Search

Background: Inactive glycogen synthase kinase-3β [phosphorylation at Serine 9 (pS9GSK-3β)] is known to regulate nuclear stabilization of β-catenin and activation of Epithelial-to-mesenchymal transition (EMT) inducing molecules. Present study is taken up to examine the prognostic impact of EMT markers in urothelial tumors with normal and immunoco-aberrantly expressed pS9GSK-3β and β-catenin. Material and methods: Expressions and subcellular localizations of pS9GSK-3β and β-catenin were checked immunohistochemically in 65 NMIBC and 55 MIBC patients. These tumors were later examined for transcriptomic and protein levels of EMT associated molecules followed by their statistical significance with patients' variables. Results: Number of clinicopathological variables exhibited statistical associations with altered EMT markers in non-muscle invasive and muscle invasive tumors with aberrantly immunoco-expressed pS9GSK-3β and β-catenin. Follow up data were collected in 53 NMIBC and 49 MIBC patients over the average timeline of 48 months. Of 25/53 NMIBC and 33/49 MIBC patients with aberrantly immunoco-expressed pS9GSK-3β and β-catenin, molecular anomaly in EMT markers (E−/M+/T+) was noted in 40% NMIBC and 27.3% MIBC patients. NMIBC patients (100%) exhibiting tumor recurrence had at least two molecular abnormalities, whereas 55.5% MIBC succumbed to death and 44.4% MIBC showed tumor progression suggesting that tumor aggressiveness could be linked to severity of abnormal phenotype. Conclusion: Survival analysis demonstrates altered expressions of pS9GSK-3β/β-catenin/EMT as prognostic markers for poor cancer specific survival (p ​= ​0.049) and short overall survival (p ​= ​0.03) probabilities of MIBC patients. Study establishes altered pS9GSK-3β/β-catenin/EMT profile as a sensitive and effective prognostic tool in a subset of bladder tumors.

Removal of hexavalent chromium from synthetic wastewater was performed by employing vegetable-tanned buffing dust, a byproduct of tanneries. Different analysis techniques such as SEM, BET, and FTIR were used to characterize the vegetable-tanned buffing dust. The experiment on adsorption was carried out in a batch manner. Investigations were conducted into the various operating parameters, such as the dose of adsorbent, contact period, and initial Cr (VI) concentration. At a dose of 1g/100 mL and a contact period of 280 minutes, the maximum adsorption capacity was noted. The Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich adsorption isotherms were examined at various concentrations. With a maximum adsorption efficiency of 14.14 mg/g, the Langmuir isotherm model was found to be the most well-fitting for the current investigation. Kinetic analysis was performed for pseudo first and second order; the pseudo-second-order model demonstrated the most optimal fit with a regression coefficient (R2) of 0.9936. [ABSTRACT FROM AUTHOR]

There is a connection between bioavailability and absorption. In the field of pharmacology, this is referred to as a category of absorption and is defined as the proportion of a particular dosage of a drug that does not change and is absorbed into the systemic circulation. Both the overall absorption of medications and their specific bioavailability are important factors to consider in treatment. In this paper, we will go into great detail about the bioavailability of phytochemicals. We will also discuss the factors that influence bioavailability, the processes that improve bioavailability, and the phytochemicals that act as important bio enhancers, which are agents that improve the bioavailability of drugs.

