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.

Background: Sudden changes in clinical practice and the altered ability to care for patients due to the COVID-19 pandemic have been associated with moral distress and mental health concerns in healthcare workers internationally. This study aimed to investigate the severity, prevalence, and predictors of moral distress experienced by Australian healthcare workers during the COVID-19 pandemic. Methods: A nationwide, voluntary, anonymous, single time-point, online survey of self-identified frontline healthcare workers was conducted between 27th August and 23rd October 2020. Participants were recruited through health organisations, professional associations or colleges, universities, government contacts, and national media. Results: 7846 complete responses were received from nurses (39.4%), doctors (31.1%), allied health staff (16.7%) or other roles (6.7%). Many participants reported moral distress related to resource scarcity (58.3%), wearing PPE (31.7%) limiting their ability to care for patients, exclusion of family going against their values (60.2%), and fear of letting co-workers down if they were infected (55.0%). Many personal and workplace predictors of moral distress were identified, with those working in certain frontline areas, metropolitan locations, and with prior mental health diagnoses at particular risk of distress. Moral distress was associated with an increased risk of adverse mental health outcomes. Feeling appreciated by the community mitigated this risk in healthcare workers. Conclusions: Safeguarding healthcare workforces during crises is important for both patient safety and workforce longevity. Targeted interventions are required to prevent or minimise moral distress and associated mental health concerns in healthcare workers during COVID-19 and other crises.

The impact of organizational accreditation and professional certification and the evidence-based measurable impact of those for both academic programs and affiliates is one of specific interest to universities and individuals in the healthcare management field [1]. The authors’ analysis examined the impact of hiring graduates from higher education programs that held external accreditation from the Commission on Accreditation of Healthcare Management Education (CAHME). Graduates’ affiliation with the American College of Healthcare Executives (ACHE) professional healthcare leadership organization was also assessed as an independent variable. Study outcomes focused on these graduates’ respective healthcare organization’s performance measures (cost, quality, and access) to assess the researchers’ inquiry into the perceived value of a CAHME-accredited graduate degree in healthcare administration and a professional ACHE affiliation [2]. The results from this study found no effect of CAHME accreditation or ACHE affiliation on healthcare organization performance outcomes. The study findings support the need for future research surrounding healthcare administration professional graduate degree program characteristics and leader development affiliations, as perceived by various industry stakeholders.

Little is known about family medicine academic staff in Taiwan, and basic data about this workforce may aid healthcare decision makers. We analysed data on Taiwan’s 13 medical schools collected by the Taiwan Association of Family Medicine from June to September 2019. Items included medical school names and total staff, and the gender, age, degree, working title (part-time/full-time), academic level, and sub-specialty of each current family medicine faculty member. A total of 116 family medicine faculty members were reported; most were male (n= 85, 73.3%). Ages ranged between 30 and 69 years, with a mean (SD) age of 43.3 (8.09). Faculty members with a master’s degree were the largest group (n= 49, 42.2%), and most were academic lecturers (n=49, 42.2%). Additionally, only about one-fourth (n=26, 22.4%) of family medicine faculty in medical schools were full-time, while the other three-fourths (n=90, 77.6%) were part-time faculty; most were located in northern Taiwan (n=79, 68.1%) and specialized in gerontology and geriatrics (n=55, 47.4%) and hospice palliative care (n=53, 45.7%). Our research provides the most complete census of family medicine academic physicians in medical schools in Taiwan. The results inform efforts to improve the establishment and development of family medicine departments in Taiwan.

Purpose: The ongoing COVID-19 crisis has created the need for social distancing between medical staff and patients, therefore, healthcare robotics is increasingly important as regards infectious control. The purpose of this study was to design and fabricate a remote controlled transport robot that could provide an optimum technology base for developing countries, having dual functions of telepresence and delivery operations inside or outside buildings, is easy to assemble and also easily able to be cleaned using standard chemical agents.Methods: This machine was designed and fabricated to incorporate two main functions; delivery and telepresence. The robot consists of a base frame, DC motors for driving and steering systems, actuator motor for driving wheel elevation, Wi-Fi AP/Repeater, network camera, and a necessary a back-up power system.Results: This robot can be used both indoors and outdoors. It can carry loads of more than 80 kg. The machine can cross obstacles greater than 3 cm. It can be cleaned by disinfectant agents. An actuator motor can lift the driving wheels above the surface to prevent gear damage. Conclusion: This article demonstrates the concept of a healthcare telepresence and delivery robot that can provide distancing during the present COVID-19 crisis, using optimum technology for low and middle-income countries. In the future, the researcher should consider development of the delivery controls, combined with the telepresence system using the internet of things, to improve the navigation system, the manipulator system for supporting multi-floor transportation, and also other multi-functional purposes.

When all countries are battling Covid-19 by adopting different policies, it could help address the issue of government response policy efficiency. This study examines the efficiency of government intervention policies in 19 countries, the efficiency of preventing the spread, and also the mortality caused by the virus. The policies are categorized based on the Oxford COVID-19 Government Response Tracker, which combines various indicators, including Containment and closure, Economic response, and Health systems. Given that the governments apply a top-down approach to design these policies, the current research evaluates the efficiency of policies based on the same approach. Here, two different models have been used to calculate the efficiency of policies. We designed a combined index in both models and applied Window DEA method to determine the output quantities in the efficiency ratio. The results of our study show that in both models, Japan, Finland and Thailand had the highest level of government response efficiency. The countries with the lowest government response efficiency were the United States, Spain, and Russia in the first model, and China, Italy, and Spain in the second.

Learning systems have been very focused on creating models that are capable of obtaining the best results in error metrics. Recently, the focus has shifted to improvement in order to interpret and explain their results. The need for interpretation is greater when these models are used to support decision making. In some areas this becomes an indispensable requirement, such as in medicine. This paper focuses on the prediction of cardiovascular disease by analyzing the well-known Statlog (Heart) Data Set from the UCI’s Automated Learning Repository. This study will analyze the cost of making predictions easier to interpret by reducing the number of features that explain the classification of health status versus the cost in accuracy. It will be analyzed on a large set of classification techniques and performance metrics. Demonstrating that it is possible to make explainable and reliable models that have a good commitment to predictive performance.

Objectives: The aim of this study was to assess the knowledge, attitude and practice of healthcare professionals regarding adverse drug reaction [ADR] monitoring and pharmacovigilance [PV] in India. Materials and Methods: It was a questionnaire based cross sectional observational study. Data was collected with the help of data collection Google form that included the demographics and twenty two survey based questions. Data were analysed by using Microsoft Excel sheet, further analysed for results, including frequency, percentage, mean and standard deviation. Result: The questionnaire was filled by two hundred ten healthcare professionals in which 52.9 % were male and 47.10% of female. Most of the respondents were pharm d students (50.47%). Out of the total 91.4% responded to the definition of pharmacovigilance correctly. 87.6% participants said all ADR should be reported. 86.20% participants think Pharmacovigilance should be taught in detail to healthcare professionals. Most of the respondents (43.8%) always informed the patients about ADR while prescribing the medicines. Conclusion: Study revealed most of the participants have good knowledge about ADR and pharmacovigilance. Difficult to decide whether ADR occur or not and extra work load being major factors responsible for under reporting.

Background: The healthcare workers are exposed to dangerous pathogen agents during the outbreak of the new coronavirus COVID-19. To minimize the risk of becoming infected by this virus, healthcare workers need to wear the most appropriate personal protective equipment (PPE). Objective: The objective of this study was to analyze the guidelines that the World Health Organization (WHO) and the Centers for the Disease Control and Prevention (CDC) recommend for the rational use of EPP to protect healthcare workers against the novel coronavirus COVID-19.Methodology: To learn how to effectively protect healthcare workers against the COVID-19, a detailed analysis and comparison of the WHO and CDC guidelines related to the proper use of personal protection equipment (PPE) in different healthcare settings was carried out. Results: The results of this study based on an analysis of PPE recommended by the World Health Organization (WHO) and the Centers for the Disease Control and Prevention (CDC) indicated that the safety and protection of healthcare workers can be maximized if the guidelines suggested by these institutions are followed. In general, the WHO and CDC recommendations based on medical practices are similar, and depending on the healthcare activities and settings where the healthcare workers perform their work, suggest wearing medical/surgical facemasks, respirators, googles and face shields (eye protection), gloves, gowns and aprons. Conclusions: The protection and safety of the healthcare workers can be maximized during the outbreak of COVID-19 by following the WHO and CDC recommendations described in this study. The general guidelines offered by these institutions are similar and based on medical practices.

In the wake of the novel coronavirus, SARS-CoV-19, the world has undergone a critical situation in which grave threats to global public health emerged. Among human populations across the planet, travel restraints, border enforcement measures, quarantine, and isolation provisions were implemented in an attempt to control and limit the spread of the contagion. Decisions on how to implement and enforce various control policies should be determined based on available real-world evidence and theoretical prediction. In this study, we propose a novel exportation- importation epidemic model associated with the quarantine and hospitalized-isolation policies by considering the two-body system: a source country of a contagious disease and a neighboring country that is initially disease-free. The model is first applied to the original COVID-19 data in China, Italy, and the Republic of Korea (ROK) and observed through consistent fitting results with equivalent goodness-of-fit. Then, the data are estimated per the fitting parameters. Driven by these parametric settings and considering the normalized population, the numerical analysis, and epidemiological exploration, this work further elucidates the substantial impact of quarantine policies, healthcare facilities, and the public counter-compliance effect.

In the area of dental healthcare services, where patients and professionals deal with multiple auditory stimuli, this cross-sectional study reports on the intricate dynamics of sound preferences, noise obstacles, and the profound impact of music on anxiety reduction within dental office set-tings. The sample comprises of 134 dental patients, primarily females (56.7%), with varying age groups, education levels, and therapy durations in the university clinics of the department of Dentistry, National and Kapodistrian University of Athens and four private dental offices at the metropolitan area of Athens, Greece. Notably, 92.5% of the participants report no hearing loss, and 56.7% exhibit some level of noise sensitivity. The study reveals a moderate to good perceived health status (M=3.84, SD=0.95) among participants, with low perceived noise disturbance in university dental clinics. Preferences for instrumental music, foreign pop, and classical music are prominent during waiting times. Potential irritations include impersonal treatment (44%) and staff behavior (41.8%). Music player usage within the settings of the dental clinic involves radios (49.3%) and headphones (41.0%). Correlations and predictors indicate associations between health status, music preferences, and noise disturbances. More specifically, visiting the university dental clinics (β = .300, p = .005) as well as younger age (β = .300, p = .034) were significant predictors of better perceived health status. Clearer perception of external sounds while using the music player (β = .190, p = .039) was a significant predictor of better perceived health status, while poorer health was predicted by the preference of Greek folk songs (β = -.200, p = .030). Also, the use of smartphones for playing music was related to poorer health (β = -.370, p < .001). Following, younger age (β = -.270, p = .015), lower education (β = -.210, p = .035), higher noise sensitivity (β = .190, p = .027), as well as feelings of anxiety and nervousness due to ambient noise from people and machines (β = .510, p = .027) were significant predictors of noise disturbance from machines. Also, visiting private clinics (β = .240, p = .018), preferences of specific playlist (β = .310, p = .012), no music (β = .280, p = .016) and use of smartphones to play music (β = .230, p = .029) were significant predictors of noise disturbance from patients or staff. Finally, the preference of listening to a specific playlist was related to better health status (r = .190, p < .05). Findings aim to optimize eco-soundscapes in dental offices, con-tributing to enhanced patient well-being. The research underscores the potential of music inter-ventions to alleviate dental anxiety and improve the overall dental experience and quality care.

The central reason behind emergence of clinically-detectable tumors is evasion from immune surveillance due to lack of cancer cells surface membrane expression of tumor-specific peptides in association with MHC class I molecules, concealment of natural killer cells-activating molecules, and absence of inflammation resulting from inefficient stimulation of innate immunity receptors and co-stimulatory molecules. The tumor microenvironment (TME) also contributes to tumor initiation, progression and resistance to therapeutic interventions because of its dense, fibrogenic, barrier-like composition, aberrant vasculature, and production of cytokines and chemokines responsible for recruitment of immune suppressive cells, notably myeloid-derived suppressor cells, M2 macrophages, regulatory T cells, extracellular trap-forming neutrophils, and cancer-associated fibroblasts. We herein show that the relentless efforts and strategies to overcome the TME elusive tumor-promoting impact produced contrasting, opposed, controversial effects, characterized by limited efficacy and proven adversity, and most importantly deterred from attempts to discover and counteract the fundamental inherent mechanisms initiating, and not consequent to, carcinogenesis.

