Health-related quality of life and its determinants among cancer patients: evidence from 12,148 patients of Indian database.

BACKGROUND: Cancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants. METHODS: Data were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics. RESULTS: Majority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45-60 years and females (49.3-58.3%). Most patients were found to be in stage III (40-40.6%) or stage IV (29.4-37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771). CONCLUSION: Older age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.

Feasibility and acceptability of a cohort study baseline data collection of device-measured physical behaviors and cardiometabolic health in Saudi Arabia: expanding the Prospective Physical Activity, Sitting and Sleep consortium (ProPASS) in the Middle East.

BACKGROUND: Physical behaviors such physical activity, sedentary behavior, and sleep are associated with mortality, but there is a lack of epidemiological data and knowledge using device-measured physical behaviors. PURPOSE: To assess the feasibility of baseline data collection using the Prospective Physical Activity, Sitting, and Sleep consortium (ProPASS) protocols in the specific context of Saudi Arabia. ProPASS is a recently developed global platform for collaborative research that aims to harmonize retrospective and prospective data on device-measured behaviors and health. Using ProPASS methods for collecting data to perform such studies in Saudi Arabia will provide standardized data from underrepresented countries. METHOD: This study explored the feasibility of baseline data collection in Saudi Arabia between November and December 2022 with a target recruitment of 50 participants aged ≥ 30 years. Established ProPASS methods were used to measure anthropometrics, measure blood pressure, collect blood samples, carry out physical function test, and measure health status and context of physical behaviors using questionnaires. The ActivPal™ device was used to assess physical behaviors and the participants were asked to attend two sessions at (LHRC). The feasibility of the current study was assessed by evaluating recruitment capability, acceptability, suitability of study procedures, and resources and abilities to manage and implement the study. Exit interviews were conducted with all participants. RESULT: A total of 75 participants expressed an interest in the study, out of whom 54 initially agreed to participate. Ultimately, 48 participants were recruited in the study (recruitment rate: 64%). The study completion rate was 87.5% of the recruited participants; 95% participants were satisfied with their participation in the study and 90% reported no negative feelings related to participating in the study. One participant reported experiencing moderate skin irritation related to placement of the accelerometer. Additionally, 96% of participants expressed their willingness to participate in the study again. CONCLUSION: Based on successful methodology, data collection results, and participants' acceptability, the ProPASS protocols are feasible to administer in Saudi Arabia. These findings are promising for establishing a prospective cohort in Saudi Arabia.

Modifications of 24-h movement behaviors to prevent obesity in retirement: a natural experiment using compositional data analysis.

BACKGROUND: Retirement often leads to a more passive lifestyle and may therefore lead to weight gain. This study aims to investigate longitudinal associations between changes in 24-h movement behaviors and BMI and waist circumference in relation to the transition from work to retirement. METHODS: The study population included 213 retiring public sector workers (mean age 63.5 years, standard deviation 1.1) from the Finnish Retirement and Aging study. Before and after retirement participants wore an Axivity accelerometer on their thigh and filled in a daily log for at least four days to measure daily time spent sleeping, in sedentary behavior (SED), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). Also, their body mass index (BMI) and waist circumference were measured repeatedly. Compositional linear regression analysis and isotemporal substitution analysis were used to study associations between one-year changes in 24-h movement behaviors and concurrent changes in BMI and waist circumference. RESULTS: An increase in MVPA in relation to sleep, SED and LPA was associated with a decreasing BMI (ß = -0.60, p = 0.04) and waist circumference (ß = -2.14, p = 0.05) over one year from before retirement to after retirement. In contrast, increasing sleep in relation to SED, LPA and MVPA was associated with an increasing BMI (ß = 1.34, p = 0.02). Reallocating 60 min from MVPA to SED or sleep was estimated to increase BMI by on average 0.8-0.9 kg/m2 and waist circumference by 3.0 cm during one year. CONCLUSIONS: During the transition from work to retirement, increasing MVPA was associated with a slight decrease in BMI and waist circumference, whereas increasing sleep was associated with an increasing BMI. Common life transitions, like retirement, should be considered when giving recommendations and guidance for physical activity and sleep.