The severe climate change has caused a drastic water level disparity around the globe, which eventually has been one of the biggest problems of this era related to land degradation. This has caused the multidimensional impact on ecology, the environment, and their components. Algae, one of the ancient micro-engineers, are involved in the functioning of soil microcosm. Therefore, this study has utilized a novel alga, Chlorella vulgaris SSAU8 to observe the impact of low water potential induced by PEG-6000 (polyethylene glycol). The study has utilized the UV-Vis spectrophotometer to explore the nature of cyanobacteria by examining biomass and pigment concentrations. The assessment also includes the photosystem response, which was recorded by the Dual-modulation kinetic fluorometer FL3500/F (PSI, Brno, Czech Republic, version 3.7.0.1). The effect of PEG-6000-induced drought was seen to inhibit growth and biomass synthesis at > 30 g L -1 concentration. It was also observed that the microbe could easily shuffle its photosystem behavior to nullify the effect of high PEG-6000 concentration, which shows the potential of the microbe in the water-deficient area and can be an important aspect to enhance soil fertility. Non-photochemical quenching and heat dissipation play a crucial role in cyanobacteria tolerating drought conditions. So, overall, this study thoroughly explores the behavior of Chlorella vulgaris SSAU8 in artificial drought stress and paves a way to combat one of the major environmental issues of the current era., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. All authors also declare that they haven’t used any animal or human subject in the study. Ethical Approval: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study explores the potential of an indigenous halo-tolerant microbe identified as Bacillus spp. SSAU-2 in enhancing soil fertility and promoting plant growth for sustainable agricultural practices under the influence of multiple abiotic stresses such as Cr(VI), high salinity, and artificial drought condition. The study investigated various factors influencing IAA synthesis by SSAU-2, such as pH (5 to 11), salinity (10 to 50 g/L), tryptophan concentration (0.5 to 1%), carbon (mannitol mand lactose), and nitrogen sources (peptone and tryptone). The highest IAA concentration was observed at pH 10 (1.695 mg/ml) and pH 11 (0.782 mg/ml). IAA synthesis was optimized at a salinity level of 30 g/l, with lower and higher salinity levels resulting in decreased IAA concentrations. Notably, the presence of mannitol and lactose significantly augmented IAA synthesis, while glucose and sucrose had inhibitory effects. Furthermore, peptone and tryptone played a pivotal role in enhancing IAA synthesis, while ammonium chloride exerted an inhibitory influence. SSAU-2 showed a diverse array of capabilities, including the synthesis of gibberellins, extracellular polymeric substances, siderophores, and hydrogen cyanide along with nitrogen fixation and ammonia production. The microbe could efficiently tolerate 45% PEG-6000 concentration and effectively produce IAA in 15% PEG concentration. It could also tolerate high concentration of Cr(VI) and synthesize IAA even in 50 ppm Cr(VI). The findings of this study provide valuable insights into harnessing the potential of indigenous microorganisms to promote plant growth, enhance soil fertility, and establish sustainable agricultural practices essential for restoring the health of ecosystems., Competing Interests: Declarations. Ethical approval: Not applicable. Consent of participate: Not applicable Conflict of interest: There is no conflict of interest for this manuscript. The authors declare that they have no known competing financial. Competing of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Haemodialysis units are now managing an increasing number of patients with varying needs and levels of acuity. To maintain safety, haemodialysis patients must be placed in the most appropriate dialysis unit that has the required human and physical resources to care for them. The first step towards achieving these goals is to develop a tool specific to haemodialysis units to effectively measure patient acuity., Objective: To develop a haemodialysis acuity tool, utilising a focus group approach, in assessing patient's suitability for a specific dialysis location thus ensuring patient safety., Design: This is a cross-sectional qualitative study via a focus group approach., Participants: Participants were nurse unit managers and team leaders of a District Renal Service., Approach: Participants were interviewed to explore their views on the elements and measures identified in the research aims. Themes for interviews were informed by current literature on acuity tools for haemodialysis patients' admission to the dialysis units. Interviews were recorded and transcribed verbatim and progressively analysed using a thematic analysis approach., Results: Ten nurse unit managers/team leaders (100%) were interviewed and thematic analysis of the transcripts was conducted utilising the deductive approach. Five themes were identified which will form the main categories in the development of the tool, namely: Age/frailty; co-morbidity; physical; dialysis; and psychosocial., Conclusion: This study is instrumental in the development of the haemodialysis acuity tool which can be used in allocating dialysis location specific to patient's needs and available resources. The tool can also be used in analysing patient care processes and resource requirements based on the patients' and unit's profile., (© 2024 The Authors. Journal of Renal Care published by John Wiley & Sons Ltd on behalf of European Dialysis & Transplant Nurses Association/European Renal Care Association.)

Hexavalent chromium (Cr (VI)) is a heavy metal that is distributed globally and poses a significant threat to the environment through various mechanisms. It can react with soil and water, leading to severe environmental damage. In this study, the toxicity of Cr (VI) was investigated by analyzing two major cyanobacteria species, Nostoc commune and Anabaena variabilis, commonly found in soil along with their consortia. The findings revealed that the toxicity mechanisms of Cr (VI) differed in individual monocultures, with Cr (VI) competing with various components. However, when the cyanobacteria species were combined, i.e., in consortia, they demonstrated an impressive retention of their functioning even in Cr (VI) concentration at 10 ppm. The study also concluded that non-photochemical quenching played a critical role in minimizing Cr (VI) toxicity. Furthermore, the research examined the role of the S-cycle in the process. The quantum yield of electron flux revealed that the Cr (VI) was competing with Qa in A. variabilis and with Qb in N. commune, albeit the photosystem dysfunction is only visible in the latter. The mechanism seemed to be quantum tunneling alteration because of the Cr (VI) having different energized quantum wells. The consortia proved to be behaving in a better manner as compared to the control. Overall, this study reveals the mode of toxicity of Cr (VI) in these two important cyanobacterial strains as well as it also discusses the mechanism of tolerance of consortia against Cr (VI) toxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plant development and yield are severely hampered by climate change. Plants are very prone to a variety of abiotic stressors during growth, making them susceptible to destruction which can reduce the productivity by 20-60%. These stresses generate reactive oxygen species (ROS), which damage lipids, proteins, and nucleic acids. Microalgae and plant growth-promoting bacteria (PGPB) are remarkably effective at reducing the effects of salt stress and promoting plant growth, thereby increasing agricultural yield, and helping ensure global food security. Through a variety of mechanisms, including the production of phytohormones, 1-aminocyclopropane-1-carboxylic acid deaminase, exopolysaccharide, siderophores, hydrogen cyanide, extracellular polymeric substances, volatile organic compounds, and modulation of antioxidants defense machinery under abiotic stresses promote plant growth after inoculation of PGPB and microalgae. These microorganisms also maintain ion homeostasis, offer osmotic balance, stimulate genes that respond to salt and drought, rewire the metabolism, modify the transcription of ion transporter genes, and more. To counteract the negative consequences of salinity stress, this study summarizes the effects of PGPB- microalgae along with a tentative protective mechanism during salinity stress for sustainable agriculture., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The morphological variations in roots and root canals vary greatly in multi-rooted teeth making it a challenge for accurate diagnosis and effective endodontic therapy. In addition to using technology appropriately, this article highlights how important it is to have a complete understanding of root canal morphology. With the assistance of cone-beam computed tomography (CBCT) images and a dental operating microscope (DOM), successful endodontic treatment was performed on a single-rooted maxillary first molar with Vertucci's type II canal configuration. CBCT and DOM proved to be valuable tools for the effective diagnosis and management of this atypical morphology., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bajaj et al.)

