The Prevalence of Frailty and Associated Factors, Including Food Security in Community Dwelling Older Adults with Multimorbidity: A Cross-Sectional Analysis from the Longitudinal Aging Study in India.

BACKGROUND: The global increase in multimorbidity among older adults is a result of ongoing epidemiological and demographic transitions. This study focuses on the prevalence and determinants of frailty in this demographic in India, accounting for the potential mediating role of food insecurity. OBJECTIVES: To determine the prevalence and determinants of frailty among older Indian adults with multimorbidity, and to ascertain the mediating effect of food insecurity on frailty. DESIGN: Cross-sectional analysis of cohort study data. SETTING: Analysis of data from the Longitudinal Aging Study in India (LASI) Wave 1 (2017-2018). PARTICIPANTS: 31,902 individuals aged 60 and above of whom 7900 were categorized as having multimorbidity. MEASUREMENTS: Frailty was assessed using a modified Fried scale. Details on sociodemographic factors, lifestyle choices, and health-related variables were collected through face-to-face participant interviews. Multimorbidity was defined as the presence of two or more chronic conditions such as hypertension, diabetes, cancer, chronic lung disease, chronic heart disease, stroke, bone disease, neurological or psychiatric problems, and high cholesterol. Statistical analysis was conducted using Stata 15.1. RESULTS: The weighted prevalence of frailty in individuals with multimorbidity was 30.31% (95% CI: 28.17, 32.54), significantly higher than those without multimorbidity (23.81%, 95% CI: 22.90, 24.74) (P<0.001). Frailty prevalence was higher in women (33.27%) than in men (26.56%) among those with multimorbidity. In the group with multimorbidity, age ≥75 (years), middle MPCE quintile, lower educational attainment, unemployment, and low body mass index was associated with higher odds of frailty. Mediation analysis showed that 3.47% of the association between multimorbidity and frailty was mediated by food insecurity. CONCLUSION: Frailty is prevalent among older adults with multimorbidity in India, with significant disparities based on gender, age, socioeconomic status, and body mass index. Food insecurity partially mediates the relationship between multimorbidity and frailty, highlighting the need for targeted interventions addressing both health and nutritional insecurities in this population.

A rare case of abdominal cocoon associated with internal hernia in an adult.

A transmesenteric internal hernia (TIH) is a protrusion of a viscus through the mesenteric defect. It is secondary to previous gastrointestinal surgery in an adult. Early diagnosis and management are warranted to prevent the strangulation of the bowel in a TIH. Here, we are reporting a case of a 24-year-old gentleman with COVID-positive status who has presented with cough, abdominal cocoon, and features of subacute intestinal obstruction (SAIO) without any previous history of abdominal surgery. A nonoperative trial is given in the management of abdominal cocoon with SAIO. In contrast, delay in surgical intervention in TIH leads to bowel gangrene. Surprisingly even on contrast-enhanced computed tomography of the abdomen, TIH was not picked up. We have diagnosed this case intraoperatively with gangrene of the bowel. In an abdominal cocoon without any history suggestive of tuberculosis or previous surgery, or any other condition that leads to an intra-abdominal reaction, an internal hernia should be kept as a differential diagnosis. The delay in diagnosis and surgical intervention is associated with potentially disastrous complications.

Severe acute pancreatitis in the early postoperative period due to afferent loop syndrome following gastrectomy for gastric cancer.

Afferent loop syndrome (ALS) is an uncommon complication of gastrojejunostomy. It may be acute or chronic depending on whether symptoms manifest within 7 days of surgery. Rarely acute ALS may give rise to acute pancreatitis. It may present early in the postoperative course and, if diagnosed late, may result in organ failure within 48h. We report a middle-aged woman with carcinoma of the stomach managed by subtotal gastrectomy with Billroth II gastrojejunostomy and Braun jejunojejunostomy. The patient developed vomiting and abdominal pain in the first postoperative day with acute renal shutdown and about 500ml drain output of dirty fluid. On investigation, a diagnosis of acute pancreatitis due to afferent loop syndrome was made, and the patient was resuscitated in the intensive care unit. However, she showed early signs of organ failure and succumbed to her condition within 6 days of surgery. Since the complication is rare following gastrojejunostomy and often mimics ALS, an early diagnosis becomes difficult. If delay in management happens, premature organ failure may lead to high morbidity and mortality.

