Rates, predictors, and causes of readmission after transcatheter aortic valve replacement in patients with chronic kidney disease.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a revolutionary procedure for severe aortic stenosis. The coexistence of chronic kidney disease (CKD) and TAVR introduces a challenge that significantly impacts patient outcomes. AIM: To define readmission rates, predictors, and causes after TAVR procedure in CKD stage 1-4 patients. METHODS: We used the national readmission database 2018 and 2020 to look into readmission rates, causes and predictors after TAVR procedure in patients with CKD stage 1-4. RESULTS: Out of 24758 who underwent TAVR and had CKD, 7892 (32.4%) patients were readmitted within 90 days, and had higher adjusted odds of being females (adjusted odds ratio: 1.17, 95%CI: 1.02-1.31, P = 0.02) with longer length of hospital stay > 6 days, and more comorbidities including but not limited to diabetes mellitus, anemia, and congestive heart failure (CHF). CONCLUSION: Most common causes of readmission included CHF (18.0%), sepsis, and complete atrioventricular block. Controlling readmission predictors with very close follow-up is warranted to prevent such high rate of readmission.

Bridging the divide: addressing discrepancies between clinical guidelines, policy guidelines, and biomarker utilization.

OBJECTIVES: This paper aims to identify and address gaps in cancer treatment and diagnosis within European health services, focusing specifically on discrepancies between clinical guidelines and policy guidelines. It seeks to highlight how the underutilization of advanced diagnostic techniques recommended by medical societies contributes to missed opportunities for improving patient outcomes. METHODS: A comprehensive analysis was conducted across multiple European countries to assess the compliance and integration of clinical guidelines with the availability of advanced diagnostic technologies. Secondary data related to clinical and policy guidelines in cancer care were collected and analyzed. Key indicators of adoption and utilization of next-generation sequencing and liquid biopsy were examined to evaluate their impact on health service efficiency and patient care. RESULTS: The analysis revealed significant discrepancies between the recommendations of medical societies regarding advanced diagnostic techniques and their adoption in health policy decisions across Europe. Country-specific assessments indicated varying levels of alignment between clinical guidelines and the availability of advanced diagnostics. These findings underscored missed opportunities for optimizing patient care and health service efficiency through better alignment and integration of clinical guidelines with policy decisions. CONCLUSIONS: This study concludes that there is a critical need for health policy decision-makers to prioritize the adoption of clinical guidelines in resource allocation and health service organization. Greater attention to the recommendations of medical societies regarding advanced diagnostic techniques could significantly enhance diagnostic accuracy, treatment efficacy, and overall patient outcomes in cancer care. The paper advocates for policy reforms that acknowledge and leverage the potential benefits of advanced diagnostics in improving health service performance and patient-centered care across Europe.

Patient satisfaction with the management of refractory and unexplained chronic cough in Canada: Results from a national survey.

BACKGROUND: Chronic cough (persisting for ≥8 weeks) is a common disorder affecting approximately 5 to 10% of adults worldwide that is sometimes refractory to treatment (refractory chronic cough [RCC]) or has no identifiable cause (unexplained chronic cough [UCC]). There is minimal information on the patient's experience of RCC/UCC in Canada. The aim of this study was to evaluate the patient journey and perceptions related to RCC/UCC management in Canada. METHODS: Our exploratory study included Canadians in the Leger Opinion Panel and focused on individuals with RCC or UCC. Key entry criteria were: age ≥18 years, cough on most days for ≥8 weeks, no smoking within 1 year, no serious respiratory disease or lung cancer, and not taking angiotensin-converting enzyme inhibitors. Individuals who met entry criteria were invited to complete an approximately 30-minute online survey with questions on demographic characteristics, healthcare professional (HCP) interactions, diagnosis of underlying conditions, current treatments, and satisfaction with HCPs and chronic cough therapies. RESULTS: A total of 49,076 individuals completed the chronic cough screening questionnaire (July 30, 2021 to September 1, 2021): 1,620 (3.3%) met entry criteria for RCC or UCC, and 1,046 (2.1%) completed the online survey (mean age of 45 years, 61% female). Most respondents (58%) reported their chronic cough was managed by a general practitioner (GP). Forty-four percent of respondents did not have a diagnosis of an underlying condition for their cough. Breathing tests (39%) and chest imaging (34%) were the most common diagnostic tests. Cough suppressants (18%) were the most frequent current treatment. Respondents were moderately satisfied with their HCPs, but more than half considered their treatment ineffective and 34% had considered no longer seeking medical attention because of a lack of treatment success. CONCLUSIONS: Individuals with RCC/UCC in Canada are largely unsatisfied with the effectiveness of treatment. Additional HCP education and new treatment options are needed to improve patient satisfaction.