Quality of life (QOL) is based on their perception of their position in life in respect to their goals, expectations, standards, and concerns, as well as their culture and value systems, their workflow and workplace situations while it influences quality of services. In this study we aim to report on dental and nursing academians’ QOL and well-being at the end of the third year of the COVID-19 pandemic. The World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF) tool, recording Physical, Psychological, Social and Environmental dimensions of QOL, was used. The WHOQOL-BREF was modified on a spiritual, coaching/mentoring approach in a two-step designing and validated procedure. The modified SHQOL-BREF (Spiritual Healthcare version) designed for this study, was uploaded, and filled in online during April-June 2023. Staff (N=120, 75% female) of both departments of Dentistry (44.2%) and Nursing (55.8%) of the National and Kapodistrian university of Athens, participated in anonymity. QOL in terms of physical health was reported at a higher level (M=72.2 points) compared to social relationships (M=69 points), psychological health (M=65 points) and environment (M=59 points) (scores reported in 0-100 score). Overall QOL was rated at 66 points while satisfaction from health at 72 points. Job satisfaction (M1=3.2) and spirituality (M2=3.0) were reported at a medium level in a 5-point scale, while personal beliefs and values were reported at a high level (M3=4.0). Participants age presented a significant, moderate to strong effect on physical health [F(3,97)=2.89, p&lt;.05, η2p=.08] and on environment [F(3,97)=2.80, p&lt;.05, η2p=.08] and marital status on social relationships [F(1,97)=9.66, p&lt;.05, η2p=.09]. Married participants reported consistently higher levels of QOL compared to single participants, for all age groups. Department had a significant moderate effect on social relationships (F(1,97)=5.10, p&lt;.05, η2p=.05) and education a significant moderate to strong effect on psychological health (F(2,97)=3.74, p&lt;.05, η2p=.07). PhD level participants in both departments presented higher levels of psychological health compared to lower educational levels. Also, participants from the department of Dentistry reported higher levels of social relationships QOL in all educational groups, compared to the department of Nursing. Strategic planning on sustainability and QOL initiatives should be introduced after the COVID-19 pandemic for dental and nursing academic personnel to promote resilience and QOL scores.

Adeno-associated viral (AAV) vectors can be used for gene delivery. AAV.CAP-Mac was recently developed; it can cross the blood-brain barrier and transduce cells throughout the CNS. However, some brain regions were not transduced in adult rhesus monkeys. Additionally, AAV vectors can only package 5 kb of DNA. Also, AAV vectors may be genotoxic and cytotoxic, especially at high doses. Finally, AAV vectors are very expensive to produce at sufficiently high titers for treatment. Off-the-shelf cell-based delivery systems wherein the cells can infiltrate the target tissue and be hyper-motile would be ideal. Also, mRNA-based gene editing would be a transient treatment, and thus be much safer.

.Background: Negative outcomes associated with medications (NOM) and drug-related problems (DRP) significantly impact individuals with kidney replacement therapy (KRT) given the complexities of managing kidney disease and associated comorbidities. The present study aims to assess the frequency of NOMs/DRPs among KRT patients and identify contributing factors. Methods: A cross-sectional study was conducted at the Virgen de las Nieves University Hospital (Granada, Spain), involving 117 outpatient adults with KRT. Data were collected from February 2021 to July 2023 using electronic records, semi-structured interviews (Dáder Method), and discussions with nephrology specialists. NOMs/DRPs were identified following treatment guidelines. Binary logistic regression determined associated factors (p-value < 0.05). Results: Across 117 patients, 2,436 NOMs and 3,303 DRPs were identified, averaging 20.82 NOMs and 28.23 DRPs per patient. Prevalent NOMs included untreated conditions (58.95%), quantitative ineffectiveness (35.43%), and non-quantitative safety problems (5.13%). Dominant DRPs were undertreated conditions (37.63%), wrong dose/posology/length (33.00%), risk of adverse drug reactions (ADR) (16.14%), and non-adherence (6.87%). Patients with ADR, undertreated condi-tions, and anemia were associated with quantitative ineffectiveness. Risk of ADR and vitamin D deficiency/insufficiency correlated with non-quantitative safety problems. Conclusions: KRT pa-tients exhibited a substantial prevalence of NOMs/DRPs. Further research is needed to deepen our understanding of these complexities for improved patient care.

Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individ-uals, leading to chronic pain and reduced quality of life. Despite antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study employs the HIV Tg26 mouse model to investigate HIV-DSP development and assess gut microbiome changes in response to chronic morphine treatment and ART using 16s rRNA sequencing. Our results reveal that chronic morphine and ART exacerbate HIV-DSP in Tg26 mice, primarily through mechanical pain path-ways. As the gut microbiome may be involved in chronic pain persistence, microbiome analysis indicated distinct bacterial community changes between WT and Tg26 mice as well as morphine and ART-induced microbial changes in the Tg26 mice. This study reveals the Tg26 mice model to be a relevant system that can help elucidate the pathogenic mechanisms of opioid and ART-induced exacerbation of HIV-associated pain. Our results shed light on the intricate inter-play between HIV infection, ART, opioid use, and the gut microbiome in chronic pain development. They hold implications for understanding the mechanisms underlying HIV-associated pain and microbial dysbiosis, with potential for future research focused on prevention and treatment strategies.

Background: Identifying genetic mutations that lead to spermatogenic impairment is essential for offering patients informed genetic counseling and preventing the transmission of genetic defects to their offspring, often through the use of advanced reproductive technologies. Objectives: The purpose of this study was to identify potential single nucleotide polymorphisms (SNPs) associated with male infertility. Methods and Materials: Genetic variants that may cause infertility are identified by combining targeted next generation sequencing (NGS) panel and whole exome sequencing (WES). The validation step of Sanger sequencing adds confidence to the identified variants. Results: Our analysis revealed five distinct affected genes covering seven SNPs: based on targeted NGS panel and WES data, namely SPATA16 (rs16846616, 1515442, 1515441), CFTR (rs213950), KIF6 (rs2273063), STPG2 (r2903150) and DRC7 (rs3809611). Infertile men have a higher mutation rate than fertile men, especially those with azoospermia. Discussion and Conclusions: These findings strongly support the hypothesis that dysfunction of microtubule-related and spermatogenesis-specific genes contributes to idiopathic male infertility. The SPATA16, CFTR, KIF6, STPG2 and DRC7 mutations are associated with male infertility, specifically azoospermia, further examination of this genetic function is required.

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis that often results in severe cognitive and neurological sequelae and increases the mortality rate in patients with sepsis. Microglia are resident macrophages in the brain that play essential roles in the pathological and physiological processes of SAE. Depending on the nature of the stimulus, microglia can adopt two polarization states (M1/M2), which correspond to altered microglial morphology, gene expression, and function. Therefore, we systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE. We demonstrated that microglia are closely related to occurrence and development of SAE and concomitant cognitive impairement. Finally, we outlined some potential therapeutic approaches that can prime microglia and neuroinflammation towards the beneficial restorative microglial phenotype in SAE.

Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDD), including Alzheimer’s disease (AD) and Parkinson’s disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM’s effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25-35 (Aβ25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediate inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1 and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells resulted to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDD.

Background: The objective of the present study was to evaluate the formation of biofilm in bone patellar tendon bone grafts (BPTB grafts) and to compare it to the formation of biofilm formation in quadrupled hamstring anterior cruciate ligament grafts (4xHt graft). Methods: A descriptive in vitro study was conducted. One 4xHt graft and one BPTB graft were prepared. They were then contaminated with a strain of S. epidermidis. Later, a quantitative analysis was carried out by means of microcalorimetry and sonication with plating. Additionally, a qualitative analysis was carried out by means of electron microscopy. Results: No significant differences were found between the bacterial growth profiles of 4xHt graft and BPTB graft in microcalorimetry and colony counting. In the samples analyzed with electron microscopy, no specific biofilm growth pattern was identified upon comparing BPTB graft to 4xHt graft. Conclusions: There were no significant differences at either the quantitative or qualitative level when comparing bacterial growth in BPTB graft to that in 4xHt graft. Therefore, the presence of sutures in 4xHt graft cannot be established as a predisposing factor for increased biofilm growth in this in vitro study.

The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a pivotal role in cancer cells’ proliferation and metastatic spreading. Considering the high expression of the fibroblast activation protein (FAP) on cell membrane, CAFs emerged as appealing TME targets, namely for molecular imaging, leading to a pan-tumoral approach. Therefore, FAP inhibitors (FAPis) have been recently developed for PET imaging and radioligand therapy, exploring the clinical application in different tumor sub-types. The present review aimed to describe recent developments on radiolabeled FAP inhibitors and evaluate the possible translation of this pan-tumoral approach in clinical practice. At present, the application of FAPi-PET has been explored mainly in single-center studies, generally performed in small and heterogeneous cohorts of oncological patients. However, preliminary results were promising, in particular in low FDG-avid tumors such as primary liver and gastro-entero-pancreatic cancer, or in regions with unfavorable tumor-to-background ratio at FDG-PET/CT (i.e. brain), as well as in radiotherapy planning of head and neck tumors. Further promising results have been obtained in the detection of peritoneal carcinomatosis, especially in ovarian and gastric cancer. Data regarding the theranostics approach are still limited at presents, and definitive conclusion about its efficacy cannot be drawn at present. Nevertheless, the use of FAPi-based radio-ligand to treat the TME has been evaluated in first-in-human studies and appears feasible. Although the pan-tumoral approach in molecular imaging showed promising results, its real impact in day-to-day clinical practice has yet to be confirmed, and multi-center, prospective studies powered for efficacy are needed.

Nucleoid-associated proteins (NAPs) play an architectural role by bending, bridging, and wrapping the DNA along with a regulatory role of controlling various transcriptional units in the cell. Previews reviews have highlighted the role of HU and its paralog IHF plays in intracellular function as a transcriptional regulator, nucleoid bending protein and sometimes also moonlights in other functions. This review highlights along with the canonical functions of HU and IHF which affects genes responsible for translational machineries, cell wall biosynthesis, aerobic respiration and virulence ; other non-canonical roles which HU plays outside the cellular milieu, notably in acting as an adhesin and playing role in host-cell adhesion, its role in biofilm architecture and its association with cationic low complexity region, resembling histone like H1 proteins. HU and IHF thus has evolved as a hub protein performing a vast type of functions which makes it a important drug target for antibacterial therapy.

The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

The excited-state lifetimes of the anticoagulant drug warfarin (W) in water and in the absence and presence of methyl-β-cyclodextrins (Me-β-CD) were recorded using time-resolved fluorescence measurements. Selective excitation of the open and cyclic protonated isomers of W were acquired with laser emitting diodes (LED) producing 320 and 280 nm excitation pulses, respectively. Formation of the inclusion complex was checked by UV–visible absorption spectroscopy, and the values of binding constants (2.9 × 10³ M^–1 and 4.2 × 10² M^–1 for protonated and deprotonated forms, respectively) were extracted from the spectrophotometric data. Both absorption and time-resolved fluorescence results established that the interior of the macromolecular host binds preferentially the open protonated form, red shifts the maximum of its absorption of light at ~305 nm, extends its excited-state lifetime, and decreases its emission quantum yield (ФF). Collectively, sequestration of the open guest molecules decreases markedly their radiative rate constants (kr), likely due to formation of hydrogen-bonded complexes in both the ground and excited states. Due to lack of interactions, no change was observed in the excited-state lifetime of the cyclic form in the presence of Me-β-CD. The host also increases the excited-state lifetime and ФF of the drug deprotonated form (W¯). These later findings could be attributed to the increased rigidity inside the cavity of Me-β-CD. The pKa values extracted from the variations of the UV–visible absorption spectra of W versus the pH of aqueous solution showed that the open isomer is more acidic in both ground and excited states. The positive shifts in pKa values induced by three derivatives of cyclodextrins: HE-β-CD, Ac-β-CD, and Me-β-CD supported the preferential binding of these hosts to open isomers over cyclic.

Some of the most promising small molecule toxins used to generate antibody drug conjugates (ADCs) include anti-mitotic agents (e.g auristatin and its derivatives) which are designed to attack cancerous cells at their most vulnerable state during mitosis. We were interested to identify a human cystostatic protein eventually showing comparable activities and allowing the generation of corresponding targeted fully human cytolytic fusion proteins. Recently, we identified the human microtubule associated protein tau (MAP tau) which binds specifically to tubulin and modulates the stability of microtubules thereby blocking mitosis and presumably vesicular transport. By binding and stabilizing polymerized microtubule filaments, MAP tau-based fusion proteins skew microtubule dynamics towards cell cycle arrest and apoptosis. This biological activity makes rapidly proliferating cells (e.g cancer and inflammatory cells) an excellent target for MAP tau-based targeted treatments. Their superior selectivity for proliferating cells confers additional selectivity towards upregulated tumor-associated antigens at their surface, thereby preventing off-target related toxicity against normal cells bearing tumor-associated antigens at physiologically normal to low levels. In this review, we highlight recent findings on MAP tau-based targeted cytolytic fusion proteins reported in preclinical immunotherapeutic studies.