A multi-scale agent-based model for avascular tumour growth.

In this paper, we have developed a multi-scale, lattice-free, agent based model of avascular tumour growth in epithelial tissue. The model integrates different events to identify the underlying diversity within intracellular, cellular, and extracellular layer dynamics. The model considers every cell as an agent. A cellular agent may proliferate, spawns two identical daughter agents, or it may be transformed into other phenotypes during its life time depending on its internal proteins' activity as well as its external microenvironment. In this context, a simplified age-structured cell cycle model is adopted from the existing literature. The model considers that the intracellular events are regulated by p27 gene expression. In this model, p27 protein controls the overall tumour growth dynamics. Moreover, p27 is controlled by the external oxygen and nutrients that are modelled with the reaction-diffusion equations. The model also considers several biophysical forces which directly effect on the tumour growth dynamics. This modelling framework offers biologically realistic outcomes and also covers important criteria of the hallmarks of cancer which include oxygen and nutrient consumptions, micro-environmental heterogeneity, tumour cell proliferation by avoiding growth suppressor signals, replication of tumour cells at an abnormally faster rate, and resistance of apoptosis. The avascular tumour growth model is validated with immunohistochemistry and histopathology data. The outcome of the proposed model is very close to the range of the patient data, which concludes that the model is capable enough to mimic these complex biophysical phenomena.

Key differences between olfactory ensheathing cells and Schwann cells regarding phagocytosis of necrotic cells: implications for transplantation therapies.

Transplantation of peripheral nervous system glia is being explored for treating neural injuries, in particular central nervous system injuries. These glia, olfactory ensheathing cells (OECs) and Schwann cells (SCs), are thought to aid regeneration by clearing necrotic cells, (necrotic bodies, NBs), as well as myelin debris. The mechanism by which the glia phagocytose and traffic NBs are not understood. Here, we show that OECs and SCs recognize phosphatidylserine on NBs, followed by engulfment and trafficking to endosomes and lysosomes. We also showed that both glia can phagocytose and process myelin debris. We compared the time-course of glial phagocytosis (of both NBs and myelin) to that of macrophages. Internalization and trafficking were considerably slower in glia than in macrophages, and OECs were more efficient phagocytes than SCs. The two glial types also differed regarding their cytokine responses after NB challenge. SCs produced low amounts of the pro-inflammatory cytokine TNF-α while OECs did not produce detectable TNF-α. Thus, OECs have a higher capacity than SCs for phagocytosis and trafficking, whilst producing lower amounts of pro-inflammatory cytokines. These findings suggest that OEC transplantation into the injured nervous system may lead to better outcomes than SC transplantation.

How close is the axillary nerve to the inferior glenoid? A magnetic resonance study of normal and arthritic shoulders.

