cholelithiasis (n = 34); C—dilated CBD without cholelithiasis (n = 16); D—dilated CBD with no cause identified and underwent CBD excision (n = 13). Causes for CBD dilatation were evaluated. The outcome of patients in Group B + C without any cause (n = 33) was compared with Group D. Result: Median age, CBD diameter, bilirubin and alkaline phosphatase were 51 years (13–79), 10 mm (8–20), 0.6 mg/dl (0.2–2.5) and 126 IU (60–214), respectively. Group-A patients who did not manifest any cause of CBD dilatation were managed conservatively. The aetiology was identified in 17/50 patients in Group B & C [acute pancreatitis (n = 6), passed CBD calculi (n = 3), perivaterian diverticulum (n = 3), viral aetiology (n = 4) and tumour (n-1)]. In Group-C, 7 patients with no obvious cause underwent endoscopic sphincterotomy, pancreatoduodenectomy (n = 1), and the rest were managed conservatively (n = 8). There was no significant difference in the complication between Group B + C (without any cause) and Group D (3/33 vs. 1/13; p = 0.58) at a median follow-up of 72 months (30–90). Conclusion: Dilated CBD with normal LFT's without apparent cause is mostly benign and of no consequence. Excision of the CBD is not required for most of these patients. [ABSTRACT FROM AUTHOR]

We study the problem of inter cell interference coordination (ICIC) with fixed transmit power in OFDMA-based cellular networks, in which each base station (BS) needs to decide as to which subchannel, if any, to allocate to each of its associated mobile stations (MS) for data transmission. In general, there exists a trade-off between the total throughput (sum of throughputs of all the MSs) and fairness under the allocations found by resource allocation schemes. We introduce the concept of τ - α - fairness by modifying the concept of α - fairness, which was earlier proposed in the context of congestion control for packet-switched networks. The concept of τ - α - fairness allows us to achieve arbitrary trade-offs between total throughput and fairness by selecting an appropriate value of α in [ 0 , ∞) . We show that for every α ∈ [ 0 , ∞) and every τ > 0 , the problem of finding a τ - α - fair allocation is NP-Complete. Further, we show that for every α ∈ [ 0 , ∞) , there exist thresholds such that if the potential interference levels experienced by each MS on every subchannel are above the threshold values, then the problem can be optimally solved in polynomial time by reducing it to the bipartite graph matching problem. Also, we propose a simple, distributed subchannel allocation algorithm for the ICIC problem, which is flexible, requires a small amount of time to operate, and requires information exchange among only neighboring BSs. We investigate via simulations as to how the algorithm parameters should be selected so as to achieve any desired trade-off between the total throughput and fairness. Finally, we compare the performance of the proposed algorithm with those of the simulated annealing based and opportunistic subchannel allocation algorithms in terms of the total throughput, fairness index and computational complexity. [ABSTRACT FROM AUTHOR]

In last few years, sensing of molecules has gained a huge attention of scientists and researchers. Small molecules (drugs, pesticides, and others) are being consumed directly or indirectly by us in our daily life. Often, these molecules enter the environment and interact with different non-target organisms. Consumption of drugs/pesticides emerged as a major concern for public health, environment, ground-water and agricultural soil. Pesticides can have odd impacts such as degradation of soil properties, environmental pollution, pollution of groundwater as well as the consumption of unwanted drugs can have serious health impacts. Therefore, the sensing of drugs/pesticides plays an important role in detecting and preventing the unwanted usage of drugs/pesticides. Quantitative and qualitative determination of pesticides and drugs can be achieved using electrochemical techniques. This review offers a concise examination of the literature about the electrochemical sensing of drugs and pesticides. The review provides a comprehensive summary of different electrochemical investigations and outlines the reported analytical performance metrics, including limits of detection and linearity ranges. Furthermore, it underscores the progress made in pesticide detection using electrochemical methods for the selected compounds, highlighting the challenges ahead and emphasizing the necessary efforts to develop sensors suitable for in-situ applications.Graphical Abstract: In last few years, sensing of molecules has gained a huge attention of scientists and researchers. Small molecules (drugs, pesticides, and others) are being consumed directly or indirectly by us in our daily life. Often, these molecules enter the environment and interact with different non-target organisms. Consumption of drugs/pesticides emerged as a major concern for public health, environment, ground-water and agricultural soil. Pesticides can have odd impacts such as degradation of soil properties, environmental pollution, pollution of groundwater as well as the consumption of unwanted drugs can have serious health impacts. Therefore, the sensing of drugs/pesticides plays an important role in detecting and preventing the unwanted usage of drugs/pesticides. Quantitative and qualitative determination of pesticides and drugs can be achieved using electrochemical techniques. This review offers a concise examination of the literature about the electrochemical sensing of drugs and pesticides. The review provides a comprehensive summary of different electrochemical investigations and outlines the reported analytical performance metrics, including limits of detection and linearity ranges. Furthermore, it underscores the progress made in pesticide detection using electrochemical methods for the selected compounds, highlighting the challenges ahead and emphasizing the necessary efforts to develop sensors suitable for in-situ applications. [ABSTRACT FROM AUTHOR]