Healthcare crises occur occasionally are very disruptive and resource consuming. The Covid-19 pandemic provided an example of inefficient wasteful resource management that would be unsustainable in the long term. This paper presents a framework for sustainable crisis management that will be applicable for future crises. The methodology is also applicable to other pandemics, wars, multi-casualty natural disasters, industrial disasters, etc. Attention focuses on rapid crisis resolution such as lockdowns. Despite unprecedented investments in healthcare, lack of capacity and timeliness are still problems affecting every country, even the wealthier ones. During the Covid19 pandemic, some healthcare systems around the world have collapsed. For example, Brazil, Spain, Italy, and more. This is due to the lack of a clear methodology for handling such crises. This paper presents a resource-based methodology to cope with healthcare crises considering three scenarios: “Peace”, “War” and “Tsunami”. The paper outlines a methodology for identifying the system bottlenecks for coping with the crisis in each scenario by using established simple tools. These tools assure significant resource frugality that will enhance sustainability. The paper also analyses where the system constraint should be and prescribes how to prepare for such scenarios. A large medical center case study demonstrates our approach. During “peace” times, evolutionary strategies should be used exclusively. During “war” times, a hybrid – evolutionary/disruptive (revolutionary) strategy. During the “Tsunami” scenario, one should rely only on the disruptive (revolutionary) strategy. This methodology can be extended to other scenarios and other lines of research.

Background Community infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased rapidly since the emergence of the Omicron strain. During the eighth and ninth pandemic waves—when movement restrictions in the community were eased—the all-case registration system was changed, and the actual status of infection became uncertain. Methods We conducted regular rapid antigen tests (R-RAT) once or twice a week to examine the actual state of coronavirus disease (COVID-19) diagnosis among healthcare employees. Results Overall, 320 (1.42/day) and 299 (1.76/day) employees were infected in the eighth and ninth pandemic waves. During both periods, 59/263 doctors (22.4%), 335/806 nurses (41.6%), 92/194 administrative employees (47.4%), and 129/218 clinical laboratory technicians (59.2%) were infected. In the eighth wave, 56 of 195 employees were infected through close contact; in the ninth wave, 26 of 62 employees were infected. No significant difference was observed in the number of vaccinations between infected and non-infected employees. The positivity rate of R-RAT was 0.41% and 0.45% in the eighth and ninth waves. R-RAT detected infection in 212 and 229 employees during the eighth and ninth waves, respectively; the ratio of R-RAT-detected positive employees to those who reported infection was significantly higher during the ninth wave (odds ratio: 1.67, 95% confidence interval: 1.17–2.37, p

Any Hospital’s primary goal is to restore human health and save lives through health services provided to patients, but at the same time, hazardous wastes are produced. Inconsistent management of unsafe wastes might cause adverse effects and other issues to workers, the environment and public health. Segregation is considered the critical stage for a successful Healthcare Waste Management. Mixing hazardous waste with non-hazardous waste will be avoided by correctly applying practices at the segregation stage. This study aimed to assess personnel’s knowledge about Infectious Medical Waste and segregation practices used at six wards in Nicosia General Hospital. An analytical cross-sectional study was conducted, and data were collected through a structured self-administered questionnaire. The Statistical Package of Social Science (SPPS) version 25 was used with a minimum statistical significance α=0.05. The study population was nurses, nurse assistants, ward assistants and cleaners working at the study wards. Out of 191 questionnaires, 82 were received, with a response rate of 42.93%. Most participants were female (72%) and nurses (85,4%). Participants had medium to good knowledge about Infectious Medical Waste management and good knowledge regarding segregation practices applied in their ward. Segregation was not carried out as it should have since most participants stated that Infectious Medical Wastes were mixed with non-hazardous waste. Correct answers given by the participants regarding color-coding of different Healthcare Waste categories was 67.5%, and only four answered correctly to all questions. Although participants knew segregation practices and the colour-coding process applied for Healthcare Waste, they didn’t use them satisfactorily. They applied methods regarding segregation without specific training, knowledge and guidance. Due to the issue's importance, training programs must be implemented and performed.

In this paper, the filtering method of biomedical image denoising is described comprehensively. Firstly, it introduces the biomedical image denoising, describes the relationship between biomedical image denoising and medical care, introduces the filtering methods, the filtering methods of biomedical image denoising, the challenges encountered by the current filtering methods, and other application fields of filtering methods. Firstly, the background of biomedical image denoising is introduced. Biomedical image denoising is a challenge. Different imaging modes have different noise characteristics, and noise levels can vary greatly depending on the specific application. Secondly, it describes that biomedical image denoising plays an important role in medical care, and the biomedical image directly affects the patient's diagnosis, treatment plan and the overall quality of medical care service. Then the filtering method is introduced in detail, describing the core concepts and related features of linear filtering, nonlinear filtering and frequency domain filtering, and then focusing on the adaptive filtering method, describing the characteristics, conditions of use, common algorithms and advantages of adaptive filtering method. Then the filter methods of biomedical image denoising are introduced, and the core concepts of Gaussian filter, median filter, total variation denoising and Wiener filter are introduced respectively. Then, the challenges encountered by filtering methods are described, such as the accurate selection of filters, the balance between noise reduction and image detail preservation are introduced. Finally, the application of filtering method in other fields is mentioned, such as audio processing, speech recognition and so on. In summary, this paper comprehensively expounds the denoising and filtering methods of biomedical images, the filtering methods of medical image denoising, the relationship between medical image denoising and medical care, and the challenges encountered by filtering methods.

Despite the Australian Government’s attempts to reduce domestic violence (DV) incidences, impediments that exist within the social and health systems and interventions designed to identify DV victims may contribute to female victims’ reluctance to disclose DV experiences to their primary healthcare providers. This scoping review aimed to provide the state of evidence about reasons for such reluctance to reveal DV, symptoms and comorbidities patients present to healthcare providers, detection and interventions in the clinical setting, and recommendations to generate more effective responses to DV. Female victims are reluctant to reveal DV because they do not trust or believe that general practitioners can help them to solve the issue, they do not acknowledge they are in an abusive relationship or are unaware that they are, or had been, victims of DV. The most common symptoms and comorbidities victims present with are sleep difficulties and fear. DV screening programs are the most prominent intervention type within Australian primary health services. This scoping review provides formative evidence that further research and interventions are required to increase professional skills, knowledge, sensitivity and referral processes among primary healthcare professionals treating patients experiencing DV in Australia.

A medical entity (hospital, nursing home, rest home, revalidation center, etc.) usually includes a multitude of information systems that allow for quick decision-making close to the medical sensors. The Internet of Medical Things (IoMT) is an area of IoT that generates a lot of data of different natures (radio, CT scan, medical reports, medical sensor data). However, these systems need to share and exchange medical information in a seamless, timely, and efficient manner with systems that are either located within the same entity or located in other healthcare entities. The lack of inter and intra entity interoperability causes major problems in the analysis of patient records and leads to additional financial costs (e.g., redone examinations). In order to develop a medical data interoperability architecture model that will allow providers and different actors in the medical community to exchange patient summary information with other caregivers and partners in order to improve the quality of care, the level of data security, and the efficiency of care, we take stock of the state of knowledge.

This paper is a review of the current state of IoT-based technologies in the healthcare field for the elderly population. The increasing population of elderly people has led to a greater demand for healthcare services to meet their unique needs. IoT-based technologies have emerged as a promising solution to address this demand. The paper analyses the current trends, challenges, and future opportunities for research in this area. It highlights how IoT-based technologies can be utilized to improve healthcare for older adults, from remote monitoring and telemedicine to fall detection and medication management. The paper also acknowledges that there are still challenges to be addressed, such as data privacy and security, but the potential benefits for older adults outweigh the challenges. The paper also examines the impact of the industrial revolution on the aging population and the corresponding increase in demand for geriatric healthcare. In summary, this paper delves into the current status of IoT-based technologies in geriatric healthcare and its future prospects, with a focus on addressing the needs of the aging population and improving their quality of life.

No-show appointments in healthcare is a problem faced by medical centers around the world, and understand the factors associated with the no-show behavior is essential. In the last decades, artificial intelligence took place in the medical field and machine learning algorithms can work as a efficient tool to understand the patients behavior and to achieve better medical appointment allocation in scheduling systems. In this work, we provide a systematic literature review (SLR) of machine learning techniques applied to no-show appointments aiming at establishing the current state-of-the-art. Based on a SLR following the Kitchenham methodology, 24 articles were found and analyzed, in which the characteristics of the database, algorithms and performance metrics of each studies were synthesized. Results regarding which factors have a higher impact on missed appointment rates were analyzed too. The results indicate that the most appropriate algorithms for building the models are decision tree algorithms. Furthermore, the most significant determinants of no-show were related to the patients age, whether the patient missed a previous appointment, and the distance between the appointment and the patients scheduling.

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs) knowledge, attitudes and behaviours on antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1,315 respondents. Results: 2,404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the last week due to fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals.

Big data analytics tools are the use of advanced analytic techniques targeting large and diverse volumes of data that include structured, semi-structured, and unstructured data from different sources and in different sizes from terabytes to zetabytes. The health sector is faced with the need to generate and manage large data sets from various health systems, such as electronic health records and clinical decision support systems. This data can be used by providers, clinicians, and policymakers to plan and implement interventions, detect disease more quickly, predict outcomes, and personalize care delivery. However, little attention is paid to the connection between big data analytics tools and the health sector. Thus, a systematic review of the bibliometric literature (LRSB) was developed to study how the adoption of big data analytics tools and infrastructures will revolutionize the healthcare industry. The review integrated 77 scientific and/or academic documents indexed in SCOPUS presenting up‐to‐date knowledge on current insights on how big data analytics technologies influence the healthcare sector and the different big data analytical tools used. The LRSB provides findings related to the impact of Big Data analytics on the health sector by introducing opportunities and technologies that provide practical solutions to various challenges.

Background: Observational health data has the potential to be a rich resource to inform clinical practice and regulatory decision making. However, the lack of standard data quality processes makes it difficult to know if these data are research ready. The EHDEN COVID-19 Rapid Col-laboration Call presented the opportunity to assess how the newly developed open-source tool Data Quality Dashboard (DQD) informs the quality of data in a federated network. Methods: 15 Data Partners (DPs) from 10 different countries worked with the EHDEN taskforce to map their data to the OMOP CDM. Throughout the process at least two DQD results were collected and compared for each DP. Results: All DPs showed an improvement in their data quality between the first and last run of the DQD. The DQD excelled at helping DPs identify and fix conformance is-sues but showed less of an impact on completeness and plausibility checks. Conclusions: This is the first study to apply the DQD on multiple, disparate databases across a network. While study-specific checks should still be run, we recommend that all data holders converting their data to the OMOP CDM use the DQD as it ensures conformance to the model specifications and that a database meets a baseline level of completeness and plausibility for use in research.

This study investigated the prevalence and severity of depression, anxiety, and stress and determined the association between various factors, social support, and depression and anxiety among university healthcare workers in Malaysia after the government lifted the movement control order (MCO) put in place to curb the coronavirus disease 2019 (COVID-19) pandemic. This online, cross-sectional survey recruited 399 participants from two university hospitals, and they were administered a self-reported questionnaire on demographic, personal, and clinical characteristics; COVID-19-related stressors; and coping. In addition, they completed the Multidimensional Scale of Perceived Social Support (MSPSS) to measure perceived social support, as well as the 21-item Depression, Anxiety, and Stress Scale (DASS-21) to assess depression, anxiety, and stress. We found that the prevalence of depression, anxiety, and stress were 21.8%, 31.6%, and 29.1%, respectively. Participants with moderate to extremely severe depression, anxiety, and stress made up 13.3%, 25.8%, and 8.1% of the sample, respectively. Being single or divorced, fear of frequent exposure to COVID-19 patients, those who agreed that their area of living had a high prevalence of COVID-19 cases, and uncertainty regarding the prevalence of COVID-19 cases in the area of living were associated with higher odds of depression and anxiety. Conversely, having more than three children and greater perceived friend support were associated with lower odds of depression and anxiety. The prevalence of depression, anxiety, and stress remained elevated even after the MCO was lifted.

The world is currently, subjected to the worst health crisis documented in modern history; an epidemic led by the novel coronavirus disease 2019 (COVID-19). At the epicenter of this crisis, healthcare professionals continue working to safeguard our well-being. To the regular high levels of stress, COVID new heights even more to healthcare professionals so depending on the area, specialty, and type of work. Here we investigated what are the tendencies, or areas most affected. Through an adaptation of the original COVID-stress scale, we developed a remote, fast test designed for healthcare professionals of the Northeastern part of Mexico, an important part of the country with economic and cultural ties to the US. Our results showed 4 key correlations as highly dependent: Work area – Xenophobia (p &lt; 0.045), Work with COVID patients - Traumatic stress (p &lt; 0.001) and Total number of COVID patients per day – Traumatic stress (p &lt; 0.027), and Total number of COVID patients - Compulsive checking and reassurance. Overall concluding that normal levels of stress have increased (mild – moderate). Additionally, we further determine that the fear of being an asymptomatic patient (potential to spread without knowing) continues being a concern.

