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Background: Noise acts as a stressor and is reported to have impact on individual health depending on nature, type, intensity and perception. Modern medicine has no effective drugs or cure to prevent its consequences. Being an environmental stressor noise cannot be avoided; instead minimizing its exposure or consuming anti-stressor and adaptogens from plants can be considered. Objectives: The present study was carried out to evaluate the anti-stressor, adaptogen and immunostimulatory activity of Scoparia dulcis against noise-induced stress in Wistar rat models. Material and methods: Noise stress in rats was created by broadband white noise generator, 100 dB A/4 h daily/15 days and S. dulcis (200 mg/kg b.w.) was administered orally. 8 groups of rats were used consisting of 6 animals each; 4 groups for unimmunized and 4 groups for immunized. For immunization, sheep red blood cells (5 × 109 cells/ml) were injected intraperitoneally. Results: Sub-acute noise exposed rats showed a significant increase in corticosterone and IL-4 levels in both immunized and unimmunized rats whereas lymphocytes, antibody titration, soluble immune complex, IL-4 showed a marked increase with a significant decrease in IL-2, TNF-α, IFN-γ cytokines only in unimmunized rats. Immunized noise exposed rats presented increased leukocyte migration index and decreased foot pad thickness, IL-2, TNF-α, IFN-γ with no changes in the lymphocytes. Conclusion: S. dulcis (SD) has normalized and prevented the noise induced changes in cell-mediated and humoral immunity and it could be the presence of anti-stressor and immuno stimulant activity of the plant.

The present study focuses on the development of environmentally friendly bio-composite films using poly(lactic acid) (PLA) as a biopolymer matrix. This is achieved by incorporating amine functionalized green mesoporous silica (GMS) and employing a solution casting method for film fabrication. The motivation behind the work is to improve the compatibility between PLA and green mesoporous silica sourced from rice husk by functionalizing GMS with APTES (3-Aminopropyltriethoxy silane). The primary objective is to explore how the inclusion of GMS influences both the physicochemical attributes and the efficacy of active food packaging in PLA. The introduction of GMS to the PLA matrix not only improves the flexibility of PLA/GMS composite films but also enhances their overall performance. The reinforcement of GMS in the PLA matrix has also significantly contributed towards the reduction in oxygen transmittance rate and provided an anti-bacterial effect towards pathogen i.e. S. aureus and E. coli. The PLA/GMS composite films exhibit antioxidant activity acting as potential scavengers with around 78 % efficacy against DPPH (2,2-diphenyl-1-picrylhydrazyl). Consequently, the PLA/GMS composite formulation proposed in this study shows promising outcomes in terms of strength, flexibility, antioxidant properties, and antibacterial characteristics. Also, the PLA/GMS films extended the shelf life of cut apple samples for seven days., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Corneal transplantation serves as the standard clinical therapy for serious corneal disorders. However, rejection of grafts, significant expenditures, and most crucially, the global donor shortage, may affect the outcome. Recently, 3D bioprinting using biodegradable polymeric materials has become a suitable method for creating tissue replicas with identical architecture. One such most renowned material is GelMA, for its scaffold's three-dimensional structure, biocompatibility, robust mechanics, and favourable optical transmittance. However, GelMA's inadequate viscosity to print at body temperature with better form integrity remains an obstacle. The aim of this work is to create 3D printed GelMA/MC hydrogels for corneal stroma tissue engineering using MC's printability at room temperature and GelMA's irreversible photo cross-linking with UV irradiation. The print speed and pressure conditions for 3D GelMA/MC hydrogels were tuned. Thermal, morphological and physicochemical characteristics were studied for two distinct concentrations of GelMA/MC hydrogels. The hydrogels achieved a transparency of ~78 % (at 700 nm), which was on par with that of the normal cornea (80 %). The in vitro studies conducted using goat corneal stromal cells demonstrated the ability of both hydrogels to promote cell adhesion and proliferation. Expression of Vimentin and keratan sulphate validated the phenotype of keratocytes in the hydrogel. This 3D printed GelMA/MC hydrogel model mimics biophysical characteristics of the native corneal stroma, which may hold promise for clinical corneal stromal tissue engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: India is the world's most populous country, and overseas Indians the world's largest diaspora. Many of the more than 1·4 million UK-based Indians will be providing care at a distance for parents living in India. Globalisation has contributed to a shift in India from traditional joint family systems to more nuclear structures. We investigated how commonly Indian parents consider and use long-term care facilities and attitudes to their use., Methods: We did a secondary mixed-methods statistical analysis of the LASI (Longitudinal Ageing Study in India), a national, cross-sectional household survey administered in 2017-18 to 73 396 randomly selected adults aged 45 years and older in all Indian states and Union Territories (42 261 [58%] women, 31 135 [42%] men). We report the proportion and sociodemographic predictors of respondents' parent(s) living in a care home. We also did a secondary thematic analysis of the qualitative interviews from the Moving Pictures India Study, exploring attitudes to long-term care in 2022. These interviews included 19 carers (nine [47%] women; age range 31-79 years) for people with dementia and 25 professionals (19 [76%] women; age range 24-56 years) purposively selected for diversity from networks of the team based at a Bangalore hospital, India., Findings: 24 LASI participants reported that their parent was living in a long-term care facility (father [n=8], mother [n=15], both parents [n=1]). Although rare overall, use and consideration of