Evaluating iodine deficiency and goiter in hilly areas of District Poonch Azad Jammu Kashmir.

Background & Objectives: Iodine deficiency is considered as a global challenge, even after decades of efforts to solve the issue. Our objective was to assess the iodine deficiency status and associated prevalence of goiter in population groups (school-age children and women) from rural areas of District Poonch, and to assess the determinants of iodine deficiency in the area. Methods: Cross-sectional study was conducted in District Poonch Azad Jammu and Kashmir from 25 April 2022 to 30 June 2023. A total of 150 goiter patients from different villages of the District Poonch was included. Their urinary iodine concentration and goiter prevalence was assessed. Using palpation techniques, a trained and experienced public health officer assessed the presence of goiters based on WHO/ UNICEF/ICCIDD criteria. Descriptive statistics were computed for continuous variables and presented in frequency and percentage, based on the distributional characteristics of the data. chi-square was used to check association between socio-demographic factors and goiter. It was a HEC Project No.: 20-16988/NRPU/R&D/HEC/2021. Results: Iodine status and associated goiter prevalence was high and 59.3% of them were severely iodine deficient. Within the district, the highest severe iodine deficiency was observed in 81.1% goiter patients of the Rawalakot subdivision, Hajira and Abbaspur subdivisions. Regarding goiter status 40% of the patients were classified with palpable-visible goiter and 56% were characterized with visible but nodular goiter. Conclusion: Study showed that there was a severe iodine deficiency and associated goiter prevalence in the area. Policymakers should take actions for future to overcome iodine deficiency in future.

Assessing anticancer, antidiabetic, and antioxidant capacities in green-synthesized zinc oxide nanoparticles and solvent-based plant extracts.

Cancer and diabetes represent significant challenges in the field of biomedicine, with major and global impacts on public health. Acacia nilotica, commonly called 'gum arabic tree,' is recognized for its unique biomedical properties. The current study aimed to investigate the pharmacological potential of A. nilotica-based zinc-oxide nanoparticles (ZnO-NPs) in comparison to the ethanol and methanol-based extracts against cancer, diabetes, and oxidative stress. Green synthesis of ZnO-NPs was performed using barks of Acacia nilotica. Different techniques for the characterization of ZnO-NPs, including UV-Visible spectroscopy, Scanning Electron Microscopy, Fourier Transmission Infrared (FT-IR) spectroscopy, and X-ray Diffraction (XRD), were utilized. The morphological analysis of ZnO-NPs revealed that the fine NPs have mean particle sizes of 15 ± 1.5 nm. For the solvent based-extraction, leaves and barks were utilized and dissolved into ethanol and methanol for further processing. The MTT assay revealed that the optimum concentration of ZnO-NPs to inhibit the proliferation of liver cancer cell line HepG2 was 100 µg/mL where 67.0 % inhibition was observed; and both ethanol- and methanol-based extracts showed optimum inhibition at 100 µg/mL. The DPPH assay further demonstrated that 250 µg/mL of ZnO-NPs and 1000 µg/mL of both ethanol- and methanol-based extracts, as the optimum concentration for antioxidant activity (with 73.1 %, 68.9 % and 68.2 % inhibition respectively). The α-Glucosidase inhibition assay revealed that 250 µg/mL of ZnO-NPs and 10 µg/mL of both ethanol- and methanol-based extracts as the optimum concentration for antidiabetic activity (with 95 %, 93.7 % and 93.4 % inhibition respectively). The study provided interesting insights into the efficacy and reliability of ZnO-NPs for potential pharmacological application. Further research should be focused on examining specific pathways and the safety of ZnO-NPs in comparison to solvent-based extracts.

