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Animal diseases are a major concern to animal welfare, human health and the global economy. Early detection, prevention and control of these animal diseases are crucial to ensure sustainability of livestock sector, to reduce farm losses and protecting public health. Points of care (POC) devices are small, portable instruments that provide rapid results thus reduce the risk of disease transmission and enable early intervention. CRISPR based diagnostics offer more accurate and efficient solution for monitoring animal health due to their quick response, can detect very low level of pathogenic organism or disease markers and specificity. These diagnostics are particularly useful in the in area with limited resources or access to common diagnostic methods, especially in developing countries. The ability of electrochemical sensors to detect accurately very low analyte concentration makes them suitable for POC diagnostics and field application. CRISPR base electrochemical biosensors show great potential in revolutionizing disease detection and diagnosis including animal health. However, challenges, such as achieving selectivity and sensitivity, need to be addressed to enhance the competitiveness of these biosensors. Currently, most CRISPR based bioassay research focuses on nucleic acid target detection, but researchers exploring to monitor small organic/inorganic non-nucleic acid molecules like toxins and proteins. Emerging diagnostics would be centered on CRISPR-Cas system will offer great potential as an accurate, specific and effective means to identify microorganism, virus, toxins, small molecules, peptides and nucleic acid related to various animal health disorders particularly when integrated into electrochemical biosensing platform. • Overviewed the potential of electrochemical CRISPR based diagnostics for monitoring animal health. • Application of cis-clevage activity of CRISPR- Cas system for Electrochemical bioassay has reviewed. • Emphasized the application of Electrochemical CRISPR-Cas system in clinical diagnosis and food safety. [ABSTRACT FROM AUTHOR]

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Most of the long-term care for older adults with chronic or debilitating illnesses is provided by unpaid family members or informal caregivers. There is limited information on caregiver burden among caregivers of older patients with cancer in India. Hence, we assessed the prevalence and severity of caregiver burden among caregivers of older Indian patients with cancer. This was an observational study conducted at the geriatric oncology clinic at Tata Memorial Centre, Mumbai, India. Caregivers of patients aged 60 years and over with a diagnosis of cancer were assessed for caregiver burden using the Zarit Burden Interview. Descriptive statistics were used for demographic and clinical variables. Factors impacting caregiver burden were analyzed using multiple linear regression analysis. Caregiver burden was assessed among 127 caregivers of older Indian patients with cancer. The median patient age was 69 years (range 60–90). Most patients were men (75.6%). There were 33 female caregivers (26%), and 94 male caregivers (74%). The median caregiver burden score was 12 (IQR 6–20). Caregiver burden was "little/none" in 97 (76.4%), "mild-moderate" in 25 (19.7%), "moderate-severe" in four (3.1%) and "severe" in one (0.8%) of the caregivers assessed. On multivariate analysis, factors that significantly impacted caregiver burden scores were the presence of psychological issues in the patient and the caregiver's educational level. Caregiver burden was low among caregivers of older Indian patients with cancer seen at a single center. Caregivers of patients with psychological disorders, and those who had less schooling reported higher caregiver burden. [ABSTRACT FROM AUTHOR]

Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) are quick and easy-to-use screening tools, developed and validated in older patients living in North America and Europe for predicting abnormalities in the subsequent geriatric assessment. The applicability of these screening tools in older Indian patients with cancer is not known. An observational study in 308 Indian patients with cancer aged ≥60 years, who were evaluated in the Geriatric Oncology clinic at the Tata Memorial Hospital, Mumbai, India, between June 2018 and November 2020. Patients underwent the G8 and VES-13 screening tools followed by a geriatric assessment. The objectives were to determine the diagnostic accuracy of the G8/VES-13 screening tools to detect an abnormal geriatric assessment, to determine their association with the Eastern Cooperative Oncology Group (ECOG) performance status (PS)/Cancer Aging and Research Group (CARG) scores, to determine the optimal cut-off value on the G8 scale for older Indian patients with cancer, and to determine whether an abnormal G8/VES-13 score was associated with shorter survival. We also aimed to assess the utility of combining the G8 and VES-13 scores to predict for an abnormal geriatric assessment and poorer survival. The sensitivity and specificity of the G8 (cut-off, ≤14) score were 84.4% and 17.6%, respectively, whereas those for the VES-13 score (≥3) were 34.9% and 82.4%, respectively. The appropriate abnormal G8 cut-off score was noted to be 12. Abnormal G8 (≤14) and VES-13 scores were not associated with an abnormal subsequent geriatric assessment [ p = 0.736 (G8)], while abnormal G8 (≤14) scores did not predict for worse survival outcomes. Lowering the cut-off of the G8 score to <12 and/or combining an abnormal G8 (<12) with the VES-13 score were found to be associated with an abnormal subsequent geriatric assessment [ p < 0.001 (G8), p < 0.001(G8 + VES-13)] and predicted for worse survival. An abnormal G8 cut-off score < 12 is therefore appropriate in older Indian patients with cancer. G8 < 12 predicts for the presence of non-oncological vulnerabilities and shorter survival. Lowering the cutoff of G8 to 12translated to a 35% reduction in the number of patients undergoing a complete geriatric assessment. Combined with VES-13, the G8 can be reliably used to identify those patients who would benefit the most from a geriatric assessment and help in optimal resource utilization especially in busy Indian centers. [ABSTRACT FROM AUTHOR]

