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 safety is one of the indicators of the quality of health services in the hospital, for that, it is necessary to have efforts from the hospital to create a system that can minimize the occurrence of errors and unexpected events that can harm patients, nurses as health workers who are the most numerous in the home. sick and with the patient for 24 hours, has an important role in maintaining patient safety. This study aims to explain how the role of nurses and cooperation between health workers in implementing patient safety measures in the hospital. The method used in this study is a literature review by analyzing and exploring relevant articles and focusing on interprofessional collaboration to improve patient safety. The articles used in this study were taken from 3 direct, Proquest, Pubmed science databases published in the last 3 years, namely between 2019-2021, nurses as part of the health team are required to be able to work together with other health professionals in hospitals with various characteristics, including education, gender, age, employment status and length of work, nurses are required to be committed to maintaining patient safety in the hospital.

Access to medical care is a global issue. Technology-aided approaches have been applied in addressing this. Interventions have however not focused on medical diagnosis as a fully automated procedure and available applications employ mainly text-based inputs rather than conversation in natural language. We explored the utility of ontology-based chatbot technology for the design of intelligent agents for medical diagnosis through a systematic review of the most recent related literature. English articles published in 2011-2016 returned 233 hits which yielded 11 relevant articles after a 3-stage screening. Findings showed that the creation of expert systems had been the focus of many the studies which utilize the physician-system-patient framework with system training based mostly on expert knowledge for designing web- or mobile phone-based applications that serve assistive purposes. Findings further indicated gaps in the design and evaluation of more effective systems deployable as standalone applications, for example, on an embodied robotic system. The need for technology supporting the physical examination part of diagnosis, connection to data sources on patients’ vitals and medical history are also indicated in addition to the need for more qualitative work on natural language-based interaction. The system should be one that is continuously learning. Future works should also be directed towards the building of more robust knowledge base as well as evaluation of theory-based diagnostic methodological options

An outbreak caused by coronavirus disease 2019 (COVID-19) occurred in Wuhan City, Hubei Province, China, in December 2019. Up to March 2, 2020, at least 80180 cases have been reported. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province, or exposed to symptoms. Some patients got infected only from asymptomatic contacts. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection only from asymptomatic contact.

The microtubule-associated protein TAU is sorted into the axon in healthy brain neurons. Somatodendritic missorting of TAU is a pathological hallmark of many neurodegenerative diseases called tauopathies, including Alzheimer’s Disease (AD). Cause, consequence, and (patho)physiological mechanisms of TAU sorting and missorting are understudied, in part also due to the lack of readily available human neuronal model systems. The human neuroblastoma cell line SH-SY5Y is widely used for studying TAU physiology and TAU-related pathology in AD and related tauopathies. SH-SY5Y cells can be differentiated into neuron-like cells (SH-SY5Y-derived neurons) using various substances. This review evaluates whether SH-SY5Y-derived neurons are a suitable model for i) investigating intracellular TAU sorting in general, and ii) with respect to neuron subtype-specific TAU vulnerability. I) SH-SY5Y-derived neurons show pronounced axodendritic polarity, high levels of axonally localized TAU protein, expression of all six major human brain isoforms, and TAU phosphorylation similar to the human brain. As proliferative cells, SH-SY5Y cells are readily accessible for genetic engineering, stable transgene integration and leading-edge genome editing are valuable and promising tools for TAU-related studies. II) Depending on the used differentiation procedure, SH-SY5Y-derived neurons resemble cells of distinct subcortical nuclei, i.e. the Locus coeruleus (LC), Nucleus basalis (NB) and Substantia nigra (SN), all of which early affected in many tauopathies. This allows to analyse neuron-specific TAU isoform expression and intracellular localization, also in the context of vulnerability to TAU pathology. Limitations are e.g. the lack of mimicking age-related tauopathy risk factors and the difficulty to define the exact neuronal subtype of SH-SY5Y-derived neurons. In brief, this review discusses the suitability of SH-SY5Y-derived neurons for investigating TAU (mis)sorting mechanisms and neuron-specific TAU vulnerability in disease paradigms.

Pharmacists’ roles in providing patient care remain limited in Indonesia, hence this study aimed to determine the preparedness of pharmacy graduates from one university in Indonesia to deliver patient care. Pharmacy graduates (both registered pharmacists [104] and recent graduates eligible for registration [45]) were sent a validated self-administered survey. The survey sought their perceptions about whether they had acquired 16 patient care related attributes. Further, it sought their opinion on the desirability of having those attributes. Data were analysed using SPSS version 22.0. Sixteen of 104 (15.4%) registered pharmacists and 40 of 45 (88.9%) recent pharmacy graduates participated in the study. More than 50% of participants in both groups were female and most participants were aged in their 20s. Of the recent pharmacy graduates the majority perceived they had at least partially acquired four of 16 list attributes. Male and female recent graduates had significantly different beliefs about their leadership ability (p=0.004). In comparison, most registered pharmacists perceived they had 10 out of the 16 listed attributes. The findings of this study suggested that pharmacy graduates should be better prepared to deliver patient care, and that curriculum redesign with expansion of experiential learning is required.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

ABSTRACT Objectives: Typical Diagnostic Reference Levels (DRL) in terms of Computed Tomography Dose Index (CTDI) and patient dose in terms of Effective Dose (ED ) and Size Specific Dose Estimate (SSDE) were estimated in Computed Tomography (CT) guided biopsy procedures. Materials and Methods: A total of 226 CT biopsy procedures - Iliac bone, liver, lung, mediastinum and para-aortic tissue - were retrospectively analyzed and Typical DRL extracted based on ICRP 135 instructions. Results: For helical mode acquisitions, DRLs in terms of CTDIvol were 9.7 mGy for Iliac bone, 8.9 mGy for liver, 8.8 mGy for lung, 7.9 mGy for mediastinal mass and 9 mGy for para-aortic lymph nodes biopsy procedures. For biopsy acquisitions, DRL values were 7.3 mGy, 7.7 mGy, 5.6 mGy, 5.6 mGy and 7.4 mGy respectively. Also, SSDE median values ranged from 7.6 mGy to 10 mGy for biopsy acquisitions and 11,3 mGy to 12,6 mGy for helical acquisitions, as well as the median values for effective dose ranged from 1.6 mSv to 5,7 mSv for biopsy scans and 3.9 to 9.3 mSv for helical scans. Conclusions: The use of DLR as an optimization tool for CT-guided biopsy procedures revealed that helical scans across the entire anatomical region greatly affect radiation dose compared to biopsy acquisitions.

The modification the gut microbiota in metabolic syndrome and associated chronic diseases is among leading tasks of microbiome research and needs for clinical use of probiotics. Evidence lack for the implications for microbiome modification to improve metabolic health in particular when applied impersonalized. Probiotics have tremendous potential in personalized nutrition and medicine to develop healthy diets. The aim was to to conduct comprehensive overview of recent updates of role of microbiota on human health and development of metabolic syndrome and efficacy of microbiota modulation considering specific properties of probiotic strain and particular aspects of metabolic syndrome and patient`s phenotype to fill the gap between probiotic product and individual to facilitate development of individualized / personalized probiotic and prebiotic treatments. We discuss the relevance of using host phenotype-associated biomarkers, those based on imaging and molecular and patrient`s history, reliable and accessible to facilitate person-specific appication of probiotics and prebiotic substances. Microbiome phenotypes can be parameters of predictive medicine to recognize patient`s predispositions and evaluate treatment responses; the number of phenotype markers can be effectively involved to monitor microbiome modulation. The studied strain-dependent properties of probiotic strains are potentially relevant for individualized treatment for gut and distant sites microbiome modulation. The evidence regarding probiotic strains properties can be taken to account via pathophysiology-based approach for most effective individualized treatment via gut, oral and vaginal and other sites microbiome modulation according to phenotype of the patient providing individualized and personalized medical approaches. Preventive potential of probiotics is strong and well-documented. Recommendations for individualized clinical use of probiotics, and for probiotic studies design have been suggested.

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.

All empirical water column correction methods have consistently been reported to require existing depth sounding data for the purpose of calibrating a simple depth retrieval model; they yield poor results over very bright or very dark bottoms. In contrast, we set out to (i) use only the relative radiance data in the image along with published data, and several new assumptions, (ii) in order to specify and operate the simplified radiative transfer equation (RTE), (iii) for the purpose of retrieving both the satellite derived bathymetry (SDB) and the water column corrected spectral reflectance over shallow seabeds. Sea truth regressions show that SDB depths retrieved by the method only need tide correction. Therefore it shall be demonstrated that, under such new assumptions, there is no need (i) for formal atmospheric correction, (ii) nor for conversion of relative radiance into calibrated reflectance , (iii) nor for existing depth sounding data, to specify the simplified RTE and produce both SDB and spectral water column corrected radiance ready for bottom typing. Moreover, the use of the panchromatic band for that purpose is introduced. Altogether, we named this process the Self-Calibrated Supervised Spectral Shallow-sea Modeler (4SM). This approach requires a trained practitioner, though, to produce its results within hours of downloading the raw image. The ideal raw image should be a “near-nadir” view, exhibit homogeneous atmosphere and water column, include some coverage of optically deep waters and bare land, and lend itself to quality removal of haze, atmospheric adjacency effect, and sun/sky glint.

Background: Handover is a critical process for ensuring quality and safety in healthcare. Considerable research suggests that poor handover results in significant morbidity, mortality, dissatisfaction, and excess financial costs. Despite this, little formal attention, education, and evaluation has been given to handover. There is also paucity of data on the opinions of practitioners on the safety of handover.Objectives: The aim of this study was to measure the perceived risk, degree of patient harm and the systems used to support handover, and to understand how this varied by care setting, type of clinical practice, location, or level of experience. Methods: An open, anonymous and confidential online questionnaire covering: (a) respondent characteristics; (b) peer-to-peer handover; (c) internal referrals; (d) discharges and transfers between organisations; and (e) leading and improving handover was conducted with healthcare practitioners and managers from various settings. Results: We gathered a total of 432 completed responses from 26 countries. The average reported performance of handover was rated as 3.9 out of 5.For each type of handover, 12 - 14% reported errors occurring more than weekly. Of those that knew the outcome of such errors, between 29% and 34% reported that they had witnessed moderate or severe harm. 12% and 17% of respondents believed that handover was high or very high risk (See table 4). These respondents were more likely to have witnessed moderate or severe harm, or to be more senior.A wide combination of handover systems was utilised by respondents. 28% - 32% relied exclusively on EPRs (with or without face-to-face contact). 21% used Office documents such as Word and Excel for peer-to-peer handover, and over 30% used hand-written or manual systems. Conclusions: This study suggests the need to do more — and go further — to improve communication and reduce risk during all types of handovers. Clinical leaders should find ways to train and support handover with effective systems, with less experienced staff being the primary focus. More research is needed to demonstrate the interventions that improve the safety of handover.