The tribal belt of Pakistan-the Pak-Afghan border region is famous for its unique culture, ethnography and wild food plants and traditional knowledge. People of these regions gather wild plants for number of purposes including plants or plant parts for direct use, use it in the traditional cuisines and selling in local markets. However, there is huge lack of documentation of food system particularly the Wild Food Plants (WFPs). In current study we have focused on the uses and contributions of the WFPs in the tribal traditional food system. The ethnobotanical data were gathered through questionnaire surveys with Eighty-four informants 69 men and 15 women belonging to 21 different villages. We documented Sixty-three WFP species belonging to 34 botanical families, of which 27 were used as vegetables, 24 as fruits, 6 in different kinds of chutneys (starters) formation and six as fresh food species. Fruits were the mostly used part (40%) followed by leaves (24%), aerial parts (24%), seeds (7%), stem (3%), legume (2%) and young inflorescence (1%). Use of Carthamus oxycanthus & Pinus roxburghii seeds and Marsillea quadrifolia leaves were the novel reports for the gastronomy of Pakistan. The results elucidate that WFPs have a significant contribution in the Tribal Food Systems. Tribal people use WFPs not only due to their nutritional importance but also as a cultural practice - an inseparable component of the tribal communities. This important traditional Knowledge about the consumption of WFPs has been eroding with an alarming speed among the younger generations due to introduction of fast food chains, modernization, and globalization. Therefore, appropriates strategies are imperative not only to safeguard traditional knowledge but also the cultural heritage, food security and hence public healthcare via food supplement in the region.

Contact tracing has become an indispensable tool of various extensive measures to control the spread of COVID-19 pandemic due to novel coronavirus. This essential tool helps to identify, isolate and quarantine the contacted persons of a COVID-19 patient. However, the existing contact tracing applications developed by various countries, health organizations to trace down the contacts after identifying a COVID-19 patient suffers from several security and privacy concerns. In this work, we have identified those security and privacy issues of several leading contact tracing applications and proposed a blockchain-based framework to overcome the major security and privacy challenges imposed by the applications. We have discussed the security and privacy measures that are achieved by the proposed framework to show the effectiveness against the security and privacy issues raised by the existing mobile contact tracing applications.

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

Background: The evolution of names, from “medical informatics” to “connected health”, implies that the evolvement of technology in health care has been shifted from technology-oriented to healthcare-oriented implementation. Connected healthcare, a healthcare platform of remote monitoring and self-management through technological measures, is suggested to contribute to the efficiency, cost effectiveness, and satisfaction of healthcare recipient enhancement. However, limited understanding of related connected health (CH) terminology may constrain its implementation. Whether CH is a Buzzword only or a practice that can contribute to an ageing society is controversial. Objective: This study aims to distinguish CH-related terminology and to identify the trend of CH through reviewing its definition, initiation, development, and evolvement, in order to offer management insights and implications. The objective is to understand what is connected and who is cared about in the connected health model, so that better applications can be addressed for the benefit of society. Method: This study reviews the evolution of names, from “medical informatics” in the 1970s to “connected health” after 2000, as well as relevant literature of CH, including e-health, telemedicine, telehealth, telecare, and m-health, to discover the trend of technology-related healthcare implementation. The current status and issues facing CH will be presented and its future trends will be explored through reviewing how changes in healthcare are managed, in addition to its operation and practice. Issues of accessibility, quality, and cost will be discussed, as well as its market status. Results: Preconditions and requirements for implementing CH are identified to select a typical case to study. Areas with a complete business ecosystem, including advanced technology and medical services, a payment system, an ageing population, geographic isolation, integrated health, and social care, are prevalent. These findings may be beneficial to designing and establishing comprehensive CH implantation and environments. Conclusion: The evidence and tendency of technological convergence create a demand for innovation and partnering with start-up companies that offer a competitive advantage in innovation. Specifically, it is necessary to innovate both the public and private operation model of the CH ecosystem. This focus will be further explored in future work.

This study explored the effects of a comprehensive health care program (CHCP) on blood pressure, blood glucose, body composition, and depression in older adults living alone. We used a quasi-experimental, two-group, pre-posttest design. The CHCP consisted of open lectures, health counseling, exercise classes, nutrition counseling, and self-help group meetings at a local senior welfare center. Fifty-eight subjects participated in this study, with thirty subjects in the experimental group and twenty-eight subjects in the control group. Data were analyzed using the descriptive statistics, χ²-test, and t-test. Comparisons of the pretest and posttest systolic blood pressure (t = - 2.530, p < .016) and blood glucose (t = 3.089, p < .004) between the experimental and control groups showed significant differences. In both the experimental (t = 3.949, p < .001) and control groups (t = 3.816, p < .002), depression symptoms showed a significant decrease post-test, compared with pre-test. Our findings infer that older adults require physical and psychosocial healthcare and that more efforts must be made to improve the general health and wellbeing of this population group.

After conducting a detailed survey among the villagers of Pallissery and Karukutty, it was observed that in most of the villages the native people have to travel long distances for their basic health needs. Also most of the villagers lack knowledge regarding live health updates. At times, these problems have even resulted in death of many people including pregnant women and children. The objective of our research is to propose an integrated and easy to use Medical Kiosk that can be installed at various locations in rural areas. The Kiosk will provide an integrated environment for all medical related activities and would perform numerous functions like sending notifications regarding medical camps, mobile medical help, important dates for vaccinations, child care, insurance policies and provide other live medical updates to the villagers. It would also support the basic facilities for measurement of body parameters like height, weight, BMI, blood pressure, and heartbeat and also facilitate live consultation facilities with specialized doctors through video and voice chats.

Organ transplantation centers set criteria for candidate qualification, which has led to disparate healthcare resource allocation practices affecting those with a substance use history. These individuals are denied organ transplants by committees and healthcare providers who assign them lower priority status. The lower priority argument claims that healthcare resources should not be provided equally to individuals failing to share responsibility for not doing enough in addressing the diseases associated with substance use. The purpose of this work is to explore the interrelatedness between the ethics of a merit-based system of moral responsibility and lower priority setting involved in healthcare resource allocation pertaining to those with substance use histories. An integral approach to the argument against the lower prioritists with a focus on the relationship between different organ allocation practices affecting substance users and the justification for resource allocation practices in healthcare and transplant committees. Lower priority setting is challenged, and an argument offered in which substance users are assigned higher priority when relying on “doing enough” in a merit-based system of moral responsibility. It is determined that one cannot substantiate assigning a lower priority status since a lack of success in rehab does not imply a lack of effort. Additionally, neither to confirmatory behavior, nor to non-conforming behavior may freedom be justifiably ascribed in a merit-based system of responsibility because freedom to choose can neither be established a priori, nor a posteriori with respect to meritorious behavior.

Background: Health insurance (HI) run by government is providing health care service to large population. Due to poor accountability, participation and sustainability, cooperative health insurance is becoming more popular and effective in low and middle income and some high-income countries too. In Nepal, there are public and cooperative HI is in practice. The aim of this study is to compare the effectiveness of public (government) and cooperative HI in relation to benefit packages, population coverage, inclusiveness, health care utilization, and promptness for treatment in these two health insurance models in Nepal. Method: This is an institution based concurrent mixed study consists of qualitative and quantitative variables from public and cooperative groups. We included all public HI operated by government hospitals and cooperatives groups those purchased hospital service in contract. Two separate study tools were applied to access the effectiveness of insurance models. The key questions were asked for the representatives of government and private health insurance. The numeric information consisted of in quantitative data and subjective response was included in qualitative approach. Descriptive statistics and Mean Whitney U test was applied in numeric data and qualitative information were analyzed by inductive approach Results: The study revealed that new enrolment was not increased, health care utilization rate was increased and the benefit package was almost same in both groups. The overall inclusiveness was higher for the government HI, but enrolment from the religious minority, proportion of negotiated amount during treatment were significantly higher (p<0.05). During illness, the response time to reach hospital was significantly faster in cooperative health insurance than government health insurance. Qualitative findings showed that level of participation, accountability, transparency and recording system was better in cooperative health insurance than public. Conclusion: Cooperative HI could be more sustainable and accountable to the community for all; low, middle and high-income countries.

Trichoderma has been widely studied for its potential as a biocontrol agent against plant pathogenic organisms. Trichoderma's biological control mechanisms include competition, modification of environmental conditions, antibiosis, induction of plant defensive mechanisms, and mycoparasitism. Trichoderma species are known to produce a variety of secondary metabolites that have antifungal activity. These metabolites include peptaibols, gliotoxin, and trichokonins. Trichoderma also produces chitinases and β-1,3-glucanases that can degrade the cell walls of fungal pathogens. In addition to direct antagonism against fungal pathogens, Trichoderma can also induce systemic or localised resistance in plants, which is achieved through the production of elicitors such as chitin oligosaccharides and β-glucans that activate plant defence responses. Trichoderma can also form mutualistic associations with plants. In these associations, Trichoderma colonises the roots of plants and promotes plant growth by increasing nutrient uptake and inducing systemic resistance. Using Trichoderma as a biocontrol agent has several advantages over conventional crop protection techniques based on applying synthetic pesticides.

Graft injury affects over 50% of liver transplant (LT) recipients, but non-invasive biomarkers to diagnose and guide treatment are currently limited. We aimed to develop a biomarker of graft injury by integrating serum metabolomic profiles with clinical variables. Serum from 55 LT recipients with biopsy confirmed metabolic-dysfunction associated steatohepatitis (MASH), T-cell mediated rejection (TCMR) and biliary complications was collected and processed using a combination of LC-MS/MS assay. The metabolomic profiles were integrated with clinical information using a multi-class Machine Learning (ML) classifier. The efficacy of the model was assessed through the evaluation of the Out-of-Bag (OOB) error estimate. Our ML model yielded an overall accuracy of 79.66% with an OOB estimate of the error rate at 19.75%. The model exhibited a maximum ability to distinguish MASH, with an OOB error estimate of 7.4% compared to 22.2% for biliary and 29.6% for TCMR. The metabolites serine and serotonin emerged as the topmost predictors. When predicting binary outcomes using 3 models: Biliary (biliary vs. rest), MASH (MASH vs. rest) and TCMR (TCMR vs. rest), the AUCs were 0.882, 0.972 and 0.96 respectively. Our ML tool integrating serum metabolites with clinical variables shows promise as a non-invasive, multi-class serum biomarker of graft pathology.

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

Dystonias, characterized by excessive muscle contractions resulting in involuntary postures and movements, impact 3 million people globally, making them the third most common movement disorder. Often accompanied by tremors, dystonias have epidemiological links and non-motor features shared with isolated tremor, such as essential tremor. Both dystonia and tremor present with balance dysfunction and abnormal involuntary movements, potentially linked to abnormal cerebellar function. This study explores the perception of one’s own linear movement, heading, particularly discrimination of heading direction, in isolated cervical dystonia, isolated tremor, and their combination. The focus is on the perception of heading direction during isolated visual star-cloud movement (visual heading perception) and en bloc body movement (vestibular heading perception). Nineteen participants underwent a two-alternative forced-choice task in the vestibular and visual domains. Results reveal elevated vestibular heading perception thresholds in cervical dystonia with or without tremor, and isolated tremor compared to healthy controls. Vestibular heading perception threshold was comparable in cervical dystonia with tremor and isolated tremor, but it was even worse in isolated cervical dystonia. Visual heading perception, however, remained less affected all three conditions – isolated cervical dystonia, isolated tremor, and their combination. These findings indicate shared deficits and distinctions in the perception of linear translational heading across movement disorders, such as isolated cervical dystonia, tremor, or their combination, offering insights into their pathophysiology, particularly the involvement of cerebellum regions responsible for vestibular processing.

Aim. The analysis of incidence, clinical and morphological manifestations, and the prognosis of IgA nephropathy in the Northeastern Europe (NEE). Materials and methods. We enrolled cases with primary IgA nephropathy (IgAN) from 2005 to 2020 in the single-center retrospective study. Demographic and clinical parameters, histology data, and the treatment were analyzed. The outcomes were the occurrence of complete (PR) or partial remission (CR), renal replacement therapy (RRT), eGFR<15 ml/min/1.73m² and eGFR decrease ≥ 50%. The composite endpoint included all renal outcomes and was used to evaluate the risk of IgAN progression and associated factors. Results. The incidence of IgAN cases was 23.6% of all indication biopsies and 41.2% of primary immune glomerulopathies. At the time of the kidney biopsy, the proteinuria was 2.5 (1.5-5.0) g/24h, eGFR - 69 ± 32 ml/min/1.73 m². Proportions of cases with arterial hypertension and eGFR <60 ml / min / 1.73 m² were 75% and 36%, respectively. The prevalence of histological changes in accordance with the Oxford (MEST-C) classification was M1 - 40.5%, E1 -22.9%, S1-70.2%, T1-22%, T2 - 9%, C1-16.7%, C2 - 4.4%. In the follow-up of 27 (11; 61) months, 6 deaths occured (1.7%). The 10-year cumulative dialysis-free survival was 80% and progression-free survival was 56%. Remissions registered in 50% of cases, being more frequent in patients who received immunosuppression vs renoprotection (60% vs. 40%, p = 0.001). In multivariable Cox regression, the independent factors associated with the increased probability of IgAN progression were male gender, a younger age, higher blood pressure and hematuria, lower eGFR, interstitial fibrosis/ tubular atrophy (≥50%), the presence of peritubular capillaritis and any crescents. Compared to the cohorts of other ethnic or geographical origin, IgAN in the studied cohort were found to have more severe clinical and morphological presentations and faster progression rate. Conclusion. Being the most common glomerulopathy in the NEE population, IgAN has more pronounced clinical and morphological presentations. Considering the distinctive features of the disease, further research is warranted in order to establish approaches for enhancing risk stratification and treatment efficacy.