Frailty, characterized by ageing-related vulnerability, influences outcomes in older adults. Our study aimed to investigate the relationship between frailty and clinical outcomes in older Indian patients with cancer. Our observational single-centre study, conducted at Tata Memorial Hospital from February 2020 to July 2022, enrolled participants aged 60 years and above with cancer. Frailty was assessed using the Clinical Frailty Scale (CFS), G8, and Vulnerable Elders Survey (VES)-13. The primary objective was to explore the correlation between baseline frailty and overall survival. Statistical analyses include Kaplan-Meier, Cox proportional hazards, and Harrell's C test. A total of 1,177 patients (median age 68, 76.9% male) were evaluated in the geriatric oncology clinic. Common malignancies included lung (40.0%), gastrointestinal (35.8%), urological (11.9%), and head and neck (9.0%), with 56.5% having metastatic disease. Using CFS, G8, and VES-13 scales, 28.5%, 86.4%, and 38.0% were identified as frail, respectively. Median follow-up was 11.6 months, with 43.3% deaths. Patients fit on CFS (CFS 1–2) had a median survival of 28.02 months, pre-frail (CFS 3–4) 13.24 months, and frail (CFS ≥5) 7.79 months (p < 0.001). Abnormal G8 (≤14) and VES-13 (≥3) were associated with significantly lower median survival (p < 0.001). Multivariate analysis confirmed CFS's predictive power for mortality (p < 0.001), with hazard ratios [HRs] for pre-frail at 1.61(95% confidence interval [CI] 1.25 to 2.06) and frail at 2.31 (95%CI 1.74 to 3.05). G8 ≤ 14 had HR 2.00 (95%CI 1.42 to 2.83), and abnormal VES-13 had HR 1.36 (95%CI 1.11–1.67). In the likelihood ratio test, CFS significantly improved the model fit (p < 0.001). Harrell's C index for survival prediction was 0.62 for CFS, 0.54 for G8, and 0.58 for VES-13. In conclusion, our study highlights varying frailty prevalence and prognostic implications in older Indian patients with cancer, emphasizing the need for personalized care in oncology for this aging population. We would recommend using CFS as a tool to screen for frailty for older Indian patients with cancer. [ABSTRACT FROM AUTHOR]