Context: With the ageing of Indian society, providing a healthy life among older people is a public health precedence. Therefore, beforehand discovery and possible forestalment of frailty may help promote healthy ageing and dwindle the social, mental and financial burden of their families and caregivers., Aims: The study aimed to assess the proportion of frailty and its associated factors among the elderly aged 65 years and above in a rural community of West Bengal., Settings and Design: A community-based cross-sectional study was conducted among 270 elderlies selected from 15 villages out of a total 64 villages of Singur under the Hooghly District of West Bengal from January 2019 to February 2020., Materials and Methods: Cluster sampling technique was used. Data was collected using a pre-designed, pre-tested structured schedule including Fried frailty phenotype (FFP), geriatric depression scale short form (GDS 15) and mini nutritional assessment (MNA) tool., Statistical Analysis Used: Associated factors of frailty were assessed by univariate and multivariable logistic regression using SPSS version 16 software and MS Excel 2019., Results: The proportion of frailty was observed to be 23.7% and that of prefrailty 40.7%. Frailty was significantly associated with increasing age [AOR(CI) 1.2(1.1-1.3)], decreasing years of schooling [AOR(CI) 1.3(1.1-1.5)], loss of spouse [AOR(CI) 4.2(1.2-15.2)], financial dependency [AOR(CI) 19.3(2.7-139.0)], staying at home [AOR(CI) 16.3(2.7-98.2)], presence of anaemia [AOR(CI) 3.6(1.3-9.5)], at risk of malnutrition [AOR(CI) 6.5(1.9-22.3)], increasing number of falls in the last 1 year [AOR(CI) 4.3(1.2-15.6)], presence of 3 or more chronic diseases [AOR(CI) 154.7(12.1-1981.9)] and depression [AOR(CI) 8.3(2.5-27.0)]., Conclusion: The burden of frailty among the study population is relatively high. It's an intimidating situation that needs bettered screening provisions for early discovery with special stress on nutritive upliftment. Screening for depression should also be done regularly., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

The escalating prevalence of neurodegenerative diseases (NDDs) within an aging global population presents a pressing challenge. The multifaceted pathophysiological mechanisms underlying these disorders, including oxidative stress, mitochondrial dysfunction, and neuroinflammation, remain complex and elusive. Among these, the AMPK/SIRT1/PGC-1α pathway emerges as a pivotal network implicated in neuroprotection against these destructive processes. This review sheds light on the potential therapeutic implications of targeting this axis, specifically emphasizing the promising role of flavonoids in mitigating NDD-related complications. Expanding beyond conventional pharmacological approaches, the exploration of non-pharmacological interventions such as exercise and calorie restriction (CR), coupled with the investigation of natural compounds, offers a beacon of hope. By strategically elucidating the intricate connections within these pathways, this review aims to pave the ways for novel multi-target agents and interventions, fostering a renewed optimism in the quest to combat and manage the debilitating impacts of NDDs on global health and well-being., 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.)