use of long-term care were more frequently reported in urban areas (n=14, 58%), by people in middle-income quintiles (n=17, 71%) with higher levels of education (n=7, 29%), who rated their health as good or very good (n=15, 63%). The themes identified in qualitative interviews were the use of long-term care facilities as a last resort, social expectations, and limited availability of long-term care facilities., Interpretation: Although interviews were only conducted in Bangalore and respondents could misrepresent living arrangements due to ongoing societal stigma, the data show that very few people reside in old age homes across India, with strong preference towards intergenerational and community care. With the UK home to a growing diaspora of nuclear Indian families, our findings illustrate the contexts in which they provide care at a distance, navigating cross-cultural attitudes and social norms around long-term care., Funding: Alzheimer's Association US., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Poly(lactic acid) (PLA) based sustainable composites incorporated with cholecalciferol (Vitamin D3) (CC) at different concentrations (1, 3, 5 and 10 wt%) were prepared using solvent casting method. Performance analysis of PLA/CC composite films in terms of food packaging properties like thermal, optical, oxygen barrier, mechanical, anti-bacterial as well as anti-oxidant effect is carried out. The PLA/CC-5 composite showed complete blockage of UV-B light at 320 nm, which is known to significantly induce the photo-chemical degradation of polymers. The incorporation of CC in the PLA matrix brought in improvement in mechanical and oxygen barrier properties. The PLA composite films showed effective antibacterial activity against food borne bacteria (S. aureus and E. coli), in addition to excellent antioxidant activity. All these important traits exhibited by PLA/CC composite films suggest its potential for food packaging application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In the recent years, bone tissue engineering is regarded as the promising solution for treatment of bone defects which arises due to trauma, infection and surgical intervention. In view of this, several polymer or ceramic based constructs are envisaged for bone tissue engineering potential. However, scaffolds based on pure polymeric materials suffer from slow bioactivity characteristics. On the other hand, scaffolds based on ceramic materials do not offer sufficient strength for load bearing applications. In order to overcome these drawbacks, the current work aims to develop mixed matrix scaffolds based on poly (L-lactic acid)/mesoporous bioactive glass composite with the formulation of 30:70 weight ratio, which mimics the natural bone composition. In the current work, PLA/MBG (30:70) composite based bioink suitable for 3D bioprinting is indigenously developed and its rheological characteristics are evaluated. The 3D architecture for PLA/MBG composite scaffold is designed using Solidworks CAD 2015 and the scaffolds are fabricated using pneumatic based 3D bioprinting technology, which has not been documented earlier for this formulation in view of bone tissue engineering in the best of our knowledge. Followed by this, optimization of printing parameters in order to develop 3D PLA/MBG composite constructs with hierarchical pore architecture suitable for bone tissue engineering is performed. The SEM analysis confirmed that the pore size of the 3D printed PLA/MBG composite scaffolds falls in the range of 500-700 μm, which corresponds to the macroporous nature of the scaffolds useful for bone cell growth. The mechanical analysis confirmed the superior compressive modulus and yield strength for PLA/MBG composite scaffold in comparison with neat PLA. The in-vitro bioactivity assessment showed rapid apatite crystallization by attaining Ca/P ratio of 1.66 equivalent to natural bone mineral within 3rd day of SBF treatment for PLA/MBG composite scaffold, thus indicating the excellent bioactivity behaviour. The 3D bioprinted PLA/MBG composite scaffold showed promising response in terms of cell attachment and proliferation, mineralization as well as gene expression characteristics while assessed through of in-vitro biological assessment using MG-63 osteosarcoma cells. In this regard, the 3D bioprinted PLA/MBG scaffold could be applied as potential implant for bone tissue engineering application., (Copyright © 2022. Published by Elsevier B.V.)

Congenital Erythrocytosis (CE) can be primary or secondary due to the mutations in genes involved in the erythropoietin receptor and oxygen sensing pathway. In this study, 42 patients with 38 unrelated patients and one family (4 patients) who were JAK-2 mutation (both exon 12 and exon 14) negative with high haematocrit values were investigated. The Endogenous Erythroid colony (EEC) assay was performed in all patients, interestingly EEC colonies were high in EPAS1 and EPOR mutated patients compared to non-mutated patients. The sequence analysis of EPAS1 (exon 12), EPO-R (exon-8), VHL (exon-3), and EGLN1 (exon-1) genes in all these patients showed 19% of patients (8/42) had mutations, in exon12 of EPAS1 and exon 8 of EPO-R genes. Two novel missense mutations MW_600850:c.1183G>C, MW_600851:c.1028A>C in EPO-R gene were observed in the study group. One new MW_600849:c.1969C>T nonsense mutation and five MW_619914:c.1715A>G, MW_619915:c.1694G>T, MW_619916:c.1634T>C, MW_600852:c.1771C>G, MW_600848:c.1859G>A novel missense mutations were observed in the EPAS1 gene. Among them, 4 mutations p. (Gln572Arg), p. (Ser565Ile), p. (Ile545Thr), p. (Gln591Glu) in the ODD (Oxygen-dependent degradation) domain of HIF2α, all these variations contributed to the formation of non-functional HIF2α. No mutations were observed in VHL and EGLN1 genes. Using in silico analysis we observed that these mutations contributed to major conformational changes in the HIF2α protein making it non-functional. The mutations in the EPAS1 gene were heterozygous and show autosomal dominant inheritance patterns and we observed in one family. These novel mutations in the EPAS1 (75% (6/8)) and 25% (2/8) EPO-R genes correlating with EEC positivity were observed for the first time in India in CE patients., (Copyright © 2022. Published by Elsevier Masson SAS.)