Airway proteomics reveals broad residual anti-inflammatory effects of prednisolone in mepolizumab-treated asthma.

BACKGROUND: Mepolizumab is an anti-interleukin-5 monoclonal antibody treatment for severe eosinophilic asthma (SEA) that reduces asthma exacerbations. Residual airway inflammation on mepolizumab may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations. OBJECTIVE: Our study aimed to explore the corticosteroid-responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms beyond the IL-5 pathway. METHOD: The MAPLE trial was a multi-centre, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in 27 patients treated with mepolizumab for SEA. We analysed paired sputum (n=16) and plasma (n=25) samples from the MAPLE trial using high-throughput Olink® proteomics. We also analysed additional sputum proteins using ELISA. RESULTS: In patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type-2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Neutrophilic pathways were upregulated. Type-2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated. CONCLUSION: At stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab. These effects are heterogeneous and may be clinically relevant in residual exacerbations.

Clonal gamete-mediated polyploid genome design for stacking genomes.

Hybrid vigor in plants confers better agronomically significant traits in offspring compared with either parent. Recently, Wang et al. reported a mitosis instead of meiosis (MiMe) system in tomato for clonal gamete production, showing the potential to exploit autopolyploid progressive heterosis by stacking genomes from four grandparents in tetraploid hybrids, developed from crossing MiMe hybrids.

Toward Modeling the Complexity of the Chemical Mechanism in SERS.

Surface-enhanced Raman scattering (SERS) provides detailed information about the binding of molecules at interfaces and their interactions with the local environment due to the large enhancement of Raman scattering. This enhancement arises from a combination of the electromagnetic mechanism (EM) and chemical mechanism (CM). While it is commonly accepted that EM gives rise to most of the enhancement, large spectral changes originate from CM. To elucidate the rich information contained in SERS spectra about molecules at interfaces, a comprehensive understanding of the enhancement mechanisms is necessary. In this Perspective, we discuss the current understanding of the enhancement mechanisms and highlight their interplay in complex local environments. We will also discuss emerging areas where the development of computational and theoretical models is needed with specific attention given to how the CM contributes to the spectral changes. Future efforts in modeling should focus on overcoming the challenges presented in this review in order to capture the complexity of CM in SERS.

Suture closure AFtEr large bore vein access (SAFE-VEIN): A randomized, prospective study of the efficacy and safety of venous closure device.

BACKGROUND: Perclose ProGlide (PPG) Suture-Mediated Closure System™ is safe and can reduce time to hemostasis following procedures requiring arterial access. AIMS: We aimed to compare PPG to figure of 8 suture in patients who underwent interventional catheter procedures requiring large bore venous access (LBVA) (≥13 French). METHODS: In this physician-initiated, randomized, single-center study [clinicaltrials.gov ID: NCT04632641], single-stick venous access was obtained under ultrasound guidance. Eligible patients were randomized 1:1, and 100 subjects received allocated treatment to either PPG (n = 47) or figure of 8 suture (n = 53). No femoral arterial access was used in any patient. Primary outcomes were time to achieve hemostasis (TTH) and time to ambulation (TTA). Secondary outcomes were time to discharge (TTD) and vascular-related complications and mortality. Wilcoxon rank-sum test was used to compare TTH, TTA, and TTD. RESULTS: TTH (minutes) was significantly lower in PPG versus figure of 8 suture [median, (Q1, Q3)] [7 (2,10) vs. 11 (10,15) respectively, p < 0.001]. TTA (minutes) was significantly lower in PPG compared to figure of 8 suture [322 (246,452) vs. 403 (353, 633) respectively, p = 0.005]. TTD (minutes) was not significantly different between the PPG and figure of 8 suture arms [1257 (1081, 1544) vs. 1338 (1171,1435), p = 0.650]. There was no difference in minor bleeding or access site hematomas between both arms. No other vascular complications or mortality were reported. CONCLUSION: PPG use had lower TTH and TTA than figure of 8 suture in a population of patients receiving LBVA procedures. This may encourage same-day discharge in these patients.