Objective: To map the literature pertaining to adult Person-Centered Rehabilitation (PCR).Data Sources: Following our previously published scoping review protocol, data were identified through: three major databases, snowball searches and expert consultation.Study Selection: Two independent reviewers identified English-language papers which addressed adult physical rehabilitation and met one or more of the six pre-defined inclusion categories for PCR content. Data Extraction: Two independent reviewers extracted key characteristics of included papers (e.g. aims, methods, participants). Quantitative methods (descriptive statistics, regression analysis) and qualitative content analyses were used to synthesize the results. Data synthesis: Of 5084 unique records initially screened, 145 papers were included: 111 empirical, including 11 systematic reviews. Empirical papers had data from 13498 clients and 3849 providers, in total. Yearly publications grew exponentially from 2000 to 2017 (r²= 0.65; p<0.01). Publications were unevenly distributed by countries (e.g. United States’ publications per population size was 45 times lower than New Zealand’s). Most papers focused in more than one profession, setting-type or health conditions, respectively 57.2%, 66.2%, and 60.7%. Finally, more than half of the empirical papers (53.2%) studied implementation of PCR approaches, including its effect. Conclusion: This scoping review synthesizes key characteristics and publication trends in the PCR literature, which is mainly empirical and growing exponentially over time. Stakeholders can use the identified trends, gaps, and literature map to guide further PCR research, and both clinical and organizational practices. The high prevalence of papers focused on multiple professions, settings-type, or health conditions reinforces the need for developing a transdisciplinary, trans-service model of PCR, which will be derived from a thematic analysis of this body of literature.

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.

This paper aims to review the challenges, toxicity, and routes of synthesis and usage of silver nanoparticles in different applications but also highlighting their sustainability from both medical and environmental issues. Regarding their toxicity, it is known that silver nanoparticles can destroy over 650 microorganisms comparing with antibiotics. Supplementary, will be presented in a comparative manner some conventional synthesis routes (physical and chemical methods) and green synthesis routes using plant extracts. The approach using plant extracts have various advantages comparing with physical, chemical and microbial synthesis methods because there is no need to use chemicals, wasteful purifications and high energy requirements. The paper presents an overview on “green nanotechnology” focused on using either biological micro-organisms or plant extracts as an alternative to the classical chemical and physical methods. An important issue discussed in the paper is an overview of the synthesis routes of silver nanoparticles, some expected applications of silver based active agents and their toxicity and challenges that must be overcome. Also, it needs to focus our attention on the dismissal of silver nanoparticles into the environment and especially in water systems, fact which suggests that this issue must be fully understood and applied the law.

Access to reliable, clean, modern cooking enhances life chances. One option is photovoltaic cooking systems. Accurate solar data is needed to ascertain to what extent these can satisfy the needs of local people. This paper investigates how to choose the most accurate satellite derived solar irradiance database for use in Africa. This is necessary because there is a general shortage of ground measurements for Africa. The solar data is needed to model the output of solar cooking systems, for instance, a solar panel, battery and electric pressure cooker. Four easily accessible satellite databases are validated against ground measurements using a range of statistical tests. Results demonstrate the impact of the mathematical measure used and the phenomenon of balancing errors. Fitting of the satellite model to appropriate climate zone and/or nearby measurements improves accuracy, as does higher spatial and temporal resolution of input parameters. That said, all the four databases reviewed were found to be suitable for simulating PV yield in East Africa.

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.

Bone is a dynamic tissue with the capacity of repair and regeneration in specific conditions. Nevertheless, due to the increased incidence of bone disorders, the need of bone grafts has been growing over the past decades and the development of an ideal bone graft with optimal properties remains a clinical challenge. This review addresses the bone properties (morphology, composition and their repair and regeneration capacity) and puts the main focus on the potential strategies for developing bone repair and regeneration materials. It describes the requirements for designing a suitable scaffold material, types of materials (polymers, ceramics and composites) and techniques to obtain the porous structures (additive manufacturing techniques/robocasting or derived from marine skeletons) for bone tissue engineering applications. The main objective of this review is to gather the knowledge on the materials and methods for the production of scaffolds for bone tissue engineering and highlighting the potential of natural porous structures such as marine skeletons as promising alternative bone graft substitute materials without any further mineralogical changes, or after partial or total transformation into calcium phosphate. The suitability of the marine-derived porous bone graft substitutes for the intended applications will be also discussed.

Objective. To describe patient satisfaction with pre-hospital emergency knowledge and determine if patients and professionals share a common vision on the satisfaction predictors. Methods. A qualitative study conducted in two phases. First, a systematic review following the PRISMA protocol was carried out searching publications between January 2000 and July 2016 in Medline, Scopus, and Cochrane. Second, three focus groups involving professionals (advisers and healthcare providers) and a total of 79 semi-structured interviews involving patients were conducted to obtain information about what dimensions of care were a priority for patients. Results. Thirty-three relevant studies were identified. A majority conducted in Europe using questionnaires. They pointed out a very high level of satisfaction of callers and patients. Delay with the assistance and the ability for resolution of the case are the elements that overlap in fostering satisfaction. The published studies neither reviewed the overall care process nor related the measurement of the real time in responding to an emergency with the satisfaction. The patients and professionals concurred in their assessments about the most relevant elements for patient satisfaction, although safety was not a predictive factor for patients. Response capacity and perceived capacity for resolving the situation were crucial factors for satisfaction. This qualitative approach yielded assistance targets to be improved. Conclusions. Published studies have assessed similar dimensions of satisfaction. Furthermore, despite the fact that few explanations may be given due to the no face to face attention, taking into account the patient’s emotional needs or maintaining contact with the patient until the emergency services arrive are high predictors of the satisfaction.

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.

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins, miRNAs) that allow the identification of their cell- or tissue-origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. As regards, a large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve informations about the onset of peculiar disease manifestations. In this Review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

The concept of patient confidentiality is nearly as old as the practice of health professions and, has evolved and transformed over the years, from one jurisdiction to the other. Patient confidentiality can be a fundamental human right, an ethical duty or, a legal duty. The Saudi laws have evolved around its Shari’ah-based legal culture, its history and the international human right laws (IHRLs). These elements have moulded the Saudi Arabia’s unique perspective on patient confidentiality. Its confidentiality laws are found scattered in several legislations. Is the Saudi patient confidentiality law able to adequately deal with the contemporary challenges? The study reviewed the relevant Saudi laws in the light the International Humana Rights Laws. Findings suggest that there are issues bordering on the lack of quality comprehensive data protection laws, on clarity and foreseeability of the existing laws, and on the accessibility of the courts. Furthermore, the lack of a system of law reporting and stare decisis potentially gave the judges a wider latitude of discretion in interpreting the laws. Therefore, the study recommends for a comprehensive data protection law with a clear definition of “confidential information”, of data controllers and their role, and of specific safeguards against potential abuses. Others include defining legitimate purposes for using the patient’s data, and his role, and the extent to which he can control the use of his own data. Consistency in legal interpretations, and an improved law reporting system could positively enhance the overall outcome.

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.

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

Diffuse intrinsic pontine gliomas (DIPGs) account for ~15% of pediatric brain tumors, which invariably present with poor survival regardless of treatment mode. Several seminal studies have revealed that 80% of DIPGs harbor H3K27M mutation coded by HIST1H3B, HIST1H3C and H3F3A genes. The H3K27M mutation has broad effects on gene expression and is considered a tumor driver. Determination of the effects of H3K27M on posttranslational histone modifications and gene regulations in DIPG is critical for identifying effective therapeutic targets. Advanced animal models play critical roles in translating these cutting-edge findings into clinical trial development. Here, we review current molecular research progress associated with DIPG. We also summarize DIPG animal models, highlighting novel genomic engineered mouse models (GEMMs) and innovative humanized DIPG mouse models. These models will pave the way towards personalized precision medicine for the treatment of DIPGs.

Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with myeloid-derived suppressor cells (MDSCs) in tumor microenvironments regulates cancer progression. Immunodeficient mice lacking T cells are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The xenograft tumor microenvironment, comprising human cancer and mouse host cells, exhibits more complex bidirectional signaling and function than a syngeneic tumor microenvironment. Here human and mouse colorectal cancer cells were transplanted into nude mice to elucidate differences in macrophage, DC, and MDSC functions in human xenograft and mouse allograft tumor models. Plasma interferon-γ and interleukin-18 concentrations in the former model after intraperitoneal lipopolysaccharide (LPS) administration were significantly higher than those in the latter model and non-transplanted control group. Splenic MHC class I, II, and CD80 expression increased in CD11b+ and MDSC populations after LPS administration in only the xenograft tumor model. The number of CD80- and MRC1-expressing cells decreased upon LPS administration in only the xenograft tumor. These results suggxest that macrophages and DCs function normally in xenograft tumor models, whereas their functions in response to LPS administration vary in allograft tumor models.

High density polyethylene (HDPE) and poly(lactic) acid (PLA) blends with different ratios of both polymers, namely 30:70, 50:50 and 70:30, were produced. Polyethylene grafted maleic anhydride and a random copolymer of ethylene and glycidyl methacrylate, were also proposed as compatibilizers to modify HDPE-PLA optimal blends and were added in the amounts of 1, 3 and 5 wt.%. Blends properties have been evaluated through different aspects by performing tensile tests, scanning electron microscopy to analyze blend morphology and interfaces, and thermomechanical analysis through differential scanning calorimetry, thermo-gravimetric analyses and infrared spectroscopy. The second blend, the one with equal amounts of HDPE and PLA seems to represent a good balance between high amount of bio-derived charge and acceptable mechanical properties. This suggests a good potential of these blends, which would be a good starting point for the production of composites with lingo-cellulosic fillers.

