Management of sarcomas in specialist centers delivers significant benefits. In much of the world specialists are not available and development of expertise is identified as a major need. However the terms ‘specialist’ or ‘expert’ center are rarely defined. Our objective is to offer a definition for patient advocates and a tool for healthcare providers to underpin improving the care of people with sarcoma. SPAGN developed a discussion paper for a workshop at the SPAGN 2023 Conference, attended by 75 delegates. A presentation to the Connective Tissue Oncology Society (CTOS) and further discussion led to this paper. Core Principles were identified that underlie specialist sarcoma care. The primary principle is the multi-disciplinary team discussing every patient, at first diagnosis and during treatment. Principles for optimal sarcoma management include accurate diagnosis followed by safe, high-quality treatment, with curative intent. These Principles are supplemented by Features describing areas of healthcare, professional involvement, and service provision and identifying further research and development needs. These allow for variations because of national or local policies and budgets. We propose the term ‘Sarcoma Intelligent Specialist Network’ to recognize expertise wherever it is found in the world. This provides a base for further discussion and local refinement.

Background: Dental education blends theoretical and practical training to prepare students for independent patient care. This study examines the confidence levels of dental students in Umeå regarding independent performance of general dentistry tasks, and whether this confidence changes after clinical training. Methods: Surveys were conducted before and after a summer clinical internship, with s tudents rating their comfort levels on a scale from 0 to 10 for various procedures. Results: Results from 64 initial surveys and 54 follow-up surveys showed no significant difference in confidence before and after the internship. However, confidence levels varied based on whether students had practiced specific tasks during the internship. Students felt least confident in managing acute dental trauma and treating cavities in young children, while they were most confident in tasks like obtaining radiographic surveys and debriding periodontally compromised dentition. Tooth extraction and dental fillings were the most practiced procedures during the internship. Conclusions: The study concludes that the internship between the ninth and tenth semesters does not notably boost students' confidence in specific dental procedures, possibly due to the short duration of the training. Further exploration, including input from clinical supervisors, is suggested to optimize clinical training in dental education.

Background: Gender stereotypes and biases can influence perceptions of competence and suitability for certain medical specialties. Empathy is an important component of an optimal doctor-patient relationship. The scope of our study is to verify the correlation between “empathetic" behavioral style with attention and sensibility to the gender differences of patients of the medical students. Methods: An online survey was conducted using the Jefferson Scale for Empathy (JSE), to measure empathy in the context of health professions education and patient care; and the Nijmegen Gender Awareness in Medicine Scale (N-GAMS), which measures attitudes and assumptions about gender. A total of 234 students (52.1% M; mean age: 22.68±2.48) from Medicine and Surgery at the University of Salerno (Italy) participated, of whom n° 175 were third-year students and n° 59 were fifth-year students. Results: The JSE score shows that male students have higher scores (77.29±12.38) than females (75.91±10.39). Conversely, female students have higher perspective-taking (JSE Factor 1: Male= 51.26±11.84; Female= 52.72±11.88). In addition, third-year students are much more empathetic than their fifth-year colleagues (JSE Score: 3°ys= 77.35±11.46; 5°ys= 74.49±11.33). With reference to the GS, we found that male students have greater sensitivity than their female colleagues (GS: Male= 2.67±0.68; Female= 2.37±0.48); conversely, they have higher scores of gender stereotype towards patients (GRIP: Male= 2±0.88; Female= 1.59±0.61) and doctors (GRID: Male= 1.88±0.89; Female= 1.64±0.63). Also, the third-year students compared to their fifth-year colleagues are characterized by greater gender sensitivity (GS: 3°ys= 2.57±0.62; 5°ys= 2.42±0.57), less bias with respect to patients (GRIP: 3°ys= 1.77±0.79; 5°ys= 1.90±0.78) but, on the other hand, show more stereotypes and prejudices towards doctors (GRID: 3°ys= 1.77±0.81; 5°ys= 1.75±0.74). Conclusions: Humanistic attitudes, including empathy, should be instilled, and evaluated among trainees as an essential part of their postgraduate medical education.

Introduction: In recent years, platelets have been in short supply and high demand. Approximately one in five cardiac surgery patients require platelets. In our safety-net hospital, however, the incidence is over 40%. Renal dysfunction, long cardiopulmonary bypass (CPB) times, and absence of tranexamic acid (TXA) are common risk factors for requiring platelet transfusions. Methods: Our hypothesis was fewer platelets would be transfused within two hours after bypass under these three conditions: creatinine is low, predicted surgery duration is short, and TXA is uniformly administered. Our anesthesia department designed this retrospective before-and-after observational study when the surgery department decided to narrow preoperative criteria respective to these three elements. The Institutional Review Board of Louisiana State University Health Sciences Center Shreveport approved of the protocol and waived individual informed consent. We compared timing of platelet transfusions (within 7 days) in consecutive patients who had CPB during the first ninety days of 2022 to those in 2023 using t-tests in SAS 9.3. Confounders included age, weight, anticoagulants, gender, and the platelet counts and hemoglobin immediately prior to platelet transfusion. Secondary outcomes were postoperative day two creatinine and other components transfused. Results: Preoperatively creatinine tended to be higher in 2022 at 1.5 vs 1.1, reaching significance postoperatively at 1.9 vs 1.1 (p=0.02). Bypass times decreased from 174 to 124 minutes (p=0.06). TXA use increased from 18 of 28 to 26 of 29 patients. Platelet counts increased on bypass from 142 to 173 (p=0.06). Platelet and hemoglobin nadirs were higher (day 3: 8g/dL vs 8.8, p=0.04; 98 vs 138, p=0.005). Platelet units transfused per patient tended to increase (0.75+/-1 vs 0.93+/-1.5); if exposed, patients tended to receive more units (2.1+/-1.3 vs 2.5+/-1.4) sooner. Changes in transfusions for red cells were nonsignificant at 1.97 per patient to 1.21, cryoprecipitate 0.36 to 0.69, and FFP 0.93 to 0.83. Conclusions: This is the first study examining timing of platelet transfusions after bypass. In the present investigation, we measured platelet count during bypass and prothrombin hours after arrival in the intensive care. Platelets were often administered in sets of two because of scarce immediate supply, partly from lack of an agitator table. More importantly, these data support a need for point-of-care thromboelastograms intraoperatively, but the cost has been prohibitive. Some centers’ algorithms list triggers for transfusion by fibrinogen and prothrombin times, available immediately after separation from bypass.

Artificial intelligence (AI) has grown in healthcare in recent years. The UK government recognises AI’s potential to enhance NHS services, yet research on AI in primary care (PC) has received limited attention. AI acceptance presents unique challenges in PC, characterised by fragmented structures, heterogeneous data sources, and multiple government departments. The organisational levels within PC are categorised as macro, meso, and micro levels. Existing research has predominantly focused on micro-level stakeholders. Our online survey addressed this research gap by encom-passing stakeholder perspectives at all levels. The results demonstrate the critical role of me-so-level stakeholders in facilitating AI acceptance. Importantly, a lack of understanding of AI terminology and concepts, concerns over potential job displacement, and the importance of em-pathy in patient care are highlighted as key challenges. Stakeholders also express the need for standardised AI terminology, comprehensive training, and regulatory standards to ensure equi-table and effective AI utilisation. This study lays the foundation for future in-depth interviews and further exploration of AI's role in PC. Observations in secondary care indicate that practitioners have substantial concerns about AI, how it works, and its limitations. Explainable AI can help technologists address such concerns, but first, we need to understand primary care's information needs.

Background: Machine learning can analyze vast amounts of data and make predictions for events in the future. Our group created machine learning models for vital sign predictions. To transport the information of these predictions without numbers and numerical values and make them easily usable for human caregivers, we aimed to integrate them into the Philips Visual-Patient-avatar, an avatar-based visualization of patient monitoring. Methods: We conducted a computer-based simulation study with 70 participants in three European university hospitals. We validated the vital sign prediction visualizations by testing their identification by anesthesiologists and intensivists. Each prediction visualization consisted of a condition (e.g., blood pressure low) and an urgency (a visual indication of the timespan in which the condition is expected to occur). To obtain qualitative user feedback, we also conducted standardised interviews and derived statements that participants later rated in an online survey. Results: The mixed logistic regression model showed 77.9% (95%CI 73.2-82.0%) correct identification of prediction visualizations (i.e. condition and urgency both correctly identified) and 93.8% (95%CI 93.7-93.8%) for conditions only (i.e. without considering urgencies). Forty-nine of 70 participants completed the online survey. The online survey participants agreed that the prediction visualizations were fun to use (32/49, 65.3%), and that they could imagine working with them in the future (30/49, 61.2%). They also agreed that identifying the urgencies was difficult (32/49, 65.3%). Conclusions: This study found that care providers correctly identified >90% of the conditions (i.e. without considering urgencies). The accuracy of identification decreased when considering urgencies in addition to conditions. Therefore, in future development of the technology, we will focus on either only displaying conditions (without urgencies) or improve the visualizations of urgency to enhance usability for human users.

The patient's satisfaction level concerning hospitalization has certain particularities, related to the geographical area, medical/non-medical assistance, the age, incomes, morbidity and mortality of the population. The objective of this study is to emphasize the degree of patients' satisfaction, depending on the specialty of the hospitalization department: surgical, medical, oncological, psychiatry, and to evidence the factors influencing the reliability and accuracy of patients' answers, such as: the patient's health condition upon admission, the duration of the admission, the level of physical pain and the emotional state. Patients and methods: The research was conducted between April and December 2021 on patients hospitalized in two public hospitals from the north-west of Romania, both of them being independent Legal Entities: the Municipal Clinical Hospital of Oradea (MCHO) and the County Clinical Emergency Hospital of Oradea (CCEHO). Results: The lowest score of PSS recorded in these two analyzed public hospitals from the north-western of Romania was appointed for the Pharmaceutical availability of patients medical treatment (2.24), attitude of the staff (2.56) and the quality of nursing care offered (2.58). Conclusions: The hospital management’s focus has been set to improve the communication skills among medical staff, to evidence their compassion, politeness, and to ensure the availability of essential drugs.

Chronic pain is a source of major alterations in quality of life. It represents significant costs for health systems, and reduces the competitiveness of the working population. Vulnerability can drive the incidence of chronic pain, through its influence on modifiable risk factors, and reduced utilization of health care systems. But vulnerability can also be the consequence of a chronic pain: illness can push people into precariousness. We analysed the factors associated with pain intensity among vulnerable persons with a chronic condition, in five European countries (N=1,364). Pain was, among the whole set of variables, the main predictor of sleep problems, fatigue, depression, self-perceived health, physical and mental quality of life. This is in line with other studies showing the major impact of pain on an individual’s health and life. Multivariable analyses, adjusting for the whole set of variables, showed that women had more intense pain, as well as participants with a lower education level. These results confirm the social component in the complex etiology of pain and clearly plaid in favor of integrated care, taking into account individual characteristics and environment.

A human case of dengue virus 2 was detected from a febrile patient living in the Sare yoba, Kolda region (Southern Senegal). Phylogenetic analysis based on the partial sequence of the NS5 gene reveals that the virus belongs to the DENV2 Sylvatic genotype and is closely related to a strain (JF260983/ 98.98% identity) detected in Spain from a tourist who travelled to Guinee Bissau (bordering Kolda region) in 2009. This highlights a potential recent underreported circulation of sylvatic Dengue in the southern part of Senegal and calls for re-enforced integrated surveillance among humans, non-human primates and arboreal mosquitoes throughout a one-health approach.

Diabetes mellitus (DM) and obesity account for the highest burden of non-communicable diseases. There is increasing evidence showing therapeutic patient education (TPE) as a clinically and cost-effective solution to improve biomedical and psychosocial outcomes among people with DM and obesity. The present systematic review and meta-analysis presents a critical synthesis of development of TPE interventions for DM and obesity and the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. A total of 54 of these RCTs were identified among patients with obesity and diabetes and were thus, qualitatively synthesized. Out of these, 47 were included into quantitative synthesis. There was substantial heterogeneity in reporting of these outcomes (I²= 88.35%, Q= 317.64), with significant improvement (SMD=0.36, 95% CI: 0.23 to 0.49) noted in biomedical outcomes in the intervention group. The effect sizes were comparable across interventions delivered by different modes and delivery agents. These interventions can be delivered by allied health staff, doctors or electronically as self-help programs, with similar effectiveness (P < 0.001). These interventions should be implemented in healthcare and community settings to improve health of patients suffering from DM and obesity.