Since the last few decades, the green synthesis of metal nanoparticles was one of the most thrust areas due to its widespread application. The study proposed using wasted and unusable Humulus lupulus (Hops) extract to synthesize silver nanoparticles for biomedical application. The environment around us gives us many scopes to use the waste from environmental sources and turn it into something valuable. The spent Hops extract was used to synthesize silver nanoparticles (AgNP@HOPs), and the synthesized product exhibited an excellent therapeutic effect in terms of anti-bacterial and anti-cancer agents. The synthesis was optimized considering different factors like time and the concentration of AgNO 3 . The silver nanoparticles were characterized in detail using different characterization techniques XRD, DLS, TEM, BET, XPS, Raman Spectroscopy, SEM, EDAX, AFM, which revealed the uniqueness of the silver nanoparticles. The average hydrodynamic size was found to be 92.42 ± 2.41 with a low polydispersity index. The presence of Ag-C and Ag-O bonds in the AgNP@HOPs indicated that it is composed of organo-silver and silver oxides. The nanoparticles were found to be spherical with an average size of 17.40 nm. The AgNPs were lethal to both E. coli and S. aureus with a MIC-50 of 201.881 μg/mL and 213.189 μg/mL, respectively. The AgNP@HOPs also exhibited an anti-cancer effect with an IC-50 of 147.175. The AgNP@HOPs exhibited less cytotoxicity and genotoxicity against normal cells and exhibited superior haemocompatibility (major criteria for drug selection). There are indeed various reports on the synthesis of silver nanoparticles, but this study proposes a green method for producing non-genotoxic, non-hemolytic organometallic silver nanoparticles using waste material with considerable therapeutic index from the environmental source with potential application in the medical industry. This work could be taken forward for in-vivo studies and for pre clinical studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Warm ischemia followed by blood reperfusion is associated with reduced myocardial contractility. Circulatory death (CD) hearts are maintained by machine perfusion (MP) with blood. However, the impact of MP with histidine-tryptophane-ketoglutarate (HTK) or novel HTK-N solution on reconditioning of CD-heart contractility is unknown., Methods: In a porcine model, native hearts were directly harvested (control), or CD was induced before harvesting, followed by left ventricular (LV) contractile assessment. In MP-groups, CD-hearts were maintained for 4 h by MP with blood (CD-B), cold oxygenated HTK (CD-HTK) or HTK-N (CD-HTK-N) before contractile evaluation (all groups n = 8). We performed immunohistochemistry of LV myocardial samples. We profiled myocardial expression of 84 oxidative stress-related genes and correlated the findings with myocardial contractility via a machine learning algorithm., Results: HTK-N improved end-systolic pressure (ESP=172±10 vs 132±5 mmHg, p = 0.02) and maximal slope of pressure increment (dp/dt max =2161±214 vs 1240±167 mmHg/s, p = 0.005) compared to CD, whereas CD-B failed to improve contractility. Dp/dt max (2161±214 vs 1177±156, p = 0.08) and maximal rate of pressure decrement (dp/dt min =-1501±228 vs -637±79, p = 0.005) were also superior in CD-HTK-N compared to CD-B. In CD-HTK-N, myocardial 4-hydroxynonenal (marker for oxidative stress; p<0.001), nitrotyrosine (marker for nitrosative stress; p = 0.004), poly(adenosine diphosphate-ribose)polymerase (marker for necrosis; p = 0.028) immunoreactivity and cell swelling (p = 0.008) were decreased compared to CD-B. Strong correlation of gene expression with ESP was identified for oxidative stress defense genes in CD-HTK-N., Conclusion: During harvesting procedure, MP with HTK-N reconditions CD-heart systolic and diastolic function by reducing oxidative and nitrosative stress and preventing cardiomyocytes from cell swelling and necrosis., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Trastuzumab-dkst is a biosimilar of trastuzumab. The phase 3 HERITAGE trial demonstrated equivalent overall response rate (ORR) with trastuzumab-dkst or originator trastuzumab at 24 weeks in patients with HER2-positive metastatic breast cancer receiving chemotherapy. We now present the correlation of ORR with progression-free survival (PFS) for maintenance monotherapy with trastuzumab-dkst vs trastuzumab at 48 weeks of treatment, and the safety, tolerability, and immunogenicity., Methods: HERITAGE is a multicenter, double-blind, randomized, parallel-group, phase 3 study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab in combination with taxane followed by continued monotherapy until disease progression. The analysis included PFS at 48 weeks to support the primary efficacy endpoint of ORR and safety, tolerability, and immunogenicity of trastuzumab-dkst vs trastuzumab as maintenance monotherapy., Results: Of 500 randomized patients, 342 entered the monotherapy phase; 214 patients received ≥48 weeks of treatment. There were no statistically significant differences between PFS, ORR, or interim overall survival at week 48 between trastuzumab-dkst and trastuzumab. Week 24 ORR was highly correlated with week 48 PFS (r b  = 0.75). Cumulative treatment-emergent adverse events (TEAEs) and serious AEs were similar in both groups, with few grade ≥3 TEAEs. Immunogenicity was low and similar in both groups at 48 weeks., Conclusion: The correlation between ORR and PFS supports the design of first-line metastatic trials assessing biosimilar trastuzumab. Overall, trastuzumab-dkst and trastuzumab were well tolerated with similar efficacy, including ORR and PFS, in combination with a taxane followed by monotherapy., Competing Interests: Declaration of competing interest HS Rugo has received travel, accommodations, and expenses from Amgen, Merck, Viatris Inc, Pfizer, and Puma Biotechnology and research funding (provided to the Regents of the University of California) from Eisai, Genentech/Roche, Lilly, Macrogenics, Merck, Novartis, OBI Pharma, Daiichi, Immunomedics, and Pfizer. EJ Pennella was a paid employee of Mylan Inc (now Viatris Inc) during the time of the study and may hold stock with the company. U Gopalakrishnan, HF Koch, and A Barve are paid employees of Viatris Inc and may hold stock with the company. M Hernandez-Bronchud