Purpose: "Just culture" is an element of safety culture, and in a broader sense – a part of quality culture. It is the subject of studies, especially in healthcare. This phenomenon is almost unknown in Polish medical facilities. For this reason, the aim of the article is to present the essence and significance of "just culture" in healthcare. The other aim of the research is to present the results of the validation of "just culture" assessment instrument used to recognize the "just culture" maturity level and evaluate the nurses’ beliefs and behaviours in the light of "just culture" criteria. Methodology/Approach: The verified questionnaire consisted of 28 statements in relation to which respondents expressed their opinion on a 5-point Likert scale. The questionnaire was distributed among nurses in one of the largest hospitals in Pomorskie Voivodeship, in Poland. The results based on 68 responses were statistically processed with Statistica 13.1 software. Findings: The obtained results allowed to confirm the reliability of the assessment tool, to recognize the level of „just culture” as wisdom (68%) and to indicate strengths and weaknesses of observed beliefs and behaviours. On this basis, improvement actions were proposed. Originality/Value: We use the original, own prepared questionnaire. This is the first study on "just culture" in healthcare in Poland. There are only few studies devoted to patient safety culture in Poland and no research addressed to "just culture" phenomenon, as well in Poland as in Central Europe. The results in this area allow to recommend the assessment tool for other hospitals and seem to help in understanding the essence of "just culture" implementation.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease prevalent in 1 in 3500 to 5000 males worldwide. As a result of mutations that interrupt the reading frame of the dystrophin gene (DMD), DMD is characterized by a loss of dystrophin protein which leads to decreased muscle membrane integrity, which increases susceptibility to degeneration. CRISPR/Cas9 technology has garnered interest as an avenue for DMD therapy due to its potential for permanent exon skipping, which can restore the disrupted DMD reading frame in DMD and lead to dystrophin restoration. An RNA-guided DNA endonuclease system, CRISPR/Cas9 allows for the targeted editing of specific sequences in the genome. The efficacy and safety of CRISPR/Cas9 as a therapy for DMD has been evaluated by numerous studies in vitro and in vivo, with varying rates of success. Despite the potential of CRISPR/Cas9-mediated gene editing for the long-term treatment of DMD, its translation into the clinic is currently challenged by issues such as off-targeting, immune response activation, and sub-optimal in vivo delivery. Its nature as being mostly a personalized form of therapy also limits applicability to DMD patients, who exhibit a wide spectrum of mutations. This review summarizes the various CRISPR/Cas9 strategies that have been tested in vitro and in vivo for the treatment of DMD. Perspectives on the approach will be provided, and the challenges faced by CRISPR/Cas9 in its road to the clinic will be briefly discussed.

The intensive care units in North West London are part of one of the oldest critical carenetworks in the UK, forming a mature and established strategic alliance to shareresources, experience and knowledge for the benefit of its patients. North WestLondon saw an early surge in COVID-19 admissions, which urgently threatened thecapacity of some of its intensive care units even before the UK government announcedlockdown. The pre-existing relationships and culture within the network allowed itsmembers to unite and work rapidly to develop agile and innovative solutions, protectingany individual unit from becoming overwhelmed, and ultimately protecting its patients.Within a short 50-day period 223 patients were transferred within the network todistribute pressures. This unprecedented number of critical care transfers, combinedwith the creation of extra capacity and new pathways, allowed the region to continue tooffer timely and unrationed access to critical care for all patients who would benefitfrom admission. This extraordinary response is a testament to the power and benefitsof a regionally networked approach to critical care, and the lessons learned maybenefit other healthcare providers, managers and policy makers, especially in regionscurrently facing new outbreaks of COVID-19.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

Ultrafast laser 3D lithography based on non-linear light-matter interactions, widely known as multi-photon lithography (MPL), offers unrivaled precision rapid prototyping and flexible additive manufacturing options. 3D printing equipment based on MPL are already commercially available, yet there is still no comprehensive understanding of factors determining spatial resolution, accuracy, fabrication throughput, repeatability, and standardized metrology methods for the accurate characterization of the produced 3D objects and their functionalities. The photoexcitation mechanisms, spatial-control or photo-modified volumes, and the variety of processable materials are topics actively investigated. The complexity of the research field is underlined by limited understanding and fragmented knowledge of light-excitation and material response. Research to date has only provided case-specific findings on photoexcitation, chemical modification, and material characterization of the experimental data. In this review, we aim to provide a consistent and comprehensive summary of the existing literature on photopolymerization mechanisms under highly confined spatial and temporal conditions, where, besides the excitation and cross-linking, parameters such as diffusion, temperature accumulation, and the finite amount of monomer molecules start to become of critical importance. Key parameters such as, photoexcitation, polymerization kinetics, and the properties of the additively manufactured materials at the nanoscale in 3D are examined, whereas, the perspectives for future research and as well as emerging applications are outlined.

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.

Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signalling takes part in all four wound healing phases: hemostasis, inflammation, proliferation and remodelling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration and treatment of dermal diseases, including the stem cell-derived, plant-derived and engineered EVs.

Background: Healthcare attention is sometimes considered purely technical, but communication has proven to be closely related to clinical results and patient satisfaction. Therefore, evaluation of communication in the scope of healthcare is a priority. The purpose of this study was to validate and adapt, if necessary, the Spanish version of the Communication Styles Inventory (CSI) in a sample of nursing professionals. (2) Methods: The sample was made up of 2313 nursing professionals selected at random from various medical centers in Spain, and is therefore a sample actively employed at the time data were acquired. We started out from the Communication Style Inventory, a questionnaire for evaluating the predominance of certain individual communication behaviors on six scales (expressiveness, preciseness, verbal aggressiveness, questioningness, emotionality and impression manipulativeness). (3) Results: Confirmatory Factor Analysis of the model proposed showed god fit indices. The reliability of the model shown by the Cronbach’s alpha of α=.81 was adequate, and so was single-level and aggregate consistency. Finally, in the analysis of variance by type of contract, configural, metric and scalar invariance was acceptable, but not strict invariance. (4) Conclusions: This instrument progresses in measuring non-technical attributes, such as communication styles, in nursing personnel.

The advent of RNA-sequencing (RNA-Seq) technologies has markedly improved our knowledge and expanded the compendium of small non-coding RNAs, most of which derive from the processing of longer RNA precursors. In this review article, we will discuss about the biogenesis and function of small non-coding RNAs derived from eukaryotic ribosomal RNA (rRNA), called rRNA fragments (rRFs), and their potential role(s) as regulator of gene expression. This relatively new class of ncRNAs remained poorly investigated and underappreciated until recently, due mainly to the a priori exclusion of rRNA sequences—because of their overabundance—from RNA-Seq datasets. The situation surrounding rRFs resembles that of microRNAs (miRNAs), which used to be readily discarded from further analyses, for more than five decades, because we could not believe that RNA of such a short length could bear biological significance. As if we had not yet learned our lesson not to restrain our investigative, scientific mind from challenging widely accepted beliefs or dogmas, and from looking for the hidden treasures in the most unexpected places.

The aim of the study was to determine the attitude of dentist toward learning communication skills and to recognize the factors influencing attitude toward learning communication skills. A cross-sectional study using a self-administered, 26-item, adapted Communication Skills Attitude Scale (CSAS) was carried out among dentist working in a public sector hospital in Qatar. Overall, two scores could be ascertained from the adapted CSAS: the mean positive attitude score (PAS) and negative attitude score (NAS). Non-parametric tests for statistical significance were utilized to assess relation between PAS and NAS scores and demographics. Fifty-nine dentists completed the survey giving an overall response rate of 53.6%. The mean (SD) PAS and NAS scores were 3.98 (SD=0.54) and 3.26 (SD=0.49) respectively. Female dentist was more positive towards learning communication skills than male. No statistically significant correlation was found between both PAS and NAS scores and respondents’ age. Dentists’ had both positive and negative attitudes towards learning communication skills. Considering the high NAS scores, it is recommended to introduce communication skills formal training sessions

Satellite derived bathymetry methods over coastal areas were born to deliver basic and useful information like bathymetry. However, the process is not straightforward, the main limitation being the need of field data. The Self-calibrated Spectral Supervised Shallow-water Modeler (4SM) method was tested to obtain coastal bathymetry without the use of any field data. Using LANDSAT-8 multispectral images from 2013 to 2016, a bathymetric time series was produced. Groundtruthed depths and an alternative method, Stumpf’s Band Ratio Algorithm, were used to verify the results. Retrieved (4SM) vs groundtruthed depths scored an average r2 (0.90), and a low error (RMSE = 1.47 m). Also 4SM showed, over the whole time series, the same average accuracy of the control method (40%). Advantages, limitations and operability under complex atmosphere and water column conditions, and high and low-albedo bottom processing capabilities of 4SM are discussed. In conclusion, the findings suggest that 4SM is equally accurate as the commonly used Stumpf’s method, the only difference being the independence of 4SM to previous field data, and the potential to deliver bottom spectral characteristics for further modelling. 4SM represents a significative advance in coastal remote sensing potential to obtain bathymetry and optical properties of the marine bottom.

Patients satisfaction with fast and high-quality services is the most important in the healthcare settings and specially in outpatient departments and private clinics. High quality services on health sector are indicated by continuous quality improvement (CQI). CQI is a progressive incremental process focused on safety of all participants, outcomes, systematic process, regulated and improved working environment at the later than earlier stages. Among the various suggested strategies, we adopted the patents feedback to improve the quality of services our clinic. All of the patient visited hospital were sent a massage on mobile and requested to provide their feedback on our services. Roughly around 5% of all visitors responded and filled up questionnaire. Majority of them were satisfied with the services in various department. However, they provided us some suggestions to identify the further gaps and improve the services in improving patients experience at our clinic. We considered their feedback, identified problems, redesigned the policies and implemented. After implementation of new strategies, we preliminary again evaluated the patients’ feedback on our services. Patients feedback explores that optimized methods of services for the has considerably increased the patients’ satisfaction. Taken together, our this shows that patients’ feedback is very important factor to improve patients’ experience at outpatient clinics using continuous quality improvement tools. For that reason, this study would serve as reference for public health stack holders, administrators and researchers.

Today, across the most critical problems faced by hospitals and health centers are those caused by the existence of patients who do not attend their appointments. Among others, this practice generates waste of resources and increases the patients’ waiting list. To handle these problems, hospitals are actively trying to implement methods to reduce the idle time caused by patient no-shows. Many scheduling systems developed require predicting whether a patient will show up for an appointment or not. Although, a challenging problem resides in obtaining these estimates precisely. The goal of this work is to analyze how objective factors influence a patient not to attending their appointment, to identify the main causes that contribute to a patient’s decision, and to be able to predict whether or not the patient will attend the scheduled appointment. As a result, the obtained model is tested on a real dataset collected in a health center linked to the University of Vale do Itajaí (UNIVALI), which includes 25 features and about 5000 samples. The algorithm that produced the best results for the available dataset is the Random Forest classifier. It reveals the best recall rate (0.91), since it measures the ability of a classifier to find all the positive instances and achieves a receiver operating characteristic curve rate of 0.969.

Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Of particular interest in this regard are bioactive peptides and peptide-rich protein hydrolyzates, which represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant in rats. The anti-arthritic effect of CETH was studied on the 28th day of the experiment after two weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X-ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non-steroidal anti-inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose-dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammatory edema, inhibition of osteolysis, prevention of osteophitosis, reduction of the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents a potential theoretical strategy for the safe correction of this pathological process and, for the first time, shows that CETH may be a powerful potential nutraceutical agent or bioactive component of functional products in the treatment of rheumatoid arthritis.

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.

There is little understanding of patients' experiences and perceptions with satisfaction by health professionals such as medical and dental clinicians. Furthermore, patient satisfaction is not well understood. The objective of this article is to better understand patients' satisfaction with their medical and dental care. The methods of the current article are based on a narrative review of the literature strategy. Patient satisfaction's multidimensional nature has been established since the perceived reasons for satisfaction varied widely among patients. Many aspects of the treatment influence participant satisfaction at different stages of the intervention's process. An improved understanding of the basis for managing patients' expectations with information reiteratively and efficiently may ultimately reduce patients' potential for negative feelings toward the medical and dental treatment experience. The consumerist method may misrepresent the concept of satisfaction in health service.

Malaria is a serious infection affecting millions of people in Africa. Our study investigated the personal preferences and applications of antimalarial medicines in Ghana. Based on over 1000 questionnaires distributed in Ghana from January to May 2019, we noticed that although Western medications to fight this disease are widely available, most patients in Ghana prefer treatment with locally produced herbal remedies. This preference appears to be due to a combination of traditional venues for obtaining medicines “on the street” rather than in licensed pharmacies, trust in local and “green” products, extensive advertisement of such local products, and an inherent distrust of imported and synthetic or unnatural medicines. Going local and natural is a trend also observed in other countries across the globe, and adds to the acceptance or rejection of drugs regardless of their activity or toxicity. In fact, adverse side effects associated with herbal remedies, such as general weakness and swollen, sore mouth, do not seem to deter the respondents of this study in Ghana. We propose a combination of (a) increasing public awareness of the benefits of modern medicine and (b) an improvement and control of the quality of herbal remedies to raise the standard of malaria treatment in countries such as Ghana.

This initial report of a longitudinal study of 192 English hospital nurses has measured Nursing Values (the 6Cs of nursing); Personality, Self-Esteem and Depression; Burnout Potential; Work-Life Balance Stress; ‘Hardy Personality’; and Intention to Leave Nursing. Correlational, component and cluster analysis identifies four groups: “The Soldiers” (N = 79) , with medium scores on most measures, who bravely ‘soldier on’ in their nursing roles, in the face of numerous financial cuts to the National Health Service, and worsening nurse-patient ratios; “Cheerful Professionals” (N = 54), coping successfully with nursing roles, and a variety of challenges, in upwardly mobile careers; “High Achievers” (N = 39), senior nurses with strong profiles of a ‘hardy personality’, and commitment to fundamental nursing values; “Highly Stressed, Potential Leavers” (N = 20), with indicators of significant psychological distress, and difficulty in coping with nursing role challenges. We propose a model of co-counselling and social support for this distressed group, by nurses who are coping more successfully with multiple challenges. We discuss the role of nurse educators in fostering nursing values, and developing and supporting ‘hardy personality’ and emotional resilience in recruits to nursing. This study is framed within the disciplinary approach of Critical Realism, which identifies the value basis for research and dialogue in developing strategies for social change.

Mesenchymal stem cells (MSCs) have emerged as a promising treatment for inflammatory diseases. It is described that the immunomodulatory effect of MSCs takes place both by direct cell-to-cell contact and by means of soluble factors that leads to an increased accumulation of regulatory immune cells at the sites of inflammation. Similar efficacy of MSCs has been described regardless the route of administration used, the inflammation conditions and the MHC context. These observations arise the question as to whether the migration of the MSCs to the inflamed tissues is a pre-requisite to achieve their beneficial effect. To address this, we examined the biodistribution and the efficacy of intraperitoneal luciferase-expressing human expanded adipose derived stem cells (Luci-eASCs) in a mouse model of colitis. Luci-eASC-infused mice were stratified according to their response to the Luci-eASC treatment. According to the stratification criteria, there was a tendency to increase the bioluminescence signal in the intestine at the expense of a decrease in the bioluminescence signal in the liver in the `responder´ mice. These data thus suggest that the accumulation of the eASCs to the inflamed tissues is beneficial to achieve an optimal modulation of inflammation.

This paper presents an OSA patient interactive monitoring system based on the Internet of Things (IoT) framework. This system allows OSA patients to get timely rescue when they are sleepy outside. Because the Beidou position marker has an interactive function, it can reduce the anxiety of the patient while waiting for the rescue. At the same time, if a friend helps the OSA patients to call the doctor, the friend can also report the patient's condition in time. This system uses the popular IoT framework. At the bottom is the data acquisition layer, which uses wearable sensors to collect vital signs from patients, with a focus on ECG and SpO2 signals. The middle layer is the network layer that transmits the collected physiological signals to the Beidou indicator using the Bluetooth Low Energy (BLE) protocol. The top layer is the application layer, and the application layer uses the mature rescue interactive platform of Beidou. Since the GPS indicator has not included the communication satellite, So it has no SMS function. OSA patients can only passively wait for a rescue. Moreover, due to the lack of satellites in Asia and the insufficient density of the ground-enhanced system, the positioning error of OSA patients is large. The Beidou system developed by China itself, the main coverage of the satellite is in Asia, and is equipped with a high-density ground-based augmentation system. Therefore, the Beidou model improves the positioning accuracy and is equipped with a special communication satellite, which increases the short message interaction function. Therefore, patients can report disease progression in time while waiting for a rescue. After our simulation test, the effectiveness of the OSA patient rescue monitoring system based on the Internet of Things framework and the positioning accuracy of OSA patients have been greatly improved. Especially when OSA patients work outdoors, the cell phone base station signal coverage is relatively weak. The satellite signal is well covered, plus the SMS function of the Beidou indicator. Therefore, the system can be used to provide timely patient progress and provide data support for the medical rescue team to provide a more accurate rescue plan. After a comparative trial, the rescue rate of OSA patients using the detection device of this system was increased by 15 percentage points compared with the rescue rate using only GPS satellite phones.

If an algebra of type $A$ contains a subalgebra which is also an algebra of type $B$, then it is a Smarandache $B$-type $A$-algebra provided the subalgebra of type $B$ contains at least two elements. This generalizes the notion of Smarandache group, where the group of order $\geq 2$ is a subsemigroup of a semigroup. In this paper we investigate a number of such pairings and we deduce a number of conclusions as a consequence.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

Cachexia is a syndrome characterized by an ongoing loss of skeletal muscle mass associated with poor patient prognosis in non-small cell lung cancer (NSCLC). However, prognostic cachexia biomarkers in NSCLC are unknown. Here, we analyzed computed tomography (CT) images and tumor transcriptome data to identify potentially secreted cachexia biomarkers (PSCB) in NSCLC patients with low-muscularity. We integrated radiomics features (pectoralis muscle, sternum, and T10 vertebra) from CT of 89 NSCLC patients, which allowed us to identify an index for screening muscularity. Next, a tumor transcriptomic-based secretome analysis from these patients (discovery set) was evaluated to identify potential cachexia biomarkers in patients with low-muscularity. The prognostic value of these biomarkers for predicting recurrence and survival outcome was confirmed using expression data from eight lung cancer datasets (validation set). Finally, C2C12 myoblasts differentiated into myotubes were used to evaluate the ability of the selected biomarker, IL-8, in inducing muscle cell atrophy. We identified 75 over-expressed transcripts in patients with low-muscularity, which included IL6, CSF3, and IL8. Also, we identified NCAM1, CNTN1, SCG2, CADM1, IL8, NPTX1, and APOD as PSCB in the tumor secretome. These PSCB were capable of distinguishing worse and better prognosis (recurrence and survival) in NSCLC patients. IL8 was confirmed as a predictor of worse prognosis in all validation sets. In vitro assays revealed that IL-8 promoted C2C12 myotube atrophy. Tumors from low-muscularity patients presented a set of upregulated genes encoding for secreted proteins, including pro-inflammatory cytokines that predict worse overall survival in NSCLC. Among these up-regulated genes, IL8 expression in NSCLC tissues was associated with worse prognosis and the recombinant IL-8 was capable of triggering atrophy in C2C12 myotubes.

Individuals with low health literacy (HL) are known to have poorer health outcomes and to have higher mortality rates compared to individuals with higher HL: hence, the improvement of HL is a key outcome in modern healthcare systems. Healthcare providers are therefore asked to support patients’ literacy skills by encouraging the implementation of autonomy-supportive patient centered communication (PCC), which in turn requires the enhancement of patient engagement. Our main hypothesis is that the well-known relationship between autonomy-supportive PCC and HL is mediated by patient engagement which is known to play a role in HL promotion and that is related to PCC as well. The purpose of this study was to formulate a hypothetical structural equation model (SEM) linking PCC to patient engagement and HL. A cross-sectional survey design was employed involving 1007 Italian chronic patients. The hypothetical model was tested using SEM to verify the hypothesized mediation of patient engagement between PCC and HL. Results show that the theoretical model has a good fit indexes and that patient engagement fully mediates the relationship between PCC and HL. This finding suggests healthcare systems to implement a new paradigm where patients are supported to play an autonomous role in their own healthcare.

Sporotrichosis is a subcutaneous mycosis affecting humans and other animals that can be transmitted a zoonosis with cats as the main vector. The conventional anti-fungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 hours and analyzed for the surface expression of co-stimulatory molecules and TLR-4, as well as the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 hours and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile, known to be protective against other fungal diseases. This result could lead to evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.

This review examines the categorization of Essentially Derived Varieties (EDV) introduced in the 1991 revision of the Convention of the Union internationale pour la protection des obtentions végétales (UPOV). Challenges in the implementation of the concept and progress made on a crop-by-crop basis to provide greater clarity and more efficient implementation are reviewed. The current approach to EDV remains valid provided i) clarity on thresholds can be achieved including through resource intensive research on an individual crop species basis and ii) that threshold clarity does not lead to perverse incentives to avoid detection of essential derivation. However, technological advances leading to new varieties resulting from the simultaneous introduction or change in expression of more than “a few” genes will so challenge the concept to require a new Convention. Revision could include deletion of the concept of essential derivation and revision on a crop-by-crop basis of the breeder exception. Countries that allow utility patents for individual plant varieties per se should consider removing that possibility unless plant breeders utilize those encouragements for risk taking and investment to broaden the germplasm base upon which the long-term sustainability of plant breeding resides.

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.

