Metabolic and behavioural risk factors for cardiovascular diseases in Southern Latin America: analysis of the Global Burden of Disease 1990-2019.

OBJECTIVES: Cardiovascular diseases (CVDs) are the leading causes of global mortality. Modifiable behavioural and metabolic risk factors significantly contribute to the burden of CVD. Given the vast socio-demographic and health outcome heterogeneity in Latin America, similar southern Latin American countries (Argentina, Chile, and Uruguay) were analysed as a distinct group to describe the CVD death rates related to metabolic and behavioural risk factors. STUDY DESIGN: An ecological study was performed using data from the Global Burden of Disease Study 2019. METHODS: Metabolic and behavioural risk factors-related CVD death were examined by analysing age-standardised rates per 100,000 individuals in the three countries between 1990 and 2019. RESULTS: While exposure to behavioural risk is decreasing, an upwards trend was observed in metabolic risks. Among the assessed risk factors, metabolic factors emerged as the primary contributors to deaths. High fasting plasma glucose exhibited a remarkable increase in relative importance across most studied contexts. Dietary risks stood out among behavioural factors due to their complexity and substantial changes observed. Although mortality rates have declined for overall CVD, peripheral artery disease mortality is rising. CONCLUSION: Modifiable behavioural and metabolic risk factors significantly influence CVD mortality in Southern Latin America. Despite the increasing exposure to metabolic risks, advancements in prevention and treatment are evidenced in the decline of mortality rates for most CVD. These findings emphasise the need for targeted interventions and comprehensive strategies to address their impact on cardiovascular health, advocating for healthy lifestyle behaviours to mitigate the progression and CVD development.

Somatic mutational landscape across Indian breast cancer cases by whole exome sequencing.

Breast cancer (BC) has emerged as the most common malignancy among females. The genomic profile of BC is diverse in nature and complex due to heterogeneity among various geographically different ethnic groups. The primary objective of this study was to carry out a comprehensive mutational analysis of Indian BC cases by performing whole exome sequencing. The cohort included patients with a median age of 48 years. TTN, TP53, MUC16, SYNE1, and OBSCN were the frequently altered genes found in our cohort. The PIK3CA and KLC3 genes are driver genes implicated in various cellular functions and cargo transportation through microtubules, respectively. Except for CCDC168 and PIK3CA, several gene pairings were found to be significantly linked with co-occurrence. Irrespective of their hormonal receptor status, RTK/RAS was observed with frequently altered signaling pathways. Further analysis of the mutational signature revealed that SBS13, SBS6, and SBS29 were mainly observed in our cohort. This study supplements the discovery of diagnostic biomarkers and provides new therapeutic options for the improved management of BC.

A Prospective Questionnaire-Based Study Evaluating Genetic Literacy and Impact of Brief Educational Intervention Among Breast Cancer Patients in a Low- to Middle-Income Country.

INTRODUCTION: A significant proportion of breast cancer cases are hereditary and are potentially preventable. However, adoption of the preventive measures remains a significant challenge, particularly because of to lack of knowledge and awareness in low- to middle-income countries. METHODS: This prospective study conducted at a high-volume tertiary care cancer center in North India to assess the knowledge, awareness, and attitudes of female breast cancer patients and impact of a brief educational intervention. The study involved three phases: pre-interventional assessment, educational intervention, and post-interventional assessment utilizing a structured questionnaire. RESULTS: The study involved 300 newly diagnosed breast cancer patients; 16.7% were familial. At the outset, 87.0% patients had low knowledge of risk factors, 90.3% about screening, and 32.7% about treatment. Awareness levels were low: 13.7% aware of familial risk and 2.7% of breast cancer genes. Affordability of genetic testing was low (15.2%), and interest in testing for self and family members was limited (32.0% and 26.3%). Following educational intervention, a significant positive percentage change was noticed in knowledge (risk factors: 12.8%, screening: 36.2%, treatment: 82%), awareness (familial risk: 66.7%, BRCA gene: 12.3%), and attitude (testing for self: 17.8%, family: 19.5%). CONCLUSIONS: This study highlights the significant knowledge gaps among breast cancer patients regarding genetics. The educational intervention led to notable improvements in knowledge, awareness, and attitudes, underscoring the importance of tailored patient education in breast cancer care.

Feasibility of the ERAS (Enhanced Recovery After Surgery) Protocol in Patients Undergoing Gastrointestinal Cancer Surgeries in a Tertiary Care Hospital-A Prospective Interventional Study.

