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

IIt is important that Master’s Degree students in psychology, regardless of their future specialisa-tion, know about Attention Deficit Hyperactivity Disorder (ADHD). The aim is evaluate and an-alyse the ADHD-related knowledge held by students of Early Childhood Education and Primary Education. The findings that were obtained in this study (on the chronicity of the disorder, changes in manifestations throughout the life cycle, and the importance of early and multidisci-plinary intervention) have clear implications in relation to the specific training in ADHD for fu-ture teachers. It is essential to broaden the specific training in relation to ADHD in studies for the Master’s Degrees in Early Childhood Education and Primary Education and through contin-uous training.

(1) Background: Central nervous system (CNS) development is characterized by dynamic changes in cell proliferation and differentiation. Key regulators of these transitions are the transcription factors such as SOX2 and SOX9. SOX2 is involved in the maintenance of progenitor cell state and neural stem cell multipotency, while SOX9, expressed in neurogenic niches, plays an important role in neuron/glia switch with predominant expression in astrocytes in the adult brain. (2) Methods: To validate SOX2 and SOX9 expression pattern in dissociated primary neuronal cultures derived from opossum (Monodelphis domestica), we used immunohistochemistry (IHC) and the isotropic fractionator method on fixed cortical tissue from comparable postnatal ages; (3) Results: Neurons positive for both neuronal (NeuN or TUJ1) and stem cell (SOX2) markers were identified and their presence was confirmed with all methods and postnatal age groups (P4-6, P6-18 and P30) analyzed. SOX9 showed exclusive staining in non-neuronal cells, and it was coexpressed with SOX2. (4) Conclusions: The persistence of SOX2 expression in developing cortical neurons of M. domestica during first post-natal month implies the functional role of SOX2 during neuronal differentiation and maturation, which was not previously reported in opossums.

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.

Abstract Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Because of the multiplicity of roles in cell function, it is not surprising that deficiency of CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation.

Background: The importance of community health psychology in providing complex bio-psycho-social care is well-documented. We present a mixed-method study monitoring the efficacy of health psychology services in the Public Health Focused Model Program for Primary Care Development (2012-2017) in four disadvantaged micro-regions in North-East Hungary. Methods: Study 1 assessed the availability of the services using a sample of 17003 respondents. Study 2 applied a follow-up design to measure the efficacy of the health psychology services in a sample of 132 clients. In Study 3, we conducted focus group interviews to assess clients’ lived experiences. Results: More mental health issues and higher education predicted a higher probability of service use. Follow-up showed that individual and group-based psychological interventions resulted in lower depression and (marginally) higher well-being. Thematic analysis of the focus group interviews indicated that participants deemed topics like psychoeducation, a greater acceptance of psychological support, and heightened awareness of individual and community support important. Conclusions: The results of the monitoring studies demonstrate the important role health psychology services can play in primary health care in disadvantaged regions. Community health psychology can improve well-being, reduce inequality, support the population’s health awareness, and address unmet social needs in disadvantaged regions in Hungary.

The Portuguese health system has a universal, public, general National Health Service (NHS), tending towards free healthcare access. Created in 1979, this delivery model developed from the integration and complementarity between the different response levels (primary, hospital, continuing, and palliative care). However, over these 40 years, the initially centralized system underwent a decentralization process with the creation of Regional Health Administrations in the five mainland administrative regions. Since then, the entire NHS has settled around this new organization. The most recent step started in 2018 with decentralizing primary health care skills to 190 municipalities. This paper presents the various critical issues involved in the latest gradual decentralization process in health, intending to bring services closer to the citizens, and more focused on their needs. The article identifies and discusses the implications of this experience based on the steps foreseen in the already published legal texts.

The disruption in healthcare attention to people with alcohol dependence, along with psychological decompensation consequence of lockdown derived from COVID-19 pandemic, could have a negative impact on people who suffers from alcohol abuse disorder. Retrospective observational study of 9,966 men aged ˃16 years registered as having diagnosis of alcohol abuse disorder in the electronic medical records (EMR) of the Aragon Regional Health Service (Spain). Of those who were not infected during the study period (9,576), clinical (Glutamate-oxaloacetate -GOT-, Glutamate pyruvate -GPT-, creatinine, glomerular filtration, systolic blood pressure -SBP-, diastolic blood pressure -DBP-, total cholesterol, LDL, HDL, triglycerides, and body mass index -BMI-), pharmacological (dose per inhabitant per day -DHD- of drugs used in addictive disorders, benzodiazepines and antidepressants) and health resource use variables (primary and specialized care) were considered. Student´s T-test for matched samples was performed. After carrying out the Levene´s test, the Student´s T-test was used to analyze the changes in clinical variables between alcohol abuse disorder patients with and without COVID-19. Only creatinine and LDL show a significant but clinically irrelevant changes just after and 6 months after the end of strict lockdown. The total number of DHDs for all drugs included in the study (except for Benzodiazepines), decreased. In the same way, the use of health services by these patients also decreased. The impact of COVID-19 among this group of patients has been moderate. The reorganization of health and social services after the declaration of the state of alarm in our country, made possible the maintenance of care for this vulnerable patients.