Chylothorax, although an uncommon complication of esophagectomy, is associated with high morbidity and mortality if not treated promptly. Consequently, knowledge of the thoracic duct (TD) anatomy is essential to prevent its inadvertent injury during surgery. If the TD is injured, early diagnosis and immediate intervention are of paramount importance; however, there is still no universal consensus about the management of post-operative chylothorax. With increasing advances in the spheres of interventional radiology and minimally invasive surgery, there are now several options for managing TD injury. We review this topic in detail to provide a comprehensive and practical overview to help surgeons manage this challenging complication. In particular, we discuss an appropriate step-up approach to prevent the morbidity associated with open surgery as well as the metabolic, nutritional, and immunological disorders that accompany a prolonged illness. [ABSTRACT FROM AUTHOR]

Pancreatic schwannoma is a rare, well‑encapsulated tumor of the pancreas. Preoperative diagnosis of this tumor is uncommon due to marked degenerative change, its rarity, and overlapping clinical and imaging features with other pancreatic neoplasms. Here, we report two cases of pancreatic schwannoma, suspected preoperatively based on their multimodal imaging features, so that enucleation was possible. Extensive pancreatic surgeries can be avoided if imaging can provide clues about the benign nature of the pancreatic masses preoperatively. [ABSTRACT FROM AUTHOR]

The article explores how neutrophil extracellular traps exacerbate neurological deficits after traumatic brain injury. Topics include how hospitalized patients with Traumatic brain injury (TBI) die from secondary pathological processes that develop during supervised care; and how formation of neutrophil extracellular traps (NETs), a purported mechanism of microbial trapping, exacerbates acute neurological injury after TBI.

• A phase inversion based nanoemulsion fabrication process for vitamin D encapsulation was developed. • Out of 41 formulations, only 12 combinations resulted in the formation of nanoemulsion containing the nanoparticles of encapsulated vitamin D 3. • The nanoemulsion (NE-20), fabricated with 30% (v/v) Kolliphor, 20% (v/v) CCTG and 50% (v/v) water, was found to be the most suitable nanoemulsion • NE-20 nanoemulsion displayed the highest physico-chemical stability under different environmental stresses i.e. temp, humidity, pH and salt. • The results from sensory evaluation indicated the acceptability of the developed vitamin D 3 nanoemulsion for buttermilk fortification. A phase inversion based nanoemulsion fabrication process was developed to encapsulate vitamin D 3 by blending caprylic-/capric triglyceride (CCTG), Leciva S70, Kolliphor® HS 15, vitamin D 3 and aqueous phase (sodium chloride solution). In order to find out nanoparticle formation zone (NFZ), a ternary diagram was plotted with 41 possible combinations of three components CCTG, Kolliphor® HS 15 and aqueous phase. Out of forty one, only twelve combinations resulted in formation of stable nanoemulsion where the composition varied between 10%–40% (v/v), 10%–25% (v/v) and 35%–80% (v/v) for Kolliphor, CCTG and water respectively. Further, these 12 nanoemulsions were investigated for their particle size, zeta potential, emulsion stability, encapsulation efficiency and release kinetics (simulated digestion) of vitamin D. The nanoemulsion (NE-20) fabricated with 30% (v/v) Kolliphor, 20% (v/v) CCTG and 50% (v/v) aqueous phase was found to be the most suitable with respected to zeta potential, emulsion stability and encapsulation efficiency and also demonstrated high bioavailability of vitamin D as compared to other combinations and hence was selected for further physiochemical studies. The selected nanoemulsion was also investigated for particle size and zeta potential and stability of vitamin D 3 retention under different environmental stress conditions (i) temperature and humidity: (a) accelerated condition: 45 ± 2 °C and RH 75 ± 5%, (b) ambient condition: 25 ± 3 °C and RH 65 ± 5% and (c) refrigerated condition: 6 ± 2 °C and RH 55 ± 5% (ii) pH (3–7) under refrigerated condition and (iii) ionic strength: NaCl concentration (0 mM, 250 mM, 500 mM and 750 mM) under crefrigerated condition. Fourier transform infrared spectroscopy and High Perfomance Liquid Chromatograpy technique were used to study physico-chemical stability of encapsulated vitamin D 3 in the developed nanoemulsion. The sensory evaluation also indicated the acceptability of the selected nanoemulsion the purpose of fortification for beverages. [ABSTRACT FROM AUTHOR]