has served as a consultant/advisory board member for Viatris Inc. S Loganathan, S Deodhar, and A Marwah are paid employees of Biocon Research Ltd and may hold stock with the company. C Akewanlop has received travel, accommodations, and expenses from Amgen, AstraZeneca, Roche, and Bristol-Myers Squibb. CF Waller is a consultant/advisory board member for Viatris Inc. J Herson, A Manikhas, JD Parra, MLT Abesamis-Tiambeng, I Vynnychenko, I Bondarenko, V Sriuranpong, S Roy, and EP Yanez Ruiz have nothing to disclose., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Support for caregivers of people with dementia has been identified as an action area in the Global Action Plan on the Public Health Response to Dementia 2017-2025 by the World Health Organization (WHO). As a step towards that, WHO developed iSupport - an online program to provide support and training for caregivers of people with dementia. To address the need of caregivers in India, the iSupport program was adapted to the Indian cultural setting. The process of adaptation consisted of four phases: (a) information gathering (review of literature and focus group discussions), (b) preliminary adaptation design (modifications using an adaptation guide), (c) preliminary adaptation tests (face-to-face interviews and online test run), and (d) adaptation refinement (final modifications to the intervention and study process). The initial adaptation was carried out by effecting changes in words, names, resources, caregiving scenarios and audio files to make the English version of iSupport suitable to the Indian cultural context. The results of the qualitative adaptation tests provided additional recommendations like changing the links to India specific websites, revising the eligibility criterion for caregiving duration, re-wording of e-mail texts, inclusion of a time estimate required to complete the assessments and decreasing the numbers of screens that the caregivers had to navigate in the program, which were incorporated in the final phase. Preliminary data showed that the caregivers who participated in the adaptation process found the changes acceptable. Translation of iSupport to different Indian languages could be undertaken after initial effectiveness of the program is established., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Currently, lactate (Lac) is used to evaluate machine perfusion (MP) of hearts, donated after circulatory death (DCD). We hypothesize that monitoring of myocardial microcirculation (mLDP) by Laser-Doppler-Perfusion is superior to Lac to evaluate perfusion and predict contractility. In a pig model, DCD-hearts were perfused 4 hours followed by reperfusion and left ventricular contractility measurement. Lac and mLDP were measured every 30 min in successfully (N = 9) and unsuccessfully (N = 7) maintained hearts. Successfully maintained hearts showed decreasing Lac (5.6 to 2.8 mmol/L) and slightly downregulated (92%) mLDP. In unsuccessfully maintained hearts Lac first decreased (5.1 to 3.8 mmol/L) followed by increase and mLDP dropped to 39%. In a single-variable regression only mLDP showed a significant r² for systolic (0.514, p = 0.045) and diastolic (0.501, p = 0.049) parameters. The combination of mLDP and Lac (r 2  = 0.876, p = 0.005) showed best results. mLDP seems to be superior to Lac to show perfusion disorders and predict DCD-heart contractility., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

For high precision laser surgery, noninvasive tool for prediction of laser ablation profile beforehand is imperative. The present study proposed a method to utilize nondestructive FTIR and Raman probes for predicting laser ablation profile overcoming the challenge of heterogeneity on individual target tissue. By ascribing the chemical heterogeneity of teeth drive their differential machining capability, the study establishes a correlation between the chemical composition and their ablation parameters (ω 0 ,D eff and F th ). The chemical composition of teeth was obtained by noninvasive tools (FTIR and Raman) in terms of absorption peak intensity. To further correlate with key laser ablation parameters, the laser irradiation study was carried out using 800 nm, 100 fs, Ti:Sapphire laser. The surface morphology of irradiated sample was measured by optical profiler. A strong correlation was observed between laser ablation parameters and peak intensity of phosphate group for both FTIR and Raman spectroscopy. The concentration of phosphate group shows a positive relationship to ablation threshold fluence, while the effective Gaussian beam radius and effective energy penetration depth show negative correlation. Both nondestructive probes show good linearity which enable us to extrapolate the key laser ablation parameters for predicting laser ablation profile on random dentin and enamel samples. The ablation profiles predicted based on both FTIR and Raman are well-matched in dentin, whereas it shows a slight deviation in enamel. The predicted profiles are consistent with experimental results at lower power whereas it shows a slight deviation at higher power due to screening effect. Thus, FTIR and Raman probes can be used to predict laser ablation profile nondestructively in real-time and obviate the need for trial runs. Furthermore, the present study has predicted the laser ablation rate and ablation efficiency for performing laser surgery in optimum laser processing conditions irrespective of teeth heterogeneity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hearts are usually procured from brain-dead (BD) donors. However, brain death may induce hemodynamic instability, which may contribute to posttransplant graft dysfunction. We hypothesized that BD-donor heart preservation with a conditioned medium (CM) from mesenchymal stem cells (MSCs) would improve graft function after transplantation. Additionally, we explored the PI3K pathway's potential role. Rat MSCs-derived CM was used for conservation purposes. Donor rats were either exposed to sham operation or brain death by inflation of a subdural balloon-catheter for 5.5 hours. Then, the hearts were explanted, stored in cardioplegic solution-supplemented with either a medium vehicle (BD and sham), CM (BD + CM), or LY294002, an inhibitor of PI3K (BD + CM + LY), and finally transplanted. Systolic performance and relaxation parameters were significantly reduced in BD-donors compared to sham. After transplantation, systolic and diastolic functions were significantly decreased, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and endonuclease G positive cells were increased in the BD-group compared to sham. Preservation of BD-donor hearts with CM resulted in a recovery of systolic graft function (dP/dt max : BD + CM: 3148 ± 178 vs BD: 2192 ± 94 mm Hg/s at 110 µL, P < .05) and reduced apoptosis. LY294002 partially lowered graft protection afforded by CM in the BD group. Our data suggest that PI3K/Akt pathway is not the primary mechanism of action of CM in improving posttransplant cardiac contractility and preventing caspase-independent apoptosis., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