Background: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns(ARP) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. Methods: Retrospective pre(2018) and post-intervention(2019-21) study in ICU patients. A rapid diagnostic algorithm was applied from 2019 in patients with lower respiratory tract infection. Incidence of nosocomial infection, ARP, and AC as DDD(defined daily dose) were monitored. Results: A total of 3635 patients were included, 987(pre-intervention) and 2648(post-intervention). A median age was 60 years, 64% male, with APACHE II of 19 points and SOFA of 3 points. Overall ICU mortality of 17.2% without differences between the periods. An increase in the number of infections was observed in the post-intervention period(44.5% vs 17.9%, p<0.01), especially due to an increase in ventilator-associated pneumonia(44.6% vs 25%,p<0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021(Rate Ratio=0.51). A recovery of P.aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. Conclusion: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed a significant reduction in AC and ARP without affecting the prognosis of critically ill patients.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population, and is increasing worldwide, due to the pandemic of obesity. Insulin resistance is closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids (FA) released from adipose tissue, increase in FA synthesis and reduced FA oxidation in the liver, and hepatic overproduction of triglyceride (TG)-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease (CVD). Considering that the development of CVD determines the prognosis of MASLD patients, the ideal therapeutic interventions for MASLD should reduce body weight, improve coronary risk factors, in addition to an improvement in liver functiom. Lifestyle modification such as diet and exercise and surgical interventions such as bariatric surgery and intragastric balloons have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to improve coronary risk factors and to suppress the occurrence of CVD. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator, pemafibrate, improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs, and consider whether such drugs and the combination therapy of such drugs could be the ideal treatments for MASLD.

Pulmonary hypertension (PH) is a severe vascular complication of connective tissue diseases (CTD). Patients with CTD may develop PH belonging to different groups: 1) pulmonary arterial hypertension (PAH), 2) PH secondary to lung disease and/or hypoxia, 3) PH due to left heart disease, and 4) chronic thromboembolic pulmonary hypertension (CTEPH). PAH most often develops in systemic scleroderma (SSc), mostly in its limited variant. PAH-CTD is a progressive disease characterized by poor prognosis, therefore the early diagnosis should be established A specific treatment for PAH-CTD is currently available and recommended: prostacyclin derivative (treprostinil, epoprostenol, iloprost, selexipag), nitric oxide and natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase 5 inhibitors (PDE5i: sildenafil, tadalafil), endothelin receptor antagonists (ERA: bosentan, macitentan, ambrisentan). Moreover, novel drugs e.g. sotatercept are intensively investigated in the clinical trials. The aim of this paper is to review the literature on the recent advances in treatment strategy and prognosis of patients with PAH-CTD.

Epigenetic reprogramming represents a series of essential events during many cellular processes including oncogenesis. Genome of Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic herpesvirus is predetermined for a well-orchestrated epigenetic reprogramming once it enters into a host cell. The initial epigenetic reprogramming of KSHV genome allow restricted expression of encoded genes and helps to hide from host immune recognition. The infection with KSHV is associated with Kaposi's Sarcoma, Multicentric Castleman's disease, KSHV inflammatory cytokine syndrome and primary effusion lymphoma. The major epigenetic modifications associated with KSHV can be labelled under three broad categories: DNA methylation, modifications of Histone, and the role of noncoding RNAs. These epigenetic modifications significantly contribute towards the latent-lytic switch of the KSHV lifecycle. This review gives a brief account of the major epigenetic modifications affiliated with the KSHV genome in infected cells and their impact on pathogenesis.

(1) Background: This article reviews the available scientific literature on drug-related problems and negative outcomes associated with medications identified by medication review with follow-up for end-stage renal disease and discussed with the physicians; (2) Methods: A systematic review was conducted of the scientific literature retrieved from the following databases: MEDLINE (via PubMed), Web of Science, SCOPUS, Cochrane Library: The Cochrane Central Register and Control Trials (CENTRAL) and Literatura Latinoamericana y del Caribe (LILACS), Medicina en Español (MEDES), and the SciELO bibliographic database (collection of scientific journals). The following terms were used as descriptors and searched in free text: "end-stage renal disease", "medication review", and "drug-related problems” and “negative outcomes associated with medication". The following limits were applied: "humans" and "adults (more than 18 years)”; (3) Results: A total of 59 references were recovered and after applying inclusion/exclusion criteria, 16 articles were selected. Of these selected articles, 15 provided information on drug-related problems and only 1 on negative outcomes associated with medications; (4) Conclusions: It can be concluded that drug-related problems and negative outcomes associated with medication affect patients with end-stage renal disease, mainly those receiving renal replacement therapy. More evidence is needed, especially on negative outcomes associated with medication.

Depression and obesity are highly comorbid with one another, with evidence for bidirectional causal links between each disorder and a shared biological basis. The available evidence suggests that genetic factors play a major role in influencing both the occurrence of comorbid depression and obesity, their courses, and their response to existing treatments. The current paper is a scoping review of studies that have evaluated the contribution of specific genetic variants to the comorbidity between obesity and depression. Based on a search of the PubMed and EMBASE databases, 28 studies were included in this review, covering 54 candidate genes. Positive associations were identified for fourteen genetic loci (AKR1C2, APOA5, COMT, DAT1, FTO, KCNE1, MAOA, MC4R, MCHR2, NPY2R, NR3C1, Ob, PCSK9 and TAL1). Replicated findings across two or more independent samples were observed for the FTO and MC4R genes. Many of these gene products represent novel molecular targets for the pharmacological management of obesity which are not pharmacologically influenced by existing anti-obesity or antidepressant medications. The implications of these associations for future drug development are discussed, with an emphasis on recent evidence on the polygenic architecture of comorbid depression and obesity, and on a precision medicine approach to these conditions.

In celIs, microtubule location, length, and dynamics are regulated by a host of microtubule-associated proteins and enzymes that read where to bind and act based on the microtubule “tubulin code,” which is predominantly encoded in the tubulin carboxy-terminal tail (CTT). Katanin is a highly conserved AAA ATPase enzyme that binds to the tubulin CTTs to remove dimers and sever microtubules. We have previously demonstrated that short CTT peptides are able to inhibit katanin severing. Here, we examine effects of CTT sequences on this inhibition activity. Specifically, we examine CTT sequences found in nature, alpha1A (TUBA1A), detyrosinated alpha1A, Δ2 alpha1A, beta5 (TUBB/TUBB5), beta2a (TUBB2A), beta3 (TUBB3), and beta4b (TUBB4b). We find that these natural CTTs have distinct abilities to inhibit, most noticeably beta3 cannot inhibit katanin. Two non-native CTT tail constructs are also unable to inhibit – despite having 94% sequence identity with alpha1 or beta5 sequences. Surprisingly, we demonstrate that poly-E and poly-D peptides are capable of inhibiting katanin significantly. An analysis of the hydrophobicity of the CTT constructs indicates that more hydrophobic polypeptides are less inhibitory than more polar polypeptides. These experiments not only demonstrate inhibition, but also likely interaction and targeting of katanin to these various CTTs when they are part of a polymerized microtubule filament.

(1) Background: Heavy and chronic alcohol intake causes altered gut-permeability and dysfunction; and exhibits a unique pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by alcohol administration; however, the impact of altered gut-derived changes on thyroid function is unclear. This study investigated the role of gut-dysfunction and pro-inflammatory activity on thyroid function in patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n=44) were grouped as Gr.1 with normal thyroid stimulating hormone (TSH) levels (n=28, 0.8≤TSH≤3 mIU/L); and Gr.2 with clinically elevated TSH levels (n=16, TSH&gt; 3 mIU/l). Demographics, drinking measures, comprehensive metabolic panel, and candidate thyroid markers (TSH, circulating triiodothyronine [T3] and free thyroxine [fT4]) were tested. Plasma-derived gut-dysfunction associated markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], and LPS-induced pathogen-associated protein [CD14]), and cytokine profile (IL1-β, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were analyzed and compared with the thyroid, demographic, and drinking markers. (3) Results: Both groups presented with a borderline overweight category of BMI. Gr.2 presented with numerically higher level of chronic and heavy drinking patterns vs Gr.1. fT4 levels were elevated while T3 was within normal limits in both the groups. Gut-dysfunction markers LBP and CD14 were numerically elevated in Gr.2 vs Gr.1 suggesting subtle ongoing changes; however, the difference was not statistically significant. All pro-inflammatory cytokines were significantly elevated in Gr.2 among IL1-, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect of gut-immune-pituitary response (r=0.896, p=0.002) on TSH levels in a multivariate regression model with LBP, CD14, and PAI-1 levels as upstream variables; this assessment was not significant in Gr.1. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area=0.774, p&lt;0.001) and TNF- (area=0.708, p=0.017) among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4 as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation employing the gut-brain axis. These results also strongly emphasize potential directions to strongly consider thyroid dysregulation in the overall medical management of AUD.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment perform glycolysis to produce energy, i.e., ATP. Since the origin of CAFs is unidentified, it is not determined whether the intracellular metabolism transitions from oxidative phosphorylation (OXPHOS) to glycolysis when normal tissue fibroblasts differentiate into CAFs. In this study, we established an experimental system and induced the in vitro differentiation of mesenchymal stem cells (MSCs) to CAFs. Additionally, we performed metabolomic and RNA-sequencing analyses before and after differentiation to investigate changes in the intracellular metabolism. Consequently, we discovered that OXPHOS, which was the primary intracellular metabolism in MSCs, was reprogrammed to glycolysis. In addition, we identified CAF-specific metabolites that were expressed during this reprogramming and determined their presence in the pancreatic tumor tissues of mouse models. Thus, we conclude that normal tissue fibroblasts that differentiate into CAFs undergo a metabolic reprogramming from OXPHOS to glycolysis. Moreover, we identified the CAF-specific metabolites expressed during metabolic reprogramming as potential future biomarkers for pancreatic cancer.

The molecular evolution of medulloblastoma is more complex than was previously imagined as emerging evidence suggests that multiples interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting the sonic hedgehog (SHH)–activated medulloblastoma molecular subgroup, and provide an overview of medulloblastoma progression through SHH expression and signal transduction mechanisms into the complex tumor microenvironment. In addition, we highlight the associations between tumor and stromal cells as possible prognostic markers and new therapeutic strategies.

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment. Pre-treatment primary tumor samples were collected from 96 patients with metastatic ccRCC. Three adjacent slices were obtained from 2 tumor-core regions of interest (ROI) per patient, and immunohistochemistry (IHC) staining was performed for αSMA, Ki-67, and caspase-3 to detect CAFs, proliferating cells, and apoptotic cells, respectively. H-scores and cellular density were generated for each marker. ROIs were aligned, and spatial point-patterns were generated, which were then used to perform spatial analyses using a normalized Ripley's K function at a radius of 25μm (nK(25)). The survival analyses used an optimal cut-point method, maximizing the log-rank statistic, to stratify the IHC-derived metrics into high and low groups, and multivariable Cox regression analyses were performed accounting for age and International Metastatic RCC Database Consortium (IMDC) risk category. Survival outcomes included overall survival (OS) from the date of diagnosis, OS from the date of immunotherapy initiation (OS-IT), and OS from the date of targeted therapy initiation (OS-TT). Therapy resistance was defined as progression-free survival (PFS) <6 months, and therapy response was defined as PFS >9 months. CAFs exhibited higher cellular clustering with Ki-67+ cells than with caspase-3+ cells (nK(25): Ki-67 1.19; caspase-3 1.05; P = .04). The median nearest neighbor (NN) distance from CAFs to Ki-67+ cells was shorter compared to caspase-3+ cells (15 μm vs 37μm, respectively; P < .001). Multivariable Cox regression analyses demonstrated that both high Ki-67+ density and H-score were associated with worse OS, OS-IT, and OS-TT. Regarding CAFs, only a high H-score was associated with worse OS, OS-IT, and OS-TT. For caspase-3+, high H-score and density were associated with worse OS and OS-TT. Patients whose tumors were resistant to targeted therapy (TT) had higher Ki-67 density and H-scores than those who had TT response. Overall, this ex vivo geospatial analysis of CAF distribution suggests that close proximity clustering of tumor cells and CAFs potentiates tumor cell proliferation, resulting in worse OS and resistance to TT in metastatic ccRCC.

