Elucidating the functional impact of G137V and G144R variants in Maroteaux Lamy's Syndrome by Molecular Dynamics Simulation.

Mucopolysaccharidoses VI (Maroteaux Lamy syndrome) is a metabolic disorder due to the loss of enzyme activity of N-acetyl galactosamine-4-sulphatase arising from mutations in the ARSB gene. The mutated ARSB is the origin for the accumulation of GAGs within the lysosome leading to severe growth deformities, causing lysosomal storage disease. The main focus of this study is to identify the deleterious variants by applying bioinformatics tools to predict the conservation, pathogenicity, stability, and effect of the ARSB variants. We examined 170 missense variants, of which G137V and G144R were the resultant variants predicted detrimental to the progression of the disease. The native along with G137V and G144R structures were fixed as the receptors and subjected to Molecular docking with the small molecule Odiparcil to analyze the binding efficiency and the varied interactions of the receptors towards the drug. The interaction resulted in similar docking scores of - 7.3 kcal/mol indicating effective binding and consistent interactions of the drug with residues CYS117, GLN118, THR182, and GLN517 for native, along with G137V and G144R structures. Molecular Dynamics were conducted to validate the stability and flexibility of the native and variant structures on ligand binding. The overall study indicates that the drug has similar therapeutic towards the native and variant based on the higher binding affinity and also the complexes show stability with an average of 0.2 nm RMS value. This can aid in the future development therapeutics for the Maroteaux Lamy syndrome.

Early Predicting Tribocorrosion Rate of Dental Implant Titanium Materials Using Random Forest Machine Learning Models.

Early detection and prediction of bio-tribocorrosion can avert unexpected damage that may lead to secondary revision surgery and associated risks of implantable devices. Therefore, this study sought to develop a state-of-the-art prediction technique leveraging machine learning(ML) models to classify and predict the possibility of mechanical degradation in dental implant materials. Key features considered in the study involving pure titanium and titanium-zirconium (zirconium = 5, 10, and 15 in wt%) alloys include corrosion potential, acoustic emission(AE) absolute energy, hardness, and weight-loss estimates. ML prototype models deployed confirms its suitability in tribocorrosion prediction with an accuracy above 90%. Proposed system can evolve as a continuous structural-health monitoring as well as a reliable predictive modeling technique for dental implant monitoring.

Predictive value of nodal maximum standardized uptake value of pretreatment [18F]fluorodeoxyglucose positron emission tomography imaging in patients with esophageal cancer.

We retrospectively reviewed 102 patients with esophageal cancer (97.1% squamous cell carcinoma, 96.1% stage III) received FDG-PET staging and were treated by chemoradiotherapy with or without resection to assess whether the pretreatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) maximum standardized uptake value (SUVmax) of the primary tumor and metastatic lymph nodes can predict the prognosis of patients with esophageal cancer. Receiver operating characteristic analysis was performed to find the cutoff values for primary tumor SUVmax and nodal SUVmax. The influence of clinical factors including primary tumor SUVmax and nodal SUVmax on local progression-free survival, nodal progression-free survival (NPFS), distant metastases-free survival (DMFS), and overall survival (OS) were evaluated using univariate and multivariate analyses. A total of 40 patients received esophagectomy after neoadjuvant chemoradiotherapy (trimodality), while 62 patients received definitive chemoradiotherapy (dCRT). The median follow-up was 26.4 months. The SUVmax of primary tumor had no significant predictive value on all outcomes, while the SUVmax of metastatic lymph nodes had predictive value on several outcomes. High nodal SUVmax (≥7) predicted for worse outcomes than low nodal SUVmax (<7) in the patients who received dCRT (two-year DMFS, 17% vs. 92%, P < 0.001; NPFS, 14% vs. 81%, P = 0.001; OS, 21% vs. 50%, P = 0.003), but not in those received trimodality. On multivariate analysis of patients receiving dCRT, nodal SUVmax was the strongest independent predictor on DMFS (hazard ratio [HR] 13.93, P < 0.001), NPFS (HR 3.99, P = 0.026), PFS (HR 2.90, P = 0.003), and OS (HR 3.80, P = 0.001). High pretreatment nodal SUVmax predicts worse treatment outcomes for the patients treated with dCRT.

Myelitis in systemic lupus erythematosus frequently manifests as longitudinal and sometimes occurs at low disease activity.