INTRODUCTION: Axillary nerve injury is a major complication of shoulder surgery during glenoid exposure. The aim of this study was to measure the mean distance between the inferior glenoid and the axillary nerve in healthy shoulders and then to compare this distance between osteoarthritic and rotator cuff deficient glenohumeral joints. METHODS: The magnetic resonance images of 50 patients with normal glenohumeral joints were reviewed. The infra-glenoid tubercle was determined as a fixed point and the distance to the axillary nerve was measured. Two separate assessors measured on the same sagittal sections. With a study power of 80%, the sample needed in each comparison group was 28 patients. Measurements were then performed on scans in patients with osteoarthritis and cuff tear arthropathy. The mean distance was compared between groups. RESULTS: The mean distance between the infra-glenoid tubercle and axillary nerve was 12mm (standard deviation, SD, 5.6mm) in normal shoulders, 10.6mm (SD 5.4mm) in shoulders with osteoarthritis and 9.7mm (SD 3.7mm) in those with cuff tear arthropathy. For this sample size of 50 patients with a confidence interval of 95%, the mean range is 12mm (95% CI 10.4-13.6). A comparison between normal shoulder and osteoarthritis showed a p-value of 0.3, and between normal and cuff tear arthropathy a p-value of 0.06. This was not statistically significant. CONCLUSIONS: The axillary nerve lies on average 12mm from the infra-glenoid tubercle. The presence of inferior osteophytes in glenohumeral osteoarthritis and the proximal migration of humeral head in cuff tear arthropathy does not seem to alter the course of the nerve significantly in relation to the inferior glenoid tubercle.

Avascular tumour growth models based on anomalous diffusion.

In this study, we model avascular tumour growth in epithelial tissue. This can help us to understand that how an avascular tumour interacts with its microenvironment and what type of physical changes can be observed within the tumour spheroid before angiogenesis. This understanding is likely to assist in the development of better diagnostics, improved therapies, and prognostics. In biological systems, most of the diffusive processes are through cellular membranes which are porous in nature. Due to its porous nature, diffusion in biological systems are heterogeneous. The fractional diffusion equation is well suited to model heterogeneous biological systems, though most of the early studies did not use this fact. They described tumour growth with simple diffusion-based model. We have developed a spherical model based on simple diffusion initially, and then the model is upgraded with fractional diffusion equations to express the anomalous nature of biological system. In this study, two types of fractional models are developed: one of fixed order and the other of variable order. The memory formalism technique is also included in these anomalous diffusion models. These three models are investigated from phenomenological point view by measuring some parameters for characterizing avascular tumour growth over time. Tumour microenvironment is very complex in nature due to several concurrent molecular mechanisms. Diffusion with memory (fixed as well as variable) formation may be an oversimplified technique, and does not reflect the detailed view of the tumour microenvironment. However, it is found that all the models offer realistic and insightful information of the tumour microenvironment at the macroscopic level, and approximate well the physical phenomena. Also, it is observed that the anomalous diffusion based models offer a closer description to clinical facts than the simple model. As the simulation parameters get modified due to different biochemical and biophysical processes, the robustness of the model is determined. It is found that the anomalous diffusion models are moderately sensitive to the parameters.

Implementation of duty of candour within neurosurgery: a national survey and framework for improved application in clinical practice.

INTRODUCTION: Statutory duty of candour was introduced in November 2014 for NHS bodies in England. Contained within the regulation were definitions regarding the threshold for what constitutes a notifiable patient safety incident. However, it can be difficult to determine when the process should be implemented. The aim of this survey was to evaluate the interpretation of these definitions by British neurosurgeons. MATERIALS AND METHODS: All full (consultant) members of the Society of British Neurological Surgeons were electronically invited to participate in an online survey. Surgeons were presented with 15 cases and asked to decide in the case of each one whether they would trigger the process of duty of candour. Cases were stratified according to their likelihood and severity. RESULTS: In all, 106/357 (29.7%) members participated in the survey. Responses varied widely, with almost no members triggering the process of duty of candour in cases where adverse events were common (greater than 10% likelihood) and required only outpatient follow-up (7/106; 6.6%), and almost all members doing so in cases where adverse events were rare (less than 0.1% likelihood) and resulted in death (102/106; 96.2%). However, there was clear equipoise in triggering the process of duty of candour in cases where adverse events were uncommon (0.1-10% likelihood) and resulted in moderate harm (38/106; 35.8%), severe harm (57/106; 53.8%) or death (49/106; 46.2%). CONCLUSION: There is considerable nationwide variation in the interpretation of definitions regarding the threshold for duty of candour. To this end, we propose a framework for the improved application of duty of candour in clinical practice.