Background: Although fast-track treatment pathways are well established in colorectal surgeries, their role in oesophageal resections has not been well studied. This study aims to prospectively evaluate the short-term outcomes of enhanced recovery after surgery (ERAS) protocol in patients undergoing minimally invasive oesophagectomy (MIE) for oesophageal malignancy. Patients and Methods: We studied a prospective cohort of 46 consecutive patients from January 2019 to June 2022 who underwent MIE for oesophageal malignancy. The ERAS protocol mainly consists of pre-operative counselling, pre-operative carbohydrate loading, multimodal analgesia, early mobilisation, enteral nutrition and initiation oral feed. Principal outcome measures were the length of post-operative hospital stay, complication rate, mortality rate and 30-day readmission rate. Results: The median (interquartile range [IQR]) age of patients was 49.5 (42, 62) years, and 52.2% were female. The median (IQR) post-operative day of intercoastal drain removal and initiation of oral feed was 4 (3, 4) and 4 (4, 6) days, respectively. The median (IQR) length of hospital stay was 6 (6.0, 7.25) days, with a 30-day readmission rate of 6.5%. The overall complication rate was 45.6%, with a major complication (Clavien-Dindo ≥3) rate of 10.9%. Compliance with the ERAS protocol was 86.9%, and the incidence of major complications was associated with failure to follow the protocol (P = 0.000). Conclusions: ERAS protocol in minimally invasive oesophagectomy is feasible and safe. This may result in early recovery with shortened length of hospital stay without an increase in complication and readmission rates. [ABSTRACT FROM AUTHOR]

We encountered a 73-year-old patient who presented with right upper abdominal pain and jaundice. On evaluation, he was found to have cholelithiasis with choledocholithiasis. Endoscopic retrograde cholangiography was attempted, but during the procedure, the wire snapped and the dormia basket got retained in the common bile duct (CBD). Laparoscopic CBD exploration was performed and the basket with calculus was found impacted in the lower CBD. The basket was disengaged by holding its tip through another dormia introduced through choledochoscope and basket with all calculi retrieved. Clearance of CBD was ascertained with choledochoscopy and CBD was closed primarily. He did well in the post-operative period and was discharged on the 5th post-operative day. At 1-year follow-up, the patient was doing well. Laparoscopic CBD exploration is a feasible and safe option for the retained dormia basket. We utilised the 'dormia with dormia technique' to retrieve the impacted basket which has not been reported before. [ABSTRACT FROM AUTHOR]

Extrahepatic portal venous obstruction (EHPVO) usually presents with upper gastrointestinal bleed in the first decade of life. Symptomatic portal hypertensive biliopathy is seen in a minority of patients with EHPVO. With use of endoscopic intervention, biliary drainage is maintained in these patients. Various procedural complications have been linked while performing endoscopic retrograde cholangiography and stenting; however, these are managed conservatively. Here, we are highlighting a case of EHPVO with symptomatic portal biliopathy in which the patient bled from paracholedochal collateral after biliary stenting and was managed successfully with a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

The article discusses research which indicates that portal hypertension (PHTN) with gall bladder carcinoma (GBC) requires careful evaluation, and it mentions how patients with early-stage carcinoma often do well with surgical resection. It states that the safe and adequate performance of lymphadenectomy procedures might not be feasible in all cases. Survival rates and patient prognosis are assessed, along with mortality, bleeding complications, sepsis, and liver failure.

Background The GMF class of the ADF-H domain family proteins regulate actin dynamics by binding to the Arp2/3 complex and F-actin through their Site-1 and Site-2, respectively. CeGMF of C. elegans is analogous to GMFγ of human and mouse and is 138 amino acids in length. Methods We have characterized the solution structure and dynamics of CeGMF by solution NMR spectroscopy and its thermal stability by DSC. Results The solution structure of CeGMF shows canonical ADF-H fold with two additional β-strands in the β4-β5 loop region. The Site-1 of CeGMF is well formed and residues of all three regions of Site-1 show dynamic flexibility. However, the β4-β5 loop of Site-2 is less inclined towards the C-terminal, as the latter is truncated by four residues in comparison to GMF isoforms of human and mouse. Regions of Site-2 show motions on ns-ps timescale, but dynamic flexibility of β4-β5 loop is low in comparison to corresponding F-loop region of ADF/cofilin UNC-60B. A general difference in packing of α3 and α1 between GMF and ADF/cofilins was noticed. Additionally, thermal stability of CeGMF was significantly higher than its ADF/cofilin homologs. Conclusion We have presented the first solution structure of GMF from C. elegans , which highlights the structural differences between the Site-2 of CeGMF and mammalian GMF isoforms. Further, we have seen the differences in structure, dynamics, and thermal stability of GMF and ADF/cofilin. General significance This study provides a useful insight to structural and dynamics factors that define the specificity of GMF towards Arp2/3 complex. [ABSTRACT FROM AUTHOR]