Malawi has developed an excellent, nation-wide system for monitoring people infected with HIV and keeping track of key epidemic markers. Their success lies in two things: the focus on simplicity and the use of data collection not only to track the epidemic and identify problems but also to give regular feedback and support to every clinic in the country. This achievement is the more remarkable given that Malawi is one of the poorest countries in the world, ranking 190 out of 194 countries by GDP, but has one of the most severe epidemics of HIV in the world, ranking 9th out of 168 countries by HIV prevalence. We first discuss the current state and likely future epidemic trends in Malawi: unless we know where we are and where we are going we cannot decide what to do or how to do it to in order to achieve a better outcome. We then discuss the history and development of Malawi’s patient monitoring system, as reported in their Integrated HIV Program Reports,ix which have been published quarterly since the beginning of 2004. We consider the current state of patient monitoring and support as reflected in the most recent report for the third quarter (Q3) of 2016 and comment on some of the questions that this raises. Finally, we consider ways in which the current system could be improved by strengthening Malawi’s analytical capacity and making better use of this unique data set. The focus here is on HIV in adultsv because if ART is initiated early in all adults living with HIV this should include testing all pregnant women for HIV and starting them on treatment immediately. However, PMTCT is especially important and care must be given to reducing MTCT and identifying the long-term child survivors of mother-to-child transmission and this demands a complementary assessment. There is an ongoing debate about the relative merits of treatment and prevention in reducing transmission and it should be made clear that the primary reason for starting people on treatment early is that it is in the best interest of the individual patient to start treatment as soon as possible after becoming infected. Allowing a person’s immune system to deteriorate to any degree is not consistent with the clinician’s commitment to ‘first do no harm’ and even those with the highest CD4⁺ cell count are at a substantially increased risk of death. What matters, therefore, is to get as many people as possible onto ART, ensure that they remain virally suppressed, and consider prevention in this context.

Background: Developing an efficient and standardized method to isolate and characterize adipose-derived stem cells (ASCs) from the stromal vascular fraction (SVF) of the adipose tissue for clinical application represents one of the major challenges in cell therapy and tissue engineering. Methods: In this study, we proposed an innovative, non-enzymatic protocol to collect clinically useful ASCs within freshly isolated SVF from adipose tissue by centrifugation of the infranatant portion of lipoaspirate and to determine the characteristic cytofluorimetric pattern, prior to in vitro culture. Results: The SVF yielded a mean of 73,32 \pm\ 10,89% cell viability evaluated with CALCEINA-FITC, i.e. cell-permeant dye. The ASCs were positive for PC7-labeled mAb anti-CD34 and negative for both PE-labeled mAb anti-CD31 and APC-labeled mAb anti-CD45. The frequency of ASCs estimated according to the panel of cell surface markers used was 51,06%\ \pm 5,26% versus the unstained ASCs subpopulation that was 0,74%\pm0,84% (P<0.0001). The ASCs events/\muL were 1602,13/\muL \pm 731,87/\muL. Conclusion: Our findings suggested that ASCs found in freshly isolated adipose SVF obtained by centrifugation of lipoaspirate can be immunophenotypically identified with a basic panel of cell surface markers. These findings aimed to provide standardization and contribute to reducing the inconsistency on reported cell surface antigens of ASC derived from the existing literature.

Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1-2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance with it is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: a) periodic interviews by nutritionists; b) clinical follow-up; c) serological controls of specific antibodies; d) endoscopies with collection of duodenal biopsies; e) structured questionnaires; f) determination of gluten peptides derived from gluten in feces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within 2 years, while it is more delayed in adults, whose mucosa take longer to heal completely.

The generation of isogenic induced pluripotent stem cell (iPSC) lines using CRISPR-Cas9 technology is a technically challenging, time-consuming process with variable efficiency. Here we use fluorescence-activated cell sorting (FACS) to sort biallelic CRISPR-Cas9 edited single-cell iPS clones into high-throughput 96-well microtiter plates. We used high-content screening (HCS) technology and generated an in-house developed algorithm to select the correctly edited isogenic clones for continued expansion and validation. In our model we have gene-corrected the iPSCs of a Parkinson’s disease (PD) patient carrying the autosomal dominantly inherited heterozygous c.88G>C mutation in the SNCA gene, which leads to the pathogenic p.A30P form of the alpha-synuclein protein. Undertaking a PCR restriction-digest mediated clonal selection strategy prior to sequencing, we were able to post-sort validate each isogenic clone using a quadruple screening strategy. Subsequent transfection with mRNA encoding excision-only transposase allows for the generation of footprint-free isogenic iPSC lines. These monoclonal isogenic iPSC lines retain a normal molecular genotype, express pluripotency markers and have the ability to differentiate into the three germ layers. This combinatory approach of FACS, HCS and post-sorted restriction digestion facilitates the generation of isogenic cell lines for disease modelling to be scaled-up on an automated platform.

ME/CFS (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome) is a chronic, complex, heterogeneous disease that affects millions and lacks both diagnostics and treatments. Big data, or the collection of vast quantities of data that can be mined for information, has transformed the understanding of many complex illnesses like cancer (1,2) and multiple sclerosis (3,4), by dissecting heterogeneity, identifying subtypes, and enabling the development of personalized treatments. It is possible that big data can reveal the same for ME/CFS. Solve M.E. developed and launched the You + ME Registry to collect longitudinal health data from people with ME/CFS, people with Long COVID (LC) and control volunteers using rigorous protocols designed to harmonize with other groups collecting data from similar groups of people. The Registry is an invaluable resource because it integrates with a symptom tracking app, as well as a biorepository, to provide a robust and rich dataset that is available to qualified researchers. Accordingly, it facilitates collaboration that may ultimately uncover causes and help accelerate the development of therapies.

Currently, in the scientific literature there is a great interest on the study of strategies to implement patient-centered care. One of the main tools for this is the therapeutic relationship. Some studies suggest that the perception of the environment in which the physical therapy treatment takes place can influence the perception of its quality. A qualitative study using focus groups was performed. Two researchers conducted the focus groups, using a topic guide with predetermined questions. The focus group discussions were audio-recorded, transcribed verbatim and analyzed thematically using a modified grounded theory approach. The setting was three hospitals and six public health centers located in Spain. The inclusion criteria were patients who had received a minimum of 15 physical therapy sessions and with no communication impairments. Thirty-one participants in four focus groups. Participants described a series of specific experiences relating to the environment, which they felt were influential in the establishment of therapeutic patient-centered relationships, including eight physical factors and five organizational factors. The results of this study highlight environmental factors that affect the quality of the therapeutic patient-centered relationship in physical therapy and emphasize the need for physical therapists and administrators to rethink the situation and propose strategies for improvement.

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-5 cytokine and infiltration of eosinophils. Humanized monoclonal antibodies targeting IL-5 or its receptor, represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in CRS patients is associated to the epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their typical phenotype acquiring a mesenchymal phenotype. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered in EMT during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these altered signaling pathways are able to interfere with EMT; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells which can be easily isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to delineating inflammatory process underlying the development of nasal polyps.

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.

Calcium (Ca) is an essential element constituting sedimentary carbonate in subducting sediments. Ca isotopic characteristics of subduction-related rocks could provide insight into the behavior and budget of carbonate and carbon cycles in subduction zones, due to the distinctive δ^44/40Ca ranges of sedimentary carbonate with respect to the mantle. Here, we studied the Ca isotopic compositions of arc magmas from the Northern Luzon arc (NLA), which are evolved from a depleted mantle metasomatized by slab-derived fluids and sediment melts. The δ^44/40Ca values range from 0.76 ± 0.04‰ to 1.01 ± 0.03‰ and cover the typical ranges for bulk silica earth (BSE, ~ 0.94‰) and fresh mid-ocean ridge basalt (MORB, ~ 0.83‰). The Ca isotopes of NLA volcanics are not dominantly determined by the effects of mantle partial melting or fractional crystallization, nor significantly modified by secondary alteration. Instead, the δ^44/40Ca values of NLA volcanics are controlled by the subduction-related metasomatism. The metasomatism by slab-derived fluids (mainly expelled from altered oceanic crust, AOC) dramatically elevated the contents of fluid-mobile elements (e.g., Ba and Pb) with respect to fluid-immobile elements (e.g., Ce). This process, however, rarely modified the Ca isotopes, possibly ascribed to the δ^44/40Ca similarity between AOC and the depleted mantle. The δ^44/40Ca values significantly correlated with subduction indicators (e.g., Sr-Nd isotopes, Ba/Nb, Ce/Pb, and Nb/La), demonstrating the Ca isotopes of NLA volcanics are mainly controlled by the metasomatism of sediment melts subducting from the South China Sea (SCS). Based on the thermal structures and chemical compositions of sediments subducting into global trenches, we propose that carbonate Ca isotopic signals can only be observed in the arcs with high sedimentary Ca fluxes and temperature-pressure conditions well beyond the solidus of H₂O-saturated sediment melting, e.g., NLA, Nicaragua, Guatemala, Colombia, Peru, South Chile, North Vanuatu, New Zealand, and Kermadec. The absence of such signals in other arcs suggests either limited sedimentary fluxes or much of the subducting sedimentary carbonate has been survived during plate subduction to enter the deep mantle.

There is a strong anticipated future for human pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g. Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, LDL and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker TNFα was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling NASH. Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease characterized by profound fatigue, post-exertional malaise (PEM), and neurocognitive dysfunction. Immune dysregulation and gastrointestinal symptoms are commonly observed in ME/CFS patients. Despite affecting approximately 0.89% of the general population, the underlying pathophysiological mechanisms remain poorly understood. This study aimed to elucidate the relationship between immunological characteristics and intestinal barrier function in ME/CFS patients. ME/CFS patients were stratified into two groups based on their immune competence. After documentation of detailed medical records, serum and plasma samples were collected for assessment of inflammatory immune mediators and biomarkers for intestinal barrier integrity by ELISA. We found reduced complement protein C4a levels in immunodeficient ME/CFS patients suggesting a sub-group specific innate immune dysregulation. ME/CFS patients without immunodeficiencies exhibit a mucosal barrier leakage, as indicated by elevated levels of Lipopolysaccharide-binding protein (LBP). Stratifying ME/CFS patients based on immune competence enabled the distinction of two subgroups with different pathophysiological patterns. The study highlights the importance of emphasizing precise patient stratification in ME/CFS, particularly in the context of defining suitable treatment strategies. Given the substantial health and socioeconomic burden associated with ME/CFS, urgent attention and research efforts are needed to define causative treatment approaches.