Objectives: Tailored models of home-based palliative care aimed to support death at home, should also ensure optimal symptom control. This study aimed to explore symptom occurrence and distress over time in Palliative Extended And Care at Home (PEACH) model of care recipients., Design: This was a prospective cohort study., Setting and Participants: Participants were consecutive recipients of the PEACH rapid response nurse-led model of care in metropolitan Sydney (December 2013-January 2017) who were in the last weeks of life with a terminal or deteriorating phase of illness and had a preference to be cared or die at home., Outcome Measures: Deidentified data including sociodemographic and clinical characteristics, and symptom distress scores (Symptom Assessment Score) were collected at each clinical visit. Descriptive statistics and forward selection logistic regression analysis were used to explore influence of symptom distress levels on mode of separation ((1) died at home while still receiving a PEACH package, (2) admitted to a hospital or an inpatient palliative care unit or (3) discharged from the package (alive and no longer requiring PEACH)) across four symptom distress level categories., Results: 1754 consecutive clients received a PEACH package (mean age 70 years, 55% male). 75.7% (n=1327) had a home death, 13.5% (n=237) were admitted and 10.8% (n=190) were still alive and residing at home when the package ceased. Mean symptom distress scores improved from baseline to final scores in the three groups (p<0.0001). The frequency of no symptom distress score (0) category was higher in the home death group. Higher scores for nausea, fatigue, insomnia and bowel problems were independent predictors of who was admitted., Conclusion: Tailored home-based palliative care models to meet preference to die at home, achieve this while maintaining symptom control. A focus on particular symptoms may further optimise these models of care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenia, marrow dysplasia and has a propensity to develop into acute myeloid leukemia. The disease progression is majorly affected by genetic defects. However, about 40-50% of patients with MDS present with a normal karyotype and develop different courses of disease. Hence, there remains a room to advance the biological understanding and find molecular prognostic markers for cytogenetically normal MDS., Methods: We performed a high-resolution CGH + SNP array along with next-generation sequencing (NGS) of 77 primary diagnosed MDS patients, and also they were clinically followed up., Results: Our study revealed 82 clinically significant genomic lesions (losses/gains) in 49% of MDS patients. CGH + SNP array reduced the proportion of normal karyotype by 30%. SNP array in combination with NGS confirmed the biallelic loss of function of the TP53 gene (2/6), which is a clinically relevant biomarker and new genetic-based MDS entity, i.e., MDS-biTP53, as per the new WHO classification 2022. Genomic region 2p22.3 presented with frequent lesions and also with a more hazard ratio (2.7, 95% CI: 0.37-21) when analyzed by Kaplan-Meier survival analysis., Conclusion: CGH + SNP array changed the cytogenetic and IPSS-R risk group in 18% and 13% of patients, respectively, with an improved prediction of prognosis. This study emphasizes the cytogenetic heterogeneity of MDS and highlights that abnormality with chromosome 2 may have a diagnostic and prognostic impact., (© 2024 S. Karger AG, Basel.)

Background: Cinchonine is one of the Cinchona alkaloids that is commercially extracted from the Peruvian bark of Cinchona officinalis L. (Family: Rubiaceae). It is also obtained in much lower quantities from other species of Cinchona, such as Cinchona calisaya, Cinchona succirubra, and Cinchona pubescens, and in some other plants, such as Remijia peruviana. Cinchonine has been historically used as an anti-malarial agent. It also has a wide range of other biological properties, including anti-cancer, anti-obesity, anti-inflammatory, anti-parasitic, antimicrobial, anti-platelet aggregation, and anti-osteoclast differentiation., Aim and Objective: This review discusses the pharmacological activity of cinchonine under different experimental conditions, including in silico , in vitro , and in vivo . It also covers the compound's physicochemical properties, toxicological aspects, and pharmacokinetics., Methodology: A comprehensive literature search was conducted on multiple online databases, such as PubMed, Scopus, and Google Scholar. The aim was to retrieve a wide range of review/research papers and bibliographic sources. The process involved applying exclusion and inclusion criteria to ensure the selection of relevant and high-quality papers., Results: Cinchonine has numerous pharmacological properties, making it a promising compound for various therapeutic applications. It induces anti-cancer activity by activating caspase-3 and PARP-1, and triggers the endoplasmic reticulum stress response. It up-regulates GRP78 and promotes the phosphorylation of PERK and ETIF-2&#945;. Cinchonine also inhibits osteoclastogenesis, inhibiting TAK1 activation and suppressing NFATc1 expression by regulating AP-1 and NF-&#954;B. Its potential anti-inflammatory effects reduce the impact of high-fat diets, making it suitable for targeting obesity-related diseases. However, research on cinchonine is limited, and further studies are needed to fully understand its therapeutic potential. Further investigation is needed to ensure its safety and efficacy in clinical applications., Conclusion: Overall, this review article explains the pharmacological activity of cinchonine, its synthesis, and physicochemical properties, toxicological aspects, and pharmacokinetics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The therapeutic potential of natural stilbenes, with a particular focus on pterostilbene (PTE), has emerged as a promising avenue of research targeting age-associated conditions encompassing cardiovascular diseases (CVD), diabetes mellitus (DM), and cognitive decline. This comprehensive investigation delves into the intricate mechanisms through which PTE, a polyphenolic compound abundant in grapes and blueberries, exerts its advantageous effects as an anti-aging agent. Central to its action is the modulation of hallmark aging processes, including oxidative damage, inflammatory responses, telomere attrition, and cellular senescence. PTE's ability to effectively penetrate the blood-brain barrier amplifies its potential for safeguarding neural health, thereby facilitating the regulation of neuronal signalling cascades, synaptic plasticity, and mitochondrial functionality. Through engagement with sirtuin proteins, it orchestrates cellular resilience, longevity, and metabolic equilibrium. Encouraging findings from preclinical studies portray PTE as a robust candidate for counteracting age-linked cognitive decline, augmenting memory consolidation, and potentially ameliorating neurodegenerative maladies such as Alzheimer's disease (AD). The synthesis of current scientific insights accentuates the promising translational prospects of PTE as a potent, naturally derived therapeutic agent against cognitive impairments associated with aging. Consequently, these collective findings lay a solid groundwork for forthcoming clinical inquiries and innovative therapeutic interventions in this realm., 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.)