The major source of heart transplantation comes from brain-dead (BD) donors. However, brain death and myocardial ischemia/reperfusion injury during transplantation may lead to cardiac dysfunction and hemodynamic instability. A previous work demonstrated that pre-treatment of BD donors with dopamine improved the graft survival of heart allograft in recipient after transplantation. However, low-dose dopamine treatment might result in tachycardia and hypertension. Our previous experimental study showed that pre-treatment of BD donor rats with the dopamine derivate N-octanoyl dopamine (NOD), devoid of any hemodynamic effects, improved graft function after transplantation. Herein, we hypothesized that NOD confers superior myocardial protection than dopamine, in terms of graft function. Male Lewis donor rats were either subjected to sham-operation or brain death via a subdurally placed balloon followed by 5.5 h monitoring. Then, the hearts were explanted and heterotopically transplanted into Lewis recipient rats. Shortly before the onset of reperfusion, continuous intravenous infusion of either NOD (14.7 μg/kg/min, BD + NOD group, n = 9), dopamine (10 μg/kg/min, BD + Dopamine group, n = 8) or physiological saline vehicle (sham, n = 9 and BD group, n = 9) were administered to the recipient rats. In vivo left-ventricular (LV) graft function was evaluated after 1.5 h reperfusion. Additionally, immunohistochemical detection of 4-hydroxy-2-nonenal (HNE, an indicator of oxidative stress) and nitrotyrosine (a nitro-oxidative stress marker), was performed. After heart transplantation, systolic and diastolic functions were significantly decreased in the BD group compared to sham. Treatment with NOD but not dopamine, resulted in better LV graft systolic functional recovery (LV systolic pressure BD + NOD 90 ± 8 vs BD + Dopamine 66 ± 5 vs BD 65 ± 4 mmHg; maximum rate of rise of LV pressure dP/dt max BD + NOD 2686 ± 225 vs BD + Dopamine 2243 ± 70 vs BD 1999 ± 147 mmHg/s, at an intraventricular volume of 140 μl, p < 0.05) and myocardial work compared to BD group. The re-beating time (time to restoration of heartbeat) was significantly shorter in BD + NOD group than that of BD hearts (32 ± 4 s vs. 48 ± 6 s, p < 0.05), Dopamine treatment had no impact on all of these parameters. Furthermore, NOD as well as dopamine decreased HNE and nitrotyrosine immunoreactivity to the same level. NOD is superior to dopamine in terms of protecting LV graft contractile function when administered to the heart transplant recipients from BD donors., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Pressure ulcers pose an important quality-of-care challenge in nursing homes, with serious consequences for residents' health. We assessed the scalability of the On-Time Pressure Ulcer Prevention (On-Time) intervention strategy, developed by the Agency for Healthcare Research & Quality, in nursing homes nationwide., Intervention: On-Time uses electronic health record reports to identify changes in resident pressure ulcer risk and facilitate multidisciplinary input into clinical decision making., Objective: To assess the scalability and impact of On-Time on pressure ulcer incidence in nursing homes., Design: We used quasi-experimental methods, employing a difference-in-differences design, to compare the pre-post trends in pressure ulcer incidence in the treatment and comparison homes., Setting and Participants: The study population included long-stay residents at high risk for developing pressure ulcers in 47 nursing homes and matched comparison homes in 17 states., Measures: Stage 2 to 4 pressure ulcer incidence among long-stay residents who met the criteria for high risk, identified using an algorithm adapted from the Minimum Data Set 3.0 Percent of High-Risk Residents with Pressure Ulcers (Long Stay) measure., Results: The overall decline in pressure ulcer rates for treatment relative to matched comparison homes was statistically insignificant (P > .05). A subgroup of heterogeneous homes experienced a statistically significant decline of 3.24 percentage points (61.0% relative decrease) in pressure ulcer rates relative to matched comparison homes, but no uniting characteristic common across homes readily explained their success., Conclusions/implications: Scalability of future health information technology-based quality improvement interventions in nursing home settings requires nuanced implementation support, particularly around electronic health record report accessibility and accuracy., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Heart transplantation is the definitive treatment for end-stage heart failure. A shortage of donor hearts forced transplant programs to accept older donors and longer ischemic times. Previous studies have suggested that administration of mesenchymal stem cells (MSCs) or their conditioned medium (CM) protects the heart against ischemia/reperfusion injury (IRI). We hypothesized that the preservation of donor hearts with a CM would protect the graft from IRI after prolonged storage in 15-month-old rats and investigated mRNA changes attributable to CM., Methods: Rat MSCs were isolated and cultured. The CM was used and characterized by a 90-antibody array, revealing the presence of 28 factors involved in apoptosis, inflammation, and oxidative stress. Hearts from 15-month-old donor rats were explanted and continuously perfused for 5 hours with oxygenated, 4°C cardioplegic solution, and supplemented with either regular cell culture medium (control group) or CM. The hearts were then heterotopically