Pharmacy personnel often answer telephones to respond to pharmacy customers (subjects) who received messages from automated systems. This research examines the communication process in terms of how users interact and engage with pharmacies after receiving automated messages. No study has directly addressed automated telephone calls and subjects’ interactions. The purpose of this study is to test the interpersonal communication (IC) process of uncertainty in subjects in receipt of automated telephone calls from pharmacies. Subjects completed a survey of validated scales for Satisfaction (S); Relevance (R); Quality (Q); Need for Cognitive Closure (NFC). Relationships between S, R, Q, NFC, and subject preference to an automated telephone call (ATC) were analyzed to determine whether subjects contacting pharmacies display information seeking behavior. This research demonstrates that seeking information occurs if subjects: are dissatisfied with the content of the ATC; perceive that the Q of the ATC is high; perceive that the Q of ATC is high, and like receiving the ATC or with high NFC, and do not like receiving ATCs. Other interactions presented complexities amongst uncertainty and tolerance of NFC within the IC process.

A risk of ischemic stroke increases exponentially after menopause. Even a mild-ischemic stroke can result in increased frailty. Frailty is a state of increased vulnerability to adverse outcomes, which subsequently increases risk of cerebrovascular events and severe cognitive decline, particularly after menopause. Several interventions to reduce frailty and subsequent risk of stroke and cognitive decline have been proposed in laboratory animals and patients. One of them is whole body vibration (WBV). WBV recuperates cerebral function and cognitive ability that deteriorates with increased frailty. The goal of the current study is to test the efficacy of WBV in reducing post-ischemic stroke frailty and brain damage in reproductively senescent female rats. Reproductively senescent Sprague–Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO) and randomly assigned to either WBV or control groups. Animals placed in the WBV group underwent 30 days of WBV (40 Hz) treatment performed twice daily for 15 min each session, 5 days each week. The motor functions of animals belonging to both groups were tested intermittently and at the end of treatment period. Brains were then harvested for inflammatory markers and histopathological analysis. The results demonstrate a significant reduction in inflammatory markers and infarct volume with significant increases in brain-derived neurotrophic factor and improvement in functional activity after tMCAO in middle-aged female rats that were treated with WBV as compared to the control group. Our results may facilitate a faster translation of the WBV intervention for improved outcome after stroke, particularly among frail women.

Introduction: The attitudes of doctors and nurses toward patient safety is a significant factor in hospital safety climates and medical error rates. Yet, there are very few studies of patient safety attitudes in Saudi hospitals and none conducted in hospital emergency departments. Aims: The current study aims to investigate the discrepancy between the patient safety attitudes of doctors and nurses in a Saudi hospital emergency department. Materials and Method: The study employed a qualitative research designvia semi-structured interviews with Saudi and non-Saudi doctors and nurses working in a Saudi hospital emergency department to determine their attitudes and experiences about the patient safety climate. Results: The findings showed doctors and nurse held some similar safety attitudes, however, nurses reported issues with doctors with respect to their teamwork, communication, and patient safety attitudes. Moreover, several barriers to the patient safety climate were identified such as limits to resources, teamwork, communication, and incident reporting. Conclusion: The findings provide one of the few research contributions to knowledge on the differential patient safety attitudes of Saudi and non-Saudi doctors and nurses and suggest the application of such knowledge would enhance positive patient outcomes in emergency departments.

Patient group engagement is increasingly used to inform the design, conduct, and dissemination of clinical trials and other medical research activities. However, the priorities of industry sponsors and patient groups differ, and there is currently no framework to help these groups identify mutually beneficial engagement activities. Methods: We conducted 28 qualitative, semi-structured interviews with representatives from research sponsor organizations (n=14) and patient groups (n=14) to determine: 1) how representatives define benefits and investments of patient group engagement in medical product development and, 2) to refine a list of 31 predefined patient group engagement activities. Results: Patient group and sponsor representatives described similar benefits: engagement activities can enhance the quality and efficiency of clinical trials by improving patient recruitment and retention, reduce costs, and help trials meet expectations of regulators and payers. All representatives indicated that investments include both dedicated staff time and expertise, and financial resources. Factors to consider when evaluating benefits and investments were also identified as were suggestions for clarifying the list of engagement activities. Discussion: Using these findings, we refined the 31 engagement activities to 24 unique activities across the medical product development lifecycle. We also developed a web-based prioritization tool (https://prioritizationtool.ctti-clinicaltrials.org/) to help clinical research sponsors and patient groups identify high priority engagement activities. Use of this tools can help sponsors and patient groups identify the engagement activities that they believe will provide the most benefit for the least investment and may lead to more meaningful and mutually beneficial partnerships in medical product development.

During mechanical ventilation, a disparity between flow, pressure or volume demands of the patient and the assistance delivered by the mechanical ventilator often occurs. Asynchrony effect and ventilator performance are frequently studied from ICU datasets or using commercially available lung simulators and test lungs. This paper introduces an alternative approach of simulating and evaluating patient-ventilator interactions with high fidelity using the electro-mechanical lung simulator xPULM™ under selected conditions. The xPULM™ approximates respiratory activities of a patient during alternating phases of spontaneous breathing and apnoea intervals while connected to a mechanical ventilator. Focusing on different triggering events, volume assist-controlled (V/A-C) and pressure support ventilation (PSV) modes were chosen to test patient-ventilator interactions. In V/A-C mode a double-triggering was detected every third breathing cycle leading to an asynchrony index of 16.67%, being classified as severe. This asynchrony causes a major increase of Peak Inspiratory Pressure PIP = 12.80 ± 1.39 cmH2O and Peak Expiratory Flow PEF = -18.33 ± 1.13 L/min when compared to synchronous phases of the breathing simulation. Additionally, events of premature cycling were observed during PSV mode. In this mode, the peak delivered volume during simulated spontaneous breathing phases almost doubles compared to apnoea phases. The presented approach demonstrates the possibility of simulating and evaluating disparities in fundamental ventilation characteristics caused by double-triggering and premature cycling under V/A-C and PSV ventilation modes. Various dynamic clinical situations can be approximated and could help to identify undesired patient-ventilation interactions in the future. Rapidly manufactured ventilator systems could also be tested using this approach.

Oncology clinical pharmacists are uniquely positioned to make interventions to increase patient activation and engagement. To accomplish this goal, pharmacists can target health system-related, provider-related, and patient-related factors to help enhance patient-centered care and drive behavioral health changes. Interventions that pharmacists must tackle include educating team members and patients on the medication acquisition process, communicating urgency of treatment, optimizing workflows, facilitating guideline recommendations, preventing, and managing treatment toxicities, and promoting patient self-advocacy through education and shared decision-making. As crucial members of the healthcare team, oncology clinical pharmacists can simplify highly complex treatment regimens to facilitate and optimize patients’ ownership of their care. This review will focus on the example of venetoclax treatment in acute myeloid leukemia to demonstrate the impact that pharmacists provide that leads to behavioral change of patients and clinicians.

Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.

Human pluripotent stem cells (hPSCs) have become a powerful tool to generate various kinds of cell types comprising the human body. Recently, organoid technology emerged as a platform to build a physiologically relevant tissue-like structure from the PSCs, which provides a more relevant three-dimensional microenvironment to the actual human body than the conventional monolayer culture system for transplantation, disease modeling, and drug development. Although it holds so many advantages, the organoid culture system still has various problems related to culture methods, which became a challenge to get similar physiological properties to their original tissue counterparts. Here, we discuss the current development of organoid culture methods, including the problem that may arise from the currently available culture systems as well as the possible approach to overcoming the current limitation and improving their optimum utilization for translational application purposes.

Study background and aims: Laparoscopic cholecystectomy is one of the most frequently performed interventions in departments of general surgery. One of the most important aims in achieving perioperative stability of these patients is diminishing the impact of general anesthesia on the hemodynamic stability and the optimization of anesthetic drug doses based on the individual clinical profile of each patient. The objective of this study is the evaluation of the impact monitoring the depth of anesthesia through Entropy (state entropy – SE and response entropy -RE) has on the hemodynamic stability and on the doses of volatile anesthetic. Material and Methods: This is a prospective, observational, randomized, monocentric study carried out between January 2019 and December 2019 in the Clinic of Anesthesia and Intensive Care from the “Pius Brînzeu” Emergency County Hospital in Timișoara, Romania. The patients included in the study were divided in two study groups; patients in Group A (target group) received multimodal monitoring that included monitoring of standard parameters and of Entropy (SE and RE), while patients in Group B (control group) only received standard monitoring. Anesthetic dose in group A were optimized to achieve a target entropy of 40-60. Results: 68 patients met the inclusion criteria and were allocated to one of the two study groups, Group A (N=43) and Group B (N=25). There were no statistically significant differences identified between the two groups for both demographical and clinical data (p>0.05). Statistically significant differences have been identified for the number of hypotensive episodes (p = 0.011, 95% CI 0.1851 to 0.7042) and for the number of episodes of bradycardia (p < 0.0001, 95% CI 0.3296 to 0.7923). Moreover, there was a significant difference in the Sevoflurane consumption between the two study groups (p = 0.0498, 95% CI -0.3942 to 0.9047). Conclusions: The implementation of the multimodal monitoring protocol that includes the standard parameters and the measurement of Entropy for determining the depth of anesthesia (SE and RE) lead to a considerable improvement in perioperative hemodynamic stability. Optimizing the doses of anesthetic drugs based on the individual clinical profile of each patient leads to a considerable decrease in drug consumption as well as to a lower incidence of hemodynamic side-effects.

Periodontitis is microbial infection affecting periodontium, the tooth supporting structure and affects >743 million people worldwide. Neural crest-derived stem cells (NCSCs) hold the promise to regenerate the damaged periodontium. These cells have been identified within adult adipose tissue, periodontal ligament, and palatal tissue. Typical enzymatic isolation protocols are expensive, time consuming and often not clinically compliant. Enzyme-free, mechanical dissociation has been suggested as an alternative method of generating cell suspensions required for cell separation and subsequent expansion ex vivo. In our study, samples of rat skeletal muscle tissue were used to appraise the suitability of a novel mincing method of mechanical dissociation against enzymatic digestion with collagenase and dispase. Skeletal muscle is readily available and has been shown to contain NCSC populations. We used a Rigenera-Human Brain Wave^® prototype mincer to produce a suspension of skeletal muscle-derived cells modeling NCSCs. We have compared the resulting cell cultures produced via mechanical dissociation and enzymatic dissociation, producing single cell suspensions suitable for Magnetic Cell Sorting (MACs) and Fluorescence-activated cell sorting (FACS). Despite the Countess Automated Cytometry data demonstrating that cell suspensions produced by mechanical dissociation (n=24) contain on average 26.8 times as many viable cells as enzymatic cell suspensions (n=18), enzymatic suspensions produced more successful cell cultures. Spheroids and subsequently adherent cells formed from 4 enzymatic cell suspensions (44.4%) vs. 1 mechanical cell suspension (8.3%). Enzymatic digestion protocols formed spheroids faster and more plentifully than mechanical cell suspensions. Adherent cells and spheroids isolated via both methods appear morphologically similarly to NCSCs from our previous studies.