BACKGROUND: Transverse myelitis (TM) is a relatively infrequent but severe complication in systemic lupus erythematosus (SLE). Owing to its rarity and unfavorable outcome, we investigated its general features on MRI and incidence in the context of lupus activity, to facilitate early recognition and treatment. METHODS: We report a case of a young man with clinically inactive lupus nephritis but who presented with a sudden attack of myelitis. We performed systematic literature search in Medline to study the clinical features of SLE-related TM. RESULTS: From 1960 to April 2013, a total of 72 articles containing 194 cases of lupus myelitis were found. Among acquired articles, 93 patients fulfilled the inclusion criteria. The majority of the cases (88.8%) were female. Longitudinal myelitis was the predominant imaging finding on MRI (71.4%, 45/63). Nearly two-thirds (61/94) of lupus myelitis occurred in association with active lupus, and one-third (33/94) occurred in low disease activity. CONCLUSIONS: Upon literature review, we found myelitis in SLE more frequently manifested as longitudinal on MRI. Although lupus myelitis often presented at an active phase of SLE, one-third of events happened in the presence of low disease activity. Early initiation of effective immunosuppressive therapy facilitated recovery.

Contralateral Nodal Relapse in Well-lateralised Oral Cavity Cancers Treated Uniformly with Ipsilateral Surgery and Adjuvant Radiotherapy With or Without Concurrent Chemotherapy: a Retrospective Study.

AIMS: To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. RESULTS: Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. CONCLUSION: The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck.

Training the trainees: an evaluation exercise using the TLH and BSO model.

Our aim was to evaluate surgical training in gynaecological oncology by assessing the time required by a trainee to complete a single laparoscopic gynaecologic-oncological operation. A total of 135 patients with a BMI < 40 kg/m2, diagnosed with endometrial cancer, underwent a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (TLH and BSO). Patients in Group I (n = 78) were operated on by a consultant gynaecological oncology surgeon and in Group II (n = 57) by sub-specialist trainees (SSTs). The mean patient age and BMI was 63.5 years and 29.6 kg/m2, respectively, in Group I and 64.5 years and 29.9 kg/m2, respectively, in Group II. Median operating times for Groups I and II were 58 and 90 min, respectively (p < 0.05). Furthermore, significant improvement was noted when comparing the average operating time between the first and second half of SST training. Even experienced gynaecological trainees take significantly longer to perform a reproducible laparoscopic operation. At the completion of training, an SST demonstrates improvement with respect to operation duration but is still not as fast as the trainer.

Artificial intelligence and machine learning as a viable solution for hip implant failure diagnosis-Review of literature and in vitro case study.

The digital health industry is experiencing fast-paced research which can provide digital care programs and technologies to enhance the competence of healthcare delivery. Orthopedic literature also confirms the applicability of artificial intelligence (AI) and machine learning (ML) models to medical diagnosis and clinical decision-making. However, implant monitoring after primary surgery often happens with a wellness visit or when a patient complains about it. Neglecting implant design and other technical errors in this scenario, unmonitored circumstances, and lack of post-surgery monitoring may ultimately lead to the implant system's failure and leave us with the only option of high-risk revision surgery. Preventive maintenance seems to be a good choice to identify the onset of an irreversible prosthesis failure. Considering all these aspects for hip implant monitoring, this paper explores existing studies linking ML models and intelligent systems for hip implant diagnosis. This paper explores the feasibility of an alternative continuous monitoring technique for post-surgery implant monitoring backed by an in vitro ML case study. Tribocorrosion and acoustic emission (AE) data are considered based on their efficacy in determining irreversible alteration of implant material to prevent total failures. This study also facilitates the relevance of developing an artificially intelligent implant monitoring methodology that can function with daily patient activities and how it can influence the digital orthopedic diagnosis. AI-based non-invasive hip implant monitoring system enabling point-of-care testing.

A cross-sectional study on exploring the antecedents of patient's revisit intention: Mediating role of trust in the hospital among patients in India.

BACKGROUND: In the healthcare domain, patients' trust in the hospital plays an instrumental role in determining the behavioral intention of the patient. This article attempts to investigate the impact of service quality perception on behavioral intention with the mediating effect of trust in the hospital and patient satisfaction. METHODS: This research was carried out in multispecialty hospitals located in Bangalore Urban and Mysore districts of Karnataka during August 2021. This was a questionnaire-based study and the sample size was 242. Statistical Package for the Social Science (SPSS) 27.0 and SmartPLS 3.0 software was used to analyze the data. RESULTS: The findings revealed that perceived service quality significantly influences trust through patient satisfaction (observed partial mediation) and patient satisfaction significantly impacts behavioral intention through trust (observed partial mediation). CONCLUSION: This study empowers hospital managers to understand the factors influencing behavioral intention. Healthcare professionals must ensure that good quality service is delivered to enhance patient satisfaction and trust in adverse services, which influence behavioral intention among the patients.