• To recognize one of the major mechanical complications of late presenting acute myocardial infarction in the COVID-19 era. • To understand the role of mechanical circulatory support in acute myocardial infarction complicated by ventricular septal rupture • To outline the decision making process in the management of ventricular septal rupture with consequent cardiogenic shock. • To highlight the importance of a multidisciplinary cardiogenic shock team. The COVID 19 pandemic resulted in a total reduction in the number of hospitalizations for acute coronary syndromes. A consequence of the delay in coronary revascularization has been the resurgence of structural complications of myocardial infarctions. Ventricular septal rupture (VSR) complicating late presenting acute myocardial infarction (AMI) is associated with high mortality despite advances in both surgical repair and perioperative management. Current data suggests a declining mortality with delay in VSR repair; however, these patients may develop cardiogenic shock while waiting for surgery. Available options are limited for patients with VSR who develop right ventricular failure and cardiogenic shock. The survival rate is very low in patients with cardiogenic shock undergoing surgical or percutaneous VSR repair. In this study we present two late presenting ST elevation MI patients who were complicated by rapidly declining hemodynamics and impending organ failure. Both patients were bridged with venoarterial extracorporeal membrane oxygenation (ECMO) to cardiac transplant. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Outlines the management protocol that was utilised in OFD followed by aPDT in the treatment of chronic periodontitis. • Demonstrates the beneficial role of adjunctive aPDT in improving clinical parameters. • Demonstrates role of aPDT in providing a bactericidal effect after surgical periodontal therapy. • Indicates that the adjunctive use of aPDT can be achieved regardless of any post-operative complications. • Emphasizes on how aPDT can be beneficial in achieving uneventful and faster wound healing. Abstract Background Antimicrobial photodynamic therapy (aPDT) has proved to be an effective adjunctive modality with potential benefits in the management of chronic periodontitis. The combination of photothermal and photodynamic effects of Indocyanine green (ICG) dye, when it is photoactivated with a diode laser of 810 nm wavelength, has been well documented in literature. Aim This study was conducted to evaluate whether a single session of antimicrobial photodynamic therapy using ICG dye-810 nm diode laser combination can provide a substantial benefit when it is utilised as an adjunct to open flap debridement (OFD) in the management of chronic periodontitis. Materials and method Following thorough scaling and root planing, a comparative split mouth randomized controlled clinical trial was carried out on 20 recruited subjects who provided one test (OFD + aPDT) and one control site (OFD alone) each (total 40 treatment sites). The test group was subjected to a single episode of aPDT using ICG photosensitiser dye (1 mg/ml) activated with 810 nm diode laser. The laser was used in a continuous wave, non-contact mode at a power output of 100 mW applied for 30 s/spot (the total of 4 spots per tooth) and delivered by 400 μm fibre, to provide a fluence (energy density) value of 0.0125 J/cm² per spot and generate a total energy of 3 J. The following clinical parameters were assessed at baseline and 3 months: probing pocket depth (PPD), relative attachment level (RAL), relative gingival margin level (RGML), plaque index (PI), gingival index (GI), and gingival bleeding index (GBI). Intragroup and intergroup comparison was performed using paired t -test and independent samples t -test respectively. Results Intragroup comparison revealed a statistically significant improvement from baseline visit (p < 0.05). Intergroup comparison showed a statistically significant improvement in RAL, RGML and GI in the test group (p < 0.05). Conclusion Utilisation of ICG dye activated with 810 nm diode laser, which mediated aPDT, has demonstrated surplus clinical improvement following OFD in the management of chronic periodontitis. [ABSTRACT FROM AUTHOR]

The number of older patients with cancer is increasing exponentially worldwide, and a similar trend has also been noted in India. The Multidimensional Prognostic Index (MPI) strongly correlates the presence of individual comorbidities with mortality, and the Onco-MPI prognosticates patients accurately for overall mortality. However, limited studies have evaluated this index in patient populations beyond Italy. We evaluated the performance of the Onco-MPI index in predicting mortality in older Indian patients with cancer. This observational study was conducted between October 2019 and November 2021 in the Geriatric Oncology Clinic at Tata Memorial Hospital in Mumbai, India. The data of patients aged ≥60 years with solid tumors who underwent a comprehensive geriatric assessment was analysed. The study's primary aim was to calculate the Onco-MPI for patients in the study and correlate it with one-year mortality. A total of 576 patients aged ≥60 years were included in the study. The median age (range) of the population was 68 (60–90) years, and 429 (74.5%) were male. After a median follow-up of 19.2 months, 366 (63.7%) patients had died. The proportion of patients classified as low risk (0–0.46), moderate risk (0.47–0.63) and high risk (0.64–1.0) were 38% (219 patients), 37% (211 patients) and 25% (145 patients), respectively. There was a significant difference in one-year mortality rates between the low-risk patients compared to medium and high-risk patients (40.6% vs 53.1% vs 71.7%; p < 0.001). The current study validates the Onco-MPI as a predictive tool for estimating short-term mortality in older Indian patients with cancer. Further prospective studies need to build on this index to obtain a score with greater discrimination in the Indian population. [ABSTRACT FROM AUTHOR]

Abstract: Tuberculosis, the infection on the verge of eradication once, is now a great threat to mankind. Emergence of MDR and XDR-TB synergised with HIV and other immune-compressive diseases have increased the life threatening capacities of the disease. A small molecule has been identified here, which showed potent anti-tubercular activity. The identified hit compound has also been proved active against nearly 25 clinical isolates comparable with isoniazid. [Copyright &y& Elsevier]