Background Twinstar is an ADF/cofilin family protein, which is expressed by the tsr gene in Drosophila melanogaster . Twinstar is one of the main regulators of actin cytoskeleton remodelling and is essential for vital cellular processes like cytokinesis and endocytosis. Methods We have characterized the structure and dynamics of Twinstar by solution NMR spectroscopy, the interaction of Twinstar with rabbit muscle actin by ITC, and biochemical activities of Twinstar through different biochemical assays using fluorescence spectroscopy and ultra-centrifugation. Results The solution structure of Twinstar shows characteristic ADF-H fold with well-formed G/F-site and F-site for interaction with actin. The structure possesses an extended F-loop, which is rigid at the base, but flexible towards its apical region. Twinstar shares similar dynamics for the G/F-site with C . elegans homologs, UNC-60A and UNC-60B. However, the dynamics of its F-loop are different from its C . elegans homologs. Twinstar shows strong affinity for ADP-G-Actin and ATP-G-Actin with K d s of ~7.6 nM and ~0.4 μM, respectively. It shows mild F-actin depolymerizing activity and stable interaction with F-actin with a K d of ~5.0 μM. It inhibits the rate of the nucleotide exchange in a dose dependent manner. Conclusion On the basis of structure, dynamics, and biochemical activity, Twinstar can be taken to execute its biochemical role by facilitating directional growth and maintenance of length of actin filaments. General significance This study characterizes the structure, backbone dynamics, and biochemical activities of Twinstar of Drosophila , which provides an insight into the regulation of actin dynamics in the member of phylum insecta. [ABSTRACT FROM AUTHOR]

Abstract: BACKGROUND: A randomized block design experiment was performed to investigate the influence of drying on the physical, chemical and nutritional quality attributes of five prominent cultivars of India under sun drying (SD) (mean temperature 35.5 °C, average daily radiation 5.26 kW h m−2 and mean relative humidity 73.66% RH), hot air drying (HD) at 65 °C, microwave vacuum drying (MVD) (800 W, 5 kPa) and freeze drying (FD) (−50 °C, 5 kPa). Water activity, pH, total phenolic content (TPC), ascorbic acid (AA), capsaicin, β‐carotene, color and Scoville heat unit were studied. RESULTS: TPC, AA, capsaicin content, β‐carotene, color and water activity were significantly affected by the drying method. FD was observed to be most efficient in minimizing the loss of color, capsaicin and β‐carotene. The hotness of analyzed samples decreased in the order ‘Bird's Eye’ > ‘Sannam S4’ > ‘CO‐4’ > ‘PLR‐1’ > ‘PKM‐1’ among the studied cultivars, and FD > MVD > HD > SD among the drying methods. CONCLUSION: The FD method was observed to be the most efficient drying method for retaining capsaicin content over other drying methods (SD, HD, MVD), whereas MVD was found to be most efficient in minimizing the loss to nutritional attributes for all five pepper cultivars. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

This case series aimed to review the significance of revisiting papilledema after successful cerebral venous sinus thrombosis (CVST) management with sinus angioplasty. Four patients presented with blurring and transient obscuration of vision with papilledema, headache, tinnitus, and vomiting. On magnetic resonance venography and digital subtraction angiography, chronic transverse sinus thrombosis was diagnosed for which patients underwent endovascular intervention (stenting). After the resolution of CVST, patients developed the recurrence of symptoms which on digital subtraction angiography revealed dural arteriovenous malformation (DAVM). DAVM and papilledema resolved with endovascular embolization. This case series highlights a need of constant monitoring of CVST cases after the endovascular intervention. [ABSTRACT FROM AUTHOR]

We study the inter-cell interference coordination (ICIC) problem in a multicell orthogonal frequency division multiple access based cellular network employing universal frequency reuse. In each cell, only a subset of the available subchannels are allocated to mobile stations (MSs) in a given time slot so as to limit the interference to neighboring cells; also, each base station (BS) uses a fixed transmit power on every allocated subchannel. The objective is to allocate the available subchannels in each cell to the MSs in the cell for downlink transmissions taking into account the channel qualities from BSs to MSs as well as traffic requirements of the MSs so as to maximize the weighted sum of throughputs of all the MSs. First, we show that this problem is NP-complete. Next, we show that when the potential interference levels to each MS on every subchannel are above a threshold (which is a function of the transmit power and the channel gain to the MS from the BS it is associated with), the problem can be optimally solved in polynomial-time via a reduction to the matching problem in bipartite graphs. We also formulate the ICIC problem as a noncooperative game, with each BS being a player, and prove that although it is an ordinal potential game in two special cases, it is not an ordinal potential game in general. Also, we design two heuristic algorithms for the general ICIC problem: a greedy distributed algorithm and a simulated annealing (SA) based algorithm. The distributed algorithm is fast and requires only message exchanges among neighboring BSs. The SA algorithm is centralized and allows a tradeoff between quality of solution and execution time via an appropriate choice of parameters. Our extensive simulations show that the total throughput obtained using the better response (BR) algorithm, which is often used in game theory, is very small compared to those obtained using the SA and greedy algorithms; however, the execution time of the BR algorithm is much smaller than those of the latter two algorithms. Finally, the greedy algorithm outperforms the SA algorithm in dense cellular networks and requires only a small fraction of the number of computations required by the latter algorithm for execution. [ABSTRACT FROM PUBLISHER]