Predisposing factors of pituitary hemorrhage.

BACKGROUND AND PURPOSE: The clinical features of pituitary adenomas were retrospectively analyzed, focusing on the factors that contribute to the development of pituitary hemorrhage. Although many causes of pituitary adenoma hemorrhage have been identified, it is difficult to distinguish which conditions are truly causative. We determined the independent variables that contribute to pituitary hemorrhage in pituitary adenoma. METHODS: Two hundred and eighty-eight consecutive patients diagnosed as pituitary adenoma were enrolled. These patients underwent tumor removal through endoscopic transsphenoidal approach. The subjects were divided into hemorrhagic and non-hemorrhagic groups, based on magnetic resonance images and histological findings. The predisposing factors were reviewed in the medical records for all patients. Univariate and multivariate analyses were performed to assess the relationships between variables of pituitary adenoma hemorrhage. RESULTS: We investigated 81 patients in whom hemorrhage from pituitary adenoma occurred. The incidence of pituitary hemorrhage was 28.1% (81/288). The predisposing factors surveyed for pituitary hemorrhage were significantly associated with macroadenoma, non-functional adenomas, anticoagulation therapy, end-stage renal disease, dopamine agonist treatment, and underlying malignant disease (all P < 0.05). Sex, age, hypertension, diabetes mellitus, and previous radiation therapy were not related to pituitary hemorrhage. CONCLUSIONS: In this pooled cohort, the predisposing factors of pituitary adenoma characteristic for pituitary hemorrhage were macroadenoma and non-functional adenoma. Patients who received dopamine agonist and anticoagulation therapy are implicated as precipitating factors. Underlying end-stage renal disease and malignant disease are also factors that contribute to pituitary adenoma hemorrhage.

Total laparoscopic hysterectomy for early stage endometrial cancer in obese and morbidly obese women.

This is a retrospective observational study, where we have evaluated the role of total laparoscopic hysterectomy (TLH) in obese and morbidly obese patients with early stage endometrial cancer. Our study illustrates that low conversion rates are achievable when appropriately trained surgeons undertake this procedure. All the women with high BMI were operated on laparoscopically in preference to laparotomy, unless there was an obvious contraindication such as a very large uterus or disseminated disease. We have also shown low conversation and complication rates for our patients, in particular a low rate of wound infection. This is in contrast to the high rate of wound infection and prolonged hospital stay reported for obese patients in the literature. Our study shows that TLH for endometrial cancer in obese women is feasible, safe and is likely to be cost-effective and adds to the weight of evidence for its use in this condition.

Can Positive Emotions Predict Consumer Satisfaction in Adverse Services?

Background: Managing emotions during hospital visits is important to enhance patient satisfaction. The purpose of this paper is to explore the relationship between patients' happiness and satisfaction through patients' mood and perceived service quality at a healthcare setup. Methods: This study was conducted in a tertiary care hospital located in coastal Karnataka during the period from November to December 2021. Primary data was collected through a structured questionnaire from 227 respondents. "Statistical Package for the Social Sciences (SPSS) 27.0" and "SmartPLS 3.0" software was used for data analysis. Results: Hypotheses proposed in this study were examined by comparing the direct effect of patients' happiness level on perceived service quality and the indirect effect of the level of patients' happiness on patient satisfaction. The influence of all the exogenous latent variables namely, happiness, mood, perceived service quality, on the endogenous latent variable of patient satisfaction is estimated to be moderate (R 2=62.5%). Conclusion: This study empowers hospital managers to recognize how patient satisfaction is dependent on patients' happiness. In order to enhance patient satisfaction, the quality of care provided by health services, human resources, and infrastructure must be improved. As a result, the entire service encounter can be made enjoyable to the customers by reducing the distress caused by adverse services. Managers can utilize the outcomes of the study to develop marketing strategies to influence patients' emotions in the healthcare setup by modifying the servicescape elements.

Total hip replacement monitoring: numerical models for the acoustic emission technique.