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.

Patients with chronic obstructive pulmonary disease (COPD) often require frequent hospitalization due to worsening symptoms. Preventing prolonged hospital stay and readmission becomes a challenge for healthcare professionals treating patients with COPD. Although the integration of health and social care supports greater collaboration and enhanced patient care, organizational structure and poor leadership may hinder the implementation of patient-oriented goals. This paper presents a case of a 64-year-old chronic smoker with severe COPD who was to be discharged on long-term oxygen therapy (LTOT). It further highlights the healthcare decisions made to ensure the patient’s safety at home and further provides a long-lasting solution to the existing medical and social needs. The goal was accomplished through a discharge plan that reflects multidisciplinary working, efficient leadership, and change management using Havelock’s theory. While COPD is characterized by frequent exacerbation and hospital readmission, it was emphasized that most failed discharges could be attributed to bureaucratic organizational workflow which might not be in the patient’s best interest. It was further demonstrated that healthcare professionals are likely to miss the window of opportunity to apply innovative and long-lasting solutions to the patient’s health condition in an attempt to remedy the immediate symptoms of COPD

Cost-effective and functionalized scaffolds are in high demand for stem-cell-based regenerative medicine to treat refractory bone defects in craniofacial abnormalities and injuries. One potential strategy is to utilize pharmacological and cost-effective plant polyphenols and biocompatible proteins, such as gelatin. Nevertheless, the use of chemically modified proteins with plant polyphenols in this strategy has not been standardized. Here, we demonstrated that gelatin chemically modified with epigallocatechin gallate (EGCG), the major catechin isolated from green tea, can be a useful material for dedifferentiated fat cells and adipose-derived stem cells and can induce bone regeneration in a rat congenial cleft-jaw model in vivo. Vacuum-heated gelatin sponge modified with EGCG (vhEGCG-GS) induced superior osteogenesis from these two cell types compared with vacuum-heated gelatin sponge (vhGS). The EGCG-modification converted the water wettability of vhGS to a hydrophilic property (contact angle: 110° to 3.8°) and the zeta potential to a negative surface charge; the modification enhanced the cell adhesion property and promoted calcium phosphate precipitation. These results suggest that the EGCG-modification with chemical synthesis can be a useful platform to modify the physicochemical property of gelatin. This alteration is likely to provide a preferable microenvironment for multipotent progenitor cells, inducing superior bone formation in vivo.

Background: Media coverage of Lyme disease (LD) has led to an increase in consultations for presumed LD in Europe. However, LD is confirmed in only 10-20% of patients, with a significant number remaining in a diagnostic dead-end. Objectives: To reach a deeper understanding of how patients themselves contribute to the diagnostic process. To describe the genesis of the LD hypothesis in care pathways. Methods: In 2019, 30 patients from a prospective cohort consulting in the infectious diseases department at University Hospital in Marseille for presumed LD were recruited for semi-structured interviews. The inclusion criteria were : suffering from subjective symptoms for 6 months, no clinical or paraclinical argument suggesting current LD. The patients’ medical trajectories were collected using a biographical approach. Results: The diagnosis of Lyme disease was primarily triggered by identification with personal testimonies found on the internet. Most of patients were leading their own diagnostic investigation. The majority of participants were convinced they had LD despite the lack of medical evidence and the scepticism of their referring GP. Conclusion: GPs should first systematically explore patients’ etiologic representations in order to improve adherence to the diagnosis especially in the management of medically unexplained symptoms. Long COVID-19 syndrome challenge offers an opportunity to promote active patient involvement in diagnosis.

Interferon gamma (IFNg) is a pleiotropic cytokine that can potentially reprogramme the tumour microenvironment. However, the antitumour immunomodulatory properties of IFNg still need to be validated due to variable therapeutic outcomes in preclinical and clinical studies. We developed a replication-deficient Semliki Forest virus vector expressing IFNg (SFV/IFNg) and evaluated its immunomodulatory antitumour potential in vitro in a model of 3D spheroids and in vivo in immunocompetent 4T1 mouse breast cancer model. We demonstrated that SFV-derived IFN-g stimulated bone marrow macrophages to acquire the tumoricidal M1 phenotype in 3D nonattached conditions. Coculturing SFV/IFNg-infected 4T1 spheroids with BMDMs inhibited spheroid growth. In the orthotopic 4T1 mouse model, intratumoural administration of SFV/IFNg virus particles alone or in combination with the Pam3CSK4 TLR2/1 ligand led to significant inhibition of tumour growth compared to the administration of the control SFV/Luc virus particles. Analysis of the composition of intra-tumoural lymphoid cells isolated from tumours after SFV/IFNg treatment revealed an increase in CD4+ and CD8+ and a decrease in T-reg (CD4+/CD25+/FoxP3+) cell populations. Furthermore, a significant decrease in the populations of cells bearing myeloid cell markers CD11b, CD38 and CD206 was observed. In conclusion, the SFV/IFNg vector induces a therapeutic antitumour T-cell response and inhibits myeloid cell infiltration in treated tumours.

Objective: The private healthcare providers (PHCP) are believed to improve access to healthcare services in Public-Private Mix (PPM) projects, as they are considered first point of contact for healthcare. The purpose of this study was to know the satisfaction level of TB patients. Design: A questionnaire-based, cross-sectional study was carried out during November and December 2017 for 572 under-treatment patients registered with PHCPs in the PPM project. Lot quality assurance sampling technique was used to randomly select 19 districts from sample frame of 75 districts. In each selected district, data collector retrieved TB register of 8 months (Jan – Aug 2017) and systematically selected patients by fixed periodic interval. SPSS (version 24.0) was used to analyze the data. Results: Study included 53% (n=301) of males and 47% (n=271) of females, with mean age of 38 years (SD, ±18). Almost half of the participants were illiterate (51%, n=289) and 64% (n=365) were non-earning members of the family. In practice, most of the participants visit private providers (71%, n=407), including private hospital/clinic (44%) and traditional practitioners (27%; n=153). 55% of participants visited the current doctor because of clinic’s proximity to residence. 82% of the participants (n=469) were satisfied with the TB care services and 85% (n=488) said that they would recommend this clinic to others. Conclusion: PHCPs are preferred providers for individuals, which is consistent with findings of other studies. Though they are satisfied with TB care and services, interventions should be introduced to reduce the financial burden on the patient. Partnering PHCP is a way forward to ensure universal health coverage, health system strengthening and better health outcomes of the population.

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.

Background and objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS is a common complex multi-system disease with a significant impact on the quality of life of patients and their families, yet the majority of ME/CFS patients go unrecognised or undiagnosed. For two decades the medical education establishment in the UK has been challenged to remedy these failings, but little has changed. This study was designed to ascertain the current UK medical school education on ME/CFS and to identify challenges and opportunities to inform the future of medical education. Materials and methods: A questionnaire, developed under the guidance of the Medical Schools Council, was sent to all 34 UK Medical Schools to collect data for the academic year 2018-2019. Results: Responses were provided by 22 out of a total of 34 medical schools (65%). 59% of respondents taught ME/CFS, led by specialists drawn from 6 medical disciplines. Teaching delivery was usually by lecture; however, discussion case studies and e-learning were used. 7 schools included questions on ME/CFS in their examinations and 3 schools reported likely clinical exposure to ME/CFS patients. 64% of respondents were interested in receiving further teaching aids in ME/CFS. None of the schools shared details of their teaching syllabus so it was not possible to ascertain what students were being taught. Conclusions: UK medical school teaching in ME/CFS is shown to be inadequate. Several medical disciplines, with known differences about the disease, need to set these aside to give greater clarity in teaching undergraduates so they can more easily recognise and diagnose ME/CFS. Improvements are proposed in ME/CFS medical education consistent with the international paradigm shift in biomedical understanding of this disease. Many medical schools (64% of respondents) acknowledge this need by expressing a strong appetite for the development of further teaching aids and materials. The GMC and MSC are called upon to use their considerable influence to bring about the appropriate changes to medical school curricula so future doctors can recognise, diagnose and treat ME/CFS. The GMC should also consider creating a registered speciality encompassing ME/CFS, post viral fatigue and Long Covid.

Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of neurotoxin-induced PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD, and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.

In the present day and age, cancer is still a life-limiting factor whose one of the therapeutic strategies is immunotherapy with vaccines. This research aims to prepare and characterize nanoliposomal vaccine formulation attached to HER2/neu-derived peptide (AE36) with or without CpG-ODN, and to evaluate its immunological responses to the therapy using BALB/c mice with HER2 overexpressing breast cancer. Methods: AE36 was conjugated to the liposomes containing DOTAP, DOPE and Cholesterol. Such formulations are able to produce CD8+ and CD4+ responses and induce synthesis of cytokines detectable via Enzyme-linked immunosorbent assay kits, cytotoxicity testing and intracellular cytokine staining combined with flow cytometry. Therapeutic and prophylactic effectiveness were evaluated through the formulation in samples. The highest effectiveness was found in DDC-peptide + CpG-ODN in both prophylactic and therapeutic studies, which decreased the size of tumors significantly and increased time of survival. These nanoliposomes linked to AE36 could be regarded as an appropriate candidate for the treatment and also for prophylaxis of HER2+ breast cancer; however further studies are needed.

Background: The level of students' understanding of the knowledge of patient safety concepts in infection prevention and control and awareness of treatment is in the low category. Clinical education that provides problem-based learning models in real areas helps students to better understand patient safety. This study is designed to analyze the evaluation and reflection of the role of nursing education institutions in the achievement of patient safety competencies by nursing students.Method: "Searching for articles in research journals is obtained from Sciencedirect, Ebscohost, Garuda, Proquest and Scopus. As many as 228 articles were obtained consisting of nursing journals and health journals with the keywords clinical education, competence, and patient safety. After that, the screening process was carried out based on the inclusion criteria and obtained 25 articles that met the criteria. "Results: the results of the evaluation show that there is a big role in educational institutions in designing curricula, learning models, and clinical education models in an effort to achieve patient safety competencies in nursing students.Conclusion: the learning model about patient safety organized by many educational institutions is considered ineffective in producing the achievement of patient safety competencies for nursing students. This makes it necessary to develop models, reform the patient safety curriculum that is embedded in real areas in clinical education practice

Viruses are silent enemies that intrude and take control of the plant cell's machinery for their own multiplication. Infection by viruses and the resulting damage is still a major challenge in the agriculture sector. Plants have the ability to fight back, but the ability of viruses to counteract and mutate at a fast rate helps them to hide from the host response. Therefore, classical approaches for introgressing resistance genes by breeding have obtained limited success in counteracting the virus menace. Genetic modification (GM) based strategies have been successful in engineering artificial resistance in plants. Several different approaches based on pathogen derived resistance, antisense constructs, hairpin RNA, double stranded RNA etc. have been used to enhance plant resistance to the virus. Recently, genome editing (GE) strategies mainly involving the CRISPR/Cas mediated modifications are being used for virus control. In this review, we discuss the developments and advancements in the GM and GE based methods in tackling virus infection in plants.