Enhanced Recovery After Surgery (ERAS) protocols have emerged as a promising approach to optimize perioperative care and improve outcomes in various surgical specialties. Despite feasibility studies on ERAS in various surgeries, there remains a paucity of research focusing on gastrointestinal cancer surgeries in the Indian context. The primary objective is to evaluate the compliance rate of the ERAS protocol and secondary objectives include the compliance rate of individual components of the protocol, the complications, the length of hospital stay, and the challenges faced during implementation in patients undergoing gastrointestinal cancer surgeries in our tertiary care cancer center. In this prospective interventional study (CTRI/2022/04/041657; registered on 05/04/2022), we evaluated 50 patients aged 18 to 70 years undergoing surgery for gastrointestinal malignancies and implemented a refined ERAS protocol tailored to our institutional resources and conditions based on standard ERAS society recommendations for gastrointestinal surgeries and specific recommendations for colorectal, pancreatic, and esophageal surgeries.Our study's mean overall compliance rate with the ERAS protocol was 88.54%. We achieved a compliance rate of 91.98%, 81.66%, and 92.00% for pre-operative, intraoperative, and post-operative components respectively. Fourteen (28%) patients experienced complications during the study. The median length of stay was 6.5 days (5.25-8). Challenges were encountered during the preoperative, intraoperative, and postoperative phases. The study highlighted the feasibility of implementing the ERAS protocol in a cancer institute, but specific challenges need to be addressed for its optimal success in gastrointestinal cancer surgeries. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-024-01897-y.

Comprehensive germline profiling of patients with breast cancer: initial experience from a Familial Cancer Clinic.

Introduction: Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India. Objective: The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC). Materials and methods: It is a single-centre audit of patients with a confirmed diagnosis of breast carcinoma referred to our FCC from January 2017 to 2020. All patients underwent pretest counselling. Genetic testing was done by multigene panel testing by next-generation sequencing along with reflex multiplication ligation-dependent probe amplification for BRCA1 and 2. The variants were classified based on American College of Medical Genetics guidelines. Demographic and clinicopathological details were extracted from the case record files. Results: One hundred and fifty-five patients were referred to the FCC and underwent pretest counselling. A total of 99 (63.9%) patients underwent genetic testing. Among them, 62 patients (62/99 = 62.6%) had a germline variant. A pathogenic/likely pathogenic (P/LP) germline variant was identified in 41 (41.4%) of the patients who underwent testing. Additional variants of unknown significance (VUS) were identified in seven patients who also carried a P/LP variant. VUS alone was detected in 21 patients (21/99 = 21.2%). Among the P/LP pathogenic variants (PV), BRCA 1 PV were seen in 27 patients (65.8%), BRCA 2 variants in 7 patients (17.1%), ATM variants in 3 patients (7.3%) and RAD51, TP53, CHEK2 and HMMR in 1 patient each. Variants were significantly more common in patients with a family history (FH) of malignancy than those without FH (58.5% versus 29.5%; p = 0.013). Age and triple-negative histology were not found to be significantly associated with the occurrence of P/LP PVs. Conclusion: We report a 41% P/LP variant rate in our selected cohort of breast cancer patients, with variants in BRCA constituting 83% and non-BRCA gene variants constituting 17%.

Engineered nanomicelles inhibit the tumour progression via abrogating the prostaglandin-mediated immunosuppression.

Cancer treatment is challenged due to immunosuppressive inflammatory tumour microenvironment (TME) caused by infiltration of tumour-promoting and inhibition of tumour-inhibiting immune cells. Here, we report the engineering of chimeric nanomicelles (NMs) targeting the cell proliferation using docetaxel (DTX) and inflammation using dexamethasone (DEX) that alters the immunosuppressive TME. We show that a combination of phospholipid-DTX conjugate and PEGylated-lipid-DEX conjugate can self-assemble to form sub-100 nm chimeric NMs (DTX-DEX NMs). Anti-cancer activities against syngeneic and xenograft mouse models showed that the DTX-DEX NMs are more effective in tumour regression, enhance the survival of mice over other treatment modes, and alter the tumour stroma. DTX-DEX NMs cause a significant reduction in myeloid-derived suppressor cells, alter the polarization of macrophages, and enhance the accumulation of cytotoxic CD4+ and CD8+ T cells in tumour tissues, along with alterations in cytokine expression. We further demonstrated that these DTX-DEX NMs inhibit the synthesis of prostaglandins, especially PGE2, by targeting the cyclooxygenase 2 that is partly responsible for immunosuppressive TME. Therefore, this study presents, for the first time, the engineering of lithocholic acid-derived chimeric NMs that affect the prostaglandin pathway, alter the TME, and mitigate tumour progression with enhanced mice survival.