Background: The cumulative number of patients during the COVID-19 pandemic led to a significant shortage of hospital beds. Many patients may not require hospitalization and can be clinically observed in home settings. However, some psychosocial factors are correlated with unsuccessful home isolation (HI), which might negatively affect the transmission control in the community. Therefore, we developed a new psychosocial screening tool (CCPHIET) for assessing HI suitability and examined its validity and reliability.Methods: This cross-sectional descriptive study included COVID-19 patients who were deemed to be medically safe for 14 days of HI. The CCPHIET is comprised of 8 clinical domains pertinent to HI behavioral compliance and risk. We explored its statistical validity and reliability and discussed the potential utility of this tool. Results: A total of 65 COVID-19 patients participated in this study. Most patients (58.5%) were evaluated as good candidates for HI. The CCPHIET has an acceptable content validity (IOC index > 0.5), moderate internal consistency (Cronbach’s alpha = 0.611) and substantial to excellent inter-rater reliability (Intraclass correlation coefficient = 0.944, Cohen’s kappa= 0.627).Conclusions: To compromise between strict and costly absolute institutional quarantine and the potentially unsuccessful absolute HI, the CCPHIET may help to identify good candidates for HI in mild and asymptomatic COVID-19 patients. This psychosocial information would support the physicians in matching each patient to the most suitable setting. Therefore, safe medical care is provided, unnecessary use of medical resources is spared, and local transmission is contained.

Treating a patient with traumatic brain injury requires an interdisciplinary approach because of the pervasive, profound and protean manifestations of this condition. In this review, key aspects of the medical history and review of systems will be described in order to highlight how the role of any provider must evolve to become a better patient advocate. Although this review is written from the vantage point of a vision care provider, it is hoped that patients, caregivers and providers will recognize the need for the team approach; it truly takes a village.

This study was conducted to determine whether overcrowding in the emergency department (ED) affects the occurrence of a return visit (RV) within 72 hours. The crowding indicator of index visit was the average number of total patients, patients under observation, and boarding patients during the first 1 and 4 hours from ED arrival time and the last 1 hour before ED departure. Logistic regression analysis was conducted to determine whether each indicator affects the occurrence of RV and post-RV admission. Of the 87,360 discharged patients, 3,743 (4.3%) returned to the ED within 72 hours. Of the crowding indicators pertaining to total patients, the last 1 hour significantly affected decrease in RV (p=0.0046). Boarding patients were found to increase RV occurrence during the first 1 hour (p=0.0146) and 4 hours (p=0.0326). Crowding indicators that increased the likelihood of admission post-RV were total number of patients during the first 1 hour (p=0.0166) and 4 hours (p=0.0335) and evaluationg patients during the first 1 hour (p=0.0059). Overcrowding in the ED increased the incidence of RV and likelihood of post-RV admission. However, overcrowding at the time of ED departure was related to reduced RV.

Background Critical patients with novel coronavirus pneumonia ( COVID-19) have worse outcome and high mortality. However, the histopathology of critical patient with COVID-19 remains undisclosed. Methods We performed the whole lung biopsy, and described the pathological changes of critical COVID-19 patient done with transplant by HE staining, immunohistochemistry and special staining observed under the microscopy. Findings The whole lungs displayed diffuse congestive appearance and partly haemorrhagic necrosis on gross examination. The haemorrhagic necrosis was prominently present in outer edge of the right lower lung. The cut surfaces of the lung displayed severe congestive and haemorrhagic changes. The main pathological changes showed massive pulmonary interstitial fibrosis, and partly hyaline degeneration, variable degrees of hemorrhagic pulmonary infarction. Small vessels hyperplasia, vessel wall thickening, lumen stenosis, occlusion and microthrombosis formation. Focal monocytes, lymphocytes and plasma cells infiltrating into pulmonary interstitium. Bronchiolitis and alveolitis with proliferation, atrophy, desquamation and squamous metaplasia of epithelial cells. Atrophy, vacuolar degeneration, proliferation, desquamation and squamous metaplasia in alveolar epithelial cells. Alveolar cavity congestion was prominent, and contained mucus, edema fluid, desquamated epithelial cells, and inflammatory cells. We also found several multinucleate giant cells and intracytoplasmic viral inclusion bodies. Special stains including Masson stain, sirius red staining, reticular fibers staining indicated massive pulmonary interstitial fibrosis. Immunohistochemistry showed positive for immunity cells including CD3, CD4, CD8, CD20, CD79a, CD5, CD38 and CD68. Interpretation We demonstrate the pathological findings of critical patient with COVID-19, which might provide a deep insight of the pathogenesis and severity of this disease.

Patient derived model systems are important tools for studying novel anti-cancer therapies. Patient derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient derived models for radiation research including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

Patient engagement is receiving a growing attention in the healthcare context. However, although worldwide healthcare stakeholders agree that patient engagement is a priority for quality and effective care, no shared recommendations on how to promote patient engagement are currently available. Based on these premises, a Consensus Conference (CC) was promoted to address four main issues: What is the definition of Patient Engagement? How measuring Patient Engagement? What are the most recommended methodologies and the tools to promote Patient Engagement? What is the role of new technologies in promoting of Patient Engagement? The consensus was obtained through an iterative process that began with a systematic synthesis of the available literature in each domain followed by plenary expert discussions. This CC - including the systematic analysis of internationals scientific evidences (2749 sources across the major international scientific databases) together with experiences of a multi-disciplinary consortium of investigators and key stakeholders - attempted to provide the first evidence-based Expert Consensus Statement for the promotion of Patient Engagement in chronic care. These recommendations should be envisaged as inspirational principles to promote a real eco-system of engagement and might orient health services research and interventions.

1) Public health remains a tiny portion of the undergraduate pharmacy curriculum and the material is integrated into other modules. The objective of this study is to describe the UK undergraduate pharmacy curriculum, including its public health content; 2) Methods: A qualitative method (content analysis of websites) was used to describe the UK undergraduate pharmacy curriculum and teaching and learning policy. This involved selecting relevant concepts and then quantifying their presence and the relationships between them. The NVivo software was used to carry out ‘group queries’ and visualisation of results; 3) Results: Public health remains an optional module in the curricula of many UK schools of pharmacy. Several public health-related topics are often integrated into other modules, but UK undergraduate pharmacy curricula are still dominated by traditional pharmacy modules; and 4) Conclusions: Most of the curricula analysed were dominated by traditional pharmacy modules designed to enhance students' knowledge and skills. The skill set of UK pharmacy students with respect to macro-level public health activities needs to be improved in order to enhance pharmacists’ contribution to public health.

Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies.

This article explores the relationship between convex functions defined on integers ($\mathbb{Z}$) and their extension to real numbers ($\mathbb{R}$). We introduce key definitions and investigate the hypothesis that there exists a unique convex curve within this family of functions, leading to a proof by contradiction. Our findings highlight the preservation of convexity as functions transition from integers to real numbers.

Among the alternatives pointed out as able to make livestock a more efficient activity and reduce its environmental impact, the use of feeds with high digestibility and the use of non-conventional fodder species can be highlighted. Tithonia diversifolia (Hemsl.) A. Gray (TD) has already gained attention as a feed for ruminants. Nonetheless, there has been little discussion about the impacts of this plant on the rumen dynamics that lead to better animal performance. The aim of this study was to assess how increasing levels of TD could affect ruminal microbial biomass synthesis, degradability, and in vitro gas production (IVGP) of diets. Four diets were evaluated: a control diet (TD0: 400 g kg-1 soybean meal and corn grain, and 600 g kg-1 Tifton 85 hay (Cynodon spp)) and three increasing levels of TD (TD9: 90, TD27: 270, and TD45: 450 g kg-1 – dry matter basis) as a replacement for dietary roughage. A 96-hour IVGP assay was carried out and five incubation times (2, 4, 10, 24, and 96 hours) were used for degradability determination. Gas produced, methane (CH4), degradability of organic matter (IVDOM), short-chained fatty acid (SCFA) production, partitioning factor (PF), and microbial biomass (MB) were evaluated among treatments. There was no significant effect (P&gt;0.05) between TD inclusion and IVGP at most incubation times; only at 6 hours of incubation did gas production increase linearly with TD inclusion (R2=0.19; P&lt;0.05). TD inclusion had no effects on CH4. IVDOM increased linearly with TD inclusion at 6 and 10 hours, with TD45 being more degradable than the control diet at 6 hours only. There was a positive linear relationship (R2=0.20; P&lt;0.05) between TD inclusion and PF. TD45 had significantly higher PF values than the control. MB also increased linearly (R2=0.30; P&lt;0.05) with TD inclusion, and all diets with TD had significantly more MB than the control diet. The inclusion of TD at the levels used in this work was revealed to have a positive impact on microbial protein synthesis, which could be related to the higher microbial efficiency of increased substrate quality.

Oxalate, a compound produced by many edible plants and as a terminal metabolite in the liver of mammals, is a toxin that has a detrimental role to human health. Humans and other mam-mals do produce the enzymatic machinery to degrade oxalate. However, numerous oxa-late-degrading bacteria reside in the mammalian gut and thus provide an important function for hosts. The current review focuses on the environmental factors that influence the efficacy of pro-biotic oxalate-degrading bacteria, relative to oxalate metabolism. We describe the mechanism of oxalate catabolism and its consumption by obligate and facultative anaerobic oxalate-degrading bacteria, in both in vitro and in vivo environments. We also explore the environmental variables that impact oxalate degradation. Studies on single species degrade oxalate have not shown a strong impact on oxalate metabolism especially in high oxalate conditions such as consumption of foods high in oxalate (such as coffee and chocolate for humans or halogeton in animal feed). Considering effective variables which enhance oxalate degradation could be used in application of effective probiotic as a therapeutic tool in individuals with hyperoxaluria. This study indicates probiotics can be considered a good source of naturally occurring oxalate degrading agent in human colon

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the artificial regulation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. First, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan-qPCR assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.

Bioactive fractions were isolated from the leaves extract of Kalanchoe pinnata and subjected to scrutiny for their prospective anti-obesity properties. An array of in vitro phytochemical, antioxidant, and enzyme inhibition assays were executed, which dis-cerned fractions F1 and F2 as the most effective fractions. These fractions were sub-sequently studied through in vivo experiments, affirming that F2 as the most potent fraction. Further characterization of F2 was conducted via HPTLC MS-MSn tech-niques. The outcomes demonstrated that F2 produced a notable anti-obesity effect in obese mice, reducing their body weight and lipid metrics, and leading to advanta-geous changes in their organs. An analytical examination of F2 revealed the existence of four principal compounds, which were subsequently subjected to in silco molecular docking and dynamic analysis, confirming their aptitude for binding to selected pro-teins. These findings imply that the utilization of Kalanchoe pinnata leaves could pro-vide a promising therapeutic strategy for the treatment of obesity.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

Knowledge about ecological conditions and processes in centers of endemism (CoEs) is still limited with respect to various systematic groups of organisms, ecosystem types, ecological conditions and ecosystem functions. Endemics and CoEs play a prominent role in nature conservation monitoring and management, and in the organization of zoos, aquaria and botanical gardens. We review the meaning of different groups of organisms and indicators for the characterization of endemic-rich regions, the importance of heterogeneity in space, continuity in time, isolation and ex-situ management for the survival of endemic and threatened species. Currently, conversion of land cover and land use change are the most important causes of biodiversity decline and extinction risk of endemic and endangered species concentrated in CoEs. These are followed by climate change, including severe weather, and then natural processes such as volcanism, landslides or tsunamis. For conservation purposes the management of zoos, aquaria, botanical gardens, of regional land use, and social aspects of the diversity of endemics and CoEs have to be taken into account as well. We need better answers to questions about the relationship between ecoregions, CoEs and regional awareness of biodiversity, which is linked with human culture including the management of zoos, aquaria and botanical gardens, aesthetics, wellbeing, health and trade.

Introduction: The combination of Virtual Screening (VS) techniques with in vivo screening in the zebrafish model is currently being used in tandem for drug development in a faster and more efficient way. Areas covered: We review the different virtual screening techniques, the use of zebrafish as a vertebrate model for drug discovery and the synergy that exists between them. Expert opinion: We highlight the advantages of combining virtual and zebrafish larvae screening for drug discovery. On the one hand, VS is a faster and cheaper tool for searching active compounds and possible candidates for therapy than in vivo screening when processing large compound libraries. On the other hand, zebrafish larvae form a vertebrate model which allows in vivo screening of large amounts of the compounds. Importantly physiology and chemical response are mostly conserved between zebrafish and mammals. The availability of the transgenic and mutant zebrafish lines allows an analysis of a specific phenotype upon treatment along with toxicity, off-target effect, side effects, and dosage. Advantages of VS, in vivo whole animal approach screening, and the screening combinations are also reviewed.