The Internet of Medical Things (IoMT) represents a specialized domain within the Internet of Things, focusing on medical devices that require regulatory approval to ensure patient safety. Trusted composition of IoMT systems aims to ensure high assurance of the entire composed system, despite potential variability in the assurance levels of individual components. Achieving this trustworthiness in IoMT systems, especially when using less-assured, commercial, off-the-shelf networks like Ethernet and WiFi, presents a significant challenge. To address this challenge, this paper advocates a systematic approach that leverages the Architecture Analysis & Design Language (AADL) along with Behavior Language for Embedded Systems with Software (BLESS) specification and behavior. This approach aims to provide high assurance on critical components through formal verification, while using less-assured components in a manner that maintains overall system determinism and reliability. A clinical case study involving an automated opioid infusion monitoring IoMT system is presented to illustrate the application of the proposed approach. Through this case study, the effectiveness of the systemic approach in achieving trusted composition of heterogeneous medical devices over less-assured networks is demonstrated.

India, a megadiverse nation, harbors significant biodiversity, particularly in tropical moist deciduous forests. However, these forests and valuable medicinal plants face habitat loss and overexploitation threats. While indigenous knowledge of medicinal plants exists, a comprehensive ethnomedicinal study still needs to be included, especially for Uttar Pradesh's Terai region. This study focuses on the Suhelwa Wildlife Sanctuary, a haven for medicinal plants within the Terai. We aim to document the knowledge of local healers regarding wild medicinal plants used in phytotherapy. We will employ quantitative indices and compare our findings with data from other regions to identify novel medicinal plant uses. This enriched database can serve as a springboard for future pharmacological research. Suhelwa's diverse geography and climate contribute to its rich medicinal flora, making it a prime candidate for exploring the potential of traditional knowledge for drug discovery and sustainable income generation for local communities.

Preschoolers with disabilities and their family caregivers are missed out in many public health initiatives especially in low-income countries. Yet they can benefit from early intervention to promote their development from soon after birth and to provide a better quality of life for their families. In this paper, we describe how a community-based approach has been implemented with minimal funding in two areas in Zimbabwe: a township in Harare and in rural areas of Manicaland Province. Our aim in sharing this information – allied with references to research studies recently undertaken in Africa – is that it will enable similar supports to be replicated in other communities by local personnel. A logic model is used to describe the situation in which the two projects work, the various inputs they have provided to their community and the different forms of support they have offered to the children and their caregivers. The project outputs are listed in terms of the number of beneficiaries helped and activities undertaken. The outcomes achieved for the children, the family and communities are reported. The sustainability and extensions of community-based projects to address unmet needs are discussed. The main conclusion is that disadvantaged communities can be energized to address the needs of their most marginalized residents.

Understanding and addressing dehumanization in healthcare is crucial due to its profound impact on patient care, ethical implications on patient dignity and autonomy, and its potential to affect the psychological well-being of healthcare professionals. The primary aim of this study was to develop reliable and valid instruments measuring two different types of dehumanization, namely animalistic dehumanization (i.e., stripping one of their uniquely human characteristics) and mechanistic dehumanization (i.e., striping one of their human nature characteristics) among healthcare professionals. In a cross-sectional validation study among healthcare professionals, we developed and tested measures of both animalistic and mechanistic dehumanization, focusing on dehumanization of patients (hetero-dehumanization) and oneself (self-dehumanization), respectively. All measures were developed and validated based on a concept analysis, a literature review, and an appraisal of pre-existing scales. The research was conducted among 400 nurses and medical doctors employed in Greek public hospitals. Coefficient Validity Ratio results showed that 100% of items were acceptable for both measures. The newly developed hetero-dehumanization scale encompassed two-factors (factor 1: animalistic dehumanization, factor 2: mechanistic dehumanization, Cronbach’s alpha was equal to 0.86 for each measure). The self-dehumanization scale was a mono-factorial measure mechanistic dehumanization (Cronbach’s alpha = 0.97). Two validated measures of (self and hetero-) animalistic and mechanistic dehumanization measures were developed for the assessment of dehumanization among health professionals, which will form the basis for future research in this important scientific field.

Tribal healers and local practitioners possess knowledge about plant uses passed down through generations. However, habitat loss, unsustainable harvesting, and declining traditional knowledge threaten this valuable resource. India, a global biodiversity hotspot, is rich in medicinal plants. Documenting the traditional knowledge prevents it from being lost and ensures the preservation of this cultural heritage. Recording traditional practices helps bridge the gap between traditional and modern medicine. This study quantifies the ethnomedicinal uses of plants within the Sohag Wildlife Sanctuary. The findings contribute to preserving traditional knowledge and promoting the sustainable use of medicinal plants. The study documented 95 medicinal plant species from 39 families, highlighting the importance of ethnomedicinal studies for preserving traditional knowledge and ensuring the sustainable use of medicinal plants. In the future, scientific studies can be organized to understand their efficacy, leading to developing new, potentially safer, and more effective medications. Identifying and documenting medicinal plants is crucial in safeguarding cultural heritage, fostering scientific discovery, and promoting sustainable healthcare practices.

Preschoolers with disabilities and their caregivers have been neglected in health and social service provision in most low-income countries and arguably too in low resourced areas of more affluent nations. Yet as this rapid review of published literature identifies, there are low-cost, evidence-based strategies to address their needs that can be implemented in communities by local people. Five key features of the necessary supports are examined. First the leadership functions required to create and implement the support services. Second, the family-centred, home-based support provided to caregivers and the personnel undertaking this form of support. Third, providing opportunities for peer support to flourish and encouraging the formation of advocacy groups across families. Fourth, mobilizing the support of significant groups within the community; notably traditional healers and leaders; health services and poverty alleviation initiatives. Fifth, devising ways in which preschool educational opportunities can be offered to children as a prelude to their inclusion in primary schools. The review serves a further purpose. It provides an example of how public health researchers and academics could achieve more rapid implementation of evidence-based knowledge into existing and new support services through dissemination to community practitioners.

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

Understanding the dynamics of teamwork and communication among healthcare professionals is crucial in the face of evolving healthcare challenges. This study assessed relational coordination among healthcare professionals in the South Tyrolean healthcare system in Italy, focusing on communication and teamwork dynamics in a cross-sectional survey. Using the validated Relational Coordination Survey (RCS) instrument and 525 completed online responses, the questionnaire aimed to understand the implications of different levels of relational coordination ratings by general practitioners, hospital physicians, nurses, and administrative personnel (response rate 26%). The demographics of the participants revealed a predominance of female professionals (64%), with an average age of 50 and 18 years of service. The resulting RCS scores varied significantly across professional groups, with nurses reporting the highest within-group scores, indicating moderate coordination, and administrators reporting the lowest scores, reflecting areas of weak coordination. Between-group relational coordination was generally perceived as weak across professional groups, with the least weakness observed between general practitioners and nurses. German or Italian language and health district affiliation emerged as significant factors influencing relational coordination ratings, highlighting the need for differentiated understanding and strategies in multilingual and diverse regional settings. Assessments of interdisciplinary feedback and referral practices highlight the variation in teamwork and communication weaknesses and underscore the need for targeted interventions to improve relational coordination. This study provides insights into the complexity of relational dynamics in health care settings. It suggests that improving relational coordination through tailored strategies could significantly improve team effectiveness, quality of patient care, and overall system efficiency.

(1) Background: Burnout syndrome results from chronic stress in the work-place. The COVID-19 pandemic has imposed a heavy workload on health professionals, doctors and nurses to respond to first-line health care during the first two years of an emergency caused by this virus. The aim of this study was to evaluate the prevalence of burnout in healthcare personnel, doctors and nurses during the COVID-19 pandemic. (2) Methods: This was a review of reviews on the prevalence of professional burnout syndrome in healthcare personnel, doctors and nurses before or during the COVID-19 pandemic, without language restrictions or missing data from the Cochrane Library electronic databases. In total, 48,657 articles were obtained from Pub-Med/MEDLINE and the Web of Science. (3) Results: After completing the examination, 20 articles were included in the review. Of these articles, 7% included nurses in their study population, 72% interviewed doctors from different specialties, and the remaining 21% reported personnel data. Healthcare as a whole: In total, 624 articles with 233,087 participants were included. Regarding the prevalence by subscale, a PD of 33% (95% CI; 33%- 34%), an AE of 37% (95% CI; 37%- 37%) and a PR of 29% (95% CI) were found. %; 29% and 29%). ; (4) Conclusions: The incidences of DP and AE are high, and that of RP is low. These findings demonstrate the high prevalence of burnout according to subscale. Burnout is a problem of great magnitude, and as such, interventions must be implemented immediately at the individual and group levels by institutions and health systems.

The world has changed. New technologies, new trends, new protocols, new efficient algorithms, and systems have been used widely by civilized countries to have better and more convenient living. In this research, there have been introduced many new terms, technologies, and mechanisms. Moreover, threats, attacks, and vulnerabilities have been studied and a novel scenario has been proposed in order to overcome all these violations that have been presented in this paper. The scenario is based on a security model that has been proposed for critical sectors, such as hospitals, industries, etc., which need efficient solutions to go one step further and improve the secure and efficient living and treatment of people. The aim of this research has been to understand through research the IoT security issues and propose the appropriate solutions based on the most suitable security algorithms. The results, which have been based on the complexity, the throughput, the power consumption, the strength, and the memory usage of the algorithms studied, have been hopeful and helpful for future research and experimentation.

Until recently there was a paucity of published information on the demographics of themedical and surgical workforce for the subspecialty of liver transplantation. This is relevant as it relates to whether gender equity is being achieved across the workforce. This manuscript focuses on what eventually led to the recognition that more data were required along with what is now actually known. This involves exploring the genders of the liver transplant workforce along with their related academic activities. Potential solutions to address any ongoing imbalances are also examined. The extent and range of gender disparities previously reported for other cohorts of physicians and surgeons, are also apparent amongst the liver transplant workforce in most regions of the world. This also pertains to the higher leadership positions within liver transplant centers as well as for the relevant editorial and scientific congress roles. Common themes/recommendations are now emerging as to how best to address the lack of progress towards gender equity. These include the development and implementation of policies, the removal of barriers to career progression, plus adequate governance. Hence ongoing actions are going to be required to achieve gender equity across the relevant workforce in liver transplantation around the world.

This study develops a 7-layer Long Short-Term Memory (LSTM) model to enhance early diabetes detection in Oman, aligning with the theme of 'Artificial Intelligence in Healthcare'. The model focuses on addressing the increasing prevalence of Type 2 diabetes, projected to impact 23.8% of Oman's population by 2050. It employs LSTM neural networks to manage factors contributing to this rise, including obesity and genetic predispositions, and aims to bridge the gap in public health awareness and prevention. The model's performance is evaluated through various metrics. It achieves an accuracy of 99.40%, specificity and sensitivity of 100% for positive cases, a recall of 99.34% for negative cases, an F1 score of 96.24%, and an AUC score of 94.51%. These metrics indicate the model's capability in diabetes detection. The implementation of this LSTM model in Oman's healthcare system is proposed to enhance early detection and prevention of diabetes. This approach reflects an application of AI in addressing a significant health concern, with potential implications for similar healthcare challenges globally.st diagnostic capabilities, representing a significant leap forward in healthcare technology in Oman.

Fiber-based flexible sensors have promising applications potential in human motion and healthcare monitoring, owing to their merits of lightweight, flexibility, and easy processing. Now, high-performance elastic fiber-based strain sensors with high sensitivity, large working range and excellent durability are in great demand. Herein, we have easily and quickly prepared a highly-sensitive, durable fiber-based strain sensor by dip-coating of highly-stretchable polyurethane (PU) elastic fiber in MXene/ waterborne polyurethane (WPU) dispersion solution. Benefiting from the electrostatic repulsion force between the negatively charged WPU and MXene sheets in the mixed solution, very homogeneous and stable MXene/WPU dispersion was successfully obtained and the interconnected conducting networks were correspondingly formed in coated MXene/WPU shell layer, which makes as-prepared strain sensor exhibit a gauge factor of over 960, a large sensing range of over 90% and detection limit as low as 0.5% strain. As elastic fiber and mixed solution have the same polymer constitute, tight bonding of MXene/WPU conductive composite on PU fibers was achieved, enabling the as-prepared strain sensor endure over 2500 stretching-releasing cycles and thus show good durability. Full-scale human motion detection was also performed by the strain sensor, and a body posture monitoring, analysis, and correction prototype system was developed via embedding the fiber-based strain sensors into sweater, strongly indicating the great application prospect in exercise, sports and healthcare.