A phase I safety and efficacy clinical trial of plocabulin and gemcitabine in patients with advanced solid tumors.

Plocabulin (Plo) induces depolymerization of tubulin fibers with disorganization and fragmentation of the microtubule network leading to mitosis. Plo combined with gemcitabine (Gem) showed synergistic anti-tumor activity in preclinical studies. This phase I trial evaluated the safety, pharmacokinetics (PK) and efficacy of Plo 10-min infusion plus Gem on Day 1 and 8 every 3-week in patients with advanced solid tumors. Fifty-seven patients were enrolled into 8 dose levels (DLs); 74%: females; 74%: ECOG performance status 1; median age: 62 years; median number of prior lines of therapy:3. Dose-limiting toxicities (DLT) in Cycle 1 were grade (G) 3 intestinal obstruction at the maximum tolerated dose (MTD), G3 peripheral sensory neuropathy (PSN), G3 abdominal pain, and G4 thrombocytopenia (1 patient each). The highest DL (DL8: Plo 10.5 mg/m2/Gem 1000 mg/m2) was the MTD. Accrual into DL7 (Plo 10.0 mg/m2/Gem 1000 mg/m2) was stopped before it was formally defined as the recommended dose (RD). Most common treatment-related adverse events (AEs) were fatigue (56%), nausea (55%), diarrhea (31%); G3/4 hematologic toxicities comprised anemia (35%), neutropenia (27%) and thrombocytopenia (17%). No treatment-related deaths occurred. PK parameters for Gem or dFdU at all DLs were in line with reference values from the literature. Six of 46 evaluable pts were responders (overall response rate:13%). Of note, 2 partial responses (PR) and 2 stable disease (SD) ≥ 4 months occurred among 13 pts with ovarian cancer. The combination of Plo and Gem is well tolerated. The MTD was Plo 10.5 mg/m2/Gem 1000 mg/m2. No PK drug-drug interaction was found. The most encouraging outcome occurred in ovarian cancer patients.

Non-coding RNAs in Parkinson's disease: Regulating SNCA and alpha-synuclein aggregation.

Parkinson's disease is one of the vital neurodegenerative ailments attributed to a rise in Alpha-synuclein proteins leading to the advancement of motor and cognitive deterioration. Interestingly, in PD lncRNAs, miRNAs and siRNAs are also key regulators of SNCA and alpha-synuclein aggregation. This review will focus on the roles of these three types of small RNAs in trebling the development of PD through regulating SNCA expression or alpha-synuclein protein mediating the RNA from acting. Parkinson's disease is defined by the build-up of alpha-synuclein protein resulting predominantly from the elevated expression level of the SNCA gene. Non-coding RNAs have gained broad appeal as fundamental modulators of gene expression and protein aggregation dynamics, with significant implications on the aetiology of PD. LncRNAs modulate SNCA transcription and edit epigenetic modifications, while miRNA target mRNA is involved in the stability and translation of count alpha-synuclein. Considering all these data, siRNAs can achieve the precise gene silencing effect that directly induces the downregulation of SNCA mRNA. This review also summarizes some recent reports about the interaction between these ncRNAs with the SNCA gene and alpha-synuclein protein, each through its independent in addition to synergistic mechanisms. This review highlights the possibility of therapeutic interventions to perturb SNCA expression to prevent alpha-synuclein aggregation via targeting ncRNAs that might be spun off novel drug development for PD.

Theoretical insight into physical characteristics of lead-free perovskites Rb2TlSbX6 (X = Cl, Br, I) for optoelectronic devices.