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

Background: Retinal diseases such as neovascular age related macular degeneration (nAMD), diabetic macular edema (DME) or branch-/central retinal vein occlusion (B/CRVO) have significant implications for patients' social and psychological well-being. To gain a comprehensive understanding of patients' backgrounds and attitudes, we developed an exploratory questionnaire, the Basic Care and Patient Satisfaction Questionnaire (BPZ-9). Methods: The ALBATROS study aimed to assess the care situation of treatment-naïve patients diagnosed with either nAMD, DME or B/CRVO. The data collection took place at the beginning of treatment and after twelve months of anti-VEGF (vascular endothelial growth factor) therapy. The BPZ-9 instrument comprises nine questions to evaluate patients’ psychological and social situation and their satisfaction with treatment. Results: Data were collected from 1.478 nAMD (mean 78 years), 445 DME (67 years), 233 BRVO (70 years) and 144 CRVO (71 years) patients at 102 study centers throughout Germany. Approximately one third of the patients was living alone and six percent were in organized care. One in four patients had difficulties to walk and one in five needed accompany for treatment. Anxiety to lose vision was present in three out of four patients at the beginning and slightly decreased to two out of three over the 12-month treatment preriod. The distress of having a retinal disease was generally higher than the distress related to treatment. Most patients reported high treatment satisfaction (73%) and felt well informed (81%). Conclusion: Patients receiving anti-VEGF therapy commonly experience impaired mobility, dependency on others, distress and the fear of vision loss.

Outcome of redo-mitral valve replacement in the small mitral annulus with the use of the chimney technology is not well documented. From 2019 to 2020, 77 consecutive patients underwent redo-mitral valve replacement with the use of the chimney technology because of a small mitral annulus. To evaluate heart structural integrity and clinical outcomes, postoperative clinical data and echocardiograms were examined. Mean age was 56.7 ± 15.98 years. All patients underwent mitral valve surgery of which 62 were mitral valve replacements, 7 mitral valve repairs, and 8 double valve replacements. Preoperative Mitral valve mean gradient was 18.07 ± 9.40 mmHg. Postoperative mitral prosthesis size 28.51 ± 1.22 mm. The median increment of mitral size enlargement was 4 (0, 6) valve sizes. Mean mitral gradient coming out of the operating room was 10.34 ± 2.12 mmHg and at follow-up echocardiogram performed at 3 years after the procedure was 10.36 ± 1.70 mmHg. One-year survival was 93.3%, while 4-year survival was 89.3% with no reoperation. Use of the chimney technology in small mitral valve re-mitral valve replacement results in larger valve sizes. Moreover, the mean gradients over the mitral valve are acceptable intraoperatively and over time.

The intensive care unit is characterized by the critical care of the infants and children who access it, as well as the high complexity of care. This implies and requires optimal integration among the various professionals working there and their ability to work as a team. The purpose of the study was to describe how nurses perceive clinical risk and how they relate to it and to identify adverse events and related risk factors. Nine nurses, two moderators and one external observer partici-pated in the focus group. In the qualitative analysis, 9 themes describing the perception of clinical risk in PICU were identified, including teamwork, specific training, time management, team communication, management, individual errors, structural criticality, patient fac-tors/characteristics, and standardization. Safety culture can be fostered by hospital management to involve PICU nurses in promoting patient safety, which could improve breaking down barriers that prevent nurses from fulfilling their roles.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable disease. The first PREM (Patient Reported Outcome Measure) type questionnaire that has been dedicated to asses experience of care in COPD is the PREM-C9. Aim: To create a Polish version of the PREM-C9 and determine its the psychometric characteristics. Methods: The validation procedure involved forward and back translation and included 42 COPD patients. The psychometric properties were assessed using Cronbach's alpha, Bartlett's test, Kaiser-Meyer-Olkin and Spearman correlation coefficient. The validity of the questionnaire was assessed using Principal Component Analysis for the extracted principal components. The validity of the factor analysis was demonstrated by the Bartlett's sphericity test and the Kaiser-Meyer-Olkin (KMO). Factor analysis was performed using the Oblimin and Varimax rotation. The reliability of the questionnaire was assessed using the Cronbach's alpha. Results: The Polish version of the PREM-C9 questionnaire met all validation criteria: face, translation, psychometric, functional and reconstruction equivalence. The Spearman correlation results between Polish PREM-C9&amp;CAT: rho= 0,44, p=0,003539; HADS-Anxiety: rho= 0.370864, p=0,015612, HADS-Depression: rho= 0,387405, p=0,011253. Conclusion: The developed Polish PREM-C9 questionnaire is a reliable and valid tool that assesses Polish COPD patients' experiences of their disease and the care they receive.

Type 1 diabetes imposes a complex and challenging routine on patients and caregivers. Therefore, considering individual experiences and personal facilitators to promote assertive interventions is crucial. However, no studies have addressed these perspectives in the Brazilian adult population. We aimed to identify psycho-behavioral characteristics perceived as facilitators for coping with the condition. We used a biographical method to conduct semi-structured, face-to-face, in-depth interviews for each participant. Transcripts were analyzed using inductive thematic analysis. Participants (n = 22) were aged 18–57 years (mean: 30.2, standard deviation (SD): 8.7), and the duration since diagnosis was approximately 20.6 years (SD: 4.6). Twelve (54.4%) were women, 13 (59.1%) used insulin pumps, 14 (63.6%) had at least a college degree, and 13 (59.1%) had HbA1C (glycated hemoglobin) levels above 58 mmol/mol (7.5%). Five major themes emerged: 1) peer learning, 2) ownership, 3) welcoming experiences, 4) equity, and 5) reframe the path (P.O.W.E.R.). All themes appeared in the lived experiences shared by participants with HbA1C levels below 58 mmol/mol (7.5%). Improved glycemic control can be achieved, and the challenges encountered in diabetes care within similar socioeconomic contexts can be addressed, by an interdisciplinary care team that takes P.O.W.E.R into consideration when providing person-centered care strategies.

Esophageal cancer is a formidable challenge in the realm of cancer treatment. Conventional methods such as surgery, chemotherapy, and immunotherapy have demonstrated limited success rates in managing this disease. In response, targeted drug therapies have emerged as a promising strategy to improve outcomes for patients. These therapies aim to disrupt specific pathways involved in the growth and development of esophageal cancer cells. This review explores various drugs used to target specific pathways, including cetuximab and monoclonal antibodies (gefitinib) that target the epidermal growth factor receptor (EGFR), trastuzumab that targets human epidermal growth factor receptor 2 (HER-2), drugs targeting the vascular endothelial growth factor receptor (VEGFR), mTOR inhibitors, and cMET inhibitors. Additionally, the article discusses the impact of drug resistance on the effectiveness of these therapies, highlighting factors such as cancer stem cells, cancer-associated fibroblasts, immune-inflammatory cells, cytokines, hypoxia, and growth factors. While drug targeting approaches do not provide a complete cure for esophageal cancer due to drug resistance and associated side effects, they offer potential for improving patient survival rates.

Ketogenic dietary therapies (KDTs) are an effective and safe non-pharmacological treatment for drug-resistant epilepsy, but adherence can be challenging for both patients and caregivers. In Europe, there are no adequate tools to measure it other than monitoring ketosis. This study aimed to adapt and validate the Brazilian adherence questionnaire, Keto-check, into the Italian version: iKetoCheck. Using the Delphi technique, 12 judges validated the contents through agreement rate and the Content Validity Index (CVI). The iKetocheck was self-completed electronically by drug-resistant epilepsy or GLUT1 deficiency patients within an interval of 15 days to measure its reproducibility. Test-retest reliability was evaluated using Pearson correlation and relative significance test. Exploratory and confirmatory factorial analyses were made using Factor software. The final tool, iKetoCheck, consists of 10 questions with 5-point Likert scale answers. It evaluates various aspects such as informing caregivers about the diet, organization of meals, measurement of ketosis, weighing food consumed, diet negligence, use of carbohydrate-free medications, attending follow-up visits, reading food labels, consulting an expert for dietary concerns, and cooking at home. The factorial analysis resulted in three factors: "attention," "organization," and "precision," with satisfactory results for indices in exploratory and confirmatory analyses. Although higher mean values of ketonemia measurement were observed in patients with a higher adherence score, these values were not statistically significant (p=0.284). In conclusion, iKetoCheck is a valid tool for evaluating KDTs' adherence in Italian drug-resistant epilepsy or GLUT1 deficiency patients. It can provide valuable information to improve patient management and optimize the effectiveness of KDTs.

There has been limited research on improving Internet-delivered Cognitive Behavioural Therapy (ICBT) in routine online therapy clinics that serve people from diverse ethnocultural groups (PDEGs). This article describes a patient-oriented adaptation approach used to address this gap in research. A working group consisting of people with lived experience, community stakeholders, ICBT clinicians, managers, and researchers, was formed. The working group examined archival feedback on ICBT from past clients who self-identified as being from diverse ethnocultural back-grounds (N=278) and results of interviews with current patients (N=16), community stakeholders (N=6), and clinicians (N=3). The archival data and interviews revealed the majority of the pa-tients reported being satisfied with and benefitting from ICBT. Suggestions for improvement were not related to the cognitive-behavioural model and techniques, but rather to making treatment materials more inclusive. Consequently, the ICBT adaptation focused on adding content related to cultural influences on mental health, addressing stigma, diversifying case stories, examples and imagery, adding audiovisual introductions, and replacing English idioms with more descriptive language. Moreover, further training was offered to clinicians and efforts were made to improve community outreach. This study demonstrates a process for using patient-oriented research to improve ICBT within routine care serving patients of diverse backgrounds.

Cloud computing appears to be the dreamed vision of the healthcare industry; it refers to means of storing and accessing data and programs over the internet instead of the computer’s hard drive. However, the adoption of cloud computing requires solving several issues and infor-mation privacy is a major one. This work proposes a cloud architecture design for the healthcare information system. The proposed architecture enables for storing and sharing information in a privacy-preserving manner. Patients’ information in the proposed architecture is divided into four categories identified in the case study data analysis. User identity management protocol (U-IDM) is employed for controlling the access to patients’ information, and patients have means of control over who can access their information. A scenario-based instantiation validated the proposed architecture's privacy-preserving patient data exchange. The instantiation proved that the proposed architecture allows sharing healthcare information without violating the privacy of patients.

The COVID-19 pandemic has presented an unprecedented challenge to the healthcare system. Identifying the genomics and clinical biomarkers for effective patient stratification and management is critical to controlling the spread of the disease. Omics datasets provide a wealth of information that can aid in understanding the underlying molecular mechanisms of COVID-19 and identifying potential biomarkers for patient stratification. Artificial intelligence (AI) and machine learning (ML) algorithms have been increasingly used to analyze large-scale omics and clinical datasets for patient stratification. In this manuscript, we demonstrate the recent advances and predictive accuracies in AI and ML-based patient stratification modeling linking omics and clinical biomarker datasets, focusing on COVID-19 patients. Our ML model not only demonstrates that clinical features are enough an indicator of COVID-19 severity and survival but also infers what clinical features are more impactful, which makes our approach a useful guide for clinicians for prioritization of best-fit therapeutics for a given cohort of patients. Moreover, with weighted gene network analysis, we are able to provide insights into gene networks that have a significant association with COVID-19 severity and clinical features. Finally, we have demonstrated the importance of clinical biomarkers in identifying high-risk patients and predicting disease progression.

Denture wearers often complain about jeopardized function and reduced quality of life due to lack of prosthesis’ retention. Implant retained mandibular overdentures, on 2 non-connected implants (2IOD) are well-proven solutions to overcome these issues. We prospectively assessed 69 patients and scrutinized clinical records until at least 7 years of function. Thirty-six were retained on Locator ® Abutments (LA) and thirty-tree on Ball Abutments (BA). Both systems were compared regarding the type, amount and total cost of required maintenance. One implants was lost, yielding 98.7% survival after 7 years. In total 438 technical issues occurred: 121 (27.35%) in BA and 317 (72.4%) in LA. Out of these, 343 events (78%) were solved chairside: 191 (43.6%) were replacements of retention caps, 113 (25.8%) were minor acrylic repairs, in 26 (5.9%) pressure ulcers had to be relieved and 13 (3%) related to abutments. LA required 179 insert replacements compared to 12 in the BA group. The overall initial treatment cost was 3850 euro. The average total maintenance cost in relation to the initial cost for the LA and BA groups was 19.11% (range 0% - 82.24%) and 18.91% (range 0% - 113.26%) respectively (P=0.540). Conclusions: The 7-years maintenance costs for a 2IOD is acceptable when the patient is regularly checked and professionally maintained. Most events are easily solvable chairside, but a few patients required more expensive interventions, regardless of the type of attachment used.