Pure orbital blowout fractures occur within the confines of the internal orbital wall. Restoration of orbital form and volume is paramount to prevent functional and esthetic impairment. The anatomical peculiarity of the orbit has encouraged surgeons to develop implants with customized features to restore its architecture. This has resulted in worldwide clinical demand for patient-specific implants (PSIs) designed to fit precisely in the patient's unique anatomy. Fused filament fabrication (FFF) three-dimensional (3D) printing technology has enabled the fabrication of implant-grade polymers such as Polyetheretherketone (PEEK), paving the way for a more sophisticated generation of biomaterials. This study evaluates the FFF 3D printed PEEK orbital mesh customized implants with a metric considering the relevant design, biomechanical, and morphological parameters. The performance of the implants is studied as a function of varying thicknesses and porous design constructs through a finite element (FE) based computational model and a decision matrix based statistical approach. The maximum stress values achieved in our results predict the high durability of the implants, and the maximum deformation values were under one-tenth of a millimeter (mm) domain in all the implant profile configurations. The circular patterned implant (0.9 mm) had the best performance score. The study demonstrates that compounding multi-design computational analysis with 3D printing can be beneficial for the optimal restoration of the orbital floor.

It has become practically impossible to survey the literature on cells derived from adipose tissue with the aim to apply them in regenerative medicine. The aim of this review is to provide a jump start to understanding the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) in regenerative medicine. We show that serious and adequate clinical research demonstrates that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither 'fat stem cells' nor could they exclusively be isolated from adipose tissue, as ADRCs contain the same adult (depending on the definition) pluripotent or multipotent stem cells that are ubiquitously present in the walls of small blood vessels. Of note, the specific isolation procedure used has significant impact on the number and viability of the cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to further separate adipose-derived stem cells (ASCs) from ADRCs if the latter were adequately isolated from adipose tissue. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for manipulating, stimulating and/or (genetically) reprogramming the cells for this purpose. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use.

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.

Effective biomarkers are essential to the early diagnosis of non-small cell lung cancer (NSCLC). Herein, a retrospective study of 49 newly diagnosed and recurrent NSCLC patients, 31 patients with benign pulmonary disease and 24 healthy volunteers was conducted, to evaluate the diagnostic value of circulating rare cells for NSCLC. The expression of circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in peripheral blood were measured by subtraction enrichment-immunostaining-fluorescence in situ hybridization (SE-iFISH). The level of CTCs (P＜0.001) and CTECs (P＜0.001) was significantly higher in NSCLC group than that in benign pulmonary disease group. The proportion of small CTCs (P＜0.001) and CTECs (P＜0.0001) significantly increased from benign lung disease individuals to NSCLC patients. The AUC of ROC curves of total CTCs and CTECs were 0.815 (95%CI: 0.722~0.907), 0.739 (95%CI: 0.618~0.860), respectively. The cut-off values for discriminating NSCLC with benign lung disease patients were total CTCs 11.5 units/6ml and total CTECs 10.5 units/6ml, with sensitivity and specificity being 67.3% and 83.9%, 77.6% and 77.4%, respectively. When CTCs and CTECs were combined, predictive value significantly increased to 82.6% as measured by the area under the curve. Small CTCs and triploid CTCs had high positive predictive value (PPV) and positive likelihood ratio (LR+) of the diagnosis of NSCLC in early stage. CTCs and CTECs can not only be used as new biomarkers for the diagnosis of NSCLC, but can also improve diagnostic performance of the early stage NSCLC. Moreover, the combined examination of CTCs and CTECs is be superior to the single.

Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct N^ɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed AGEs are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using MG-H1 as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consisting of neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for the study of GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To address this gap, we isolated tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models. Two of 6 mice developed tumors (NEC913 and NEC1452). Over 90% of NEC913 and NEC1452 tumor cells stained positive for Ki67. NEC913 PDX tumors expressed neuroendocrine markers such as chromogranin A (CgA), synaptophysin (SYP), and somatostatin receptor-2 (SSTR2) whereas NEC1452 PDX tumors do not express SSTR2. Exome sequencing revealed loss of p53 and RB1 in both tumors. To demonstrate an application of these novel NEC PDX models for SSTR2-targeted peptide imaging, the NEC913 and NEC1452 cells were bilaterally injected into mice. Near infrared-labelled octreotide was administered and fluorescent signal was specifically observed for the NEC913 SSTR2 positive tumors. These 2 GEP NEC PDX models serve as valuable resource for GEP NEN therapy testing.

Objective: The Acute Cystitis Symptom Score (ACSS) was developed and validated as a self-reporting questionnaire for diagnosing and monitoring acute, uncomplicated cystitis (AC) in female patients. The study aims at the translation of the ACSS into Greek from original Russian as a source and American English as a new master version and at its linguistic validation. Material and Methods: Three independent professional native Greek translators, two of them experts in Russian and one in English, translated the ACSS from Russian and American English into Greek. The second group of three translators translated each of the three versions back into the original language to detect or correct any important discrepancies. These three Greek versions were then used for linguistic validation. Results: The English to Greek translation reflected more the spoken language, the two Russian to Greek translations more the written, formal language. A total of 60 randomly selected females and 30 healthcare professionals was asked about their preferences and to comment on each of the three translations. Considering all comments the scientific committee (SC) developed the Greek consensus version. For cognitive assessment additional 30 healthcare professionals and 30 females were asked to comment on the intelligibility of all items. Considering their comments the linguistically validated Greek study version was established by the SC. Conclusion: The linguistically validated Greek version of the ACSS can now be used for the clinical validation study.

Placenta-derived stem cells (PDSCs) offer the advantages of possessing mesenchymal and embryonic traits, broad differentiation potential, large-scale availability, and no ethical constraints in their utilization in therapeutic applications. Elevated protein synthesis and consequently enhanced protein maintenance networks become necessary both due to the requirement to maintain stemness and respond to different stresses. This study aimed to identify the primary determinants of proteotoxic stress response in PDSCs. We generated heat-induced dose-responsive proteotoxic stress models of three stem cell types DBMSCs, DPMSCs, and pMSCs, and measured stress induction through biochemical and cell proliferation assays. RT-PCR array analysis of 84 genes involved in protein folding and protein quality control led to the identification of Hsp70 isoforms HSPA1A and HSPA1B as the prominent ones among 17 significantly expressed genes and with further analysis at the protein level through western blotting. A 24-hours’ time series analysis of stress-response allowed a detailed kinetic analysis of HSPA1A and HSPA1B gene and protein expression. More prominent differences between the two Hsp70 isoforms were detected at the translational level eluding to a potential higher requirement for HSPA1B during proteotoxic stress in PDSCs. To conclude, consideration should be given to the manipulation of definitely characterized chaperones at their expression or functional levels when utilizing PDSCs in therapeutic and regenerative applications.

Adipose-derived stem cells (ADSCs) were suggested for treating degenerative osteoarthritis, suppressing inflammatory responses, and repairing damaged soft tissues. Moreover, the ADSCs have the potential to undergo self-renewal and differentiate into bone, tendon, cartilage, and ligament. Recently, investigation of the self-renewal and differentiation of the ADSCs becomes an attractive area. In this work, a pneumatic microdevice has been developed to study the gene expression of the ADSCs after the stimulation of multi-axial tensile strain. The ADSCs were cultured on the microdevice and experienced multi-axial tensile strain during a 3-day culture course. Self-renewal and differentiation abilities were investigated by mRNA expressions of NANOG, SOX2, OCT4, SOX9, PPAR-γ, and RUNX2. The result showed that the genes related self-renewal were significantly up-regulated after the tensile stimulation. Higher proliferation ratio of the ADSCs was also shown by cell viability assay. The microdevice provides a promising platform for cell-based study under mechanical tensile stimulation.

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.

As many as 20-25% of the population experiences harm in outpatient settings, yet these locations are underrepresented in the literature compared to hospitals. We examined results from the Medical Office Survey on Patient Safety Culture designed by the Agency for Healthcare Research and Quality. The survey administered in 2012 gathered perceptions from 23,679 individuals in 934 unique medical offices. We examined associations of organizational patient safety climate composites on frequency of safety and quality issues, overall quality score, and safety rating. We found organizational patient safety composites are all positively and significantly associated with a higher overall quality score and patient safety rating, and fewer safety and quality issues. Office processes and standardization appeared to have the most consistent influence on perceived quality outcomes. Our results indicate it may be advantageous for medical offices to improve on the factors that contribute to positive safety climate.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

Based upon 30-years of research by the author a new approach to hospital bed planning and international benchmarking is proposed. The number of hospital beds per 1000 population is commonly used to compare international bed numbers. This method is flawed because it does not consider population age structure or the effect of nearness-to-death on hospital utilization. Deaths are also serving as a proxy for wider bed demand arising from undetected outbreaks of 3000 species of human pathogens. To remedy this problem a new approach to bed modelling has been developed which plots beds per 1000 deaths against deaths per 1000 population. Lines of equivalence can be drawn on the plot to delineate countries with higher or lower bed supply. This method is extended to attempt to define the optimum region for bed supply in an effective health care system. England is used as an example of a health system descending into operational chaos due to too few beds and manpower. The former Soviet bloc countries represent a health system overly dependent on hospital beds. Several countries also show evidence for over-utilization of hospital beds. The new method is used to define a potential range for bed supply and manpower where the current most effective health systems currently reside. The method is applied to total curative beds, medical beds, psychiatric beds, critical care, geriatric care, etc., and can also be used to compare different types of healthcare staff, i.e., nurses, physicians, surgeons. Issues surrounding the optimum hospital size and the optimum average occupancy will also be discussed. The role of poor policy in the English NHS is used to show how the NHS has been led into a bed crisis. The method is also extended beyond international benchmarking to illustrate how it can be applied at a local or regional level in the process of long-term bed planning. Issues regarding the volatility in hospital admissions are also addressed to explain the need for surge capacity and why an adequate average bed occupancy margin is required for an optimally functioning hospital.