Introduction The climate crisis is essentially a public health crisis. Response is imperative to prevent economic and social crises associated with the growing burden of climate impacts on human health and the health care sector. Green Podiatry Pillars By adopting the three pillars of Exercise, Evidence, and Everyday changes, podiatrists can contribute to more sustainable health and health care. Discussion Educating our patients to use their feet for low carbon active transport, eliminating interventions not supported by evidence, and reducing fossil fuel driven supply chains and energy use, are three impactful measures that all podiatrists, and indeed, all health and medical personnel, need to adopt. The avoidable suffering, enormous and costly use of resources for diabetic foot disease, is a scourge that must realise its preventable potential. It is too late, too costly, too polluting, and too sad, to continue to direct health care and research efforts and budgets, to an expensive modifiable diabetes disease process, potentiated by poor food and physical inactivity. Affected patients require skilled support, to avert such chronic disease processes, often not of their making. Conclusions Healthcare contributes 5 to 8% of green house gases (GHG), and non-communicable diseases (NCD) are increasing, so healthcare must lead on primary health. As citizens and health professionals, we must advocate for better community health, and educate our patients. Future Directions All health and medical personnel need to consider planetary health and sustainable healthcare within their daily work. Healthcare must act to address climate change, and realise benefits for people and planet.

In bioinformatics research, traditional machine learning methods have demonstrated efficacy in addressing Euclidean data. However, real-world data often encompasses non-Euclidean forms, such as graph data, which contain intricate structural patterns or high-order relationships that elude conventional machine-learning approaches. Representation learning seeks to derive valuable data representations from enhancing predictive or analytic tasks, capturing vital patterns and structures. This method has proven particularly beneficial in bioinformatics and biomedicine, as it effectively handles high-dimensional, sparse data, detects complex biological patterns, and optimizes predictive performance. In recent years, graph representation learning has become a popular research direction. It embeds graphs into a low-dimensional space while preserving the structural and attribute information of the graph, enabling better feature extraction for downstream tasks. This study extensively reviews representation learning advancements, particularly in the research of representation methods since the emergence of COVID-19. We begin with an analysis and classification of neural network-based language model representation learning techniques as well as graph representation learning methods. Subsequently, we explore their methodological innovations in the context of COVID-19, with a focus on the domains of drugs, public health, and healthcare. Furthermore, we discuss the challenges and opportunities associated with graph representation learning. This comprehensive review presents invaluable insights for researchers as it documents the development of COVID-19 and offers experiential lessons to preempt future infectious diseases. Moreover, this study guides future bioinformatics and biomedicine research methodologies.

Attack on health has become a significant concern for non-belligerents of war, including healthcare personnel and facilities as witnessed in the ongoing Sudan conflict. About 1.5 billion people living in fragile and conflict-affected settings (FCAS) have a heightened need for essential health services. Conflicts often lead to the disruption of building blocks of health systems, lack of access to health facilities, failure of essential medical supply chains, the collapse of political, social and economic systems, migration of health care workers, and upsurges in illness. While health indicators often decline in conflict, health can also bring peace and harmony among communities. Investment in health systems and health diplomacy is a neutral starting point for bringing peace and mitigating conflicts. The international commitment towards Sustainable Development Goals (SDGs) provides the impetus to emphasize the relationship between health and peace with the amalgamation of SDG 3, SDG 16, and SDG 17. The inspection of how health should be used as a ‘tool for peace’ and not as leverage during the war must be reiterated by international institutions.

Lifestyle physical activity (PA) and nutrition are known to be effective interventions in preventing and managing obesity related comorbidities is adult populations, but less so in children and adolescents. We examined the effectiveness of lifestyle interventions in children from minority ethnic populations in western high-income countries. Our systematic review included 53 studies involving 26045 children from minority ethnic populations within western countries, who followed lifestyle intervention programs lasting between 8 weeks and 5 years with an aim to prevent and/or manage childhood obesity and associated comorbidities, including adiposity and cardiometabolic risks. Studies were heterogenous in terms of lifestyle intervention components (nutrition, PA, behavioural counselling) and settings (community vs. schools and after schools). Our meta-analysis included 31 eligible studies and showed no significant effects of lifestyle interventions when they focused on body weight and body mass index (BMI) outcomes [pooled BMI mean change = -0.09 (95% CI -0.19, 0.01), p=0.09]. This was irrespective of the intervention program duration (< 6 months vs. ≥ 6 months), type (PA vs nutrition/combined intervention) and weight status (overweight or obese vs no normal weight), all showed no significant effects in the sensitivity analysis. Nonetheless, 19 of the 53 studies reported reduction in BMI, BMI z scores and body fat percentage. However, majority of lifestyle interventions adopting a quasi-design with a combined primary and secondary obesity measures (11 out of 15 studies), were effective in reducing obesity comorbidities of cardiometabolic risks including metabolic syndrome, insulin sensitivity, and blood pressure in children with overweight and obesity. Preventing childhood obesity and associated comorbidities in children from high-risk ethnic minority groups is best achieved using a combined PA and nutrition intervention approach, which jointly target preventing obesity and cardiometabolic disease primary and secondary outcomes, especially measures of diabetes, hypertension, and cardiovascular disease.

Healthcare workers (HCWs) in long-term care (LTC) faced and continue to experience significant emotional and psychological distress throughout the pandemic. Despite this, little is known about the unique experiences of LTC workers. This scoping review synthesizes existing research on the experiences of HCWs in LTC during the COVID-19 pandemic. Following Arksey and O’Malley’s framework, data were extracted from six databases from inception of the pandemic to June 2022. Among 3,808 articles screened, 40 articles were included in the final analysis. Analyses revealed three interrelated themes: carrying the load (moral distress); building pressure and burning out (emotional exhaustion); and working through it (a sense of duty to care). Given the impacts of the pandemic on both HCW wellbeing and patient care, every effort must be made to address the LTC workforce crisis and evaluate best practices for supporting HCWs experiencing mental health concerns during and post-COVID-19.

With the advent of modern technologies, the healthcare industry is moving towards a more Personalised smart care model. The enablers of such care models are the Internet of Things (IoT) and Artificial Intelligence. These technologies collect and analyse data from persons in care to alert relevant parties if any anomaly is detected in a patient’s regular pattern. However, such reliance on IoT devices to capture continuous data extends the attack surfaces and demands high-security measures. Both patients and devices need to be authenticated to mitigate a large number of attack vectors. The biometric authentication method has been seen as a promising technique in these scenarios. To this end, this paper proposes an AI-based multimodal biometric authentication model for single and group-based users’ device-level authentication that increases protection against the traditional single modal approach. To test the efficacy of the proposed model, a series of AI models are trained and tested using physiological biometric features such as ECG (Electrocardiogram) and PPG (Photoplethysmography) signals from five publicly available datasets from Physionet and Mendeley data repositories. The multimodal fusion authentication model shows promising results with 99.8% accuracy and an Equal Error Rate (EER) of 0.16.

Background: COVID-19 booster uptake remained poor among healthcare workers (HCW) despite evidence of improved immunity against Delta and Omicron variants. While most studies used a questionnaire to assess hesitancy, this study aimed to identify factors affecting true booster hesitancy by examining actual vaccine uptake across time. Method: COVID-19 vaccination database records among HCW working at 7 Singaporean public primary care clinics between January to December 2021 were extracted, with gender, profession, place of practice, vaccination type and dates. Time to booster was calculated from the date of vaccination minus date of eligibility. Chi-square test was used to compare relationship between 1st dose and booster hesitancy, Kaplan-Meier method and Log-rank test were adopted to evaluate differences in cumulative booster uptake. Multivariate cox regression was used to investigate predictors for timely booster vaccination. Vaccination rate was charted across time and corroborated with media releases pertaining to legislative changes. Results: 877 of 891 (98.9%) primary care HCW were fully vaccinated, 73.8% of eligible HCW had taken the booster. HCW were less booster hesitant [median 16 (5-31.3) days] compared to the 1st dose [median 39 (13-119.3) days]. 1st dose hesitant HCW were more likely to be booster hesitant (OR=3.66, 95%CI 2.61-5.14). Adjusting for sex, workplace and time to 1st dose, ancillary (HR=1.53, 95%CI 1.03-2.28), medical (HR=1.8, 95%CI 1.18-2.74) and nursing (HR=1.8, 95%CI 1.18-2.37) received boosters earlier compared with administrative staff. No temporal relationship was observed between booster uptake, legislative changes and COVID-19 infection numbers. Conclusion: Vaccine hesitancy among HCW had improved from booster to 1st dose, with timely booster vaccination among medical and nursing staff. Tailored education, risk messaging and strategic legislation might help to reduce delayed booster vaccination.

Type 2 diabetes (T2D) is associated with increased cardiovascular morbidity, mortality, and hospital admissions. There is variability in clinical practice. The objectives are to analyze the variability in the control of Blood Pressure (BP), HbA1c, and LDL-C in T2D patients and its influence on admissions due to cardiovascular events (CVE) Methods: We analyzed the electronic records in Primary Care Health centers in Navarra (Spain) and hospital admission for CVE. We follow 480637 people from 2012 to 2016. We calculated indicators of control of patients with T2D for each year, percentage with: HbA1c &lt; 7%; HbA1c &gt;= 9%; BP &lt;140/90 mmHg; LDL-C &lt;100 mg/dl. We used logistic and Cox regression. Results: Patients in the best control GP practices cluster are 2.5 times more likely to have HbA1c &lt;7% [OR: 2.46 (95% CI: 2.29-3.64)]. Poor HbA1c control ≥ 9% is more likely in the worst control cluster [OR: 1.73 (95% CI:1.63-1.83)]. The probability of admission for CVE increases with age, being male, low income, obesity, history of CVE, having HbA1c ≥ 9%, and belonging to a GP practice in the cluster of HbA1C ≥ 9% worst control. In contrast, it decreases in patients with HbA1c &lt;7%, BP&lt;140/90 mmHg and LDL &lt;100 mg/dl.

Tinnitus is a complex and heterogeneous psycho-physiological disorder responsible for causing a phantom ringing or buzzing sound albeit the absence of an external sound source. It has a direct influence on affecting the quality of life of its sufferers. Despite being around for a while, there hasn’t been a cure for tinnitus, and the usual course of action for its treatment involves use of tinnitus retaining and sound therapy, or Cognitive Behavioral Therapy (CBT). One positive aspect about these therapies is that they can be administered face-to-face as well as delivered via internet or smartphone. Smartphones are especially helpful as they are highly personalized devices, and offer a well-established ecosystem of apps, accessible via respective marketplaces of differing mobile platforms. Note that current therapeutic treatments such as CBT have shown to be effective in suppressing the tinnitus symptoms when administered face-to-face, their effectiveness when being delivered using smartphones is not known so far. A quick search on the prominent market places of popular mobile platforms (Android and iOS) yielded roughly 250 smartphone apps offering tinnitus-related therapies and tinnitus management. As this number is expected to steadily increase due to high interest in smartphone app development, a contemporary review of such apps is crucial. In this paper, we aim to review scientific studies validating the smartphone apps, particularly to test their effectiveness in tinnitus management and treatment. We use the PRISMA guidelines for systematic identification of studies on major scientific literature sources and delineate the outcomes of identified studies.

In the context of the COVID-19 pandemic, countries around the world varied in the strength and timeliness of their responses. In Romania, specific challenges were faced with regards to managing the spread and limiting the impact of the disease, ranging from healthcare infrastructure to demographic and sociocultural aspects. As the country has a sizeable diaspora, major difficulties were faced when large numbers of individuals from highly affected areas returned to Romania. However, the fast implementation of control measures successfully averted a surge in the number of COVID-19 cases. This delayed the overburdening of an already challenged healthcare system during the initial phases of the epidemic. Furthermore, early control was facilitated by the exploitation of communication channels that penetrated all layers of society, from ordinary citizens to governmental authorities and high-ranking religious figures. The management of the COVID-19 crisis in Romania illustrates the importance of a fast initial response which takes into account the role played by sociocultural aspects in the context of an epidemic. As the challenges faced by Romania are not unique, these results could inform future public health strategies worldwide.

Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy-1, an adhesion molecule integral to fibroblasts, relevant in fibrogenesis and detectable in serum as soluble Thy-1 (sThy-1), is expressed by PMF but not hepatic stellate cells in vitro. This study aimed to elucidate the correlation between Thy-1 expression in liver histology and sThy-1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction associated steatotic liver disease (MASLD). Liver histology samples were stained for Thy-1 and sThy-1 was measured using an enzyme-linked immunosorbent assay (ELISA). In patients with PBC and MASLD, portal Thy-1 expression significantly correlated with increased fibrosis. The sinusoidal Thy-1 expression also significantly correlated with increased fibrosis in patients with PBC (p

There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines, during e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron Paramagnetic Resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ from binding to fodipir (DPDP), and hence suggest that the previously reported CIPN protective efficacy of MnDPDP is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

Soluble CD163 (sCD163) functions as a scavenger receptor for haptoglobin-hemoglobin complexes, and is mostly expressed by monocytes and macrophages. The level of soluble CD163 has been used to determine macrophage activation. Our goal was to determine whether the loading of M2 CD163 positive tumor-associated macrophages (TAMs) through the secretion of sCD163 affects overall survival in patients with DLBCL and eventually discriminates subgroups of patients with different prognosis. sCD163 levels were measured in 40 frozen serum samples from patients diagnosed with DLBCL and 30 healthy individuals (HI) using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using SPSS version 28. The results showed that patients who achieved complete response after standard-of-care immuno-chemotherapy and were alive and disease-free after 12 months of follow-up, but had elevated sCD163 levels (above median) at diagnosis, presented a significantly worse overall survival compared to those with initial serum sCD163 levels below median (p=0.03). Consequently, serum sCD163 level in DLBCL patients may constitute a marker of long-term response to chemo-immunotherapy.