Objectives: The purpose of this systematic review was to ascertain critical care nurses’ understanding and experiences of patient advocacy in adult critical care settings. The specific objectives were to identify how critical care nurses define patient advocacy, to explore the understanding and experiences of critical care nurses regarding patient advocacy, to explore critical care nurses’ role in patient advocacy, and to ascertain the barriers to encouraging advocacy in the critical care setting. Research design: Systematic literature search of CINAHL and Medline databases, Google Scholar, and Cochrane Database of Systematic Reviews, as well as grey literature search, was conducted. Search dates were restricted from January 2005 to 2015 in both CINAHL and Medline. Findings: 62 studies were identified, of which 6 qualitative research papers were included. Nurses gave varied definitions of patient advocacy, which were categorized into three themes: communication, protection, and doing. Nurses perceive advocacy as truly listening to patients and their families. Conclusion: For critical care nurses to be effective advocates, there must be support, collaboration, and improved working relationship between professional groups. Moreover, nurses must be empowered to be able to give power to patients and family.

Patient-derived xenograft (PDX) models are created by engraftment of patients’ tumor tissues into immunocompetent mice. Since PDX model keep the characteristics of primary patient’s tumor such as gene expression profiles and drug sensitivity, it now becomes most reliable in vivo human cancer model. The engraftment rate are increased with the introduction of NOD/Scid based immunocompromised mice, especially, NK cell defective NOD strains such as NOD/Scid/IL2Rγnu (NOG/ NSG) mice and NOD/Scid/Jak3null (NOJ) mice. Success ratio differs from the origin of tumor: Gastrointestinal tumors tend to higher success rate and breast cancer is lower. Subcutaneous transplantation is most popular method to establish PDX, but some tumor needs orthotropic or renal capsule transplantation, and human hormone treatment is needed to establish hormone dependent cancers such as prostate and breast cancer. PDX library with patient’s clinical data, gene-expression patterns, mutational status, drug responsiveness and tumor architecture will be the powerful tool for developing specific biomarker and novel individualized therapy and establishing precision cancer medicine.

Background: Even though a number of studies have verified the positive effect of physical activity (PA) on self-related health (SRH) no previous research has examined this association among pediatric patients with Type 1 diabetes mellitus (T1DM). Objective: The purpose of this study was to investigate the association between regular physical activity (PA) and self-rated health (SRH) in pediatric patients with Type 1 diabetes mellitus (T1DM) who lacked diabetes care. Methods: We conducted a retrospective study among pediatric patients with T1DM who lacked diabetes care and were enrolled in a diabetes education program between January 2011 to January 2015 at the endocrinology clinic of Seoul National University Children’s Hospital in South Korea. The eligible participants for this study were 37 pediatric patients with T1DM aged 9 to 17 years. PA was divided into regular PA and muscle strength exercise to analyze the relationship with SRH using binomial logistic regression analysis. Results: The results showed SRH of pediatric patients with T1DM who did not engage in regular PA was significantly lower than those who did (OR in regular PA = .199 [95% CI: .040, .995]; OR in regular muscle strength exercise = .097 [95% CI: .023, .825]). Conclusions: In conclusion, regular PA and muscle strength exercise in pediatric patients with T1DM who lacked diabetes care were effective in improving their SRH. A systematic plan is required to enhance regular PA for pediatric patients with T1DM.

Background. The Stanford Health Assessment Questionnaire-Disability Index (HAQ) is widely used to measure functional ability in persons with Rheumatoid Arthritis (RA). The instrument was developed with limited involvement from persons with RA, and their perception of the instrument has not been studied in depth. The aim of this study was to explore how persons with RA experience the use of the HAQ in care. Methods. Forty persons with RA were purposefully recruited to participate in semi-structured interviews. The interviews were then analyzed qualitatively using thematic analysis. Results. The participants questioned the relevance of the HAQ but nevertheless experienced that the instrument had a profound effect on their understanding of health and how care is delivered. The analysis resulted in three themes: Problems with individual items, meaning of the summative score, and effects on care and health perceptions. Conclusions. To make the HAQ relevant to persons with RA, it needs to be revised or to include an option to select items most meaningful to the respondent. To ensure relevance, the HAQ update should preferably be co-created by researchers, clinicians and persons with RA.

This comprehensive study delves into the implementation and effectiveness of the flipped classroom model in engineering EMI (English as a Medium of Instruction) courses in Taiwan. Situated within the strategic framework of Taiwan's Bilingual Nation 2023 policy, this research aims to enhance the global competitiveness of Taiwan's semiconducting manufacturing engineering sector. The study’s primary focus is on understanding the perceptions and learning outcomes of EFL (English as a Foreign Language) students in engineering courses. Through a methodical approach using descriptive statistics and chi-square tests, the study analyzes data from 33 junior engineering students specializing in mechanical and mechatronic fields. The findings highlight a significant positive influence of the flipped classroom model on various aspects of student learning, including increased engagement, heightened creativity, and enhanced problem-solving skills. Additionally, the study emphasizes the critical role of timely L1 support in facilitating effective learning in EMI settings. These outcomes not only demonstrate the flipped classroom's viability as a sustainable educational approach but also provide crucial insights for educators and policymakers. By aligning cutting-edge teaching methods with the evolving needs of engineering education, this study contributes to the discourse on educational innovation. It ultimately guides the development of future engineering programs that cater to diverse student needs and fosters the cultivation of skilled engineering professionals.

This study was to designed to develop sorafenib-loaded polymeric nanoparticles, surface-modified with pluronic F-127 for the effective treatment of hepatocellular (HCC) and renal cell carcinomas (RCC). Poly lactic coglycolic acid (PLGA) was used to encapsulate different concentrations of sorafenib by a simple modified solvent evaporation method applying pluronic F-127 as a surfactant and coating agent. The preformulation and characterization studies were conducted to evaluate the incompatibilities among sorafenib, PLGA and pluronic F-127, and physicochemical properties of the formulations, respectively. The sizes of the coated and plain PLGA nanoparticles were ~140 ± 14.7 nm and ~ 120 ± 10.1 nm, respectively. It has been confirmed from the in vitro release studies that PLGA sustained the release of sorafenib, avoiding the initial burst release, while the in vivo studies demonstared that surface-modified nanoparticles have greater affinity in the target aorgans than plain PLGA nanoparticles and free drug keeping the dose constant (20 mg/kg body weight). The delivery of sorafenib-loaded polymeric PLGA nanoparticles into the target tissues and their pharmacokinetic parameters have been improved significantly compared to the reported formulations.

The pinning force density FpJc,B=Jc×B (where Jc is the critical current density and B is the applied magnetic field) is one of the main parameters that characterize the resilience of a superconductor to carry a dissipative-free transport current in an applied magnetic field. Kramer (1973 J. Appl. Phys. 44 1360), and Dew-Hughes (1974 Phil. Mag. 30 293) proposed a widely used scaling law for the pinning force density amplitude: FpB=Fp,max×p+qp+qppqq×BBc2p×1-BBc2q, where Fp,max, Bc2, p, and q are free-fitting parameters. Since the late 1970-s till now, several research groups have reported experimental data on the dependence of Fp,max on the average grain size, d, in Nb3Sn-based conductors. Godeke (2006 Supercond. Sci. Techn. 19 R68) proposed that the dependence obeys the law Fp,maxd=A×ln1d+B. However, this scaling law has several problems, for instance, the logarithm is taken from a non-dimensionless variable, and Fp,maxd&lt;0 for large grain sizes, and Fp,maxd→∞ for d→0. Here, we reanalysed the full inventory of publicly available Fp,maxd data for Nb3Sn conductors and found that the dependence can be described by Fp,maxd=Fp,max0×exp-dδ law, where the characteristic length, δ, varies within a remarkably narrow range, that is, δ=175±13 nm, for samples fabricated by different technologies. The interpretation of the result is based on the idea that the in-field supercurrent flows within a thin surface layer (thickness of δ) near the grain boundary surfaces (similar to London’s law, where the self-field supercurrent flows within a thin surface layer with a thickness of the London penetration depth, λ, and the surface is a superconductor-vacuum surface). An alternative interpretation is that δ represents the characteristic length of the exponential decay flux pinning potential from the dominant defects in Nb3Sn superconductors, which are grain boundaries.

The Oxford English Dictionary includes 17 definitions for the word “model” as a noun and other 11 as a verb. Therefore, context is necessary to understand the meaning of the word model. For in-stance, “model railways” refer to replicas of railways and trains at a smaller scale and a “model student” refers to an exemplar individual. In some cases, a specific context, like cancer research, may not be sufficient to provide one specific meaning of a model. Even if the context is narrowed, specifically to the research related to the tumour microenvironment, a “model” can be understood in a wide variety of ways, from an animal model, to a mathematical expression. This paper presents a review of the different “models” of the tumour microenvironment grouped by the different def-initions of the word into four categories: model organisms, in vitro models, mathematical models, and computational models. Then, the frequency of different meanings of the word “model” related to the tumour microenvironment is measured from the number of entries in the MEDLINE database of the United States National Library of Medicine at the National Institutes of Health. The frequency of the main components of the microenvironment and the organ-related cancers modelled are also assessed quantitatively with specific keywords. Whilst animal models, in particular xenografts and mouse models are the most common used “models”, the number of entries have been slowly de-creasing. Mathematical models, prognostic and risk models follow in frequency and these have been growing in use.

In this review we look at the developments in the field of artificial intelligence (A.I) and their current impact as well as future implications in the field of cardiology, we as physicians and cardiologists have tried to put our perspective on the rapidly evolving field, In light of the fact that many of the healthcare workers and professionals across the world still find the concept of A.I quite complicated, elusive and somewhat paradoxical, we have tried to simplify the concept of artificial intelligence and make it easy for everyone to understand from all walks of life. The Databases utilized for our review are PubMed, PubMed Central, Google Scholar. The Keywords used for our Data Search are “Artificial Intelligence”, “A.I Cardiology”, “A.I in Cardiovascular Medicine”, “Machine Learning in Cardiology”. We screened all relevant since inception till March 25th and included 44 relevant articles after careful consideration into our paper. We have discussed the implementation of and scope of artificial intelligence across a broad spectrum of applications including cardiovascular imaging and diagnostics like electrocardiograms, echocardiograms, cardiac CT/MRIs to novel cardiac monitoring devices, CRISPR gene editing in cardiology and implementation of artificial intelligence in the field of Cardiovascular Bioprinting. This is the initial review in a series of reviews regarding A.I in Cardiology.

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A&gt;G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

With the rise of powerful computational technologies, healthcare systems are going through a paradigm shift to the era of healthcare 5.0, also known as" smart healthcare". This new-age healthcare system not only enhances the life of patients but also aims to reduce healthcare costs significantly. People's health data collected through various means, including various Internet of Things (IoT) devices, is too sensitive to be regulated by particular organisations owing to increasing privacy and security threats. The sheer size of data makes it difficult for centralised bodies to regulate, due to which third-party involvement is introduced, which again poses threats to the privacy of the data holder. Motivated by the abovementioned gaps, we propose a decentralised approach using Ethereum blockchain technology and Oasis protocol. The patient-driven solution approach effectively solves the privacy problem by providing complete control of data to the owner. Along with this, byproducts such as fine-grained access control and on-chain data processing capabilities are also obtained.

Abstract. Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Fifty-five SARS-CoV-2 positive and 61 negative third trimester patients were randomly selected from Montefiore Medical Center (MMC), Bronx, NY. In addition, two positive cases from Yale New Haven Hospital, CT were included as controls. All 55 placentas delivered by SARS-CoV-2 positive mothers were uninfected by the virus, based on immunohistochemistry, in-situ hybridization, and qPCR analysis. However, placental villous infarcts, mild preeclampsia, shortened gestational periods and lower Apgar scores were observed in the infected cases. These findings suggest that even without entering the placenta, SARS-CoV-2 can affect various systemic pathways culminating in altered placental development and function, which may adversely affect the fetus, especially in a high-risk patient population such as ours. These results underline the importance of vaccination among pregnant women, particularly in low resource areas.