Background: Corrosive stricture of esophagus may be associated with variable involvement of stomach. We analyzed the outcome of gastric conduit used in the management of corrosive esophageal stricture with concomitant antro-pyloric stricture. Study design: Among 101 esophageal replacements performed, 53 patients had combined esophagus and stomach strictures. Colon was used as a conduit in 43 patients, while stomach was used in ten patients. Indications, perioperative complications and early/late outcomes of patients with gastric pull-up were reviewed and compared with those undergone colon pull-up. Results: The indications of using gastric conduit were impromptu in four patients [colonic conduit ischemia ( n = 2) and an oversight of antro-pyloric stricture after forming the gastric conduit ( n = 2)]. Six patients had preconceived gastric conduit (distal antro-pyloric stricture with distended stomach). The median age was 29 years (range 16-50), and median BMI was 15.4 kg/m (range 14.5-20.1). The stomach was drained using loop gastrojejunostomy ( n = 7) or Roux-en-Y gastrojejunostomy ( n = 3). One patient died due to sepsis secondary to anastomotic leak. Median hospital stay was 9 days (range 7-22). At median follow-up of 25 months (range 14-80), the remaining nine patients are able to have solid diet and have gained weight. The level of esophageal stricture was low ( p = 0.01), and duration of surgery ( p = 0.02) and median hospital stay ( p = 0.04) were significantly less in patients with gastric conduit plus drainage as compared to patients undergone colonic pull-up. Conclusion: Gastric conduit in a subject with distal antro-pyloric stricture can be used safely along with gastrojejunostomy in selected patients of corrosive esophageal stricture. [ABSTRACT FROM AUTHOR]