This narrative review explores the evolving field of thyroid function testing, explicitly highlighting the significance of precision diagnostics and their substantial impact on clinical practice. Commencing with a comprehensive examination of the historical progression of thyroid diagnostics, the discourse proceeds to explore recent developments, highlighting the paramount importance of accuracy in testing methods. The primary issue under consideration is the crucial requirement for accuracy in the field of therapeutic practice. The review critically examines the problems related to the interpretation, standardization, and ethical considerations in examining advanced laboratory techniques, novel biomarkers, and state-of-the-art technologies like immunoassays, molecular testing, and automation. The focus on the paradigm shift towards precision diagnostics brings attention to the complex connection between test results and their direct influence on patient care. This investigation expands upon the incorporation of imaging and molecular diagnostics, highlighting the rising significance of precision in customizing treatment strategies. In summary, the study provides a prospective viewpoint, recognizing the persistent obstacles and highlighting the want for dependable, uniform methodologies in thyroid diagnostics. This narrative's primary objective is to guide physicians, researchers, and stakeholders in effectively navigating the intricate nature of contemporary thyroid function tests, with a particular emphasis on resolving the fundamental issue of precision., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Yazdaan et al.)

Background: Telemonitoring (TM) plays an important role in the self-management of chronic diseases. This study aimed to assess the feasibility of TM in early stages of chronic care for self-management and recognition of signs and symptoms of exacerbation, with a view to completing the TM program in an optimal timeframe to encourage independence and self-management., Methods: This study was conducted from 2019 to 2020. Included in the study were patients with chronic conditions at an early stage of their disease residing in the South Western Sydney region. Eligible patients were allocated a TM device for 6months. Their routine tests data were sent in real time to health care professionals. Following assessment by a TM coordinator, suitable patients were off-boarded (deactivation of monitoring device) after 6months. Data on hospitalisation/emergency department presentation and surveys were collected to assess the impact of TM on the level of the patient's understanding of their signs and symptoms of exacerbation, self-care, and quality of life., Results: Out of 44 patients approached, seven were off-boarded at the 6-month timeframe. The follow-up data on the hospitalisation/emergency department presentation during monitoring and 12months post off-boarding showed a reduction in the frequency of hospitalisation/nil admissions. Patients reported an increased understanding of their health condition and confidence in managing their own health with the support of TM., Conclusion: The result demonstrates the feasibility of TM as a tool for health education and self-management in the coordination of care for chronic disease patients; however, the small sample size was a limitation.

The spread of antimalarial drug resistance is a substantial challenge in achieving global malaria elimination. Consequently, the identification of novel therapeutic candidates is a global health priority. Malaria parasite necessitates hemoglobin degradation for its survival, which is mediated by Falcipain 2 (FP2), a promising antimalarial target. In particular, FP2 is a key enzyme in the erythrocytic stage of the parasite's life cycle. Here, we report the screening of approved drugs listed in DrugBank using a computational pipeline that includes drug-likeness, toxicity assessments, oral toxicity evaluation, oral bioavailability, docking analysis, maximum common substructure (MCS) and molecular dynamics (MD) Simulations analysis to identify capable FP2 inhibitors, which are hence potential antiplasmodial agents. A total of 45 drugs were identified, which have positive drug-likeness, no toxic features and good bioavailability. Among these, six drugs showed good binding affinity towards FP2 compared to E64, an epoxide known to inhibit FP2. Notably, two of them, Cefalotin and Cefoxitin, shared the highest MCS with E64, which suggests that they possess similar biological activity as E64. In an investigation using MD for 100 ns, Cefalotin and Cefoxitin showed adequate protein compactness as well as satisfactory complex stability. Overall, these computational approach findings can be applied for designing and developing specific inhibitors or new antimalarial agents for the treatment of malaria infections.Communicated by Ramaswamy H. Sarma.