This study reports results of focus groups with school nurses and teachers from elementary, middle, and high schools to explore their perceptions of child and adolescent oral health. Participants included 14 school nurses and 15 teachers (83% Female; 31% Hispanic, 21% White, 21% Asian, 14% African American, and 13% Others). Respondents were recruited from Los Angeles County schools and scheduled by school level for six one-hour focus groups, using Zoom. Audio recordings were transcribed, reviewed, and saved with anonymization of speaker identities. NVivo software was used to facilitate content analysis and identify key themes. The nurses’ rate of “Oral Health Education” comments statistically exceeded that of teachers, while teachers had higher rates for “Parental Involvement” and “Mutual Perception” “Need for Care” was perceived to be more prevalent in immigrants to the United States based on student behaviors and complaints. “Access to Care” was seen as primarily the nurse’s role. Strong relationships between community clinics and schools were viewed by some as integral to students achieving good oral health. The results suggest dimensions and questions important to item development for oral health surveys of children and parents to address screening, management, program assessment, and policy planning.

Background and objectives: Traditional intravenous, patient-controlled analgesia (PCA) uses a fixed-rate continuous background infusion mode. However, some patients suffer from inadequate analgesia or opioid-related adverse effects due to the biphasic pattern of postoperative pain. Therefore, we investigated the postoperative analgesic efficacy of PCA using an optimizing background infusion mode (OBIM), where the background injection rate varies depending on the patient's bolus demand. Materials and Methods: We prospectively enrolled 204 patients who underwent laparoscopic cholecystectomy in a randomized, controlled, double-blind study. Patients were allocated into either the optimizing (group OBIM) or the traditional background infusion group (group TBIM). The numeric rating scale (NRS) score for pain was evaluated at admission to and discharge from the recovery room, as well as at the 6th, 24th, and 48th postoperative hours. Data of bolus demand count, total infused volume, and background infusion rate was downloaded from the PCA device at 30-min intervals until the 48th postoperative hour. Results: The NRS score was not significantly different between groups throughout the postoperative period (P = 0.621), decreasing with time in both groups (P < 0.001). The bolus demand count was not significantly different between groups throughout (P = 0.756). The mean cumulative infused PCA volume was lower in group OBIM [84.0 (95% confidence interval: 78.9−89.1) mL) than in group TBIM [102 (97.8−106.0) mL] (P < 0.001). The background infusion rate was significantly different between groups throughout (P < 0.001); it was higher in group OBIM than in group TBIM before the 12th postoperative hour, and lower from the 18th to the 48th postoperative hours. Conclusions: The OBIM combined with bolus dosing is useful in that it reduces the cumulative PCA volume compared to the TBIM combined with bolus dosing, while yielding comparable postoperative analgesia and bolus demand in patients undergoing laparoscopic cholecystectomy.

Despite the recognition of the importance of stakeholder inclusion into decisions about new solutions offered to society, responsible innovation (RI) has stalled at the point of articulating a process of governance with a strongly normative loading, without clear practical guidelines toward implementation practices. The principles of RI direct us to involve the user early in the innovation process. However, it lacks direction of how to involve users and stakeholders into this process. In this article, we try to understand how to empower users to become a part of innovation process though empirical cases. Based on 11 cases of firms innovating in digital health and welfare services, we look on firm practices for user integration into their innovation process, as well as how user’s behavior is changing due to new trends such as availability of information and digitalization of services. We try to explore this question through lenses of responsible innovation in the emerging field of digital healthcare.

Stakeholder input into the decision-making process when developing public health programs and policies is crucial. This article presents an innovative approach, involving online participation with a wide group of stakeholders located in different geographic locations, for policy consensus by research methodology. The results of the project have been used to propose assumptions regarding a strategy for preventing blood-borne diseases in Poland. The research was conducted iteratively using a multi-stage qualitative methodology to explore risk assessment involving blood-borne infections. The final output of the entire project is a list of key problems/challenges and solutions associated with medical and nonmedical services that are connected to the breakage of tissue continuity. Qualitative research is rare in risk assessment as priority is usually given to statistical data and end-points (quantitative studies ). Statistical data on health risk allows to assess the health implications, while the methodology applied also allowed diagnosis of the processes leading to these effects. In addition to policy preparation for blood-borne illnesses, the methodology employed in the study can also be used to successfully explore other areas of public health policy decisions.

The Environmental interactions contributed to the processes of settlement and development of the first settlers at southern Peru 15,000 BC. The determination of this process is based on paleoclimatic studies at southern Peru and ethnoarchaeological evidence. The determination of this process is based on paleoclimatic studies of southern Peru and ethnoarchaeological evidence; establishing as a result of this analysis the hypothesis of environmental interaction and territorial occupation of the first hunter-gatherer populations until their consolidation, dominating the geographical space from Tacna. The Disruptive disaster events and their effects on climate during the Peruvian Paleolithic resulted in the origin of local societies that shaped the Tiawanaku societies of the early horizon at Southern Peru and Northern Chile.

This study empirically analyzes the effectiveness of resource optimization utilizing artificial intelligence (AI) within cloud computing environments. It compares systems that have been transitioned from a Monolithic structure to Microservices Architecture (MSA) with those adopting a simple Rehost strategy, to validate the operational efficiency of two systems whose resource efficiency has been enhanced compared to traditional legacy systems. The research is based on systems that determined resource efficiency post-cloud migration using APM tools. It points out the limitations of traditional heuristic operation methods in resource optimization, which lead to issues such as application performance degradation, resource over-allocation, and increased operational costs. This study aims to overcome the conventional resource optimization standards that depended on the average peak usage of CPU and memory infrastructure, by introducing AI-based optimization tools, and applying on-premise standards to cloud and container environments to achieve resource optimization. The paper emphasizes the importance of resource optimization through AI-based automation tools, exploring the possibilities of resolving real-world application performance issues in cloud environments, reducing unnecessary resource usage costs, and cutting down on labor risks and operational expenses. Through this, it presents strategic directions on how AI technology can offer financial and operational advantages in managing cloud resources.

Al has very good corrosion resistance and corrosion properties. The corrosion resistance of Al cast alloys is different because these alloys contain a lot of elements. Especially in secondary alloys which contain more impurity elements from which Fe is the most common. This study deals with secondary AlSi7Mg0.3 cast alloys which contain more Fe and are affected by a chloride corrosion environment. This environment was selected based on the application of castings in the automo-tive industry. The main object was to research the effect of such an environment on basic me-chanical properties and fatigue properties. The results show that a higher Fe content does not lead to a significant reduction in the properties of the casting and the chloride environment is not so harmful. Therefore, can be stated that the investigated secondary sand-cast experimental materials can replace the primary alloys without losing the required corrosion and mechanical properties.

The effect of the melt cooling rate on the atomic ordering of austenite and, as a consequence, on the martensitic transformation of a nonstoichiometric alloy of the Ni-Mn-In system has been studied. In-situ TEM observations revealed differences in the mechanism of phase transformations of the alloy subjected to different cooling conditions. It is shown that during quenching a high density of antiphase boundaries (APB) is formed and the alloy is in the austenite-martensitic (10M and 14M) state up to a temperature of 120K. In a slowly cooled alloy, a lower APB density is observed, and a two-stage transformation L21/B2 → 10M → 14M occurs in the range of 150–120 K.

Purpose: When it comes to improving citizen service delivery standard and processes, or broadly, management in government (MIG), many reform programs and improvement efforts are ongoing across different ministries, departments, and agencies. This paper is part of a larger empirical research where we are interested to know what those programs and projects are, and how they are doing, and what the gaps are. Design/methodology/approach: Analyzing the publicly available data on the government portal and donors’ website, this article provides an overall idea of current reforms in various places of government. In parallel, field research was conducted through visiting agency offices, observing office environment and mechanisms, and interviewing public managers who are working at district and sub-district level offices of directorates or agencies.Findings: As a trend, state-led development process and the traditional mode of administration have moved to New Public Management based quality and performance approach. All donors have their own strategy framework document like ‘Country Assistance strategy’, ‘Country Operations and Business Plan’, Logical Framework Document, Focus or Priority Streams, etc. Many of the projects are sectoral and agency or ministry specific and have an inherent limitations, due to ‘cadre’ based organizational structural arrangement. So, it is common ‘not to own the projects’, rather ‘using the fund as much as possible anyway within the given project duration’. When the fund ends, implementing units, either government or NGOs, abandon the projects. That is why many projects are actually half done without significant and sustained direction.Originality/value: We can conclude that the typical ‘top-down’ or ‘trickle down’ conception is still dominant in design and implementation of reforms programs and service quality efforts. So, how to reach systemically at the bottom where public managers provide services to citizens, needs even more deliberation.

Policies are adopted and implemented to achieve specific goals. In this regard, the Government of Zambia in 2019 adopted the higher education policy with many objectives which include, the expansion of access to higher education; reduction of gender and other forms of inequity in accessing higher education; the improvement of quality of higher education by increasing funding to higher education institutions, construction, and repair of infrastructure in higher and improvement in the provision of learning materials in higher education institutions (HEIs).This paper, therefore, sought to evaluate the higher education policy of 2019. The four criteria were used namely; effectiveness, equity, policy sustainability, and consistency. Other principles such as political and social acceptability of a policy were not used because the policy is already adopted and being implemented. Further, the principle of efficiency was not used because it would have been problematic to gauge the expenditure against the outcomes.The findings have revealed that the policy to some extent has been effective; some of the objectives such as increased access to higher education and reduction of inequality have been partially achieved. It has been established that the number of students pursuing higher education has been increased to 114,049 in 2020 from 91,969 in 2017. Further, in 2021, 48.5% of scholarships in public universities were awarded to female students while 51.5% were awarded to female students. Further, more students are encouraged to pursue science, technology, engineering, and mathematics (STEM); and more women are pursuing studies in STEM-related fields. However, the policy has not helped to achieve the quality of higher education as funding in public HEIs has not improved. Further, infrastructure remains very poor and inadequate; and access to update and relevant learning materials also remains a challenge in HEIs. However, the policy seems to be duplicated by the recent re-launched Technical Education Vocation Entrepreneurship Training (TEVET) national policy.Given the above findings, it has been recommended that the government among other things improve funding and build infrastructure in public HEIs. There is also a need to harmonise the TEVET national policy with the higher education policy.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

Academic entrepreneurship focuses on commercialization of research. Even though it is practiced worldwide for decades, Bangladesh is a newcomer in this segment. In Bangladesh only 2 Universities have Technology Transfer Offices or TTOs which are established with the sole focus of commercialization of researches of the students and the faculty members of the Universities. This article focuses on worldwide practices of technology transfer and academic entrepreneurial activities and also explores the opportunities and challenges of such entrepreneurs through detail investigation of the existing body of knowledge. Apart from exploring the problems and prospect of academic entrepreneurship in Bangladesh, this article also introduces the concept of Full-Service Knowledge Transfer Office (KTO), which existing literatures do not offer. The authors believe that by establishing such KTOs as a self-sustaining body, it is possible for an academic entrepreneur to stimulate, support and sustain their activities in Bangladesh. The concept of full service KTOs can also become models for other nations, specially the developing ones, to establish and nurture a culture of academic entrepreneurship.

Far-red fluorescent reporter genes can be used for tracking cells non-invasively in vivo using fluorescence imaging. Here, we investigate the effectiveness of the far-red fluorescent protein, E2-Crimson (E2C), for tracking mouse embryonic cells (mESCs) in vivo following subcutaneous administration into mice. Using a knock-in strategy, we introduced E2C into the Rosa26 locus of an E14-Bra-GFP mESC line, and after confirming that the E2C had no obvious effect on the phenotype of the mESCs, we injected them into mice and imaged them over 9 days. The results showed that fluorescence intensity was weak, and cells could only be detected when injected at high densities. Furthermore, intensity peaked on day 4 and then started to decrease, despite the fact that tumour volume continued to increase beyond day 4. Histopathological analysis showed that although E2C fluorescence could barely be detected in vivo at day 9, analysis of frozen sections indicated that all mESCs within the tumours continued to express E2C. We hypothesise that the decrease in fluorescence intensity in vivo was probably due to the fact that the mESC tumours became more vascular with time, thus leading to increased absorbance of E2C fluorescence by haemoglobin. We conclude that the E2C reporter has limited use for tracking cells in vivo, at least when introduced as a single copy into the Rosa26 locus.