Background: Oesophagectomy for corrosive stricture of the oesophagus (CSE) is rarely performed due to high risk of iatrogenic complications. The aims of this study were to review our experience of transhiatal oesophagectomy (THE) in patients with CSE as well as to compare results of open and laparoscopic methods. Materials and Methods: This is a retrospective analysis of prospectively maintained data of patients with CSE who underwent open transhiatal oesophagectomy (OTE) or laparoscopic-assisted transhiatal oesophagectomy (LATE) by a single surgical team from 2012 to 2016. All study patients had either failed endoscopic dilatation or had a long stricture which was not amenable to endoscopic dilatation. Results: Totally, 35 patients were included in the study, of which 19 (54.3%) were female. OTE was performed in 20 (57%) patients, and LATE was performed in 15 (43%) patients. Gastric and colonic conduits were used in 23 (65.7%) and 10 (34.3%) patients, respectively. Demographic and clinical parameters were comparable between LATE and OTE groups (P > 0.05). Median intra-operative blood loss, post-operative requirement of analgesic and hospital stay were lower in LATE group (P ≤ 0.05). There was no hospital mortality (30 days), but three patients (8.6%) died during a median follow-up of 36 months. Conclusion: THE is a safe procedure for patients with CSE, and LATE may be an alternative approach in selected patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: The coronavirus disease 2019 is a serious and highly contagious disease caused by infection with a newly discovered virus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE: A Computer Aided Diagnosis (CAD) system to assist physicians to diagnose Covid-19 from chest Computed Tomography (CT) slices is modelled and experimented. METHODS: The lung tissues are segmented using Otsu's thresholding method. The Covid-19 lesions have been annotated as the Regions of Interest (ROIs), which is followed by texture and shape extraction. The obtained features are stored as feature vectors and split into 80:20 train and test sets. To choose the optimal features, Whale Optimization Algorithm (WOA) with Support Vector Machine (SVM) classifier's accuracy is employed. A Multi-Layer Perceptron (MLP) classifier is trained to perform classification with the selected features. RESULTS: Comparative experimentations of the proposed system with existing eight benchmark Machine Learning classifiers using real-time dataset demonstrates that the proposed system with 88.94% accuracy outperforms the benchmark classifier's results. Statistical analysis namely, Friedman test, Mann Whitney U test and Kendall's Rank Correlation Coefficient Test has been performed which indicates that the proposed method has a significant impact on the novel dataset considered. CONCLUSION: The MLP classifier's accuracy without feature selection yielded 80.40%, whereas with feature selection using WOA, it yielded 88.94%. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI. In this review, we explore the burgeoning evidence implicating the acute release of damage associated molecular patterns (DAMPs), such as adenosine 5′-triphosphate (ATP), high mobility group box protein 1 (HMGB1), S100 proteins, and hyaluronic acid in the initiation of progressive neurological injury, including white matter loss after TBI. The role that pattern recognition receptors, including toll-like receptor and purinergic receptors, play in progressive neurological injury after TBI is detailed. Finally, we provide support for the notion that resident and infiltrating macrophages are critical cellular targets linking acute DAMP release with adaptive immune responses and chronic injury after TBI. The therapeutic potential of targeting DAMPs and barriers to clinical translational, in the context of TBI patient management, are discussed. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortality and poor long-term outcomes. Increasing evidence suggests an important, yet poorly defined, role for the immune system in the development of secondary neurologic injury over the days and weeks following a TBI. In this study, we tested the hypothesis that peripheral macrophage infiltration initiates long-lasting adaptive immune responses after TBI. Using a murine controlled cortical impact model, we used adoptive transfer, transgenic, and bone marrow chimera approaches to show increased infiltration and proinflammatory (classically activated [M1]) polarization of macrophages for up to 3 wk post-TBI. Monocytes purified from the injured brain stimulated the proliferation of naive T lymphocytes, enhanced the polarization of T effector cells (TH1/TH17), and decreased the production of regulatory T cells in an MLR. Similarly, elevated T effector cell polarization within blood and brain tissue was attenuated by myeloid cell depletion after TBI. Functionally, C3H/HeJ (TLR4 mutant) mice reversed M1 macrophage and TH1/TH17 polarization after TBI compared with C3H/OuJ (wild-type) mice. Moreover, brain monocytes isolated from C3H/HeJ mice were less potent stimulators of T lymphocyte proliferation and TH1/TH17 polarization compared with C3H/OuJ monocytes. Taken together, our data implicate TLR4-dependent, M1 macrophage trafficking/polarization into the CNS as a key mechanistic link between acute TBI and long-term, adaptive immune responses. [ABSTRACT FROM AUTHOR]

Background and Objectives: Depression, especially in concurrence with chronic medical disorders, is highly prevalent worldwide. An average between 9.3% and 23% of patients with one or more chronic disease have co-morbid depression. This comorbid depression has the worst health scores of all the disease states. Despite this, patients with chronic medical disorders are not commonly screened for depression. Lack of objective screening by health-care providers as well as lack of infrastructure (time/space/personnel) probably contributes to gross underdiagnosis of depression. This issue can be addressed using short objective depression screening score (Patient Health Questionnaire-9 [PHQ-9]) (validated in native languages, e.g., Hindi) and paperless self-administered interface on handheld computer (tablet), which is the objective of the study. Subjects and Methods: One hundred consecutive patients with chronic medical disorders visiting our medicine outpatient department were screened for depression using tablets with PHQ-9 Hindi on a self-administered interface. Results: The overall prevalence of depression was found to be 25% (95% confidence interval 16.6-34.8). Nearly half of the patients with depression had moderate depression (PHQ-9 score 10-14) while rest had moderately severe or very severe depression (PHQ-9 score >14). Association of depression was not found to be statistically significant with age, duration of disease, gender, the type of disease, or the number of disease. Majority of patients rated ease of the use of tablet interface (on a visual analog scale) as very easy (approx 95%). All the patients were able to complete the tablet screener without assistance, answering all of the questions. The median time of completion with interquartile range was 4 (3-5) min. Majority of the patients (63%) completed the questionnaire within 5 min while rest completed it in 5-10 min. Conclusions: It is feasible to use tablets with PHQ-9 questionnaire in native language for screening depression in chronic medical disorders. With high prevalence of comorbid depression, any comprehensive care of patients with chronic medical disorders will not be possible, unless such patients are screened and treated for depression. A self-administered screening questionnaire for depression on handheld tablets can prove to be a handy tool to achieve above aim. [ABSTRACT FROM AUTHOR]