Any mechanical instability associated with total hip replacement (THR) excites elastic waves with different frequencies and propagates through the surrounding biological layers. Using the acoustic emission (AE) technique as a THR monitoring tool provides valuable information on structural degradations associated with these implants. However, several factors can compromise the reliability of the signals detected by AE sensors, such as attenuation of the detected signal due to the presence of biological layers in the human body between prosthesis (THR) and AE sensor. The main objective of this study is to develop a numerical model of THR that evaluates the impact of biological layer thicknesses on AE signal propagation. Adipose tissue thickness, which varies the most between patients, was modeled at two different thicknesses 40 mm and 70 mm, while the muscle and skin thicknesses were kept to a constant value. The proposed models were tested at different micromotions of 2 µm, 15-20 µm at modular junctions, and different frequencies of 10-60 kHz. Attenuation of signal is observed to be more with an increase in the selected boundary conditions along with an increase in distance the signals propagate through. Thereby, the numerical observations drawn on each interface helped to simulate the effect of tissue thicknesses and their impact on the attenuation of elastic wave propagation to the AE receiver sensor.

Prognostic Value of Radiological Extranodal Extension Detected by Computed Tomography for Predicting Outcomes in Patients With Locally Advanced Head and Neck Squamous Cell Cancer Treated With Radical Concurrent Chemoradiotherapy.

Objective: Extra Nodal Extension (ENE) assessment in locally advanced head and neck cancers (LAHNCC) treated with concurrent chemo radiotherapy (CCRT) is challenging and hence the American Joint Committee on Cancer (AJCC) N staging. We hypothesized that radiology-based ENE (rENE) may directly impact outcomes in LAHNSCC treated with radical CCRT. Materials and Methods: Open-label, investigator-initiated, randomized controlled trial (RCT) (2012-2018), which included LAHNSCC planned for CCRT. Patients were randomized 1:1 to radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2) [cisplatin radiation arm (CRT)] or same schedule of CRT with weekly nimotuzumab (200 mg) [nimotuzumab plus CRT (NCRT)]. A total of 536 patients were accrued and 182 were excluded due to the non-availability of Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) data. A total of 354 patients were analyzed for rENE. Metastatic nodes were evaluated based on five criteria and further classified as rENE as positive/negative based on three-criteria capsule irregularity with fat stranding, fat invasion, and muscle/vessel invasion. We evaluated the association of rENE and disease-free survival (DFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS). Results: A total of 244 (68.9%) patients had radiologically metastatic nodes (rN), out of which 140 (57.3%) had rENE. Distribution of rENE was balanced in the two study groups CRT or NCRT (p-value 0.412). The median follow-up period was 39 months (ranging from 35.5 to 42.8 months). Complete response (CR) was seen in 204 (57.6%); incomplete response (IR), i.e., partial response plus stable disease (PR + SD), in 126 (35.6%); and progressive disease (PD) in 24 (6.8%). rENE-positive group had poor survival compared to rENE-negative group 3-year OS (46.7% vs. 63.6%), poor DFS (48.8% vs. 87%), and LRRFS (39.9% vs. 60.4%). rENE positive had 1.71 times increased risk of IR than rENE negative. Overall stage, site, clinical metastatic node (cN), response, and rENE were the significant factors for predicting OS, DFS, and LRRFS on univariate analysis. After making adjustment on multivariate analysis, rENE was an independent prognostic factor for DFS and trending to be significant for OS. Conclusion: Pre-treatment rENE is an independent prognostic marker for survival in patients with LAHNSCC treated radically with CCRT that can be used as a potential predictive marker for response to treatment and hence stratify patients into responders vs. non-responders. We propose the mahajan rENE grading system applicable on CT, magnetic resonance imaging, positron emission tomography-contrast-enhanced CT, and ultrasound.

Cardiorenal syndrome - a new classification and current evidence on its management.

Patients with chronic kidney disease (CKD) are at high risk for major cardiovascular (CV) morbidity and mortality, especially when they range among the elderly. The co-existence of renal dysfunction is common in patients with chronic heart failure (CHF), and renal failure is among the strongest predictors of mortality in patients with heart failure. Approximately one-third of dialysis patients also suffer from heart failure. The term "cardiorenal syndrome" has been increasingly described in recent literature, as there is growing recognition of the frequent association of combined renal and cardiac dysfunction. The pathophysiology of the cardiorenal syndrome involves interrelated hemodynamic and neurohormonal mechanisms, including the sympathetic nervous system, the renin-angiotensin-aldosterone system, and endothelin and arginine vasopressin system activation. Recently, a new classification of cardiorenal syndrome has been proposed with five subtypes that reflect the pathophysiology, the bidirectional nature of heart and kidney interaction and the time-frame. The management of the cardiorenal syndrome remains a challenge in spite of the advances in medical therapy and novel agents. Novel agents such as B-type natriuretic peptide (BNP) derivative, endothelin antagonist, adenosine antagonist or vasopressin antagonist have been evaluated in randomized controlled trials, and their results are discussed in this review. Mechanical support like hemodialysis and ultrafiltration are found to be useful in acute cardiorenal syndrome. There has been renewed interest in b-blockers in chronic cardiorenal syndrome patients to prevent sudden cardiac death from arrhythmia. In this review, we discuss the evidence behind the definition, pathophysiology, new proposed classification and the various therapeutic measures available for acute cardiorenal syndrome as well as chronic cardiorenal syndrome.