Clinicopathological Profile and Survival Outcomes in Patients with Localised Extremity Synovial Sarcomas.

AIMS: Synovial sarcoma is a rare but aggressive variant of soft-tissue sarcoma. Literature is sparse and reported mostly from the West. We analysed the clinical profiles and prognostic factors of extremity synovial sarcoma patients in order to study their clinical journey. MATERIALS AND METHODS: This was a retrospective analysis. All patients with extremity synovial sarcoma treated between 1992 and 2020 were included. Patients with metastases at presentation were excluded. A descriptive analysis of demographic and clinicopathological features of patients undergoing limb salvage surgery (LSS) or amputation was carried out. Overall survival and disease-free survival were calculated for the entire cohort as well as for the LSS and amputation groups. Factors prognostic for survival were identified. RESULTS: In total, 157 patients had localised extremity synovial sarcoma. Predominantly, young adults (median 31 years) and males (61%) were affected. Over 70% of patients presented after recurrence or unplanned surgeries. Sixty-seven per cent of tumours were >5 cm, 69% were deep and 23% involved bone. The limb salvage rate was 64%. In the LSS group, adjuvant radiotherapy and chemotherapy were given to 72% and 68% of patients, respectively. In the amputation group, 72% of patients received adjuvant chemotherapy. In a median follow-up of 59 months, 39.4% of patients had recurrences, the majority (61.2%) were systemic. Five-year overall survival and disease-free survival were 53.4% and 49.8%, respectively. Overall survival was 63.9% and 29.7% in the LSS and amputation groups, respectively. On multivariate analysis, tumour size, depth, omission of radiotherapy and bone invasion were found to be the adverse prognostic factors. CONCLUSION: This is one of the largest studies on extremity synovial sarcoma. Mostly males and young adults were affected. The limb salvage rate was 64%, despite most being referred after unplanned surgery. Almost 70% of patients received radiotherapy and chemotherapy. Overall survival was inferior in the amputation group. Tumour size >5 cm, depth and bone invasion were negative, whereas adjuvant radiotherapy was a positive prognostic factor for survival. Chemotherapy had no impact on survival.

Malignant Chest Wall Tumors: Complex Defects and Their Management-A Review of 181 Cases.

BACKGROUND: Chest wall tumors are a heterogeneous group of tumors that are managed by surgeons from diverse specialties. Due to their rarity, there is no consensus on their diagnosis and management. MATERIALS: This retrospective, descriptive analysis includes patients with malignant chest wall tumors undergoing chest wall resection. Tumors were classified as primary, secondary, and metastatic tumors. The analysis includes clinicopathological characteristics, resection-reconstruction profile, and relapse patterns. RESULTS: A total of 181 patients underwent chest wall resection between 1999 and 2020. In primary tumors (69%), the majority were soft tissue tumors (59%). In secondary tumors, the majority were from the breast (45%) and lung (42%). Twenty-five percent of patients received neoadjuvant chemotherapy, and 98% of patients underwent R0 resection. Soft tissue, skeletal + soft tissue, and extended resections were performed in 45%, 70%, and 28% of patients, respectively. The majority of patients (60%) underwent rib resections, and a median of 3.5 ribs were resected. The mean defect size was 24 cm2. Soft tissue reconstruction was performed in 40% of patients, mostly with latissimus dorsi flaps. Rigid reconstruction was performed in 57% of patients, and 18% underwent mesh-bone cement sandwich technique reconstruction. Adjuvant radiotherapy and chemotherapy were given to 29% and 39% of patients, respectively. CONCLUSIONS: This is one of the largest single-institutional experiences on malignant chest wall tumors. The results highlight varied tumor spectra and multimodality approaches for optimal functional and survival outcomes. In limited resource setting, surgery, including reconstructive expertise, is very crucial.

Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

The cardiovascular disease burden attributable to particulate matter pollution in South America: analysis of the 1990-2019 global burden of disease.