The purpose of this article is to review a two year long implementation of an electronic health record (EHR) system at the outpatient department of a private hospital in Kathmandu, possibly a first implementation of its kind in Nepal. Procedures: The strategy designed for EHR implementation was based on Professor John P. Kotter's work on successful change management. Main findings: We found that keeping a close watch on the social dynamics affecting adoption decisions among users of the system was crucial for implementing the EHR; this was partly because the project received limited support from an erratically changing hospital leadership and lacked an EHR system suited to the needs of the users. Conclusions: The implementation described in this article is a good lesson on moving from control to drift in information systems implementation, and we hope this work will be useful to health IT professionals working in the space of digital transformation in resource-constrained environments.

Ovariectomy appears to be the best method to control the density of wild ungulate populations. The aim of the present study was to compare two surgical approaches, via the flank and midline, in mouflon’s ovariectomy in field conditions. Twenty female mouflons were enrolled in the study. The animals were divided randomly in two groups, Group F animals were gonadectomized via flank approach, while Group A animals were sterilized via linea alba access. The parameters evaluated were duration of surgery, duration of anaesthesia, recovery time, intra- and post-operative complications, intra-operative nociception and pain in the post-operative period. There were no intra- and post-operative complications. The evaluated parameters showed a very similar trend in both groups. Both techniques are found to be effective and safe in execution.

Recently, the indications for Cochlear Implant (CI) have also been extended to subjects with Single Sided Deafness (SSD) in order to restore binaural hearing. The primary objective of this study was to investigate the advantages of CI following one year of usage in SSD subjects. Secondarily we want to assess the long-term stability of the CI. 57 participants performed a complete audiological assessment (speech audiometry in quiet and in noise and localization test). For each was also evaluated subjective hearing profile (with Speech Spatial and Qualities_SSQ questionnaire) and the impact of tinnitus (with the use of Tinnitus Handicap Inventory_THI questionnaire) After one year of CI usage, we observed a significant improvement in speech-to-noise ratio, in sound localization abilities, in the Speech (p-value 0.001) and Spatial (p-value 0.001) subscales of the SSQ questionnaire and in THI questionnaire (p-value 0.001). The improvements in speech in noise and localization abilities and the reduction of the SSQ and THI questionnaires scores were maintained over time (6th to 60th month follow-up). Only eight participants did not fully utilize the CI. CI in SSD represents an effective method for improving speech recognition in noisy environments, restoring sound localization abilities, reducing tinnitus and improve subjective listening skills.

Malignant melanoma is one of the most aggressive and resistant tumor types which is often accompanied by poor prognosis when spread to nearby or distant tissues. Even though an increasing number of second-line therapies are available for cancer patients, the 5-year survival rate of melanoma patients with regional and distant metastases is still rather low. Therefore, there is an urgent need to develop new, highly efficient treatments. Melanocortin-1-receptor (MC1R) is a cell surface receptor for α-MSH. It is responsible for melanogenesis and is shown to be overexpressed on the surface of cancer cells in a subset of melanoma patients. Here, we designed and synthesized α-MSH analogs and conjugated them to daunomycin through oxime linkage. Using our peptide-drug conjugates (Dau-α-MSHs), we performed comparative in vitro and in vivo evaluations to reveal their suitability for tumor targeting. Firstly, the expression level of MC1R was determined in various melanoma cell lines via RT-qPCR. Then, we examined the antiproliferative effect of our Dau-α-MSHs, moreover we determined the cellular uptake profile and intracellular localization of Dau-α-MSHs. The most efficient Dau-α-MSHs were investigated in vivo using a murine xenograft melanoma model. We found that various cell lines show differential expression on the mRNA levels. We also showed that healthy primary cells have lower expression of MC1R compared to tumor cell lines. Moreover, the concentration-dependent cellular uptake profile of Dau-α-MSHs was detected and the compounds exhibited a great antiproliferative effect on melanoma cell lines. We also provided evidence that our novel Dau-α-MSHs can inhibit tumor expansion significantly and are suitable for targeted tumor therapy.

The non-structural protein (NS) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NS and NP during viral infection through in-silico and in-vitro analyses. Through in-silico analysis, three possible binding sites were predicted, at NSs1-32, NSs56-82, and NSs207-237. Rationally, three mutant NSs were developed by site-directed mutagenesis and tested for NP interaction by co-immunoprecipitation. NSsW61Y failed to interact with the nucleoprotein, which was substantiated by the conformational changes observed in the structural analyses. Additionally, molecular docking analysis corroborated that the NSW61Y mutant protein does not interact well compared to wild-type NS. Over-expression of wild-type NS in HeLa cells increased the SFTSV replication by five folds, but NSsW61Y exhibited 1.9-folds less viral replication than wild-type. We demonstrated that the W61Y alteration was implicated in the reduction of NS-NP interaction and viral replication. Thus, the present study identified a critical NS site, which could be targeted for development of therapeutic regimens against SFTSV.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects the motor system of the human body. Currently, the available treatments are limited and often have undesirable side effects. In this context, the aim of this study was to develop a novel combinational formulation of Apomorphine and Quetiapine and evaluate its efficacy in a rat model of PD. The formulation was prepared using the solvent evaporation technique and characterized for its physicochemical properties. The in-vitro drug release was evaluated using the Franz diffusion cell method, and the pharmacokinetics of the combination was studied in rats. The behavioural and biochemical parameters were evaluated in the rats using the Rotarod, pole test, and biochemical assays. The results showed that the developed formulation had satisfactory physicochemical properties and exhibited sustained drug release. The pharmacokinetic studies showed that the combination exhibited a longer residence time than the individual drugs. The behavioural and biochemical parameters showed that the combination was effective in improving motor function and reducing oxidative stress. In conclusion, the developed Apomorphine and Quetiapine combination formulation showed promising results in improving motor function and reducing oxidative stress in rat model of PD. Further studies are required to evaluate the safety and efficacy of the developed formulation in humans.

The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drug, food, water treatment and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity and (epi)genotoxicity. Also, new technologies, such as organ-on-chip and sophisticated sensors, are under development and/or adaptation. All the information generated is used to develop new in silico approaches trying to predict the potential effects of newly developed materials. The overall evaluation of how from the production to final disposition chain of nanomaterials is evaluated under Life Cycle Assessment (LCA), which is becoming an important element of nanosafety considering sustainability and environmental impact. In this review we give an overview of all these elements of nanosafety.

Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular bio-molecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug-cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using ICP-OES and Trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (**p<0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer.

To mitigate the COVID-19 infection, many world governments endorsed the cessation of non-essential activities, such as the school attendance. Thereby, forcing the evolution of the teaching model to the virtual classroom. In the present work we show the application of a modified version of the adapted COVID-19 stress scales (ACSS) which also included teaching anxiety and preparedness, and resilience for academic professionals in Mexico, during the unprecedented transformation of the education system undergone in the COVID-19 quarantine. Most of the studied variables: gender, age, academic degree, household occupants, having a disease, teaching level, teaching mode, work hours, resilience, teaching anxiety and preparedness, and fear of being an asymptomatic patient (FOBAP), showed significant statistical correlation between each other (p<0.050) and to the 6 areas of the ACSS (danger, contamination, social economical, xenophobia, traumatic stress and compulsive checking). Our results further showed that the perceived stress and anxiety, fell into the category of absent to mild with only the danger section of the ACSS falling into the moderate category. Finally, resilience generated throughout the quarantine, seems to be a predictor of the adaptation the academic professional has undergone to cope with stress.

Based on the geochemical analysis of the volcanic material from the sediment core AMK-340, central zone of the Reykjanes Ridge, we could detect two ash-bearing sediment units accumulated during the Termination I. They correlate to the Ash Zone I in the North Atlantic Late Quaternary sediments having an age of 12170-12840, within the Younger Dryas cold chronozone, and 13600-14540 years, within and Bølling-Allerød warm chronozone. The ash of the Younger Dryas unit is presented mostly by the mafic and persilicic material originated from the Icelandic volcanoes; Vedde Ash is presented in one sediment sample from this unit. The ash of the Bølling-Allerød unit is presented mostly by the mafic shards which are related to the basalts of the rift zone on the Reykjanes Ridge, having presumably the local origin. A detection of Vedde Ash helped to specify the timing of the previously reconstructed paleoceanographic changes for the Termination I in the point of study: a significant warming in the area could occur as early as 300 years prior to the end of the conventional Younger Dryas cold chronozone.

Microencapsulation of polyherbal formulation (PHF) extract was carried out by freeze drying method, by employing gum arabic (GA), gelatin (GE), and maltodextrin (MD) with their designated different combinations as encapsulating wall materials. Antioxidant components (i.e total phenolic contents (TPC),Total flavonoids contents (TFC), and total condensed contents (TCT)), antioxidant activity (i.e. DPPH, β-carotene & ABTS⁺ assays), moisture contents, water activity (aw), solubility, hygroscopicity, glass transition temperature (T_g), particle size, morphology, in vitro alpha-amylase and alpha-glucosidase inhibition and bioavailability ratios of the powders were investigated. Amongst all encapsulated products, T_B (5% GA and 5% MD) and T_C (10% GA) has proven to be the best treatments with respect to the highest preservation of antioxidant components and their antioxidant potential by DPPH and β-carotene assays and noteworthy for an ABTS⁺ assays, in addition, the aforesaid treatments also demonstrated lower moisture content, aw, particle size and higher solubility, hygroscopicity and glass transition temperature (T_g). All freeze dried samples showed irregular (asymmetrical) microcrystalline structures. Furthermore, T_B and T_C also illustrated the highest in vitro anti-diabetic potential due to great potency for inhibiting alpha-amylase and alpha-glucosidase activities. In the perspective of bioavailability, T_A, T_B and T_C demonstrated the excellent bioavailability ratios (%).Futhermore, the phytochemo-profiling of ethanolic extract of PHF was also revealed to find out the bioactive compounds.

Diabetic foot ulcers (DFUs) significantly affect the lives of patients and increase the risk of hospital stay and amputation. We suggest a remote-monitoring platform for better DFU care. This system uses digital health metrics (scaled from 0 to 10, where higher scores indicate a greater risk of slow healing) to provide a comprehensive overview through a visual interface. The platform features smart offloading devices that capture behavioral metrics such as offloading adherence, daily steps, and cadence. Coupled with remotely measurable frailty and phenotypic metrics, it offers an in-depth patient profile. Additional demographic data, wound characteristics, and clinical parameters, such as cognitive function, were integrated, contributing to a comprehensive risk factor profile. We evaluated the feasibility of this platform with 124 DFU patients over 12 weeks; 39% experienced unfavorable outcomes such as dropout, adverse events, or non-healing. Digital biomarkers were benchmarked (0-10), categorized into low, medium, and high risk for unfavorable outcomes, and visually represented using color-coded radar plots. The initial results of case reports illustrate the value of this holistic visualization to pinpoint the underlying risk factors for unfavorable outcomes, including a high number of steps, poor adherence, and cognitive impairment. Although future studies are needed to validate the effectiveness of this visualization in personalizing care and improving wound outcomes, early results in identifying risk factors for unfavorable outcomes are promising.

Background. Malignant pleural mesothelioma (MPM) is still a rather incurable disease. Many classes of compounds with various mechanisms of action have been tested in vivo and ex-vivo, with rather disappointing results. This is partly due to preclinical studies mostly performed in models that fail to recapitulate MPM complexity and do not retain the intra-tumor heterogeneity, a propelling force for tumor progression. Additionally, we and others have shown that, under stress-induced chemotherapy, profound rearrangements take place in MPM cultures to fuel the emergence of chemoresistant cell subpopulations. Thus, finding clinically actionable modulators of MPM resistance is still a very urgent need. Methods. Setup and propagation of patient-derived organoid cultures from MPM pleural effusions; flow cytometry-based validation of organoid cultures, isola-tion and propagation of mesothelioma-associated fibroblasts; co-cultures, Lu-minex-based Cytokine array, ELISA assay to quantitate IL-6 in the conditioned media, qRT-PCR to assess mRNA expression of cancer stem cell markers and fibroblast markers. Results. Organoid cultures were obtained from eight MPM patients by using specific growth media and conditions to propagate pleural effusion-derived cells. We proved that primary MPM specimens and serially passaged (mesothelio-ma-Patient-Derived-Organoids) mPDOs were cytologically similar, with the obtained mPDOs expressing mesothelial markers similarly to the originating specimen. As expected from a clinically relevant model, the size and number of mPDOs were altered, in a patient-specific way, when pharmacologically relevant doses of chemotherapy drugs were added. We derived Mesothelio-ma-Associated-Fibroblasts (MAFs) and the addition of MAFs, to various ratios, altered the response of the mPDOs to pemetrexed + cisplatin, toward a reduced sensitivity to the latter anticancer agents. Additionally, organoid formation and size were altered by MAF-conditioned media, and this correlated with increased expression of cancer stem cell markers. We showed increased levels of IL-6 in the media of the treated cocultures and showed that this latter was derived from the MAFs. Conclusions. Increased secretion of IL-6 by mesothelioma-associated fibroblasts (MAFs) contributes to the resistance of the MPM to therapy.