Does it matter for health if steps are taken during work or leisure? A prospective accelerometer study using register-based long-term sickness absence.

BACKGROUND: Walking is known to be good for health. However, it is unknown whether it matters if steps are taken during work or leisure. Therefore, we aimed to examine the prospective association between accelerometer-measured steps taken during work or leisure and register-based long-term sickness absence (LTSA). METHODS: We included 937 blue- and white-collar workers from the PODESA cohort who wore a thigh-based accelerometer over four days to measure number of steps during work and leisure. Steps were divided into domain based on diary data. First event of LTSA was retrieved from a national register with four years' follow-up. We used Cox proportional hazard models to analyze the association between domain-specific and total daily steps and LTSA, adjusted for age, sex, job type, smoking, and steps in the other domain (e.g., work/leisure). RESULTS: We found more steps at work to be associated with a higher LTSA risk [Hazard Ratio (HR):1.04; 95% CI: 1.00-1.08 per 1000 steps]. No significant association was found between steps during leisure and LTSA (HR: 0.97; 95% CI: 0.91-1.02), nor between total daily steps and LTSA (HR: 1.01; CI 95% 0.99-1.04). CONCLUSIONS: More steps at work were associated with higher risk of LTSA, while steps during leisure was not clearly associated with LTSA risk. These findings partly support 'the physical activity paradox' stating that the association between physical activity and health depends on the domain.

Exploration of Indolo[3,2c]isoquinoline derived triazoles as potential antimicrobial and DNA cleavage agents: Synthesis, DFT calculations, and molecular modeling studies.

Indole and its derivatives are well-known assorted motif in drug design and development. We here in reporting synthesis of new 9-chloro-1-(4-substituted phenyl)-12H-indolo[2,3-c][1,2,4]triazolo[3,4-a]isoquinolines 7 (a-h). Structures of the newly synthesized compounds were confirmed by making use of spectroscopic techniques like IR, NMR and Mass. The DFT calculations were taken for the selected molecules using CAM-B3LYP hybrid functional with a 6-31 + g(d) all-electron basis set using the Gaussian 09 package. The drug-likeness predictions were described for the synthesized derivatives. The In vitro antimicrobial and DNA cleavage activities were reported for all compounds 7 (a-h). The compounds 7a, 7b, and 7h showed excellent microbial inhibition and DNA cleavage activity as compared to standard drugs. Furthermore, the docking studies for the newly synthesized molecules were carried out by Auto dock software with two molecular targets Epidermal Growth Factor Receptor tyrosine kinase (1 M17) and C-kit Tyrosine Kinase (1 T46) exhibited better binding affinity of all synthesized compounds. In addition, the docking results were observed to be in full agreement with the in vitro DNA cleavage assay suggesting the potential of synthesized metal complexes in biological applications. Lastly, the protein stability, fluctuations of APO-Protein, and protein-ligand complexes were investigated through Molecular Dynamics (MD) simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified.

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections.

BACKGROUND: COVID-19 has proved to be a fatal disease of the year 2020, due to which thousands of people globally have lost their lives, and still, the infection cases are at a high rate. Experimental studies suggested that SARS-CoV-2 interacts with various microorganisms, and this coinfection is accountable for the augmentation of infection severity. METHODS AND RESULTS: In this study, we have designed a multi-pathogen vaccine by involving the immunogenic proteins from S. pneumonia, H. influenza, and M. tuberculosis, as they are dominantly associated with SARS-CoV-2. A total of 8 antigenic protein sequences were selected to predict B-cell, HTL, and CTL epitopes restricted to the most prevalent HLA alleles. The selected epitopes were antigenic, non-allergenic, and non-toxic and were linked with adjuvant and linkers to make the vaccine protein more immunogenic, stable, and flexible. The tertiary structure, Ramachandran plot, and discontinuous B-cell epitopes were predicted. Docking and MD simulation study has shown efficient binding of the chimeric vaccine with the TLR4 receptor. CONCLUSION: The in silico immune simulation analysis has shown a high level of cytokines and IgG after a three-dose injection. Hence, this strategy could be a better way to decrease the disease's severity and could be used as a weapon to prevent this pandemic.