Background: Craniovertebral angle (CVA) alteration is a causative factor for the neck, shoulder, and temporomandibular joints disorders. Therefore, as an outcome measure for therapeutic intervention, measuring the craniovertebral angle with the Surgimap smartphone app is a cost-effective, easily accessible, and reliable tool. This study's objective was to assess the clinimetric properties of the Surgimap smartphone application with Surgimap system software to measure the Craniovertebral Angle in different age groups and positions., Method: Ninety subjects with neck pain were randomly allocated to aged between 18 and 30 years (Group A; n = 45) and 45-60 years (Group B; n = 45). Using the Surgimap smartphone application and Surgimap system software, the craniovertebral angle was measured objectively in the sagittal plane. Intraclass correlation coefficients were used to determine validity and reliability. Receiver operating characteristic (ROC) curves and the area under the curves (AUC) were determined to distinguish participants with and without forward head posture., Result: The result of this study shows that Smartphone Surgimap Application and Surgimap System Software correlate 0.95 and have p-values of 0.01 for diverse positions and ages. CVA measurement in the sitting position was significantly lower than in the standing position, regardless of methodology or age. Both positions demonstrated high intra-rater reliability, as evidenced by Intraclass Correlation Coefficients (ICC) between 0.972 and 0.991. The minimum detectable change (MDC) values ranged from 1.3 to 1.733, indicating high measurement accuracy. The smartphone application demonstrated outstanding diagnostic sensitivity (100.00% for Group A standing) and specificity (93.55% for Group B standing)., Conclusion: The Surgimap smartphone application is a reliable and accurate method for craniovertebral angle measurement and is useful for measuring outcomes. Also standing posture was found to be better than sitting posture while measuring the CVA., Competing Interests: 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., (© 2023 The Authors.)

Palliative Extended and Care at Home (PEACH) is a rapid response nurse-led package of care mobilized for palliative care patients who have an expressed preference to die at home. This study aimed to identify the demographic and clinical predictors of home death for patients receiving the package. Deidentified data were used from administrative and clinical information systems. Univariate and multivariate analyses were conducted to assess association of sociodemographic factors with mode of separation. Furthermore, 1754 clients received the PEACH package during the study period. Mode of separation was home death (75.7%), hospital/palliative care unit admission (13.5%), and alive/discharged from the PEACH Program (10.8%). Of participants with clear preference to die at home, 79% met their wish. Multivariate analysis demonstrated cancer diagnosis, patients who wished to be admitted when death was imminent, and patients with undecided preference for location of death were associated with an increased likelihood of being admitted to the hospital. Compared with those with spousal caregivers, those cared for by their child/grandchild and other nonspouse caregivers were significantly associated with a decreased likelihood of being admitted to the hospital/palliative care unit. Our results show that opportunities to tailor home care based on referral characteristics to meet patient preference to die at home, at individual, system, and policy levels, exist., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 by The Hospice and Palliative Nurses Association. All rights reserved.)

Mutation or overexpression renders pan-RAS (rat sarcoma) proteins insensitive to inactivation. Activated pan-RAS communicates signal from the cell surface receptor to activate RAS-MAPK/ERK (RAS-mitogen-activated protein kinases/extracellular signal regulated kinases) signaling and orchestrates epithelial-to-mesenchymal transition-activating transcription factors (EMT-ATFs) reprogramming to induce EMT. Owing to limited studies available in bladder cancer, the present study is taken up to examine the expressions of the EMT-associated markers in pan-RAS-pERK1/2 (pan-RAS-phosphoERK1/2)-positive well-characterized cohort of forty-two non-muscle invasive bladder cancer (NMIBC) and forty-five muscle invasive bladder cancer (MIBC) patients. Immunohistochemical staining was performed on paraffin embedded tissue sections to determine the immunolevels and cellular localization of marker proteins. Semi-quantitative expressions of pan-RAS, pERK1/2, and EMT markers (E-cadherin, Vimentin, N-cadherin, Snail, Slug Twist, and Zeb1) were statistically examined with clinicohistopathological profile of the patients using SPSS, version 20.0 software. The study documents the diagnostic relevance of immunohistochemical expressions of pan-RAS-pERK1/2/EMT-associated markers in order to stratify NMIBC and MIBC patients. Follow-up studies supported the role of altered EMT phenotype in pan-RAS-pERK1/2-activated positive tumors with disease aggressiveness. To the best of our knowledge, our study is the first concluding the impact of altered EMT phenotype via pan-RAS-pERK1/2 axis on the short survival outcome [short overall survival (OS) (p = 0.04), short progression-free survival (PFS) (p = 0.02) and short cancer-specific survival (CSS) (p = 0.03)] of muscle invasive bladder cancer patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The current study is focused on using tannery waste called buffing dust to remove hexavalent chromium from an aqueous solution. The buffing dust was characterised by using different technique like FTIR, SEM, and BET analysis. The adsorption experiment was conducted in batch mode. The different operating factors including contact time, dose and initial Cr (VI) concentration were investigated. The optimum adsorption capacity was observed at contact time of 240 min and dose of 1g/100 mL. The adsorption isotherm such as Langmuir, Freundlich and Temkin were investigated at different initial concentration. It was observed that Langmuir isotherm model was best fitted for present study with maximum adsorption efficiency of 11.33 mg/g. The kinetic study was performed for pseudo first order and pseudo second order and it was found that pseudo second order model was provided the best match with regression coefficient (R 2 ) of 0.9991., (©2023PublishedbyElsevierLtd.)