The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13-82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the Global quality of life scale and 18% of the TESS so psychometrically it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed.

Machine learning (ML) techniques can help predict survival among cancer patients and might help with a timely integration in palliative care. We aim to explore the importance of subjective variables self-reported and collected via electronic patient reported outcome measure (ePROM) for survival prediction. A total of 256 advanced cancer patients met the eligible criteria. We analyzed objective variables collected from electronic health records, subjective variables collected via ePROM and all clinical variables combined. We used logistic regression (LR), decision trees, and random forests to predict 1-year mortality. Receiver operating characteristic (ROC) curve - area under the curve (AUC) and the ML models feature importance were analyzed. The performance of all variables for predictions (LR reaches 0.80 [ROC AUC] and 0.72 [F1 Score]) does not improve over the performance of only clinical non-patient reported outcome (non-PRO) variables (LR reaches 0.81 [ROC AUC] and 0.72 [F1 Score]). Our study indicates that patient-reported outcome (PRO) variables, which measure subjective burden, cannot be reliably used to predict survival. Further research in this area is needed to clarify the role of self-reported patient's burden and mortality prediction via ML.

Background: Measuring vital signs has always been a central task for Critical Care Nurse´s (CCNs) and Registered Nurse Anesthetist`s (RNAs) providing care in the post-anesthesia care unit (PACU) and a prerequisite for their decision-making. Properly measuring and understanding pediatric vital signs is a challenge in younger pediatric patients up to 36 months old. Purpose: gain a greater understanding of CCNs' and RNAs' perceptions of decision-making regarding the level of vital sign monitoring children require in the PACU. Method: A qualitative study design involving the critical-incident technique was used. Interviews were carried out with a purposeful sample of CCNs and RNAs (n=17) from two different hospitals. Findings: According to the nurses' experience, grounds for decisions concerning children’s need of vital-sign monitoring were both adequate and inadequate. They used actions to adjust the monitoring of vital signs to optimise conditions for assessment and the prospects of a safe recovery for the child. Conclusions: Evidence-based care and safety are compromised when the technology has limitations and is not adapted for children. Its use means that experience and clinical assessment are relied on to a greater extent. This not only makes experience important for reliable assessment, but also means that greater risks are accepted.

Background: The oldest old people (≥ 85 years) represent the fastest growing age group in Western populations. Knowledge on early outcomes of acute ischemic stroke (AIS) in very old female patients remains limited. Methods: We assessed gender differences and female-specific clinical data and in-hospital mortality in very old patients with AIS. Acute cerebral infarction was diagnosed in 506 very old female patients from a total of 4,600 acute cerebrovascular infarctions available in an ongoing 24-year hospital stroke data bank. A comparative analysis of vital status at discharge (alive versus dead) was performed in terms of cardiovascular risk factors, clinical data, and early outcomes. Results: The overall in-hospital mortality rate was 20.4%. In multivariate analysis, sudden onset, altered level of consciousness, and neurological, respiratory, cardiological or hemorrhagic complications, and lacunar infarcts appeared to be independent predictors of in-hospital mortality. Conclusions: Female patients ≥85 years with AIS are an unfavorable subgroup of stroke patients with a high risk of early mortality, which may be due to comorbidity, stroke subtype distribution, and higher frequency of medical complications. However, the presence of lacunar infarcts showed a significant protective effect.

As medical care aiming to maintain the quality of life for elderly patients is increases, implant treatment for elderly patients is increasing worldwide. Therefore, we aimed to investigate implant stability and the reliability of different measuring devices according to implant placement site and duration in patients aged over 65 years. The study evaluated 60 implants in 60 patients aged ≥ 65 years. The implant placement sites were divided into six evenly distributed sections (n=10) i.e., maxillary right- posterior, A; maxillary anterior, B; maxillary left-posterior, C; mandibular right-posterior, D; mandibular anterior, E; mandibular left-posterior, F. Participants visited the hospital seven times: preoperatively, 1V; implant surgery, 2V; stitch removal, 3V; 1-month follow-up, 4V; 2-months follow-up, 5V; before final-restoration delivery, 6V; and after final-restoration delivery, 7V. The implant stability was evaluated with the Osstell Mentor (ISQ), Periotest M (PTV), and Anycheck (IST). The mean values of ISQ, PTV, and IST were analyzed (α=.05). ISQ, PTV, and IST results of 5V and 6V were significantly higher than those of 2V (P<.05). The lowest ISQ results occurred in E location at 5V and 6V (P<.05). In all mandibular locations, IST results of 7V were significantly higher than those of 2V, 3V, 4V, and 5V (P<.05). ISQ results were negatively correlated with PTV and positively correlated with IST, and PTV was negatively correlated with IST. By considering various factors that affect implant stability, the appropriate implant load application time was determined. This could help increase the implant success rate in elderly patients. And as a diagnostic device for implant stability for evaluation of osseointegration in elderly patients, Anycheck was also able to prove its relative reliability compared to Osstell ISQ Mentor and Periotest M.

The past several decades have seen a shift in patient care towards digitalisation, which has ushered in a new era of health care delivery and improved sustainability and resilience of health systems, with positive impacts on both internal and external stakeholders. This study’s aim was to understand the role of digital virtual consultations in improving internal and external stakeholders’ health, as well as wellbeing among hospital doctors. A qualitative research approach was used with semi-structured online interviews administered to hospital doctors. The interviews showed that the doctors viewed digital virtual consultations as supplementary to in-person consultations, and as tools to reduce obstacles related to distance and time. If the necessary infrastructure and technology were in place, doctors would be willing to use these options. Implementing these technologies would improve the medical profession’s flexibility on the one hand; but it might affect doctors’ work–life balance if consultations extended beyond standard working hours.

Mandibular advancement devices (MAD) are an effective alternative treatment to CPAP. However, different maneuvers have been performed during the performance of drug sleep-induced endoscopy (DISE) to mimic the effect of MAD. Using the Selector Avance Mandibular (SAM) device, we aimed to identify MAD candidates during DISE using a titratable, reproducible, and measurable maneuver. This DISE-SAM protocol may help to find the relationship between the severity of the respiratory disorder and the degree of response, and to determine the advancement required to improve the collapsibility of the upper airway. Explorations were performed in 161 patients (132 males; 29 females) with a mean age of 46.81 (SD = 11.42) years, a BMI of 27.90 (SD = 4.19) kg/m2 and a mean AHI of 26.51 (SD = 21.23). Results showed no relationship between severity and MAD recommendation. Also, there was a weak positive relationship between the advancement required to obtain a response and the disease severity. Using the DISE-SAM protocol, the response and the range of mandibular protrusion were assessed, avoiding the inter-examiner bias of the jaw thrust maneuver. We suggest prescribing MAD as a single, alternative, or multiple treatment approaches following the SAM recommendations in a personalized design.

Persistent Pain after Spinal Surgery can be successfully addressed by Spinal Cord Stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outcomes, WITH OR WITHOUT lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that ma-chine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, Regularized Logistic Regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient boosted trees to test this hypothesis and to perform internal and external validations, the objec-tive being to confront model predictions with lead trial results using a 1-year composite out-come from 103 patients. While almost all models have demonstrated superiority on lead trial-ing, the RLR model appears to represent the best compromise between complexity and inter-pretability in prediction of SCS efficacy. These results underscore the need to use AI based-predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.

Background: ED overcrowding is described as one of the main issues in emergency departments (EDs) of any hospital. In Saudi Arabia, the ministry of health applied new telemedicine technology to serve patients by using the mobile application which include Sehha application and 937 medical call center. The main aim of this study is to determine the role of different telemedicine services in reducing non-urgent visits to EDs in Saudi Arabia. Methods: A cross-section study was conducted during August 2020 - May 2021 among 319 patients were using two telemedicine services in Saudi Arabia, including medical call center, and Sehha smart phone application. The primary endpoint of this study aims to determine the role of different telemedicine services in reducing non-urgent visits to EDs in Saudi Arabia. Results: This study analyzed the data from 319 patients who completed the survey provided by the Saudi Ministry of Health that concerning on information related to their health status, and ED visits. Among patients that had the intention to visit the ED (N=159), 53 of them did not go to EDs after using telemedicine services (p-value < 0.01). Regarding medical call center and Sehha application, 9.6% and 24.4%, respectively of the patients used these telemedicine services had changed their mind concerning visiting ED after taking the medical advice (p-values < 0.01).Conclusion: The implemented telemedicine services in Saudi Arabia, namely Sehha application and medical call center showed to be effective in reducing ED overload by providing medical advices to less- and non-urgent patients and deal with their minor medical issues.

Dupilumab is used to treat atopic dermatitis patients who have proven to be refractory to previous treatments. The aim of this study was to assess evolution and patient reported outcome measures in adult patients with moderate-to-severe atopic dermatitis treated with Dupilumab in routine clinical practice. The outcomes were evaluated and registered at baseline and weeks-16, 40 and 52. The variables evaluated were: diseases severity, pruritus, stressful life events, difficulty to sleep, anxiety and depression, quality of life, satisfaction, adherence to the treatment, efficacy and safety. Eleven patients were recruited between Nov 14th 2017 and Jan 16th 2018. Demographic variables: 90% Caucasian, 82% women. Clinical variables: Mean duration of AD =17.7 (±12.8), 91% had severe disease severity. At baseline, SCORAD mean score = 61.7 (±15.5); itch was reported by 100% of patients; itch Visual Analogue Scale mean range of 8 (6-10); HADS mean total score =13.9 (±5.5); DLQI mean score =13.3 (±8.3): EQ-5D-3L mean range = 57 (30-99). At week-52 there is a significant reduction of SCORAD scores, HADS total score and improved quality of life. ¡This study confirms that Dupilumab, used for 52-weeks under routine clinical practice, maintains the improved atopic dermatitis signs and symptoms obtained at week-16, with a good safety profile.

Background: New regional techniques can improve pain management after nephrectomy. Methods: This study was a randomized controlled trial conducted at two teaching hospitals. Patients undergoing elective open and laparoscopic nephrectomy were eligible to participate in the trial. A total of 100 patients were divided into a quadratus lumborum block (QLB) group and a control (CON) group. At the end of surgery, but while still under general anesthesia, unilateral QLB with ropivacaine was performed on the side of nephrectomy for patients in the QLB group. The main measured outcome of this study was oxycodone consumption via a patient-controlled anesthesia (PCA) pump during the first 24 hours following surgery; other measured outcomes included postoperative pain intensity assessment, patient satisfaction with pain management, and persistent pain evaluation. Results: Patients undergoing QLB needed less oxycodone than those in the CON group (34.5 mg [interquartile range 23–40 mg] vs. 47.5 mg [35–50 mg]; p<0.001). No difference between the groups was seen in postoperative pain intensity measured on the visual analog scale, except for the evaluation at hour 2, which was in favor of the QLB group (p=0.03). Patients who received QLB were more satisfied with postoperative pain management than the CON group. Persistent postoperative pain was assessed with the Neuropathic Pain Symptom Inventory (NPSI) at months 1, 3, and 6 and was found to be significantly lower in the QLB group at each evaluation (p<0.001). We also analyzed the impact of the surgery type on persistent pain severity, which was significantly lower after laparoscopic procedures than open procedures at months 1, 3, and 6. Conclusions: QLB reduces oxycodone consumption in patients undergoing open and laparoscopic nephrectomy and decreases persistent pain severity months after hospital discharge.