OBJECTIVES: Fine particulate matter <2.5 microns (PM2.5) is the most studied air pollutant. Both short- and long-term exposure to PM2.5 have been linked to cardiovascular disease (CVD). Studies evaluating air pollution in South America are scarce. Therefore, the impact of exposure to PM2.5, household air pollution (HAP), and ambient air pollution (AAP) on CVD mortality and CVD disability-adjusted life years (DALYs) in South American countries from 1990 to 2019 was explored. STUDY DESIGN AND METHODS: The Global Burden of Disease initiative exposure-response function was used to analyze the total PM2.5, ambient PM2.5, and household PM2.5-related CVD deaths and DALYs rates, per 100,000 individuals, in 12 South American countries between 1990 and 2019. The relative change in burden was also assessed by comparing the 1990-1994 to 2015-2019 periods. RESULTS: In 2019, 70,668 deaths and 1,736,414 DALYs due to CVD were attributed to total PM2.5 exposure in South America. Substantial regional heterogeneity was observed concerning the absolute change in PM2.5 concentration levels comparing 1990 to 2019. All South American countries observed a relative decline in CVD deaths and DALYs comparing the 1990-1994 to 2015-2019 periods. No country was able to reach the current World Health Organization 5 µg/m3 recommended limit in 2019. Predominantly, AAP was the greatest contributor to the CVD burden. CONCLUSION: Air pollution substantially impacted CVD in South America; however, this impact was heterogenous, and the relative reduction of HAP and AAP burden was also not uniform. Recognizing PM2.5 importance is key for developing target population and individual-level interventions, which could ultimately alleviate its burden.

No Doppler Single Position-Lateral Intercostal Artery Perforator Flap (NDSP-LICAP): a Safe and Versatile Flap for Breast Oncoplasty in Resource-Limited Setting.

INTRODUCTION: The lateral intercostal artery perforator flap (LICAP) has emerged as one of the safest and less morbid flaps for lateral and central breast defects. We hereby describe a reproducible no Doppler single position (NDSP) technique to harvest it in single position without handheld Doppler, making it a versatile flap for lateral breast defects in resource-limited setting also. MATERIALS AND METHODS: With this technique, we performed a total of 22 LICAP turnover flaps over a period of 18 months from January 2020 to June 2021. In all 22 cases, the indication of flap was to fill the post-breast conservation surgery (BCS) defects in outer quadrant of breast. All LICAP flaps were harvested by surface marking of anatomical landmarks and without handheld Doppler. RESULTS: Out of 22 LICAP turnover flaps, thirteen were harvested for left breast and nine for right breast. The median width and length of the flap were 12.2 cm and 19.6 cm, respectively. The additional mean operative time was 41 min. All LICAP flaps survived well, and grade 1 Clavien-Dindo morbidity was documented in four cases. Mean hospital stay was 2.6 days. All patients received radiotherapy on their stipulated schedule. Early cosmetic outcome was good, and long-term outcomes are awaited. CONCLUSION: NDSP-LICAP flap is a workhorse for lateral breast defects. Precise knowledge of perforators and anatomical landmarks can be used for harvesting these flaps, thus avoiding ultrasound Doppler and dedicated training for perforator localization. This technique has short learning curve without the need for any plastic surgery training. The early cosmetic outcomes are good.

Combination of 3PO analog PFK15 and siPFKL efficiently suppresses the migration, colony formation ability, and PFK-1 activity of triple-negative breast cancers by reducing the glycolysis.