Purpose: To compare the outcome of pars-plana-modified Ahmed glaucoma valve (AGV) versus limbal-based conventional AGV into the anterior chamber, in patients undergoing penetrating keratoplasty (PK) for glaucoma with coexisting corneal diseases. Method: In this prospective randomized clinical trial, 58 eyes of 58 patients with glaucoma and coexisting corneal disease were divided into two groups. Group 1 (29 eyes of 29 patients) included patients undergoing limbal-based conventional AGV into the anterior chamber (AC) along-with PK and group 2 (29 eyes of 29 patients) included those undergoing pars-plana-modified AGV along-with PK. Outcome measures included corneal graft clarity, intraocular pressure (IOP), number of antiglaucoma medications, and postoperative complications. Patients were followed up for a minimum period of 2 years. Results: Out of 58 eyes (58 patients), 50 eyes (50 patients: 25 eyes of 25 patients each in group 1 and group 2) completed the study and were analyzed. Complete success rate for AGV (group 1: 76%; group 2: 72%;p= 0.842) and corneal graft clarity (group 1: 68%; group 2: 76%;p= 0.081) were comparable between the two groups at 2 years. Graft failure was more in conventional AGV (32%) as compared to pars plana-modified AGV (24%) but not statistically significant (p= 0.078) at 2 years. Conclusion: Though both procedures were comparable in various outcome measures, pars-plana-modified AGV is a viable option for patients undergoing PK, as it provides a relatively better corneal graft survival rate and lesser complications that were associated with conventional AGV. [ABSTRACT FROM AUTHOR]

A 31-year-old man with steroid-refractory severe ulcerative colitis was planned for a two-stage robotic total proctocolectomy with ileal pouch-anal anastomosis using the da Vinci Xi system (see Supplementary file Video S1). The proctocolectomy specimen was retrieved using a Pfannenstiel incision, an ileal J-pouch was created, the anvil was secured to the pouch, the pouch was placed inside the abdomen and the incision was closed. Robotic total proctocolectomy with ileal pouch-anal anastomosis using indocyanine green fluorescence imaging in a case of medically refractory ulcerative colitis - a video correspondence. [Extracted from the article]

The article presents a case study of a 40-year-old man presented with a complaint of persistent dull aching pain in the right upper abdomen for six months. Topics include Budd-chiari syndrome (BCS) being a heterogeneous disorder that occurs because of hepatic vein (HV) outflow obstruction; and how there was no predisposing risk factor, idiopathic BCS with membranous occlusion of inferior vena cava (IVC) at the IVC-RA (right atrium ) junction was kept as a working diagnosis.

Anserine and carnosine represent histidine-containing dipeptides that exert a pluripotent protective effect on human physiology. Anserine is known to protect against oxidative stress in diabetes and cardiovascular diseases. Human carnosinases (CN1 and CN2) are dipeptidases involved in the homeostasis of carnosine. In poikilothermic vertebrates, the anserinase enzyme is responsible for hydrolyzing anserine. However, there is no specific anserine hydrolyzing enzyme present in humans. In this study, we have systematically investigated the anserine hydrolyzing activity of human CN1 and CN2. A targeted multiple reaction monitoring (MRM) based approach was employed for studying the enzyme kinetics of CN1 and CN2 using carnosine and anserine as substrates. Surprisingly, both CN1 and CN2 can hydrolyze anserine effectively. The observed catalytic turnover rate (V max /[E] t) was 21.6 s−1 and 2.8 s−1 for CN1 and CN2, respectively. CN1 is almost eight-fold more efficient in hydrolyzing anserine compared to CN2, which is comparable to the efficiency of the carnosine hydrolyzing activity of CN2. The Michaelis constant (K m) value for CN1 (1.96 mM) is almost three-fold lower compared to CN2 (6.33 mM), representing higher substrate affinity for anserine-CN1 interactions. Molecular docking studies showed that anserine binds at the catalytic site of the carnosinases with an affinity similar to carnosine. Overall, the present study elucidated the inherent promiscuity of human carnosinases in hydrolyzing anserine using a sensitive LC-MS/MS approach. • Employed sensitive LC-MS/MS approach to study anserine hydrolyzing activities of human carnosinases (CN1 and CN2). • First report on detailed kinetic characterization of anserinase activity of human CN1 and CN2. • Dis sec ting the molecular interactions involved in anserine-CN1 and anserine-CN2 binding using molecular docking approach. [ABSTRACT FROM AUTHOR]

Achalasia cardia is an oesophageal motility disorder characterised by aperistalsis and failure of relaxation of the lower oesophageal sphincter. The management is predominantly palliative with focus on addressing the sphincter that involves either pneumatic dilatation or Heller myotomy which relieves dysphagia in the majority of the cases. End-stage achalasia (ESA) is characterised by failed myotomy, massively dilated and tortuous oesophagus with nutritional deterioration due to progressive dysphagia and vomiting. In these subgroups of patients, oesophagectomy may be the last resort. While oesophagectomy has been described for ESA before, thoracoscopic oesophagectomy has not been reported previously. Hereby, we report our experience of performing minimally invasive oesophagectomy (thoracoscopic) with the gastric pull-up. [ABSTRACT FROM AUTHOR]