CONTEXT: Novel optoelectronic and thermoelectric properties with broad compositional range, non-toxic nature and structural stability make halide-based double perovskites fascinating for flexible optoelectronic devices. In this work, the structural electronic, optical and transport properties of Rb2TlSbX6 (X = Cl, Br, I) were studied using density functional theory for optoelectronic devices. The elastic analysis demonstrates ductile nature, mechanical stability, anisotropic behaviour and feasibility for flexible optoelectronic devices. The band structure study using Tran-Blaha-modified Becke-Johnson (TB-mBJ) potential shows that all studied materials have direct bandgap. In addition, the bandgap of Rb2TlSbCl6 is more appropriate for optoelectronic devices. The small loss and maximum absorption in visible regions make these materials prime candidates for optoelectronic devices. The transport features indicate that all the studied double perovskites reflect p-type semiconducting behaviour as highlighted by positive Seebeck coefficient values. Furthermore, the high power factor values of Rb2TlSbX6 (X = Cl, Br, I) double perovskites make them suitable for thermoelectric device applications at high temperatures. Based on electronic optical and thermoelectric properties Rb2TlSbCl6 is the best candidate for flexible optoelectronic devices. METHODS: In this paper, structural optimization of Rb2TlSbX6 (X = Cl, Br, I) double perovskites was conducted utilizing the Wien2k software based on first principle calculations with Perdew-Burke-Ernzerhof's generalized-gradient approximation (PBE-sol approximation). The TB-mBJ potential was employed to compute the accurate band gap of studied materials. The thermoelectric properties are evaluated with BoltzTraP code, showing a predominance of P-type charge carriers in all studied perovskites. This methodological strategy verifies the material's remarkable stability and optical properties and offers a solid framework for examining its potential in optoelectronic devices.

Mitochondrial Function After Normothermic Regional Perfusion or Direct Procurement Followed by Hypothermic Oxygenated Machine Perfusion in Heart Transplantation After Circulatory Death.

BACKGROUND: Strategies to minimize ischemic damage during heart transplantation (HTX) by donation after circulatory death (DCD) are warranted because the inevitable ischemic injury linked to DCD HTX deteriorates mitochondrial respiratory capacity and ultimately graft quality. This study aimed to examine the myocardial mitochondrial function during DCD HTX with hypothermic oxygenated machine perfusion (HOPE) and compare the effect of normothermic regional perfusion (NRP) with that of direct procurement and perfusion (DPP). METHODS: A porcine DCD HTX model was used with hearts subjected to either DPP (n = 6) or NRP (n = 7) followed by HOPE and orthotopic HTX. Mitochondrial respiratory function was analyzed by high-resolution respirometry in left ventricle biopsies at baseline, after 180 min of HOPE, and after 60 min of reperfusion post-HTX. RESULTS: Mitochondrial oxidative phosphorylation (P = 0.0008), respiratory control ratio (P = 0.04), and coupling efficiency (P = 0.04) declined during DCD HTX. Fatty acid oxidation was preserved after 3 h of HOPE with a modest, statistically nonsignificant decline after reperfusion (P = 0.2). Oxidative phosphorylation was inversely correlated with troponin-T levels (r = -0.70, P = 0.0004). No statistically significant difference in mitochondrial respiratory capacity was observed between participants exposed to NRP and DPP. CONCLUSIONS: Mitochondrial respiratory capacity declined gradually throughout the course of DCD HTX and correlated with the degree of myocardial damage. Following HOPE, the extent of mitochondrial deterioration was comparable between NRP and DPP.

Awareness level of idiopathic normal pressure hydrocephalus among health-care providers.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a disease that primarily affects the geriatric population. It was first introduced by Adams et al. in 1965. A gradual decline in cognitive function, urinary incontinence, and gait disturbances characterizes the disease. This condition is believed to be underdiagnosed, and awareness of such pathology is vital, as the treatment is very effective and can reverse the symptoms. Methods: This questionnaire-based cross-sectional study aimed to assess awareness levels regarding iNPH among non-neuroscience healthcare providers in Saudi Arabia. Results: A total of 269 healthcare providers participated in this study, with data collected through an online questionnaire. About 80.6% of the participants had heard of the disease, while 56.5% were aware of the disease symptomology. About 50% of physicians did not encounter iNPH patients in clinical practice. Previous clinical exposure to iNPH patients correlates significantly with an awareness of disease symptoms, investigation, treatment modalities, and outcome. Clinical experience positively impacts physicians' awareness as it correlates with a better understanding of diagnostic methods and disease outcomes. Conclusion: The study highlights the need for targeted educational interventions, especially among family physicians and general practitioners with no previous experience with iNPH patients, as well as interdisciplinary collaboration to address gaps in awareness and enhance early diagnosis of iNPH patients.