transplanted. We evaluated in-vivo left ventricular graft function 1.5 hours after transplantation and the myocardial expression of 120 genes using polymerase chain reaction arrays., Results: Systolic contractility and relaxation parameters were significantly reduced in 15-month-old rats compared with the young rats. After transplantation, systolic function (dP/dt max : 1,197 ± 94 vs 1,825 ± 279 mm Hg/s at 140 µl; p < 0.05) and diastolic function (dP/dt min : 737 ± 168 vs 1,200 ± 166 mm Hg/s at 140 µl, p < 0.05) were significantly improved in the CM group compared with controls. Among the genes surveyed, the expressions of 66 were altered. Genes of pro-inflammatory cytokines and interleukins were down-regulated, whereas expression of the anti-oxidant gene superoxide dismutase-2 was up-regulated in the CM-treated grafts compared with the control group grafts., Conclusions: Perfusion of donor hearts with CM protects against myocardial IRI in 15-month-old rats., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This paper mainly deals with the isovaleraldehyde degradation with the help of a nonthermal plasma surface discharge (NPSD) coupled with photocatalysis. The efficiency of NPSD reactor, for gas treatment, was studied for different binary mixtures: (1) mixture of aldehydes (Isovaleraldehyde and Butyraldehyde) and (2) mixture of aldehyde and amine (Isovaleraldehyde and Trimethylamine). A planar continuous reactor is used to investigate the effect of addition of another pollutant on the performance of oxidation process. A synergetic effect was observed by combining NPSD and photocatalysis for the degradation of mixture of pollutants. In addition, combined NPSD/photocatalysis has significantly enhanced the CO 2 selectivity, as compared to NPSD alone. This is attributed to the formation of more reactive species due to the presence of TiO 2 in the plasma discharge zone. Moreover, ozone and UV light on TiO 2 , produced by plasma, have activated the surface leading to enhanced mineralization. In addition, the byproducts of each binary mixture were identified and evaluated., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Ischaemia reperfusion (IR) injury occurs during vascular graft harvesting and implantation during vascular/cardiac surgery. Elevated intracellular cyclic guanosine monophosphate (cGMP) levels contribute to an effective endothelial protection in different pathophysiological conditions. The hypothesis that the phosphodiesterase-5 inhibitor vardenafil would protect vascular grafts against IR injury by upregulating the nitric oxide-cGMP pathway in the vessel wall of the bypass graft was investigated., Methods: Lewis rats (n = 6-7/group) were divided into Group 1, control; Group 2, donor rats received intravenous saline; Group 3, received intravenous vardenafil (30 μg/kg) 2 h before explantation. Whereas aortic arches of Group 1 were immediately mounted in an organ bath, aortic segments of Groups 2 and 3 were stored for 2 h in saline and transplanted into the abdominal aorta of the recipient. Two hours after transplantation, the implanted grafts were harvested. Endothelium dependent and independent vasorelaxations were investigated. TUNEL, CD-31, ICAM-1, VCAM-1, α-SMA, nitrotyrosine, dihydroethidium and cGMP immunochemistry were also performed., Results: Compared with the control, the saline group showed significantly attenuated endothelium dependent maximal relaxation (R max ) 2 h after reperfusion, which was significantly improved by vardenafil supplementation (R max control, 91 ± 2%; saline 22 ± 2% vs. vardenafil 39 ± 4%, p < .001). Vardenafil pre-treatment significantly reduced DNA fragmentation (control 9 ± 1%, saline 66 ± 8% vs. vardenafil 13 ± 1%, p < .001), nitro-oxidative stress (control 0.8 ± 0.3, saline 7.6 ± 1.3 vs. vardenafil 3.8 ± 1, p = .036), reactive oxygen species level (vardenafil 36 ± 4, control 34 ± 2 vs. saline 43 ± 2, p = .049), prevented vascular smooth muscle cell damage (control 8.5 ± 0.7, saline 4.3 ± 0.6 vs. vardenafil 6.7 ± 0.6, p = .013), decreased ICAM-1 (control 4.1 ± 0.5, saline 7.0 ± 0.9 vs. vardenafil 4.4 ± 0.6, p = .031), and VCAM-1 score (control 4.4 ± 0.4, saline 7.3 ± 1.0 vs. vardenafil 5.2 ± 0.4, p = .046) and increased cGMP score in the aortic wall (control 11.2 ± 0.8, saline 6.5 ± 0.8 vs. vardenafil 8.9 ± 0.6, p = .016). The marker for endothelial integrity (CD-31) was also higher in the vardenafil group (control 74 ± 4%, saline 22 ± 2% vs. vardenafil 40 ± 3%, p = .008)., Conclusions: The results support the view that impairment of intracellular cGMP signalling plays a role in the pathogenesis of the endothelial dysfunction of an arterial graft after bypass surgery, which can effectively be prevented by vardenafil. Its clinical use as preconditioning drug could be a novel approach in vascular/cardiac surgery., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

The prevalence of dementia is increasing rapidly, specifically in low and middle income countries (LAMIC) due to demographic aging. Help seeking is delayed and usually sought at an advanced stage of illness and many are yet to receive a formal diagnosis. We interviewed 35 caregivers of persons with Dementia (as per ICD-10) using a semi-structured questionnaire, the Short Explanatory Model Interview (SEMI). We explored the pathways taken by caregivers of people with dementia en route to a tertiary care centre and the interactions they had with different health care providers. Qualitative data analysis was done using ATLAS.ti. We identified three major pathways: I) The Neuropsychiatric pathway II) The General Practitioner pathway and III) The Non-cohesive pathway. In general, the caregivers were poorly informed about the illness details such as diagnosis, course and outcome. Neurologists communicated the diagnosis of 'Dementia' more frequently. When information was made available, the caregivers were satisfied with proper information about illness and with at least, partial improvement of symptoms. There is a need for increasing the awareness of dementia in community at large. Health services and systems that address this important public health problem need strengthening. Sensitization and training of primary care physician and staff to identify dementia at an early stage are the need of the hour., (Copyright © 2017 Elsevier B.V. All rights reserved.)