Gall bladder carcinoma is an aggressive malignancy with varied presentation. Liver is most commonly involved initially with distant metastasis in virtually all possible organs. We report a case of middle aged female who presented with pain in upper abdomen and progressive jaundice. Imaging studies were suggestive of gall bladder carcinoma involving hilum with disseminated osteosclerotic lesions and metastasis to Urinary Bladder (UB). Patients of carcinoma gall bladder with disseminated metastatic disease have poor prognosis and are managed with palliative chemotherapy. To the best of our knowledge, this is one of the rare initial presentation of gall bladder carcinoma in the literature. [ABSTRACT FROM AUTHOR]

[Display omitted] • The solution structure of free Skp1 reveals that the helices, particularly H8, are disordered in the unbound form. • Structural conservation allows Cul-1 binding at the NTD (N-terminal domain) of Skp1, whereas structural plasticity allows different F-box recognition at the C-terminal helices of Skp1. • Conformational sampling of excited sub-states by Skp1 residues, which are involved in F-box interactions, indicates that the excited state may be responsible for recruiting F-box proteins. Skp1(S-phase kinase-associated protein 1 - Homo sapiens) is an adapter protein of the SCF(Skp1-Cullin1-Fbox) complex, which links the constant components (Cul1-RBX) and the variable receptor (F-box proteins) in Ubiquitin E3 ligase. It is intriguing how Skp1 can recognise and bind to a variety of structurally different F-box proteins. For practical reasons, previous efforts have used truncated Skp1, and thus it has not been possible to track the crucial aspects of the substrate recognition process. In this background, we report the solution structure of the full-length Skp1 protein determined by NMR spectroscopy for the first time and investigate the sequence-dependent dynamics in the protein. The solution structure reveals that Skp1 has an architecture: β1-β2-H1-H2-L1–H3-L2-H4-H5-H6-H7(partially formed) and a long tail-like disordered C-terminus. Structural analysis using DALI (Distance Matrix Alignment) reveals conserved domain structure across species for Skp1. Backbone dynamics investigated using NMR relaxation suggest substantial variation in the motional timescales along the length of the protein. The loops and the C-terminal residues are highly flexible, and the (R 2 /R 1) data suggests μs-ms timescale motions in the helices as well. Further, the dependence of amide proton chemical shift on temperature and curved profiles of their residuals indicate that the residues undergo transitions between native state and excited state. The curved profiles for several residues across the length of the protein suggest that there are native-like low-lying excited states, particularly for several C-terminal residues. Our results provide a rationale for how the protein can adapt itself, bind, and get functionally associated with other proteins in the SCF complex by utilising its flexibility and conformational sub-states. [ABSTRACT FROM AUTHOR]

Purpose Cisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics. Methods and results Here, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6 ± 9.6 nm and 140.5 ± 10.9 nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH ∼ 5.6 (cervical cancer pH) and pH ∼ 7.4. In addition, a significant ( P < 0.05) decrease in IC 50 value (8.3 μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1 μM) and cisplatin solution (40.2 μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54 ± 7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P < 0.05) greater than 51.68 ± 9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs. Conclusion Therefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation. [ABSTRACT FROM AUTHOR]

Perillyl alcohol (PA) is a monoterpene found in essential oils of mints, cherries, citreous fruits and lemon grass, reported to have antioxidant and anti-inflammatory properties. However, the role of PA in stroke is still illusive. Since oxidative stress and inflammation play a pivotal role in ischemia–reperfusion (I–R) injury, this study was designed to elucidate the potential effects of PA against I–R induced pathology in rat׳s brain. Middle cerebral artery occlusion (MCAO) for 2 h followed by 22 h reperfusion in Wistar male rats (250–280 g, 14–16 weeks old) induced the behavioral and histological alterations along with exhausted antioxidant status and enhanced inflammatory mediators. However, PA administration (25, 50 and 100 mg/kg b.wt orally once daily for 7 days) prior to MCAO significantly attenuated neurological deficits related to flexion test and spontaneous motor activity, improved grip strength and motor coordination in a dose dependent manner. PA treatment also inhibited oxidative stress in MCAO rats as evident from decreased lipid peroxidation and augmented level of reduced glutathione and restored activities of catalase, glutathione peroxidase, and glutathione reductase and thus, reduced infarct volume and protected the brain histology after I–R injury. Furthermore, PA markedly suppressed the level of proinflammatory cytokines (IL-1β, TNF α and IL-6) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS-2) and nuclear factor κB (NF-κB) in MCAO group. In conclusion, PA mediates neuroprotection against I–R injury via mitigation of oxidative stress and inflammation and thus, may be a good therapeutic approach in stroke prone patient. [ABSTRACT FROM AUTHOR]