Enhanced photocatalytic property of Cu doped Ce2Zr2O7 toward photodegradation of methylene blue under visible light.

Widespread ecosystem degradation from noxious substances like industrial waste, toxic dyes, pesticides, and herbicides poses serious environmental risks. For remediation of these hazardous problems, present study introduces an innovative Cu-doped Ce2Zr2O7 nano-photocatalyst, fabricated via a simple, eco-friendly hydrothermal method, designed to degrade toxic textile dye methylene blue. Harnessing Cu doping for pyrochlore Ce2Zr2O7, structure engineering carried out through a hydrothermal synthesis method to achieve superior photocatalytic performance, addressing limitations of rapid charge carrier recombination in existing photocatalysts. Photoluminescence analysis showed that doped pyrochlore slows charge carrier recombination, boosting dye degradation efficiency. UV-Visible analysis demonstrated an impressive 96 % degradation of methylene blue by Cu-doped Ce2Zr2O7 within 50 min, far exceeding the performance of pristine materials. Trapping experiments clarified the charge transfer mechanism, deepening our understanding of the photocatalytic process. These findings highlight the potential for developing innovative, highly efficient photocatalysts for environmental remediation, offering sustainable solutions to combat pollution. This study not only addresses the limitations of existing photocatalysts but also opens new avenues for enhancing photocatalytic performance through strategic material design.

Identifying risk factors for blood culture negative infective endocarditis: An international ID-IRI study.

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE. Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses. Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963-0.987, p < 0.001). Additionally, factors such as rheumatic heart disease (OR 2.036, 95 % CI 0.970-4.276, p = 0.049), aortic stenosis (OR 3.066, 95 % CI 1.564-6.010, p = 0.001), mitral regurgitation (OR 1.693, 95 % CI 1.012-2.833, p = 0.045), and prosthetic valves (OR 2.539, 95 % CI 1.599-4.031, p < 0.001) are associated with higher likelihoods of negative blood cultures. Our model can predict whether a patient falls into the culture-negative or culture-positive groups with a threshold of 0.104 (AUC±SE = 0.707 ± 0.027). The final model demonstrates a sensitivity of 70.3 % and a specificity of 57.0 %. Conclusion: Caution should be exercised when diagnosing endocarditis in patients with concurrent cardiac disorders, particularly in younger cases.

Chikungunya virus vaccine: a decade of progress solving epidemiological dilemma, emerging concepts, and immunological interventions.

Chikungunya virus (CHIKV), a single-stranded RNA virus transmitted by Aedes mosquitoes, poses a significant global health threat, with severe complications observed in vulnerable populations. The only licensed vaccine, IXCHIQ, approved by the US FDA, is insufficient to address the growing disease burden, particularly in endemic regions lacking herd immunity. Monoclonal antibodies (mAbs), explicitly targeting structural proteins E1/E2, demonstrate promise in passive transfer studies, with mouse and human-derived mAbs showing protective efficacy. This article explores various vaccine candidates, including live attenuated, killed, nucleic acid-based (DNA/RNA), virus-like particle, chimeric, subunit, and adenovirus vectored vaccines. RNA vaccines have emerged as promising candidates due to their rapid response capabilities and enhanced safety profile. This review underscores the importance of the E1 and E2 proteins as immunogens, emphasizing their antigenic potential. Several vaccine candidates, such as CHIKV/IRES, measles vector (MV-CHIK), synthetic DNA-encoded antibodies, and mRNA-lipid nanoparticle vaccines, demonstrate encouraging preclinical and clinical results. In addition to identifying potential molecular targets for antiviral therapy, the study looks into the roles played by Toll-like receptors, RIG-I, and NOD-like receptors in the immune response to CHIKV. It also offers insights into novel tactics and promising vaccine candidates. This article discusses potential antiviral targets, the significance of E1 and E2 proteins, monoclonal antibodies, and RNA vaccines as prospective Chikungunya virus vaccine candidates.