Among all the subtypes of breast cancer, triple-negative breast cancer (TNBC) has been associated with the worst prognosis. Recently, for many solid tumors (including breast cancer) metabolic reprogramming has appeared as a cancer cell hallmark, and the elevated glycolytic pathway has been linked to their aggressive phenotype. In the present study, we evaluated the prognostic and therapeutic relevance of PFKFB3 (6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase) in TNBCs. Prognostic significance of PFKFB3 expression was evaluated in overall breast cancers as well as in TNBCs. PFKFB3 inhibitor (3PO potent analogue i.e., PFK15) cytotoxicity in TNBC cell lines (MDA-MB-231 and MDA-MB-468) was analyzed using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cancer cell physiological characteristics like clonogenicity and migration were also investigated after PFK15 treatment. As fructose-2,6-bisphosphate (F-2,6-BP), has been associated with increased PFK-1 activity, the effect of PFKFB3 inhibition by PFK15 was investigated on two major isoforms of phosphofructokinase-1 (PFK-1) in breast cancer, that is, phosphofructokinase-platelet type (PFKP) and phosphofructokinase-liver type (PFKL) (relevant to breast cancer). For PFKL inhibition, the siRNA approach was used. PFKFB3 expression was significantly correlated with inferior overall survival in breast cancer patients including TNBCs. PFK15 treatment in TNBC cells (i.e., MDA-MB-231 and MDA-MB-468) resulted in a decreased PFKP expression, thereby leading to reduced colony formation ability, migration rate, and extracellular lactate levels. However, to our surprise PFK15 treatment in both TNBC cells also resulted in elevated PFKL levels. Our results demonstrated that the combinatorial inhibition of PFK15 with siPFKL was more effective in TNBC cells, as it led to a decrease in colony formation ability, migration rate, extracellular lactate levels, and PFK-1 activity when compared with individual treatments. Using bona fide PFKFB3 inhibitor, that is, AZ67, we further show that AZ67 treatment to TNBC cells has no effect either on the expression of PFKP and PFKL, or on the lactate production. In summary, our present in vitro study demonstrated that 3PO derived PFK15 mechanism of action is totally different from AZ67 in TNBC cells. However, we advocate that the PFK15-mediated inhibition (along with PFKL) on the TNBCs migration, colony formation, and PFK-1 activity can be further explored for the therapeutic advantage of TNBC patients.

Pattern of Care in Real-World Scenario on Advanced Epithelial Ovarian Cancer in a Tertiary Referral Oncology Centre in India - ISPSM Collaborative Study.

The treatment of advanced epithelial ovarian cancer (EOC) has evolved over time. With advent of platinum-based chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC), there is a paradigm shift in the patterns of care with improved survival. In this study, we analysed our advanced EOC patients aiming to gain insights into the pattern of care. An ambispective study of 250 patients of advanced EOC was done from our prospectively maintained computerised database in the Department of Surgical Oncology, tertiary care referral centre from 2013 to 2020. We analysed the demographic profile, treatment patterns, and perioperative outcomes. In this study, there were 83.6% stage III and 16.4% stage IVA. There were 62 (24.8%) upfront and 112 (44.8%) in interval settings. There was a higher number of patients receiving neo-adjuvant chemotherapy. One hundred twenty-six (50.4%) underwent cytoreductive surgery (CRS) only and 124 (49.6%) underwent CRS and HIPEC. CC-0 was achieved in 84.4% and CC-1 in 15.6% patients. HIPEC programme was started in 2013. With advent of RCTs in HIPEC, there was a substantial increase in the number of patients receiving HIPEC from 2015 (n = 10), 2017 (n = 20) to 2019 (n = 41). We offer secondary CRS in a limited subset of patients, n = 76 (30.4%). There was 24.8% early and 8.4% late postop complications. We have median follow-up of 50 months with attrition rate of 4%. With practice changing updates, the treatment of advanced EOC has been evolving over time. Though the primary CRS followed by systemic therapy is the standard to date, there is change in pattern of care with neo-adjuvant chemotherapy followed by interval CRS and HIPEC because of various RCTs. The addition of HIPEC has acceptable morbidity and mortality. There is a definite learning curve and the team has to evolve as a whole. In a tertiary care referral centre from LMIC, good patient selection, logistics, and implementing recent advances will definitely add to improved survival.

Imaging features of breast cancer subtypes on contrast enhanced ultrasound: a feasibility study.

The objective of this research was to study the contrast enhancement patterns of the different molecular subtypes of breast cancer on contrast-enhanced ultrasound (CEUS) using both qualitative and quantitative parameters. This prospective study included females with a single breast mass which was histopathologically proven carcinoma. B mode ultrasound (USG) and CEUS were performed in all patients during baseline assessment. Qualitative CEUS assessment encompassed enhancement pattern, presence of fill-in and washout. Quantitative assessment included measurement of peak enhancement, time to peak; area under the curve and mean transit time. A p-value < 0.05 was considered statistically significant for differentiating the subtypes. The included thirty masses were categorised into two subtypes-triple negative breast cancer (TNBC) (36.7%) and non-TNBC (63.3%) subtypes. With B-mode USG, a statistically significant difference was observed between the two groups with respect to their shape and margins. TNBC lesions showed an oval shape, circumscribed margins and peripheral nodular enhancement on CEUS with the absence of fill-in even in the delayed phase (p-value - 0.04). The two subtypes did not significantly differ in terms of quantitative perfusion parameters. The various subtypes of breast cancer therefore possess distinct contrast enhancement patterns. CEUS potentially allows differentiation amongst these molecular subtypes that may aid in radiology-pathology (rad-path) correlation and follow up of the patients.