A Concise Review on Natural Products and Their Derivatives for Breast Cancer Treatment.

Cancer is a leading cause of death worldwide. Among other cancers, breast cancer has been found to produce maximum number of cases in 2020. Different factors including geographical, genetic, hormonal, oral contraceptives and modern lifestyle could be responsible for the development of breast cancer and different pathways can be targeted for breast cancer treatment. The various conventional approaches used for the treatment of breast cancer including radiotherapy, chemotherapy, hormone and immunotherapy. But due to the side effects associated with these conventional treatments such as non-selectivity, multidrug resistance and bioavailability, there is a need for the development of better therapeutic agents for breast cancer treatment. Several natural products have been explored for breast cancer treatment. However, many of these natural products suffered from the limitations of poor water solubility and possess toxic side effects. To overcome these limitations, several structural analogs of natural products have been synthesized and possess potent anti-breast cancer effects with less side effects over their precursor molecules. In the present manuscript, we describe the pathogenesis of breast cancer, some potent natural products used in the treatment of breast cancer and their selected structural analogs possessing potent anti-breast cancer effects. Database such as Science direct, Pubmed and Google scholar were searched using keywords 'risk factors', 'screening methods','receptors', and 'natural products and derivatives', Registered clinical trials on selected natural products were also analyzed. Present study concludes that eight selected natural products and their derivatives possess wide potential to exhibit anti-breast cancer effects and could be explored further to develop better chemotherapeutic agents against breast cancer.

Glycemic Variability and Its Correlation with Large for Gestation-age Babies in Gestational Diabetic Pregnancies.

BACKGROUND: Although glycemic variability (GV) has been shown to be associated with endothelial dysfunction in diabetes mellitus (DM), there is a dearth of literature on its correlation in gestational diabetic pregnancies. AIM: To compare GV and 24-hour ambulatory glucose profile (AGP) in gestational diabetic pregnancies with and without large for gestation-age (LGA) babies. MATERIALS AND METHODS: It was a cross-sectional observational study. A total of 40 pregnant females between 19 and 35 years with gestational DM (GDM) controlled on pharmacotherapy fulfilling inclusion criteria were recruited. A flash glucose monitor (FGM) was used to record AGP between 32 and 36 weeks of gestation in these women. A total of 400 patient days with 38,400 glucose values in the study group were analyzed. Various glucose measures were compared between the GDM pregnancies with or without LGA babies. RESULTS: The incidence of LGA was 15% in these pregnant women who were on pharmacotherapy and apparently controlled as evidenced by self-monitoring of blood sugar values. All the parameters of 24-hour AGP except dinner values were significantly high in the LGA group when compared with the non-LGA group [mean amplitude of glycemic excursion (MAGE) LGA vs non-LGA 74.58 ± 16.83 vs 49.86 ± 12.83 mg/dL, p = 0.002; standard deviation (SD) LGA vs non-LGA 30.19 ± 9.69 vs 20.10 ± 5.97 mg/dL, p = 0.001]. Variables of GV: MAGE and SD were significantly high in the LGA group (p < 0.001). Time below range (TBR) and time above range (TAR) were also significantly altered in the LGA group (p < 0.001). CONCLUSION: High GV and time in the range are the important parameters that can be well correlated with LGA babies in gestational diabetic pregnancies on pharmacotherapy. An FGM is a good monitoring device to measure this parameter and can be used as an adjunct to modify measures to control the glucose values within range in these pregnancies.

Identification of plastic rice in adulterated raw and cooked rice.

In the present study, attempts have been made to identify the presence of plastic rice in adulterated raw and cooked rice by comparing the compositional and morphological properties of fake rice and real rice using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) techniques. Various rice samples from the national capital region of India were studied for their compositional and morphological properties. The surface morphology of real rice and plastic rice was analyzed using scanning electron microscopy. Results suggest that plastic rice used as an adulterant in raw or cooked rice is made up of polystyrene, which is a well-known toxic chemical entity. The studies suggest that these techniques can be used as a scientific tool to detect and identify the presence of plastic rice in adulterated raw and cooked rice.

Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review.

Coronavirus disease-2019 (COVID-19) is an extremely contagious illness caused by the SARS-CoV-2 virus and has been declared a pandemic by the World Health Organization (WHO). There are currently no particular treatments, however, nebulized heparin has been offered as a viable therapy. The purpose of this systematic review is to assess the efficacy of nebulized heparin in COVID-19 patients with respiratory symptoms. Methods: Relevant studies were identified through a systematic search of the PubMed, Medline, Embase, Cochrane Library and Web of Science, and Scopus databases. The search terms included "nebulized heparin," "COVID-19," and "SARS-CoV-2." Studies that evaluated the use of nebulized heparin in COVID-19 patients with respiratory symptoms were included. The rest of the studies along with those that were not published in English were excluded. The systematic review was registered under PROSPERO-CRD42023413927. Observations: Five studies have been included in this systematic review. Case reports, case series, observational studies, and randomized controlled trial (RCT) comprised the studies. The patient sample sizes ranged from 2 to 98. The studies assessed the efficacy of nebulized heparin in COVID-19 patients with variable disease severity. The evaluated outcomes included mortality, hospital stay duration, oxygen requirements, and laboratory parameters. Conclusion: Based on the clinical studies included in this systematic review, nebulized heparin may be useful in the management of COVID-19. Oxygen saturation was greater, inflammatory indicators were lower, and hospital stays were shorter in these patients. However, the studies had limitations, including inconsistent sample sizes, varying dosages of nebulized heparin, and no control groups. Nebulized heparin in patients with COVID-19 needs to be studied further to determine its safety and effectiveness. How to cite this article: Gupta B, Ahluwalia P, Gupta N, Gupta A. Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review. Indian J Crit Care Med 2023;27(8):572-579.

Nebulized Heparin to Reduce COVID-19-induced Acute Lung Injury: A Prospective Observational Study.

Background: High mortality due to COVID-19 disease has been a serious concern, a few of the causes being disseminated intravascular coagulation (DIC) and venous thromboembolism. Considering this, some experts have used heparin. However, its role still needs to be validated. Materials and methods: This study predicts the role of nebulized heparin in decreasing the severity of lung injury caused by COVID-19. Thirty patients admitted with COVID-19 acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) of All India Institute of Medical Sciences, Rishikesh, were included in this study, which was conducted over a period of 3 months. Patients were nebulized with 2 mL of heparin 5,000 units/mL IV formulation diluted with 3 mL of 0.9% sodium chloride, every 6 hours for a total duration of 7 days. Improvement in oxygenation (ratio of partial pressure of oxygen in blood and fraction of inspired oxygen delivered, pO2/FiO2 ratio) was calculated as the primary outcome. Other parameters like effect on inflammatory markers (neutrophil-lymphocyte ratio, total leukocyte count, interleukin (IL-6), and D-dimer values), time to liberate from mechanical ventilation, and hospital stay were calculated as secondary outcomes. Results: In our study population, the mean age was 54.5 years and the majority of patients were males (79.0%). All patients received prone ventilation and none of them required tracheostomy. However, 5 patients (16.6%) succumbed to illness. After nebulization with unfractionated heparin, no statistically significant difference was seen in the neutrophil-lymphocyte ratio (mean = 6.87, p = 0.318) and interleukin (IL-6) levels (mean = 62.85, p = 0.6) over 7 days. Similarly, the D-dimer level also had no statistically significant change (mean = 1853.73 p = 0.570). However, there was a statistically significant improvement in oxygenation (pO2/FiO2 ratio) over 7 days (mean = 184.96, p = 0.00). Similarly, there was a significant improvement in PaO2 (84.17 ± 33.82) and SO2 (92.30 ± 3.49). Although, no significant changes were seen in the partial pressure of carbon dioxide on nebulized heparin administration. Conclusion: Administration of nebulized heparin in COVID-19 pneumonia with mild ARDS may improve oxygenation and result in the improvement of inflammatory markers with variable sensitivity and specificity. How to cite this article: Gupta B, Chandrakar S, Gupta N, Jain G. Nebulized Heparin to Reduce COVID-19-induced Acute Lung Injury: A Prospective Observational Study. Indian J Crit Care Med 2023;27(3): 222-224.