Carbohydrate-binding proteins play vital roles in many important biological processes. The study of these protein-carbohydrate interactions, at residue level, is useful in treating many critical diseases. Analyzing the local sequential environments of the binding and non-binding regions to predict the protein-carbohydrate binding sites is one of the challenging problems in molecular and computational biology. Existing experimental methods for identifying protein-carbohydrate binding sites are laborious and expensive. Thus, prediction of such binding sites, directly from sequences, using computational methods, can be useful to fast annotate the binding sites and guide the experimental process. Because the number of carbohydrate-binding residues is significantly lower than the number of non-carbohydrate-binding residues, most of the methods developed for the prediction of protein-carbohydrate binding sites are biased towards over predicting the negative class (or non-carbohydrate-binding). Here, we propose a balanced predictor, called StackCBPred, which utilizes features, extracted from evolution-driven sequence profile, called the position-specific scoring matrix (PSSM) and several predicted structural properties of amino acids to effectively train a Stacking-based machine learning method for the accurate prediction of protein-carbohydrate binding sites (https://bmll.cs.uno.edu/). Image 1 • Stacking based Prediction of Protein-Carbohydrate Binding Sites from Sequence. • Designed and developed a balanced predictor. • Developed model outperformed state-of-the-art method. [ABSTRACT FROM AUTHOR]

Global guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. This was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. Between June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65–73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2–not reached) months, compared with 11.2 (10.1–12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41–0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41–0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0–1 group was 33.0 months (95% confidence interval 24.31–not reached) in the fit group versus 14.4 months (95% confidence interval 12.25–18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34–0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52–0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48–0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49–0.91, P = 0.011). The geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy. • Frailty in older cancer patients predicts lower survival, regardless of age, sex, primary tumour and metastatic status. • The results of the geriatric assessment were predictive even in patients with performance status 0 and 1. • Domains such as function, nutrition and cognition are predictors of survival. [ABSTRACT FROM AUTHOR]

Highly infectious and obvious withstand ability of Mycobacterium avium subspecies paratuberculosis (MAP) to environment as well as lack of on-site field diagnostic methods notably hampers the paratuberculosis (PTB) control. The existing intricacy, time-consuming and complicated diagnostic methods of PTB accentuate the development of novel and easy-to-perform on-site test. A gold nanoparticle (GNP) based lateral-flow assay (LFA) using MAP recombinant protein (44 kDa) has been developed for sensitive and specific detection of PTB in field conditions. The diagnostic sensitivity and specificity of the LFA for MAP specific antibodies was found approximately 84.2% and 83.3% in comparison to indirect enzyme-linked immunosorbent assay. Consequently, the newly developed GNP based LFA offers on-site and cost-effective method for the prompt diagnosis of PTB and precludes the time-consuming laboratory screening. • A gold nanoparticle based LFA using MAP recombinant protein (44 kDa) has been developed for sensitive and specific detection of PTB in field conditions. • The diagnostic sensitivity and specificity of the LFA for MAP specific antibodies was found approximately 84.2% and 83.3% in comparison to indirect ELISA. • MAP recombinant protein (44 kDa) based LFA would be an effective, easy to use, rapid, cost effective and on-site diagnostic test [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of novel pyridine-pyrimidine hybrid phosphonate derivatives were synthesized and characterized by spectral methods. • In vitro Enzyme assay and molecular docking study helped to predict the target enzyme. • Compounds 4f, 4j and 4o had shown good potential to inhibit Aurora kinase. • Compounds 4f, 4j and 4o exhibited relatively no cytotoxicity to normal LO2cells. For developing novel therapeutic agents with good anticancer activities, a series of novel pyridine-pyrimidine hybrid phosphonate derivatives 4(a–q) were synthesized by the Kabachnik-Fields method using CAN as catalyst. The compound 4o exhibited the most potent anticancer activity with an IC 50 value of 13.62 μM, 17.49 μM, 5.81 μM, 1.59 μM and 2.11 μM against selected cancer cell lines A549, Hep-G2, HeLa, MCF-7, and HL-60, respectively. Compound 4o displayed seven times more selectivity towards Hep-G2 cancer cell lines compared to the human normal hepatocyte cell line LO2 (IC 50 value 95.33 μM). Structure-Activity Relationship (SAR) studies were conducted on the variation in the aromatic ring (five-membered heterocyclic ring, six-membered heterocyclic ring) and the variation of substituents on the phenyl ring (electron donating groups, electron withdrawing groups). Furthermore, the mechanism of anticancer activity was clarified by further explorations in bioactivity by using in vitro aurora kinase inhibitory activity and molecular docking studies. The results showed that the compound 4o at IC 50 concentration demonstrated distinctive morphological changes such as cell detachment, cell wall deformation, cell shrinkage and reduced number of viable cells in cancer cell lines. Compound 4o induced early apoptosis and late apoptosis of 27.7% and 6.1% respectively. [ABSTRACT FROM AUTHOR]