India is poised to experience dramatic shifts in the age and makeup of its population. Specifically, projections havehighlighted an increase in both the percentage of the elderly and those suffering from dementia-related disorders.Previous studies have examined the demographics of aging, its impact on the healthcare infrastructure and recommended policies to better cater to the elderly. This article focuses on a summary of these findings in relation to key stakeholders in the care of the elderly including mental health professionals, family caregivers, and public health officials. We broadly conclude that there exists a general shallow level of understanding of what constitutes pathological aging (i.e. dementia) across all stakeholders, and this creates a cascade of effects including delays in treatment seeking and barriers in conducting and having accurate demographic studies. Moreover, addressing this knowledge gap can help enhance communication between these three stakeholders in the hopes of the following: (a) increased education and awareness, (b) faster seeking of care, and (c) earlier diagnoses leading to better opportunities to collect accurate demographics of those suffering from dementia-related disorders., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-octanoyl-dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham-operated (n = 9). In BDD, decreased left-ventricular contractility (ejection fraction; maximum rate of rise of left-ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left-ventricular pressure; Tau), and increased end-diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD-treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin-6, tumor necrosis factor TNF-α, NF-kappaB-p65, and nuclear factor (NF)-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro-apoptotic factor caspase-3, pro-inflammatory cytokines, and NF-kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Recently, biopolymer based plastic materials are regarded as potential alternative for conventional plastics of fossil fuel origin in order to compensate depleting petroleum resources and address environmental pollution issues. Poly(lactic acid) (PLA) is one among the biopolymers which is rapidly commercialized for food packaging application. However, the demerits accompanied with PLA like brittle nature, slower crystallization rate, poor gas barrier and high ultraviolet radiation transmission properties confines its commercial application in food packaging sector. Studies on the improvement of ductility, crystallization rate and gas barrier properties are markedly reported. Much emphasis is not given in the literature on improving UV shielding properties which plays important role in preventing oxidation degradation of PLA. Therefore, the current work is focused on fabrication of eco-friendly poly(lactic acid)/rosin (RS) based biocomposite films with improved UV shielding along with ductility and oxygen barrier properties. The PLA-RS biocomposite films containing different loadings (1, 3, 5, 10 and 20wt%) of RS with an average thickness of 50μm are fabricated via solution casting technique. The PLA-RS film demonstrated noteworthy light barrier feature by shielding the passage of ∼98%, 92% and 53% in UV-B, UV-A and visible light regime, respectively. In case of UV-C region, complete blockage of UV transmission through the PLA-RS biocomposite film is noticed. In addition to this, the presence of RS in the PLA matrix brought considerable improvement in terms of ductility and oxygen barrier characteristics. This in turn indicates PLA-RS biocomposite films hold significant potential for sustainable food packaging application., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway is an important key mechanism to protect the heart from ischemia/reperfusion injury. However, this pathway is disrupted in several cardiovascular diseases as a result of decreased NO bioavailability and increased NO-insensitive forms of sGC. Cinaciguat preferentially activates these NO-insensitive, oxidized forms of sGC., Methods: We assessed the hypothesis that targeting NO-unresponsive sGC would protect the graft against ischemia/reperfusion injury in a rat heart transplantation model. Before explantation, donor Lewis rats received methylcellulose (1%) vehicle or cinaciguat 10 mg/kg. The hearts were excised, stored in cold preservation solution, and heterotopically transplanted. We evaluated in vivo left ventricular function of the graft., Results: After transplantation, decreased left ventricular systolic pressure (77 ± 3 mm Hg vs 123 ± 13 mm Hg, p < 0.05), dP/dt(max) (1,703 ± 162 mm Hg vs 3,350 ± 444 mm Hg, p < 0.05), and dP/dt(min) (995 ± 110 mm Hg vs 1,925 ± 332 mm Hg, p < 0.05) were significantly increased by cinaciguat. Coronary blood flow was significantly higher in the cinaciguat group compared with the control group. Additionally, cinaciguat increased adenosine triphosphate levels (1.9 ± 0.4 µmol/g vs 6.6 ± 0.8 µmol/g, p < 0.05) and improved energy charge potential. After transplantation, increased c-jun messenger RNA expression was downregulated, whereas superoxide dismutase-1 and cytochrome-c oxidase mRNA levels were upregulated by cinaciguat. Cinaciguat also significantly decreased myocardial DNA strand breaks induced by ischemia/reperfusion during transplantation and reduced death of cardiomyocytes in a cellular model of oxidative stress., Conclusions: By interacting with NO-unresponsive sGC, cinaciguat enhances the protective effects of the NO/cGMP pathway at different steps of signal transduction after global myocardial ischemia/reperfusion. Its clinical use as pre-conditioning agent could be a novel approach in cardiac surgery., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Glycine is an important amino acid for building up protein synthesis. Single crystal of glycine dimer was grown from aqueous solution by slow evaporation method. Powder X-ray diffraction analysis confirms the crystalline nature of grown crystal. It is interesting to study the molecular structure of a dimer, having well-defined channels formed through amphoterism bonding between CO⋯H bonds with split-valence basis sets, and the conformer is mirror symmetrical, in which the protonated organic cation plays a significant role to