Screening for vestibular schwannoma in the context of an ageing population.

OBJECTIVE: To review the literature regarding screening for vestibular schwannoma in the context of demographic changes leading to increasing numbers of elderly patients presenting with asymmetric auditory symptoms. METHODS: A systematic review of the literature was performed, with narrative synthesis and statistical analysis of data where appropriate. RESULTS: Vestibular schwannomas diagnosed in patients aged over 70 years exhibit slower growth patterns and tend to be of smaller size compared to those tumours in younger age groups. This fact, combined with reduced life expectancy, renders the probability of these tumours in the elderly requiring active treatment with surgery or stereotactic radiotherapy to be extremely low. Vestibular schwannomas in the elderly are much more likely to be managed by serial monitoring with magnetic resonance imaging. The weighted yield of magnetic resonance imaging in the diagnosis of vestibular schwannoma in all age groups is 1.18 per cent, with almost 85 scans required to diagnose 1 tumour. CONCLUSION: An evidence-based approach to the investigation of asymmetric hearing loss and tinnitus in the elderly patient can be used to formulate guidelines for the rational use of magnetic resonance imaging in this population.

Treatment using diffuse laser energy of cochlear and vestibular fistulas caused by cholesteatoma.

OBJECTIVE: To measure the outcomes of laser treatment of cholesteatoma covering cochlear and vestibular fistulas. METHODS: Cholesteatoma matrix over the fistula was denatured; the power density was sufficient only to gradually heat, but not vaporise, the keratin-forming matrix. The denaturing speed was controlled so that the integrity of the fistula cover was maintained. The change in bone conduction threshold and the residual rate of cholesteatoma at the fistula were measured. RESULTS: Thirty-six fistulas were assessed. There were seven cochlear fistulas. All were 5 mm or less in maximum length. For the entire group, the average change in bone conduction threshold was -0.3 dB. For cochlear fistulas, the average change in bone conduction was + 0.2 dB. The distribution of hearing results for the entire group was Gaussian; the apparent changes in hearing could be attributed to errors associated with testing. All patients underwent second-stage surgery. In all cases, the cholesteatoma was completely cleared from the fistula site. There were no facial palsies. CONCLUSION: Laser denaturing of cholesteatoma matrix over fistulas measuring 5 mm or less of vestibular apparatus and the cochlea is effective at eliminating cholesteatoma, and is not associated with cochlear hearing loss or facial palsy.

Laparoscopic repair of type III/IV giant para-oesophageal herniae with biological prosthesis: a single centre experience.

PURPOSE: Repair of giant paraoesophageal herniae (GPEH) is technically challenging and requires significant experience in advanced foregut surgery. Controversy continues on suture versus mesh cruroplasty with the most recent systematic review and meta-analysis putting the onus on the operating surgeon. Study aim was to review whether the biological prosthesis (non-cross-linked bovine pericardium and porcine dermis) and the technique adopted for patients with GPEH had an influence on clinical and radiological recurrences. METHOD: A retrospective analysis of a prospectively collected data of 60 consecutive patients with confirmed 5 cm hiatus hernia and ≥ 30% stomach displacement in the thorax that were operated in the upper gastrointestinal unit of a large district general hospital between September 2010 and August 2017. Pre and post-surgery Gastro-Oesophageal Reflux Disease Questionnaire [(GORD-HRQOL)] and a follow up contrast study were completed. RESULTS: 60 included 2 (3%) and 58 (97%) emergency and elective procedures respectively with a male: female ratio of 1:3, age 71* (Median) (42-89) years, BMI 29* (19-42) and 26 (43%) with ASA III/IV. Investigations confirmed 46* (37-88) mm and 42* (34-77) mm transverse and antero-posterior hiatal defect respectively with 60* (30-100)% displacement of stomach into chest. Operative time and length of stay was 180* (120-510) minutes and 2* (1-30) days respectively. One (2%) converted for bleeding and 2 (3%) peri-operative deaths. Five (8%), 5 (8%) and 4 (7%) have dysphagia, symptomatic and radiological recurrences respectively. GORD-HRQOL recorded preoperatively was 27* (10-39) dropping significantly postoperatively to 0* (0-21) (P < 0.005) with 95% patient satisfaction at a follow up of 60* (36-84) months. CONCLUSIONS: Our technique of laparoscopic GPEH repair with biological prosthesis is safe with a reduced symptomatic and radiological recurrence and an acceptable morbidity and mortality.