Background: There is increasing evidence that COVID-19 survivors are at increased risk of experiencing a wide range of cardiovascular complications post infection; however, there are no validated models or clear guidelines for remotely monitoring the cardiac health of COVID-19 survivors., Objective: This study aims to test a virtual, in-home healthcare monitoring model of care for detection of clinical symptoms and impacts on COVID-19 survivors. It also aims to demonstrate system usability and feasibility., Methods: This open label, prospective, descriptive study was conducted in South Western Sydney. Included in the study were patients admitted to the hospital with the diagnosis of COVID-19 between June 2021 and November 2021. Eligible participants after consent were provided with a pulse oximeter to measure oxygen saturation and a S-Patch EX to monitor their electrocardiogram (ECG) for a duration of 3 months. Data was transmitted in real-time to a mobile phone via Bluetooth technology and results were sent to the study team via a cloud-based platform. All the data was reviewed in a timely manner by the investigator team, for post COVID-19 related symptoms, such as reduction in oxygen saturation and arrhythmia., Outcome Measure: This study was designed for feasibility in real clinical setting implementation, enabling the study team to develop and utilise a virtual, in-home healthcare monitoring model of care to detect post COVID-19 clinical symptoms and impacts on COVID-19 survivors., Results: During the study period, 23 patients provided consent for participation. Out of which 19 patients commenced monitoring. Sixteen patients with 81 (73.6%) valid tests were included in the analysis and amongst them seven patients were detected by artificial intelligence to have cardiac arrhythmias but not clinically symptomatic. The patients with arrhythmias had a higher occurrence of supraventricular ectopy, and most of them took at least 2 tests before detection. Notably, patients with arrhythmia had significantly more tests than those without [ t -test, t (13) = 2.29, p  < 0.05]., Conclusions: Preliminary observations have identified cardiac arrhythmias on prolonged cardiac monitoring in 7 out of the first 16 participants who completed their 3 months follow-up. This has allowed early escalation to their treating doctors for further investigations and early interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Chow, D'Souza, Ford, Marshall, San Miguel, Parameswaran, Parsons, Ramirez, Teramayi and Maurya.)

Background: Myelodysplastic syndromes (MDS) is defined as heterogenous disease, it contains heterogenous leukemic stem cells with various degree of cell differentiation. The perturbation of genes involved in myeloid progenitor cell growth, differentiation and proliferation lead to morphologic dysplasia, maturation arrest, ineffective hematopoiesis hence the cytopenias and propensity to develop into acute myeloid leukemia (AML). Heterogeneous subsets of MDS patients have been defined by their clinical and biologic abnormalities. These different features lead to the development of different prognostic system; however, these approaches are limited in predicting clinical course, and management of patients remains challenging given the uncertainty of the time course of disease progression. It is of importance to identify transcriptomic marker causing maturational and differentiation arrest which could help in understanding the pathogenesis of disease., Methods and Results: We have studied differential gene expression profiles (GEPs) in CD34 + marrow cells from myelodysplastic syndrome (MDS) patients (n = 14) and control CD34 + cells using Affymetrix Human Clariom S microarray with 20,000 well annotated genes. We found 4165 genes significantly (p < 0.05) differentially expressed in MDS. Using stringent bioinformatics analyses, we were able to identify few genes (MAPK8, JUNB, mTOR) which were differentially upregulated i.e. 5.39, 73.61 and 2.7 fold change observed in MDS than control and also validated (n = 60) these genes by RT - qPCR. Kaplan - Meier survival analysis indicated that MAPK8 and JUNB could be poor prognostic marker as patients with increased expression showed poor survival, whereas surprisingly mTOR increased expression proved to be good prognostic marker. The correlation analysis showed that the level of gene (MAPK8, JUNB, mTOR) expression was significantly (p ≤ 0.05) associated with frequency of genetic lesions. Interestingly the increased expression of MAPK8 was significantly accompanied with ASXL1 gene mutation., Conclusion: Our study showed an elevation of TNF and AMPK signalling pathways in MDS. TNF signalling might be mediating the proliferative advantage to myeloid clonal cells (mutation carrying cells) over normal cells, whereas, AMPK signalling could be acting as protector against it (favouring normal cells). Hence it would be interesting to explore the functions and pathways associated with mTOR, AMPK, MAPK8 and JUNB in myelopoiesis related diseases like MDS., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Aims: Breast surgery is associated with moderate-to-severe postoperative pain, nausea, and vomiting. For this, neuraxial anesthesia might be a better alternative to general anesthesia (GA), providing superior analgesia, with higher patient satisfaction and lesser incidence of nausea vomiting. This randomized-controlled open-label trial was done to compare segmental spinal and GA for breast cancer surgery., Material and Methods: The present study enrolled 56 female patients scheduled to undergo breast cancer surgery. They were randomly divided into two groups, group G (received standard GA) and group TS (received segmental thoracic spinal anesthesia with 0.5% isobaric levobupi vacaine at T5-T6 inter spaces). The primary objective of this study was patient satisfaction with the anesthetic technique, while secondary objectives were hemodynamic changes, perioperative complications, time of first rescue analgesic, total opioid consumption in first 24 h, and surgeon satisfaction score. Data were expressed as mean (SD) or number (%) as indicated and were compared using Chi-square, Fisher's exact, or Student's t test as appropriate., Results: Patient in group TS had significantly higher satisfaction score median 5 (IQR 1) compared to patients in group G median 4 (IQR 3.5) ( P = 0.0001). Nausea and vomiting were significantly higher in group G compared to group TS ( P = 0.01). Mean time to rescue analgesia was 33.21 ± 7.48 min in group G as compared to 338.57 ± 40.70 in group TS and opioid consumption was also significantly lower in group TS (70.00 ± 27.38) as compared to group G (366.07 ± 59.40). There was no significant difference in hemodynamic parameters (except significantly lower heart rate at 15 min in group TS ( P = 0.001) and surgeon satisfaction score between groups. Quality of postoperative analgesia was better in group TS., Conclusion: Segmental thoracic spinal anesthesia technique provides better satisfaction with superior postoperative analgesia and fewer complications in patients undergoing breast cancer surgery compared to GA., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Anaesthesiology Clinical Pharmacology.)