A Nationwide Survey on the Practice of End-of-life Care Issues in Critical Care Units in India.

Background: End-of-life (EOL) care is the care of terminally ill patients who are nearing their end. It includes important components like palliative care, supportive care, hospice care, patient's right to choose, and choice of medical intervention, including continuation of routine medical interventions. The aim of this survey was to assess the practices of EOL care in various critical care units in India. Methods: The participants included clinicians involved in EOL care of patients with advanced diseases in different hospital across India. We sent blast emails and posted links on social media for inviting participants to take the survey. Study data were collected and managed by using Google Forms. The collected information was automatically entered into a spread sheet and stored in a secure database. Results: In total, 91 clinicians took the survey. The years of experience, practice area, and setting had significant effect on the palliative care, terminal strategy, and prognostication in terminally ill patients (p < 0.05). Statistical analysis was done using software STATA. Descriptive statistics were performed, and results were presented as number (percentage). Conclusion: The years of work experience, the practice area, and the practice setting have a strong impact on EOL care management of terminally ill patients. There are a lot of gaps in providing EOL care for these patients. Many reforms are needed in the Indian health care system to make EOL care better. How to cite this article: Kapoor I, Prabhakar H, Mahajan C, Zirpe KG, Tripathy S, Wanchoo J, et al. A Nationwide Survey on the Practice of End-of-life Care Issues in Critical Care Units in India. Indian J Crit Care Med 2023;27(5):305-314.

Integrating the Various 'M' Principles of Management into the Establishment of a Palliative Care Service.

When it comes to medical caregiving, palliative care (PC) is a multidisciplinary strategy that has the goal of improving quality of life while also alleviating suffering. The doctrine of care for persons with life threatening or debilitating illnesses, as well as bereavement assistance for their families, is based on an organised, highly structured system of providing care to people with life-threatening or debilitating illnesses for the course of their lives. A coordinated continuum of care must be guaranteed throughout multiple healthcare settings, including the hospital, the patient's home, the hospice and long-term care institutions. It is essential for patients and clinicians to communicate and make decisions jointly. It is the goal of PC to provide pain relief and emotional and spiritual support to patients and the people who care for them. The best way to ensure the plan's success is to have an interdisciplinary multidimensional team of medical professionals, nurses, counsellors, social workers and volunteers coordinate it. Due to the alarming projections of cancer incidence over the next few years, a lack of hospices in developing countries, inadequate inclusion of PC, high out-of-pocket expenses for cancer treatment and the resulting financial burden on families, there is a critical need for PC and cancer hospices. To establish PC services, we stress the importance of the various M principles of management, which are divided into the following categories: Mission, Medium (setting), Men, Material including medications and Machines, Methods, Money and Management. These principles are discussed in greater detail later in this short communication. We believe that if we follow these principles, we will be able to establish PC services ranging from home-based care to the provision of care in tertiary care centres.

Surface-Engineered Mucus Penetrating Nucleic Acid Delivery Systems with Cell Penetrating Peptides for the Lungs.