Finite element modeling of stress distribution and safety factors in a Ti-27Nb alloy hip implant under real-world physiological loading scenarios.

Total hip arthroplasty (THA) is one of the most successful orthopaedic interventions globally, with over 450,000 procedures annually in the U.S. alone. However, issues like aseptic loosening, dislocation, infection and stress shielding persist, necessitating complex, costly revision surgeries. This highlights the need for continued biomaterials innovation to enhance primary implant integrity and longevity. Implant materials play a pivotal role in determining long-term outcomes, with titanium alloys being the prominent choice. However, emerging evidence indicates scope for optimized materials. The nickel-free ß titanium alloy Ti-27Nb shows promise with excellent biocompatibility and mechanical properties. Using finite element analysis (FEA), this study investigated the biomechanical performance and safety factors of a hip bone implant made of nickel-free titanium alloy (Ti-27Nb) under actual loading during routine day life activities for different body weights. The FEA modelled physiological loads during walking, jogging, stair ascent/descent, knee bend, standing up, sitting down and cycling for 75 kg and 100 kg body weights. Comparative analyses were conducted between untreated versus 816-hour simulated body fluid (SBF) treated implant conditions to determine in vivo degradation effects. The FEA predicted elevated von Mises stresses in the implant neck for all activities, especially stair climbing, due to its smaller cross-section. Stresses increased substantially with a higher 100 kg body weight compared to 75 kg, implying risks for heavier patients. Safety factors were reduced by up to 58% between body weights, although remaining above the desired minimum value of 1. Negligible variations were observed between untreated and SBF-treated responses, attributed to Ti-27Nb's excellent biocorrosion resistance. This comprehensive FEA provided clinically relevant insights into the biomechanical behaviour and integrity of the Ti-27Nb hip implant under complex loading scenarios. The results can guide shape and material optimization to improve robustness against repetitive stresses over long-term use. Identifying damage accumulation and failure risks is crucial for hip implants encountering real-world variable conditions. The negligible SBF effects validate Ti-27Nb's resistance to physiological degradation. Overall, the study significantly advances understanding of Ti-27Nb's suitability for reliable, durable hip arthroplasties with low revision rates.

Evidence based therapeutic and assessment techniques to rehabilitate post stroke dysphagia patients-A systematic review.

PURPOSE: Dysphagia is most prevalent among post stroke aging adults. This systematic review was conducted to collect evidence-based data regarding assessment and therapeutic techniques used to rehabilitate post stroke dysphagia patients. METHODS: Four major databases including PubMed, Cochrane Library, Science direct and Google scholar were searched systematically using the defined search strategy to target Randomized Controlled Trials conducted from January 2018 to 2023 using the pre-defined search strategy by three independent reviewers. RESULTS: After following PRISMA guidelines, fifteen articles matched the inclusion criteria. Several evidence based therapies like Neuromuscular Electrical Stimulation Therapy, Effortful Swallowing Training, Tongue Pressure Strength and Accuracy Training, Electrical Stimulation of Hyoid Muscles, Modified Chin Tuck Against Resistance exercise, Oral Neuromuscular Training, and Conventional Speech Therapy with Functional Electrical Stimulation were used frequently for the treatment of old age post stroke dysphagia in different rehabilitation centers. Along with this, a list of different assessment methodologies and tools was made that were used including Functional Oral Intake Scale, Fiber optic Endoscopic Evaluation of Swallowing, Penetration Aspiration Scale, Pooling Scale, Video fluoroscopic Dysphagia Scale, Iowa Oral Performance Instrument, Mann Assessment of Swallowing Ability, and Repetitive Saliva Swallowing Test. CONCLUSION: Dysphagia is known to be serious complication of stroke. This systematic review shows a significant impact of therapeutic techniques on post stroke dysphagia patients and demonstrates that neuromuscular electrical stimulation therapy is one of the most effective therapeutic techniques used to rehabilitate post stroke dysphagia patients.