Clinical and laboratory profile of anti-M.

Anti-M is a frequently detected naturally occurring antibody that has been reported in various clinical settings and also in voluntary donors. We describe here the clinical and laboratory findings of 11 cases with anti-M detected at our center. This report is a retrospective study in which we reviewed our immunohematology laboratory records for cases involving anti-M. Both donor and patient data from a 28-month period (September 2014 to December 2016) were reviewed. During this period, 11 examples of anti-M were detected (8 patients, 1 voluntary whole blood donor, and 1 hematopoietic stem cell donor. Anti-M was also detected in one external quality assessment scheme sample received during this period. In conclusion, anti-M can be detected in various clinical settings. This antibody can be clinically significant; in the laboratory, it can present as a serologic problem such as an ABO group discrepancy or an incompatible crossmatch. After detection, management and course of action is determined by both the antibody characteristics and the clinical setting.Anti-M is a frequently detected naturally occurring antibody that has been reported in various clinical settings and also in voluntary donors. We describe here the clinical and laboratory findings of 11 cases with anti-M detected at our center. This report is a retrospective study in which we reviewed our immunohematology laboratory records for cases involving anti-M. Both donor and patient data from a 28-month period (September 2014 to December 2016) were reviewed. During this period, 11 examples of anti-M were detected (8 patients, 1 voluntary whole blood donor, and 1 hematopoietic stem cell donor. Anti-M was also detected in one external quality assessment scheme sample received during this period. In conclusion, anti-M can be detected in various clinical settings. This antibody can be clinically significant; in the laboratory, it can present as a serologic problem such as an ABO group discrepancy or an incompatible crossmatch. After detection, management and course of action is determined by both the antibody characteristics and the clinical setting.

GhSTOP1, a C2H2 type zinc finger transcription factor is essential for aluminum and proton stress tolerance and lateral root initiation in cotton.

Aluminum (Al) and proton (H+ ) ions are major acid soil stress factors deleteriously affecting plant root growth and crop yield. In our preliminary studies, cotton (Gossypium hirsutum L.) seedlings displayed very sensitive phenotypes to Al and H+ rhizotoxicities. Based on previous Arabidopsis results, we aimed to characterise the Al stress responsive Sensitive to Proton rhizotoxicity 1 (GhSTOP1) transcription system in cotton using RNAi-mediated down-regulation. With the help of seed embryo apex explants, we developed transgenic cotton plants overexpressing a GhSTOP1-RNAi cassette with NPTII selection. Kanamycin-tolerant T1 seedlings were further considered for Al and H+ stress tolerance studies. Down-regulation of the GhSTOP1 increased sensitivity to Al and proton rhizotoxicities, and root growth was significantly reduced in RNAi lines. The expression profile of GhALMT1 (Aluminum-activated Malate Transporter 1), GhMATE (Multidrug and Toxic Compound Extrusion), GhALS3 (Aluminium Sensitive 3) and key genes involved in the GABA shunt were down-regulated in the transgenic RNAi lines. Additionally, the lateral root initiation process was delayed and expression of GhNAC1, which is involved in lateral roots, was also suppressed in transgenic lines. Besides, overexpression of GhSTOP1 in Arabidopsis accelerated root growth and AtMATE and AtALMT1 expression under Al stress conditions. These analyses indicate that GhSTOP1 is essential for the expression of several genes which are necessary for acid soil tolerance mechanisms and lateral root initiation.