Nucleic acids, both DNA and small RNAs, have emerged as potential therapeutics for the treatment of various lung disorders. However, delivery of nucleic acids to the lungs is challenging due to the barrier property imposed by mucus, which is further reinforced in disease conditions such as chronic obstructive pulmonary disease and asthma. The presence of negatively charged mucins imparts the electrostatic barrier property, and the mesh network structure of mucus provides steric hindrance to the delivery system. To overcome this, the delivery system either needs to be muco-inert with a low positive charge such that the interactions with mucus are minimized or should have the ability to transiently dismantle the mucus structure for effective penetration. We have developed a mucus penetrating system for the delivery of both small RNA and plasmid DNA independently. The nucleic acid core consists of a nucleic acid (pDNA/siRNA) and a cationic/amphipathic cell penetrating peptide. The mucus penetrating coating consists of the hydrophilic biopolymer chondroitin sulfate A (CS-A) conjugated with a mucolytic agent, mannitol. We hypothesize that the hydrophilic coating of CS-A would reduce the surface charge and decrease the interaction with negatively charged mucins, while the conjugated mannitol residues would disrupt the mucin-mucin interaction or decrease the viscosity of mucus by increasing the influx of water into the mucus. Our results indicate that CS-A-mannitol-coated nanocomplexes possess reduced surface charge, reduced viscosity of artificial mucus, and increased diffusion in mucin suspension as well as increased penetration through the artificial mucus layer as compared to the non-coated ones. Further, the coated nanocomplexes showed low cytotoxicity as well as higher transfection in A-549 and BEAS-2B cells as compared to the non-coated ones.

Non-invasive diagnostic potential of microRNA-203 in liquid biopsy of urothelial carcinoma of bladder.

Increased CD44 antigen activity has been reported in recurrent cases of UBC. To date, no reliable biomarker is available with high significance and specificity for non-invasive detection of UBC. This study aimed to identify a CD44-linked microRNAs (miRNAs) (miR-9, miR-34a, miR-203) for non-invasive diagnosis of bladder cancer from other urinary tract malignancies. The expression of CD44-linked miRNAs was examined in serum, urine, and tissue specimens of Indian UBC patients (N = 25). For this purpose, healthy subjects (N = 25) and benign prostatic hyperplasia (BPH) (N = 10) patients were taken as controls. The relative expression of miRNAs was analyzed in serum, urine, and tissue samples using real-time quantitative reverse transcription PCR (qRT-PCR). The diagnostic potential of these miRNAs was accessed by plotting ROC curve. Increased miR-9 expression was observed in serum of UBC patients than healthy and BPH controls. In UBC patients, miR-34a expression was lower than healthy controls but non-significant as compared to BPH. miR-203 expression was considerably higher in serum of UBC patients but non-significant as compared to BPH controls. miR-203 was found to be considerably higher in urine samples from UBC patients as compared to BPH and healthy controls. The diagnostic potential of these miRNAs was evaluated using the ROC curve. Higher miR-203 levels in the urine of Indian UBC patients demonstrate its non-invasive diagnostic ability out of the three miRNAs studied. Our results characterize the non-invasive diagnostic potential of CD44-linked miR-203 in the urine of Indian UBC patients, which could be utilized in clinical settings in future after validation in larger patient cohort.

Autophagy-associated HMGB-1 as a novel potential circulating non-invasive diagnostic marker for detection of Urothelial Carcinoma of Bladder.

Urothelial carcinoma of bladder (UBC), a highly prevalent urological malignancy associated with high mortality and recurrence rate. Standard diagnostic method currently being used is cystoscopy but its invasive nature and low sensitivity stresses for identifying predictive diagnostic marker. Autophagy, a cellular homeostasis maintaining process, is usually dysregulated in cancer and its role is still enigmatic in UBC. In this study, 30 UBC patients and healthy controls were enrolled. Histopathologically confirmed tumor and adjacent normal tissue were acquired from patients. Molecular expression and tissue localization of autophagy-associated molecules (HMGB-1, RAGE, beclin, LC-3, and p62) were investigated. Serum HMGB-1 concentration was measured in UBC patients and healthy controls. ROC curves were plotted to evaluate diagnostic potential. Transcript, protein, and IHC expression of HMGB-1, RAGE, beclin, and LC-3 displayed upregulated expression, while p62 was downregulated in bladder tumor tissue. Serum HMGB-1 levels were elevated in UBC patients. Transcript and circulatory levels of HMGB-1 showed positive correlation and displayed a positive trend with disease severity. Upon comparison with clinicopathological parameters, HMGB-1 emerged as molecule of statistical significance to exhibit association. HMGB-1 exhibited optimum sensitivity and specificity in serum. The positive correlation between tissue and serum levels of HMGB-1 showcases serum as a representation of in situ scenario, suggesting its clinical applicability for non-invasive testing. Moreover, optimum sensitivity and specificity displayed by HMGB-1 along with significant association with clinicopathological parameters makes it a potential candidate to be used as diagnostic marker for early detection of UBC but requires further validation in larger cohort.