Hip implant performance prediction by acoustic emission techniques: a review.

Nowadays, acoustic emission (AE) has its applications in various areas, including mechanical, civil, underwater acoustics, and biomedical engineering. It is a non-destructive evaluation (NDE) and a non-intrusive method to detect active damage mechanisms such as crack growth, delamination, and processes such as friction, continuous wear, etc. The application of AE in orthopedics, especially in hip implant monitoring, is an emerging research field. This article presents a thorough literature review associated with the implementation of acoustic emission as a diagnostic tool for total hip replacement (THR) implants. Structural health monitoring of an implant via acoustic emission and vibration analysis is an evolving research area in the field of biomedical engineering. A review of the literature reveals a lack of reliable, non-invasive, and non-traumatic early warning methods to evaluate implant loosening that can help to identify patients at risk for osteolysis prior to implant failure. Developing an intelligent acoustic emission technique with excellent condition monitoring capabilities will be an achievement of great importance that fills the gaps or drawbacks associated with osteolysis/implant failure. Graphical abstract.

Reperfusion using lactate Ringer's mixture partially eliminates IGF II receptor involved cardiac damage caused by hemorrhagic shock in diabetic rats.

Diabetes is a metabolic disorder that damages many organs. We investigated the effects of reperfusion using lactate Ringer's solution (LR) in a diabetic animal model. Eight-week-old rats were divided into groups: control, hemorrhagic shock induced (HS), diabetes mellitus (DM), DM plus HS (DM + HS) and DM rats that received LR after HS (DM + HS + LR). HS was induced by withdrawing blood from the femoral artery and arterial pressure was maintained at 40 mm Hg for 1 h. Animals were perfused with either withdrawn blood or LR. Rats were sacrificed and hearts were collected from all groups. Histopathological studies were performed using left ventricles and western blotting analysis was performed using protein extracted from the left ventricle. Using the TUNEL assay, we found more apoptotic cells in the DM + HS group compared to the control group, whereas in animals resuscitated with LR, the number of apoptotic cells was reduced. Western blotting showed a significant reduction in apoptotic markers, cyt c, cas 9 and cas 3, and increased survival markers, pPI3K and pAKT, in the DM + HS + LR group. Reperfusion with LR may have therapeutic effects on trauma induced HS by blocking the IGF II R facilitated apoptosis pathway in diabetic rats.

Orally administered resveratrol enhances the therapeutic effect of autologous transplanted adipose-derived stem cells on rats with diabetic hepatopathy.

Stem cell therapy is a promising treatment for hepatopathy due to diabetes mellitus (DM); oral resveratrol treatment exhibits protective effects. We investigated whether protective effects could be produced in liver of diabetic rats receiving autologous adipose-derived stem cell transplantation (ADSC) plus oral resveratrol administration. Male rats were divided into four groups: sham group; streptozotocin induced DM group; DM + ADSC group, in which DM rats were treated with 106 stem cells/rat; and DM + R + ADSC group, in which DM rats were treated with ADSC and oral resveratrol. The DM group exhibited apoptosis, inflammation and fibrosis, whereas Sirt-1 and survival signaling were suppressed. Pathological conditions other than survival signaling were improved in the DM + ADSC group. All pathological conditions were improved in the DM + R + ADSC group. Also, the oxidative stress level in the blood was reduced in the DM + R + ADSC group compared to the sham group. Oral resveratrol administration appears to reduce oxidative damage and enhances survival signaling in diabetic liver. The therapeutic response in the DM + R + ADSC group was better than in the DM + ADSC group.

An unusual case of Churg-Strauss syndrome and a shrinking renal mass.

Churg-Strauss syndrome is a multisystem disorder characterized by allergic rhinitis, asthma and eosinophilia [Churg and Strauss 1951, Noth et al. 2003]. We report a case of Churg-Strauss syndrome associated with a complex renal mass, which resolved with immunosuppressive therapy.