Natural killer cells are associated with the pathogenesis of ulcerative colitis (UC), but their precise contributions remain unclear. The present study sought to investigate the diagnostic value of activated NK-associated genes (ANAGs) in UC. Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, 92 differentially expressed genes (DEGs) were screened out by the “Batch correction” and “Robust rank aggregation” (RRA) methods. The immune infiltration landscape was estimated by single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT, which revealed a higher abundance of activated NK cells in noninflamed UC tissues. 54 DEGs correlated with activated NK cells were identified as ANAGs. Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were utilized to screen out 4 key ANAGs (SELP, TIMP1, MMP7, and ABCG2) and establish an activated NK-associated gene score (ANAG score). The ANAG score demonstrated excellent diagnostic value and was validated in three external datasets. The expression of the 4 key ANAGs was validated in UC patients and healthy controls (HC) samples. Through scRNA-seq data analysis, higher expression levels of SELP, TIMP1, MMP7, and ABCG2 were observed in post-capillary venules, inflammatory fibroblasts, enterocytes, and immature enterocytes. The cell scores based on the ANAGs showed enrichment in endothelial cells and fibroblasts. In conclusion, we established and validated an ANAG score with the ability to precisely diagnose UC. The 4 key ANAGs have the potential to serve as therapeutic targets in UC.

Background Community health workers (CHWs) drawn from the general population are an important human resource in health care systems, preventing non-communicable diseases (NCDs) and contributing to an increase in healthy life expectancy in Japan. Thus, we have developed the COmmunity health workers perceptual and behavioral Competency Scale for preventing Non-communicable diseases (COCS-N) to measure CHWs’ competence in preventing NCDs. The purpose of this study is to examine individual and community factors affecting CHWs’ COCS-N scores. Methods Municipal public health nurses and other public health professionals are responsible for training and supporting CHWs in Japan. Therefore, the existence of CHWs and their willingness to participate in the study were confirmed with the municipalities, who were asked to distribute the self-administered questionnaire to CHWs where consent was obtained (N = 6,480). Variables used included demographic characteristics, COCS-N scores, and individual- and community-related factors. Logistic regression analysis was used to assess associations between variables. Results A total of 3,120 people completed the questionnaire, a valid response rate of 48.1%. The respondents’ mean age was 67.0 years (standard deviation = 9.0), and 88.0% were female. Comparison of the high- and low- competence groups in terms of NCD prevention based on COCS-N scores identified 13 factors associated with significant differences, including years spent working as a CHW (p < 0.001), subjective sense of health (p = 0.005), European Health Literacy Survey Questionnaire (HLS-EU-Q47) scores (p < 0.001), and community commitment scale (CCS) scores (p < 0.001). Logistic regression analysis revealed that HLS-EU-Q47 scores (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02–1.03) were a significant individual factor, while CCS scores (OR: 1.14, 95% CI: 1.11–1.16) were a significant community factor. Conclusions We found that the COCS-N score was associated with the individual factors overall health literacy (HL), perceptions of HL, and subjective sense of health, and with the community factor CCS scores. These results suggest that strengthening individual factors such as HL and subjective sense of health, and community factors such as sense of community is an effective strategy for increasing CHWs’ competence in preventing NCDs.

Tumor-associated macrophages are a key component in the tumor microenvironment, secreting extracellular vesicles (EVs) such as exosomes and other various factors for intercellular communication. However, macrophage-derived EVs heterogeneity and their cytotoxicity to cancer cells has not been well understood. Here, we aimed to separately isolate various types of macro-phage-EVs by size exclusion chromatography (SEC) method and investigate EV transmission and cytotoxicity to oral cancer cells. For fluorescence-labeling of cellular and EV membranes, palmitoylation signal-fused GFP and tdTomato were expressed in THP-1 monocytic cells and HSC-3 oral cancer cells, respectively. We found that fluorescence-labeled EVs secreted by macrophages were highly transmissive to oral cancer cells than those from parental monocytic cells. In a co-culture system and conditioned medium (CM), a macrophage-secreted unidentified factor was cytotoxic to oral cancer cells. We fractionated macrophage-derived EVs by the SEC method and performed western blotting to characterize various EV types. Three fractions were characterized: small exosomes (EXO-S: < 50 nm) fraction containing HSP90α, HSP90β, CD63 (EV marker) and β-actin; large exosomes (EXO-L: 50-200 nm) fraction containing CD9 (EV marker) and HSP90β; large EVs (100-500 nm) fraction. Notably, the macrophage-derived small exosomes fraction was cytotoxic to oral cancer cells, while large exosomes and large EVs were not. There-fore, it was implicated that macrophage-derived small exosomes are cytotoxic with high trans-mission potential to cancer cells.

Epimutations are the cause of a considerable number of genetically inherited conditions in humans. All result from the mis-expression of genes due to epigenetic changes that are triggered by an underlying heritable mutation. The correction of these epigenetic defects in the context of epigenetically regulated diseases constitutes a good paradigm to probe the fundamental mechanisms underlying the development of these diseases, and the molecular basis for the establishment, maintenance and regulation of epigenetic modifications in general. Here, we review current applications of key editing tools to address the epigenetic aspects of these diseases by focusing on epimutations caused by, or relate to repetitive elements, primarily unstable noncoding repeat expansions. For each approach we summarize the efforts conducted to date, highlight their contribution to a better understanding of the molecular basis of epigenetic mechanisms, describe the limitations of each approach and suggest perspectives for further exploration in this field.

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

Improving the quality and access to healthcare services in rural areas is fundamental to develop sustainable healthcare systems. This research aims to explore the motivations of healthcare professionals to work and settle in rural island areas of Greece with limited access to secondary and tertiary care. The study suggests practical ways to encourage self-motivation and attract more health workers in rural areas. An exploratory qualitative research approach was employed, involving semi-structured interviews with 16 healthcare professionals working in primary care units that lack direct hospital or hospital-health center access. The research was conducted specifically in the rural islands of Cyclades. Thematic analysis was conducted to identify common themes and unique insights from the participants. The analysis revealed three thematic categories. Τhe «attraction» thematic was influenced by personal factors, random selection, origin, accommodation factors, professional factors and obligatoriness. The «recruitment» thematic was associated with understaffing, special care issues, unstable working environment, educational and organizational aspects, and insular lifestyle. The thematic of «retention» highlighted personal issues, accommodation difficulties, economic and work-related issues, and unique challenges posed by an insular lifestyle. This research provides valuable insights into the motivations that drive healthcare professionals to settle, work, and remain in remote island units, as well as the challenges they encounter in making this decision. The study proposes strategies to motivate and attract more healthcare professionals to rural areas. These findings should be considered when formulating or reviewing primary healthcare empowerment policies to ensure equitable healthcare access for all individuals.

Positive Health (PH) has been described as a promising transformative innovation to address the challenges of promoting well-being and reducing the burden of disease. The aim of this study is to review the current state of knowledge about PH as introduced by Huber et al. (2016) within the available scientific literature. A rapid review of the literature following the Cochrane Rapid Review recommendations. Three databases were searched (PubMed, Google Scholar, and CINAHL). Data were extracted and synthesized using a narrative approach. A total of 55 articles were included. Initial evaluation studies reveal promising results both at individual and collective levels. However, a need is expressed in several articles for further refinement of the conceptualization of PH and ways to make the effects of the PH approach more measurable. Professionals also expressed a desire for a more informed application and elaboration of the PH method across various settings and populations to enhance its effectiveness in practice. This rapid review highlights the transformative potential of PH in shifting from a disease-focused to a health-oriented paradigm of healthcare. It underscores the need for continued research regarding further development of the concept and its practical method, along with the necessity for methodological innovation.

The development of new medical monitoring applications requires precise modeling of the human body effects as well as simulating and emulating realistic scenarios and conditions. The first aim of this paper is to develop realistic and adjustable human body 3D emulation platforms which could be used for evaluating emerging microwave-based medical monitoring/sensing applications such as the detection of brain tumors, strokes, breast cancers as well as for capsule endoscopy studies. The new phantom recipes are developed for microwave ranges for the realistic shaped phantom molds. The second aim is to validate the feasibility and reliability of the phantoms for practical scenarios with electromagnetic simulations using tissue layer models and biomedical antennas. The third aim is to investigate the impact of the water temperature in the phantom cooking phase on the dielectric properties of the stabilized phantom. The evaluations show that the dielectric properties of the developed phantoms correspond closely to those of real human tissue. The error in dielectric properties varies between 0.5-8%. In the practical scenario simulations, the differences obtained with phantoms-based simulations in S21 parameters are 0.1-13dB. However, the differences are smaller in the frequency ranges targeted for medical applications.

Abstract: Integration of Medical Cyber Physical Systems (MCPS) and Internet-of-Medical Devices (IoMT) with conventional hospital networks have facilitated easy and speedy data collection, vertical and horizontal connectedness and collaborations among healthcare providers. Federated identity management (FIM) provides a solution towards the identity management challenge arising from this integration of millions of MCPSs to get personalized care and frictionless experiences for the patients, doctors, and employees. FIM protocols such as OAuth, Security Assertion Markup Language (SAML) are highly susceptible to cyber attacks like theft of barrier token, replay attack, message insertion, and Man-in-Middle attacks. IoMT devices have vulnerabilities in their firmware, operating systems, data encryption, data at store and data transmission. Combined vulnerabilities of FIM framework and IoMT devices creates major cyber risks for the current digital healthcare system. Therefore, a comprehensive and evidenced based cyber risk assessment is an urgent need for a cyber-safe digital health care system that can avoid frequent life threatening situations. This paper proposes a comprehensive and evidenced based cyber risk assessment approach for FIM and IoMT based collaborative digital healthcare systems. The novelty of the proposed approach is that it considers three dimensional vulnerabilities arising from existing IT communication protocols and infrastructure, IoMT and MCPS medical devices, protocols of FIM and their combined impact on hospitals and provides corresponding recommendations of security controls. The proposed approaches combine two industry standards including Cyber Resilience Review (CRR) asset management, NIST SP 800-30 to take advantage of both approaches. We have used a large number of IoMT and MCPS devices from multiple providers for threat modelling and produced evidence based cyber-risks using attack trees and detailed attack sequence diagrams to validate proposed approaches. The corresponding recommendation of security controls will support healthcare professionals and providers significantly for improving both the patient and medical device safety management within the FIM enabled healthcare ecosystem.

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "break-through infections" have been documented in patients with complete primary vaccination course. Most of the SARS-CoV-2 neutralizing antibodies pro-duced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of the host. The aim of this study is to compare the titers of neutralizing an-tibodies against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). 293 HCWs were enrolled and divided into three cohorts as follows: 91 recovered from SARS-CoV-2 infection (nVP); 102 vac-cinated who became positive after the primary cycle (VP); 100 vaccinated with complete primary cycle who concluded the follow-up pe-riod without becoming positive (VN). Higher neutraliza-tion titers were observed in the vaccinated subjects’ arms com-pared to the nVP arm. Differences in neutralization titers between arms for single variant were statistically significant (p<0.001) except for titers against the Alpha variant (p<0.05) between nVP and VP. Within the nVP group, the number of subjects with the absence of neutralizing antibodies was high. The presence of high-er titers in patients with a complete primary cycle compared to patients recovered from the infec-tion suggests a better efficacy of artificial immunization compared to natural im-munization, further encouraging the promotion of vaccination even in subjects with previous infection.

Cloud computing is a strong and efficient technology facing some efficiency challenges attributable to its decentralized nature. The emergence of fog computing has subdivided the expansive cloud into numerous smaller units known as "cloudlets." Fog computing is one of the most recent advancements in today’s cloud computing landscape. Each cloudlet is a novel and diminutive architectural element extending the contemporary cloud computing infrastructure. The term "cloudlets" has been integrated with fog computing due to its augmenting impact on the attributes of cloud computing. F fog computing is a significant foundation and an indispensable cloud component. Consequently, this technology holds the potential to address efficiency concerns effectively. As a result, this paper focuses on enhancing the efficiency of the cloud computing environment by fine-tuning the efficiency parameters derived from fog computing. These parameters encompass response time, latency, and network utilization. The proposed solution involves developing a simulation system to minimize task redundancy and increase performance levels in the healthcare environment. The outcomes manifest a substantial improvement in the performance of the suggested system, with a clear increase depending on the three key parameters (response time, network utilization, and latency). Therefore, these findings are encouraging and carry significant implications, promoting the application of the proposed system in the real healthcare environment.