Health-related quality of life among breast cancer patients in India.

PURPOSE: This study evaluated the health-related quality of life (HRQoL) among breast cancer patients during various phases of treatment and with different treatment modalities, which helps in monitoring treatment outcomes, assessing the well-being of patients, and conducting health technology assessments. METHODS: A total of 534 interviews were conducted among the patients of breast cancer recruited at different stages of disease and with different treatment modalities. HRQoL was determined using EuroQoL five dimensions questionnaire with five levels (EQ-5D-5L), EuroQoL Visual Analogue Scale (EQ VAS), and the EORTC QLQ-BR23 instrument. The utility values were determined based on the Indian EQ-5D-5L value set. The socio-demographic and clinico-therapeutic determinants of HRQoL were evaluated using multiple linear regression. RESULTS: The mean utility value of breast cancer patients was 0.602 (SD = 0.311) and mean EQ VAS score was 75 (SD = 12.3). The mean utility value at diagnosis was 0.628, whereas utility value was 0.55, 0.595, and 0.64 for post-surgery, post-chemotherapy, and post-radiotherapy treatment groups, respectively. The most frequently reported problem was pain/discomfort (in 84.3% patients), followed by anxiety/depression (83.5%). On EORTC QLQ-BR23, the maximum symptom scale scores for systemic therapy side effects were reported in the post chemotherapy group. The body image score and future perspective score were better in patients undergoing breast conservative surgery (BCS) compared to patients undergoing modified radical mastectomy. Age, education, and employment status of the patient, type of treatment modality, and use of taxanes are the determinants of HRQoL in breast cancer patients. CONCLUSION: Clinical interventions should focus upon management of pain and anxiety. BCS should be offered to all eligible patients as it is associated with better HRQoL. Addressing the factors that independently affect the HRQoL will help in improving the treatment compliance and outcomes.

Intensity of occupational physical activity in blue-collar workers: do self-reported rating and device-worn measurements agree?

PURPOSE: High intensity occupational physical activity (OPA) seem to aggravate health and increase risk of sick leave and early retirement. Most intensity of OPA monitoring has been self-reported, e.g. by rating of perceived exertion (RPE). However, no studies have investigated the precision and risk of bias in RPE reporting during free-living OPA. This study investigated the agreement between OPA intensity in percentage of the heart rate reserve (%HRR) estimated from RPE and device-measured heart rate (HR), and potential bias factors on this agreement. METHODS: The CR10 scale measured RPE at work. The Actiheart monitor measured HR during 24-h a day for 2-4 days. Both RPE and device-worn HR were converted to %HRR. The difference between both %HRR and their limits of agreement was determined in a Bland Altman plot. To detect bias factors, the difference between both %HRR was regressed on age, sex, cardiorespiratory fitness, occupational lifting, medication, consequences of musculoskeletal disorders and the interactions between these factors with device-work %HRR. RESULTS: Six hundred and twenty-three participants were included in the analysis. Mean difference between RPE-based and device-worn %HRR was 54.6% (SD 19.5). The limits of agreement were wide (11.6-90.1%HRR). Age (0.48%HRR, 95% CI 0.18-0.79) occupational lifting (9.84%HRR, 95% CI 3.85-15.83) and cardiorespiratory fitness (0.41%HRR, 95% CI 0.03-0.79) significantly biased the agreement between the estimations of OPA intensity. CONCLUSION: RPE overestimated OPA intensity, and was biased by several factors. Device-worn %HRR should be preferred when evaluating OPA intensity among workers with physically demanding jobs.

Physical Activity Advice for Prevention and Rehabilitation of Low Back Pain- Same or Different? A Study on Device-Measured Physical Activity and Register-Based Sickness Absence.