Spectrum and management of breast cancer patients with variant of uncertain significance mutations at a tertiary care centre in North India.

Background: The spectrum and significance of Variants of Uncertain Significance (VUS) mutations in breast cancer predisposition genes is poorly defined in the Indian population. Methods: All new female breast cancer patients from 1 March 2019 to 28 February 2020 were screened. Those providing informed consent and without previous genetic testing were recruited. Multigene panel testing (107 genes) by next-generation sequencing was performed for all patients. Descriptive statistics was used to describe the spectrum of VUS mutations. Results: Out of 236 patients recruited in the study, a VUS was detected in 89 patients (37.71%). VUS pathogenic ratio was 2.02. A total of 121 different VUS mutations in 40 different genes were detected. Fourteen patients (15.7%) had a VUS in high penetrance genes and 36 VUS mutations (29.8%) were detected in one of the genes involved in homologous recombination repair pathway. No therapeutic interventions were done based on VUS. Conclusions: In this large prospective study of genetic determinants of breast cancer from India, a high prevalence of VUS (37.71%) was detected with 15.7% patients having a VUS in high penetrance genes. More evidence needs to be generated from larger multicentric studies to better understand the implications of these genetic variants and enable their reclassification.

Prospective Clinical Pilot Study to Evaluate the Effect of Prosthodontic Rehabilitation on Psychological Status and Quality of Life in Maxillectomy Patients: An Indian Experience.

Abstract: The purpose of the study was to assess psychological status (PS) and quality of life (QOL) before surgical resection of maxilla (T0), 2 weeks after resection (T1), 2 weeks after use of intermediate obturator (T2), before (T3) and 12 weeks after use of definitive obturator (T4). 20 participants, planned for resection of maxilla and subsequent prosthodontic rehabilitation were enrolled. Assessment was done using Hospital Anxiety and Depression Scale (HADS) (HADS-A: anxiety and HADS-D: depression) for PS, World Health Organization Quality of Life BREF (WHOQOL-BREF) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Head and Neck Module (EORTC QLQ- H&N35) for QOL, and obturator functioning scale (OFS) for obturator functioning. Six cases were dropped out. Highest HADS-A score was observed presurgically (18.7 ± 1.1) and highest HADS-D score at T1 (18.5 ± 1.8). After rehabilitation, HADS-A and HADS-D decreased significantly (P < 001). Least WHOQOL-BREF score was observed at T1, followed by a consistent, significant rise after rehabilitation at all time intervals (P < 001). Highest EORTC QLQ-H&N 35 score was observed at T1, with significant reduction (P < 0.001) after rehabilitation for all questions, except those related to sexual wellness (P = 1). Highest OFS were observed at T2 (3.1 ± 10.3) and least at T4 (1.9 ± 0.2). QOL and PS decline after maxillectomy. Patient education and rehabilitation with obturator leads to improvement in QOL and PS probably due to restored oral functions, and improved health of soft tissue. Both parameters improved with enhanced obturator quality and time. Registration at Clinical Trials Registry - India ICMR-NIMS: Reg. No. CTRI/2018/04/013164 http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=67729.89030.

Comprehensive mutations analyses of FTO (fat mass and obesity-associated gene) and their effects on FTO's substrate binding implicated in obesity.

An excessive amount of fat deposition in the body leads to obesity which is a complex disease and poses a generic threat to human health. It increases the risk of various other diseases like diabetes, cardiovascular disease, and multiple types of cancer. Genomic studies have shown that the expression of the fat mass obesity (FTO) gene was highly altered and identified as one of the key biomarkers for obesity. This study has been undertaken to investigate the mutational profile of the FTO gene and elucidates its effect on the protein structure and function. Harmful effects of various missense mutations were predicted using different independent tools and it was observed that all mutations were highly pathogenic. Molecular dynamics (MD) simulations were performed to study the structure and function of FTO protein upon different mutations and it was found that mutations decreased the structure stability and affected protein conformation. Furthermore, a protein residue network analysis suggested that the mutations affected the overall residues bonding and topology. Finally, molecular docking coupled with MD simulation suggested that mutations affected FTO substrate binding by changing the protein-ligand affinity. Hence, the results of this finding would help in an in-depth understanding of the molecular biology of the FTO gene and its variants and lead to the development of effective therapeutics against associated diseases and disorders.