The time required to reach a correct diagnosis is one of the most important problems for rare disease (RD) patients. Diagnostic delay can be intolerably long, to the point that it is usually described as a “diagnostic odyssey” and, sometimes, a diagnosis might never occur. The International Rare Disease Research Consortium proposed, as ultimate goal for 2017-2027, to enable all people with a suspected RD to be diagnosed within one year if the disorder is known, and to enter a globally coordinated diagnostic and research pipeline for the unsolved cases. In-depth analysis of the genotype through next generation sequencing, together with a standardized in-depth phenotype description and sophisticated high-throughput approaches, have been applied as diagnostic tools to increase the chance of a timely and accurate diagnosis. This approach is very fruitful as, according to the Orphanet database, from 2010 to March 2017 more than 600 new RDs have been described and about 3600 genes linked to RDs have been identified. However, combination of -omics and phenotype data and international sharing of this information raise ethical concerns. Values to be assessed include not only patient autonomy but also family implications, beneficence, non-maleficence, justice, solidarity and reciprocity, which must be respected and promoted and, at the same time, balanced among each other. In this work we suggest that, to maximise patients involvement in the search for a diagnosis and identification of new causative genes, undiagnosed patients should have the possibility to: 1) actively participate in the description of their phenotype; 2) choose the level of visibility of their profile in matchmaking databases; 3) express their preferences regarding return of new findings, in particular which level of Variant of Unknown Significance (VUS) significance should be considered relevant to them. The quality of the relation between individual patients and physicians, and between the patient community and the scientific community is critically important for making the best use of available data and combining efforts in the search for matches with similar cases worldwide that will help to solve unsolved cases. The contribution of patients to collecting and coding data comprehensively is critical for efficient use of data downstream of data collection.

Different dopamine receptor (DR) subtypes are involved in pathophysiological conditions such as Parkinson´s Disease (PD), schizophrenia and depression. While many DR-targeting drugs have been approved by the FDA, only a very small number is truly selective for one of the DR subtypes. Additionally, most of them show promiscuous activity at related G-protein coupled receptors, thus suffering from diverse side-effect profiles. Multiple studies have shown that combined in silico / in vitro approaches are a valuable contribution to drug discovery processes. They can also be applied to divulge the mechanisms behind ligand selectivity. In this study, novel DR ligands were investigated in vitro to assess binding affinities at different DR subtypes. Thus, nine D2R/D3R-selective ligands (micro- to nanomolar binding affinities, D3R-selective profile) were successfully identified. The most promising ligand exerted nanomolar D3R activity (KI = 2.3 nM) with 263.7-fold D2R/D3R selectivity. Subsequently, ligand selectivity was rationalized in silico based on ligand interaction with a secondary binding pocket, supporting selectivity data determined in vitro. The developed workflow and identified ligands could aid in the further understanding of structural motifs responsible for DR subtype selectivity, thus, benefitting drug development in D2R/D3R-associated pathologies like PD.

This paper discussed the concept of quality assurance (QA) in higher education and its implications to higher education institutions (HEIs) and the possible challenges. The study evaluated literature concerning QA in Zambia and elsewhere. The findings of the study show that QA is implemented through external and internal mechanisms such as accreditation, registration, institutional auditing, and the use of external examiners, self-evaluation, and peer reviews. The QA implications to HEIs in Zambia are that there is a need for accreditation of academic programmes with the Higher Education Authority (HEA) by HEIs. Further, HEIs should establish QA units to spearhead quality issues, reactive, and introduce the use of external examiners to ensure quality. The challenges identified in the implementation of QA in HEIs include inadequate funding, infrastructure, shortage of qualified academic staff, and lack of standalone QA units in some HEIs. In this regard, it has been recommended among other things, government improve funding in public HEIs, construct infrastructure, HEIs establish QA units, and recruit and retain qualified academic staff to ensure the quality of education.

Burnout represents a concern for all healthcare providers, particularly those specializing in emergency medical care for whom burnout outcomes have been well-documented. What remains unknown is the effect of burnout on redeployed medical specialists during the COVID-19 pandemic from an appointment-centered practice to emergency care directed by public health considerations. This research aims to identify and assess the burnout responses of fourteen medical specialties noted in searched returns of the four most cited articles published since 2020 about non-emergency physicians regarding their burnout brought on by the unanticipated need for them to provide emergency care during the recent pandemic. The hypothesis is that medical specialists accustomed to planning for emergency possibilities in their appointment-centered practice would demonstrate the least burnout regarding COVID-19-related emergencies. Considering coping as a process based on Lazarus's research, comparing and ranking the COVID-19 emergency responses across the various normally appointment-centered medical specialties in their employed coping strategies determines the outcome. With the hypothesis supported, suggested interventions for future pandemics—when these specialists are, again, redeployed to emergency care directed by public health considerations—are those coping strategies identified as most effective in reducing burnout while maintaining the viability of the medical specialty and excellent patient care.

Synchronous electrical cardioversion is a relatively common procedure in the emergency department (ED), often performed for unstable supraventricular tachycardia (SVT) or unstable ventricular tachycardia (VT). However, it is also used for stable cases resistant to drug therapy, which carry a risk of deterioration. In addition to the inherent risks linked with procedural sedation, there is a possibility of malignant arrhythmias or bradycardia, which could potentially result in cardiac arrest following this procedure. Here, we present a case of complete heart block unresponsive to transcutaneous pacing and positive inotropic and chronotropic drugs for 90 minutes, resulting in multiple cardiac arrests. The repositioning of the transcutaneous cardio-stimulation electrodes, one of them placed in the left latero-sternal position and the other at the level of the apex, led to immediate stabilization of the patient. Extubation of the patient was performed the following day, while full recovery and discharge within 7 days, after insertion of a permanent pacemaker.

Measles remains a highly contagious and potentially severe infectious disease, necessitating high vaccine coverage. However, misinformation and measles vaccine hesitancy/resistance posed significant challenges to achieving this goal. The COVID-19 pandemic further exacerbated these challenges, leading to a measles outbreak in Jordan in 2023. This study aimed to investigate the acceptance of the Measles-Rubella (MR) vaccine among parents in Jordan and identify its associated determinants. This cross-sectional questionnaire-based study was conducted using a previously Arabic-validated version of the Parental Attitudes towards Childhood Vaccines (PACV) survey instrument. Data collection took place in October 2023, and the final study sample comprised a total of 391 parents, with mothers representing 69.8% of the participants (n = 273). The majority of participating parents expressed either resistance (n = 169, 43.2%) or hesitancy (n = 168, 43.0%) towards MR vaccination, while only 54 participants (13.8%) expressed MR vaccine acceptance. Multivariate analysis revealed that trust in vaccine safety/efficacy, behavior, and having fewer offspring were significantly associated with MR vaccine acceptance. The current study revealed a concerning level of MR vaccine hesitancy/resistance among parents in Jordan. Urgent and targeted interventions are strongly recommended to address this issue, including mass campaigns aimed at building trust in the MR vaccine safety/efficacy. Additionally, there is an urgent need for effective public health initiatives to ensure sufficient measles vaccine coverage to prevent future outbreaks of this serious disease.

Depression and anxiety are the most common mental health disorders worldwide. Internet-Delivered Cogni-tive Behaviour Therapy (ICBT) can reduce barriers to care for broad cross sections of the population. How-ever, People of Diverse Ethnocultural Backgrounds (PDEGs) other than White/Caucasian underutilize mental health services and are underrepresented in clinical trials of psychological interventions. To address this research gap, we adapted an evidence-based ICBT program for PDEGs. The current pilot study explores the effectiveness, satisfaction, and engagement in the adapted ICBT by PDEGs (N=41) when benchmarked against a sample of PDEGs (N=134) drawn from a previous non-adapted version of the ICBT program. Inntent-to-treat analyses showed that the adapted ICBT program is effective in reducing anxiety and de-pression symptoms among PDEGs. Large within-group pre-to-post-treatment Cohen’s effect sizes of d = 1.23, 95% CI [0.68, 1.77] and d = 1.24, 95% CI [0.69, 1.79] were found for depression and anxiety, respectively. Further, 81.8% of the PDEGs who received the adapted ICBT program reported high overall satisfaction, 90.9 % reported increased confidence in managing symptoms, and 70.7% of participants completed the ma-jority of the psychoeducational lessons in the ICBT program. No statistically significant differences in clinical outcomes, engagement, and satisfaction were found between the pilot study and benchmark sample. Future directions for ICBT research with PDEGs are described.

Patients with polycythemia vera (PV) are at increased risk of thrombosis and hemorrhages. Although hydroxyurea (HU) has been the frontline therapy for patients at high-risk of vascular complications, about 25% of patients develop resistance/intolerance to this therapy. The aim of this non-interventional, multicenter cohort study was to understand the clinical characteristics and HU treatment response of Portuguese PV patients. HU resistance/intolerance was defined according to adjusted European LeukemiaNet (ELN) criteria. 134 PV patients with a mean disease duration of 4.8±5.0 years were included and followed up for 2 years. At baseline, most patients were ≥60 years old (83.2%), at high risk for thrombotic events (87.2%), and receiving HU therapy (79.1%). A total of 10 thrombotic events and 8 hemorrhagic events were reported, resulting in a 5-year probability of thrombo-hemorrhagic events of 17.2%. Hematocrit (p=0.007), hemoglobin (p=0.012) and MPN10 symptom score (12.0±11.6 vs 10.3±9.1; p=0.041) decreased significantly at the 24-month visit compared to baseline. Overall, 75.9% of patients met at least one of the adjusted ELN criteria for HU resistance. 14.4% of patients remained on HU throughout the study. The results from this real-world study may help identify the subset of patients at higher risk of disease sequelae who may benefit from earlier second-line treatment.

Objective: This systematic review and meta-analysis compared the patient-reported outcomes of intra-articular facet joint injections of normal saline and selected active substances to identify a more effective agent for treating subacute and chronic low back pain (LBP). Methods: The PubMed, Embase, Scopus, Web of Science, and CENTRAL databases were searched for randomized controlled trials and observational studies published in English. A research quality assessment was performed using ROB2 and ROBINS-I. A meta-analysis was conducted using a random-effects model, and the mean differences (MD) with 95% confidence intervals (CI) in efficacy outcomes, including pain, numbness, disability, and quality of life, were assessed. Results: Of the 2,467 potential studies, three were included (247 patients). The active substances and normal saline had similar therapeutic effects on pain within 1 h, after 1-1.5 months, and after 3-6 months, with MD and 95% CI of 2.43 and -11.61 to 16.50, -0.63 and -7.97 to 6.72, and 1.90 and -16.03 to 19.83, respectively, as well as the quality of life after 1 and 6 months. Conclusion: The short- and long-term clinical effects of intra-articular facet joint injections of normal saline are comparable to those of other active substances in patients with LBP.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in people in the city of Wuhan at the end of December 2019, and it has since spread to all continents. Global interest has been focused on discovering a treatment and developing a successful coronavirus vaccine as a result of the emergence of this new coronavirus. In this research, we sequenced the whole genome of the SARS-COV-2 virus that were isolated from 40 patients in Duhok, Iraq. 95 different mutations were identified in our isolation when such the whole genome sequence of the SARS-COV-2 isolated from the city of Wuhan, China (Accession number: NC 045512.2) was matched to the virus's sequence using Sequencing technology (Illumina , USA ) and Assembly method (iVar 1.3.1). Sequence analysis revealed that 38 mutations were found at spike glycoprotein (S), 30 of which were found in the ORF1b , 11 mutations were found in ORF1b ,7,3,2,1 mutations were found in ( N,M,ORF6 ,ORF9 /E ) genes which had been linked to structural changes at various places. The conclusion that the cases in Iraq were of different origins of infections and had a close relationship with the isolates from different country and state were further confirmed by phylogenetic analysis and transmission. The whole genome sequence of the SARS-CoV-2 , which were identified from the Iraqi Kurdistan region, and reported as a first study in Kurdistan region.

Most existing cancer therapies negatively affect normal tissue as well as cancerous tissue. A potentially effective strategy for treating cancer that precludes off-target damage and could be an option for most patients would involve targeting one or more mutations that are ubiquitous in the given patient’s tumor(s). To effect this strategy, one would employ multi-region sequencing of a patient’s primary tumor and metastases to seek out mutations that are shared between all or at least most regions. Once the target or targets are known, one would ideally rapidly generate a molecular switch for at least one of said ubiquitous mutations that can distinguish the mutated DNA, RNA, or protein from the wild-type version and subsequently trigger a therapeutic response. I propose that the therapeutic response involve the replication of an oncolytic virus or intracellular bacterium, as any mutation can theoretically be detected by a vector that enters the cell - and automatic propagation could be very helpful. Moreover, the mutation “signal” can be easily enhanced through transcriptional and translational (if the target is an intracellular protein) enhancement. Importantly, RNA may make the best target for the molecular switches in terms of amplification of the signal and ease of targeting.