Foods rich in antioxidants such as lycopene have a major role in maintaining cardiac health. Lycopene, 80% of which can be obtained by consuming a common vegetable such as tomato, can prevent the disturbances that contribute to cardiovascular disease (CVD). The present work begins with a brief introduction to CVD and lycopene and its various properties such as bioavailability, pharmacokinetics, etc. In this review, the potential cardio-protective effects of lycopene that reduce the progression of CVD and thrombotic complications are detailed. Further, the protective effects of lycopene including in vitro, in vivo and clinical trials conducted on lycopene for CVD protective effects are explained. Finally, the controversial aspect of lycopene as a protective agent against CVD and toxicity are also mentioned.

Myelodysplastic syndromes (MDS) are a group of clonal hematological disease with high risk of progression to AML. Accurate risk stratification is of importance for the proper management of MDS. Genetic lesions (Cytogenetic and Molecular mutations) are known to help in prognosticating the MDS patients. We have studied 152 MDS patients using cytogenetics and next generation sequencing (NGS). These patients were evaluated and as per cytogenetic prognostic group, majority (92.1%) of the patients classified as good (81.6%) and intermediate (10.5%) group. The NGS identified 38 different gene mutations in our cohort. Among 111 MDS patients with mutations, the most frequent mutated genes were SF3B1 (25.2%), SRSF2 (19%) U2AF1 (14.4%) ASXL1 (9.9%) RUNX1 (9.9%) TET2 (9%), TP53 (9%), ATM (6.3%), NRAS (5.4%) and JAK2/3 (5.4%). The survival analysis revealed that the mutations in TP53, JAK2/3, KRAS, NRAS and ASXL1 were significantly (P < 0.05) associated with poor survival of the patients. The univariate cox and multivariate cox analysis of our study suggested that the age, marrow morphology, cytogenetic and gene mutations with IPSS-R should be considered for prognosticating the MDS patients. We have proposed M-IPSS-R which changed the risk stratification i.e. 66.3% patients had decreased risk whereas 33.75% showed increased risk compared to IPSS-R. The survival analysis also showed that the M-IPSS-R were more significant in separating the patients as per their risk than the IPSS-R alone. The change in risk stratification could help in proper strategy for the treatment planning., (© 2022. The Author(s).)

Context: Considering the effectiveness and safety concerns of synthetic intracanal medicaments (ICM), alternative usage of herbal ingredients in the root canal treatment may prove to be beneficial. Hence, the naturally available potent proteolytic, anti-inflammatory, and antimicrobial pineapple extract Bromelain as an ICMs needs to be studied., Aim: The aim of this study is to evaluate and compare the antimicrobial efficacy of calcium hydroxide (CaOH) and triple antibiotic paste (TAP) with Bromelain against Enterococcus faecalis bacteria using the turbidity method., Materials and Methods: Forty-four freshly extracted single-rooted teeth were collected and 6 mm sections were prepared. These samples were infected with E. faecalis bacteria (ATCC 29212), randomly divided into four groups. Negative control, CaOH paste, TAP, and Bromelain paste. After the removal of medicament, the optical density (OD) of the dentinal shavings was measured using a spectrophotometer., Statistical Analysis: The Chi-square and Kruskal - Wallis ANOVA test were used. The confidence interval was set to 95% at 5% significance level., Results: TAP showed less OD than CaOH 2 paste which is statistically significant. ( P = 0.0022). The OD reading of Bromelain paste was less than CaOH 2 with P = 0.007. The OD of Bromelain and TAP were statistically insignificant ( P = 0.095), indicating their comparable antibacterial efficacy., Conclusions: The antimicrobial efficiency of Bromelain was found to be more effective than Ca (OH) 2 paste and comparable to TAP against E. faecalis ., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Conservative Dentistry.)