Purpose We lack knowledge on whether the advice of "being physically active" should be the same for prevention and rehabilitation of low back pain (LBP). Sickness absence is a key outcome for LBP prevention and rehabilitation. We investigated the associations between physical activity and long-term sickness absence (LTSA) among employees with and without LBP. Methods Between 2011 and 2013, 925 Danish employees wore a Actigraph GTX3 accelerometer for 1-5 workdays to measure physical activity and reported LBP in past 7 days. Employees were followed for 4 years to determine their first register-based LTSA event (≥ 6 consecutive weeks). Results Among employees with LBP, increasing moderate-to-vigorous-intensity physical activity at work by 20 min and decreasing the remaining behaviors at work (ie., sitting, standing and light-intensity activity) by 20 min was associated with 38% (95% CI 17%; 63%) higher LTSA risk. Increasing light-intensity activity at work by 20 min and decreasing 20 min from the remaining behaviors was associated with 18% (95% CI 4%; 30%) lower risk. During leisure, increasing moderate-to-vigorous-intensity activity by 20 min or standing by 40 min was associated with 26% (95% CI 3%; 43%) lower and 37% (95% CI 0%; 87%) higher risk, respectively. Among employees without LBP, we found no such associations. Conclusions The physical activity advice ought to be different for LBP prevention and rehabilitation to reduce LTSA risk, and specified by domain and activity intensity. At work, employees with LBP should be advised to spend time on light-intensity physical activity and limit their time on moderate-to-vigorous-intensity physical activity. During leisure, employees should spend time on moderate-to-vigorous-intensity physical activity.

Evaluation of the Antifungal, Antioxidant, and Anti-Diabetic Potential of the Essential Oil of Curcuma longa Leaves from the North-Western Himalayas by In Vitro and In Silico Analysis.

Essential oils (EOs) have gained immense popularity due to considerable interest in the health, food, and pharmaceutical industries. The present study aimed to evaluate the antimicrobial and antioxidant activity and the anti-diabetic potential of Curcuma longa leaf (CLO) essential oil. Further, major phytocompounds of CLO were analyzed for their in-silico interactions with antifungal, antioxidant, and anti-diabetic proteins. CLO was found to have a strong antifungal activity against the tested Candida species with zone of inhibition (ZOI)-11.5 ± 0.71 mm to 13 ± 1.41 mm and minimum inhibitory concentration (MIC) was 0.63%. CLO also showed antioxidant activity, with IC50 values of 5.85 ± 1.61 µg/mL using 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and 32.92 ± 0.64 µM using ferric reducing antioxidant power (FRAP) assay. CLO also showed anti-diabetic activity with an IC50 of 43.06 ± 1.24 µg/mL as compared to metformin (half maximal inhibitory concentration, IC50-16.503 ± 0.66 µg/mL). Gas chromatography-mass spectrometry (GC-MS) analysis of CLO showed the presence of (-)-zingiberene (17.84%); 3,7-cyclodecadien-1-one, 3,7-dimethyl-10-(1-methylethylidene)-(15.31%); cyclohexene, 4-methyl-3-(1-methylethylidene) (12.47%); and (+)-4-Carene (11.89%) as major phytocompounds. Molecular docking of these compounds with antifungal proteins (cytochrome P450 14 alpha-sterol demethylase, PDB ID: 1EA1, and N-myristoyl transferase, PDB ID: 1IYL), antioxidant (human peroxiredoxin 5, PDB ID: 1HD2), and anti-diabetic proteins (human pancreatic alpha-amylase, PDB ID: 1HNY) showed strong binding of 3,7-cyclodecadien-1-one with all the selected protein targets. Furthermore, molecular dynamics (MD) simulations for a 100 ns time scale revealed that most of the key contacts of target proteins were retained throughout the simulation trajectories. Binding free energy calculations using molecular mechanics generalized born surface area (MM/GBSA), and drug-likeness and toxicity analysis also proved the potential for 3,7-cyclodecadien-1-one, 3,7-dimethyl-10-(1-methylethylidene) to replace toxic synthetic drugs and act as natural antioxidants.