have a dimer pattern. Amphiprotic molecules, like dimeric glycine which can either donate or accept a proton (H(+)) from each other. Optical absorption study reveals that the transparency of the crystal in the entire visible region and the cutoff wavelength was found to be 235nm. Powder SHG test and thermogravimetric analysis shows glycine dimer crystal is optically active and thermally stable. The molecular structure, geometry, stability and theoretical vibrational spectra were calculated for glycine as a monomer and as a dimer linked by the amphoterism hydrogen bonding. The theoretical studies were performed using the B3LYP density functional method with the 6-311G (d,p) basis set. The detailed interpretation of the vibrational spectra has been made on the basis of normal coordinate analysis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aims: Vascular smooth muscle cell (VSMC) migration, proliferation and remodeling of the extracellular matrix contribute to lumen loss after arterial injury leading to restenosis. Several studies indicated the role of the cyclic guanosine monophosphate signaling in neointimal formation. Cinaciguat, the novel soluble guanylate cyclase activator, currently being in phase IIb clinical trial, has been shown to exert antiplatelet and anti-remodeling effects in animal models of vascular pathology. In this study we investigated the effects of cinaciguat on post-injury arterial stenosis., Methods and Results: Male Sprague-Dawley rats (n=100) underwent endothelial denudation by wire injury of the right common carotid artery. Cinaciguat (10mg/kg/day orally) were administered to 50 rats (1-, 2-, 3-day and 1-, 3-week treatment time), while 50 rats received placebo. A 3-week treatment resulted in a significantly reduced vascular stenosis (17.53 ± 10.84% in the treatment group vs. 43.25 ± 30.83% in the control wire injury group) and neointima/media area ratio (0.45 ± 0.32 in the treatment group vs. 1.09 ± 0.69 in the control wire injury group). By using quantitative real-time PCR, Western blot and immunohistochemistry, matrix-metallopreoteinase-9 (MMP-9) was found to be upregulated in the control-injured carotids over the whole follow-up, and cinaciguat significantly decreased MMP-9 expression by 3 weeks. As assessed by protein immunoblot, injury-induced local decrease of soluble guanylate cyclase β1 subunit could be recovered by cinaciguat. In vitro wound healing assay with VSMCs revealed dose-dependent antimigratory and antiproliferative effects of cinaciguat. Plasma level of cyclic guanosine monophosphate was significantly elevated after 3 weeks of treatment., Conclusion: Our results show that cinaciguat prevents injury-induced neointimal hyperplasia by decreasing VSMC migration and proliferation through the regulation of MMP-9., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status., (© Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Reactive oxygen and nitrogen species (e.g., peroxynitrite) may trigger neointima formation leading to restenosis. In a rat carotid endarterectomy (CEA) model, we investigated the effects of the manganese(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP), a superoxide dismutase (SOD) mimetic and peroxynitrite scavenger on neointima formation., Methods: CEA was performed in male Sprague-Dawley rats. Animals received either vehicle (control group; n=15) or 15 mg kg(-1) day(-1) MnTBAP intraperitoneally for 3 weeks (treatment group; n=13). Four groups of carotids were analysed: the left, uninjured carotids (sham) and the right, injured carotids (control CEA) from the control group, the right, injured carotids from the treatment group (CEA+MnTBAP) and an additional group of carotids that were harvested 1h following endarterectomy. The analysis of carotid arteries was performed by histology, immunohistochemistry and real-time polymerase chain reaction (PCR). Plasma malondialdehyde (MDA) levels were measured by lipid hydroperoxidase assay., Results: Stenosis rate (10.5+/-8.1% vs. 45.4+/-28.3%), the percentage of proliferating cell nuclear antigen-positive cells (13.4+/-7.1% vs. 23.3+/-11.0%) and nitrotyrosine immunoreactivity (5.8+/-1.9 vs. 8.0+/-2.0) were significantly reduced in the vascular wall of the CEA+MnTBAP group compared with control CEA group. Ratio of Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL)-positive nuclei was significantly lower after antioxidant therapy (41.7+/-26.7% vs. 64.9+/-18.5%). Plasma MDA levels increased after endarterectomy (11.7+/-4.8 vs. 4.1+/-2.0 micromol l(-1)) and reduced in the treatment group (3.2+/-2.1 micromol l(-1)). No significant gene regulation after MnTBAP treatment could be noted., Conclusions: MnTBAP decreased neointima formation, which was associated with reduced vascular smooth muscle cell proliferation and attenuated local and systemic nitro-oxidative stress., (Copyright (c) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Benzyl isothiocyanate (BITC) has been shown to inhibit chemically induced pancreatic cancer in experimental animals. However, the mechanism responsible for the anticancer effects of BITC is not clearly understood. In this study, we tested whether BITC treatment would affect the growth of Capan-2 human pancreatic cancer cells. BITC (10 micromol/L) treatment caused marked phosphorylation of H2A.x (2.6-fold) and permanent damage to Capan-2 cells. BITC-mediated G2/M arrest was associated with up-regulation of cyclin dependent kinase inhibitor p21(Waf1/Cip1) and the activation of checkpoint kinase 2, whereas the expressions of other G2/M regulatory proteins, including CyclinB1, Cdc2, and cell division cycle 25C (Cdc25C), were down-regulated by 19, 51, and 70%, respectively, compared with control. These changes resulted in a 55% inhibition of Cdc2 kinase activity. In addition, the decline in the expression of Cdc25C was completely blocked when the cells were treated with lactacystin (proteasome inhibitor) prior to BITC treatment. However, G2/M arrest and apoptosis induced by BITC were partially blocked by pretreatment of cells with lactacystin. Taken together, the results of this study suggest the involvement of multiple signaling pathways targeted by BITC in mediating G2/M cell cycle arrest and apoptosis in Capan-2 cells and warrant further investigation.