Substrate stiffness and mechanical stress due to intercellular cooperativity guides tissue structure.

A key challenge in cell and tissue morphogenesis is to understand how a crucial balance between cell proliferation and apoptosis maintains an evolving tissue structure. These processes are mutually non-exclusive and require stiffness monitoring of the host substrate. Adhered cells actively mechanosense the tension in the extracellular matrix (ECM). They collectively alter self-organization and generate a host of tissue patterns. Using an in silico elastic fiber-network in two dimensions, we simulate cell-ECM composite structures and characterize features of the emerging tissue patterns during successive cell proliferation and apoptosis. Our data reveals that, in general, cell viability is a function of the cell-induced effective ECM stiffness supported by intercellular cooperativity. Translating this into a remodeling tissue, we find that average cell cycle duration in concert with the locally stressed regions of the ECM promote heterogeneous proliferation and apoptosis inducing finger-like protrusions along the tissue periphery - a feature normally observed during tumorigenesis. Further, we find that recovery of a scratch wound is delayed for cells harbored on a compliant or (and) in a highly collagen depleted ECM.

Concentrating molasses distillery wastewater using biomimetic forward osmosis (FO) membranes.

Treatment of sugarcane molasses distillery wastewater is challenging due to the presence of complex phenolic compounds (melanoidins and polyphenols) having antioxidant properties. Due to zero liquid discharge regulations, Indian distilleries continue to explore effective treatment options. This work examines the concentration of distillery wastewater by forward osmosis (FO) using aquaporin biomimetic membranes and magnesium chloride hexahydrate (MgCl2.6H2O) as draw solution. The operational parameters viz. feed solution and draw solution flow rate and draw solution concentration were optimized using 10% v/v melanoidins model feed solution. This was followed by trials with distillery wastewater. Under the conditions of this work, feed and draw flow rates of 1 L/min and draw solution concentration of 2M MgCl2.6H2O for melanoidins model solution and 3M MgCl2.6H2O for distillery wastewater were optimal for maximum rejection. Rejection of 90% melanoidins, 96% antioxidant activity and 84% COD was obtained with melanoidins model feed, with a corresponding water flux of 6.3 L/m2h. With as-received distillery wastewater, the rejection was similar (85-90%) to the melanoidins solution, but the water flux was lower (2.8 L/m2h). Water recovery from distillery wastewater over 24 h study period was higher with FO (70%) than reported for RO (35-45%). Repeated use of the FO membrane over five consecutive 24 h cycles with fresh feed and draw solutions and periodic cleaning showed consistent average water flux and rejection of the feed constituents.

Expression Analysis of Survivin and XIAP in Gallbladder Cancer: a Case-control Study in Indo-Gangetic Plain.

PURPOSE: Gallbladder cancer is a highly mortal disease with poor prognosis because of late presentation of disease. Survivin and X-linked inhibitor of apoptosis (XIAP) are one of the two important members of inhibitors of apoptosis. Thus, this study aimed to look at the expression of Survivin and XIAP in gallbladder cancer patients. METHODS: Survivin and XIAP expression were investigated in tissues of gallbladder cancer patients (40 cases) and compared with cholelithiasis as control (40 cases) by using immunohistochemistry. Their expression was correlated with clinicopathological parameters. RESULTS: Significantly higher (p < 0.05), Survivin protein was expressed in gallbladder cancer (n = 67.5%) than control (n = 35%). But it did not show any significant association with any of the clinicopathological parameter while XIAP was not expressed in the GBC patients (p > 0.05). CONCLUSION: Overexpression of Survivin in gallbladder cancer suggests its possible role and association with poor prognosis. But XIAP has not been found to be associated with gallbladder carcinogenesis.

Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial.

The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ⩾very good partial response (VGPR; n=679), ⩾partial response (PR; n=1 225) or ⩽stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ⩾VGPR and ⩾PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ⩾VGPR and ⩾PR, respectively. In patients with CR, ⩾VGPR or ⩾PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.