Background and Aims: Of all primary liver tumors, primary hepatic angiosarcoma (PHA) is a rare and aggressive malignant vascular tumor. The standard therapeutic care for hepatic angiosarcoma remains unclear. This study compared the survival outcomes of aggressive treatment (resection and liver transplant) and nonaggressive treatment (chemotherapy, transarterial chemoembolization [TACE], and conservative treatments) for patients with PHA and analyzed the prognostic factors influencing survival. Materials and Methods: Data of patients diagnosed as having PHA at our facility were retrospectively reviewed. The primary outcome was survival time. The secondary outcome was calculated baseline characteristics. Results: We included a total of 19 patients, who were divided into 2 treatment groups: aggressive (8 patients had undergone resection or transplants) and nonaggressive (11 patients had undergone TACE, chemotherapy, or conservative treatment). The mean survival time was 233.1 ± 189.7 days in the aggressive treatment group and 146.5 ± 115.8 days in the nonaggressive treatment group. A Kaplan-Meier plot revealed no significant difference in survival time between the 2 treatment groups (P = .3256). Conclusions: The survival time of patients receiving aggressive treatment was longer than that of those receiving nonaggressive treatment. The long term survival time in some selective cases of aggressive treatment will be achieved. Thought a difference was not significant between the groups. Because the number of patients was limited, more cases are required to confirm these findings.

This work has the purpose to demonstrate that if an adequate melt treatment is applied, it is pos-sible to obtain recycled aluminium alloy AlSi10MnMg(Fe) with as good metal cleanliness than primary AlSi10MnMg alloy. The melt quality is assessed by the thermal analysis, density index, macro- and micro-inclusions tests, of one primary and two secondary alloys, before and after the melt treatment. The melt treatment is based on deoxidation, degassing and skimming with de-tailed procedure described in this article. The different analysis are: Thermal analysis to compare the variables of the solidification cooling curve (Al primary temperature and its undercooling; Al-Si eutectic temperature and its recalescence); Density index is used to evaluate the hydrogen gas content in the melt; Macroinclusions level is analysed after solidifying the melt under vacuum of 5 mbar, favouring inclusion floatation to the sample surface; Microinclusion level is evaluate with porous disc filtration apparatus (similar to PoDFA).

The development and optimization of an effective non-viral gene delivery method for genetic manipulation of primary human T cells is a major challenge in clinical immunotherapy researches. According to the low transfection efficiency of conventional methods in human primary T cells, there is an effort in order to increase the transfection rate in these cells. Protamine is an FDA-approved compound with a documented safety profile that enhances DNA condensation for gene delivery. In this study, the effect of protamine on the transfection efficiency of standard transfection reagents, TurboFect, and Lipofectamine 2000 was evaluated in order to transfect primary human T cells. Results demonstrated that protamine condenses DNA and increases the positive charge of DNA/Cargo complex efficiently without any cytotoxic effect on the primary human T cells. The results also revealed that the DNA/Protamine/Cargo complexes effectively transfect human primary T cells.

The stability between the limited available energy resources and their consumption is an important concern of the modern world. The study deals with the development of the methods for measuring the energy performance of different renewable and non-renewable resources used for electricity generation with the help of an energy performance indicator called the Primary Energy Factor (PEF). This study takes account of all energy stages from the resources extraction to its transportation, conversion, combustion and then finally to utilization. The study conducted a comparative approach to calculate the PEF values of electricity generated in South Korea from the period of 1980 to 2017. Four different methodologies namely Eurostat methodology, Life cycle methodology, Modified Eurostat methodology, and upper-end methodology have been used. A set of Programs has been written in MATLAB to calculate the i. PEF values of electricity generated. ii. Impact of different renewable and non-renewable energy sources on PEF values. iii. Future trend of PEF values of electricity in South Korea At the national and local level, this study will help the government and other law-making institutions to make policies regarding annual purchase consumptions of energies by different industrial, residential, public and transportation sectors and at the Global level, the implementation of this study will be the catastrophe of maintaining the stability between the available energy resources, and consumptions. This, in turn, will lead to suitable living conditions for future generations

Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder frequently associated with ulcerative colitis (UC). Patients with PSC and UC have higher risk of colorectal neoplasia than patients with UC without PSC. Oncogenic properties of micro RNA 346 (miR-346) have been recently reported. In this study we investigated expressions of miR-346 and its two target genes i.e. the receptor of vitamin D (VDR) and the tumor necrosis factor α (TNF-α), which are known to modulate carcinogenesis. Biopsies from ascending and sigmoid colon were obtained from patients with PSC with and without UC, patients with UC and healthy controls. MiR-346 expression was increased in ascending but not sigmoid colon of patients with PSC and UC when compared to other analyzed groups (p<0.001 for all). In patients with UC an exceptionally low colonic expression of miRNA-346 was accompanied by the increase in VDR expression, and the extensive upregulation of TNF-α gene which protein product is known to be cytotoxic to tumor cells at high concentration. In summary, a substantial upregulation of miRNA-346 in ascending colon of patients with PSC and UC may be responsible for the inhibition of VDR and TNF-α signaling -pathway which may result in an inadequate suppression of neoplasia.

Purpose: To compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination in newly diagnosed primary open angle glaucoma patients. Methods: In this prospective, interventional case series, newly diagnosed primary open angle glaucoma (POAG) patients that had not been treated for glaucoma were included. Patients were started on Cosopt twice a day (BID) for 1 month and then switched to three times a day (TDS) for additional 1 month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP) and 24-hours heart rate (HR) measurements at baseline, month 1( BID), and month 2( TDS). IOP, systolic and diastolic pressures were measured at 8:00 AM,12:00 AM, 4:00 PM, 8:00 PM and 12:00 PM. Throughout the study, all adverse events were recorded and monitored by the investigators. Results: In 31 POAG patients that completed the study ,mean baseline IOP was 23.1±3.15 mmHg . IOP was decreased significantly 16.5 ± 2.21 at 1 month (P < 0.0001) and 13.9 ± 2.23 mmHg at 1 and 2 month follow up. (P < 0.0001) IOP was significantly lower in month 2 compared to month 1 (P = 0.0004). While Cosopt BID significantly reduced the mean 24-hour systolic BP and mean 24-hour HR from baseline (P < 0.0001), the mean 24-hour systolic BP and HR remained unchanged 2ith Cosopt TDS compared to BID (P = 0.62). Conclusions: Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profile.

Infant malnutrition remains as an important cause of death and disability, Haiti has the highest prevalence in America, so preventive strategies are needed. Our objective was to assess infant and young children malnutrition in Haiti and to study an association to World Health Organization (WHO) recommended feeding practices adherence. Cross-sectional study of children younger than 2 years old, recruited at Saint Espri Health Center, Port Au Prince (August to September 2014). We registered feeding practices, social and demographic data, and performed anthropometry (WHO-2006 standard). We evaluated 278 infants and young children, 8.08 ± 6.5 months old, 53.2% female. 18.35% had underweight; 13.31% were stunted and 13.67% had moderate or severe wasting. Malnutrition was associated to male gender, older age, lower education of mothers and higher number of siblings. The adherence to WHO recommended practices for breastfeeding was from 11.8 to 97.9% and was related to a lower prevalence of malnutrition. For complementary food, adherence was 9.7 to 90.3%, also associated to lower malnutrition. Conclusion: Prevalence of infant and young children malnutrition in this Haitian Health Center population was high, related to some risk factors. The adherence to WHO recommended feeding practices was associated to a better nutritional status.

Heart failure (HF) affects about 60 million people worldwide, making it one of the chronic conditions with the greatest health and economic impact. The primary objective was to assess the efficacy of lung ultrasound (LUS) in the management of HF in order to intervene early and reduce the rate of hospital readmissions. A systematic search was conducted on PubMed, Embase, Google Scholar, Web of Science, and Scopus, including clinical trials, meta-analysis, systematic reviews, and original articles from 2019/1/1-2023/12/31, about LUS for the assessment of HF, on an outpatient basis, for HF diagnosis or/and decompensation. There may be risk of bias because the effects are dependent on the persons delivering the intervention. The results were synthetized by PRISMA method. A total of 873 articles were identified of which 33 articles were selected: [n=19] focused on prognostic assessment of HF, [n=11] centred on multimodal diagnostic assessments, and [n=2] addressing therapeutic guidance for HF diagnosis. LUS exhibits advantages in the detection of sub-clinical congestion linked to prognostic significance in re-admission and mortality during out-patient follow-up, after hospital discharge, and in complex scenarios as the patients' homes or institutional long-term care facilities. However, there are considerable uncertainties in their interpretation and monitoring changes due to its lack of standardization. The need for an updated international consensus on the use of LUS seems obvious.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

The late diagnosis of Type 2 Diabetes Mellitus can occur due to lack of access to the primary health care system and the non-manifestation of symptoms. Faced with this problem, this work presents the creation of a mobile application, called DiabetesCheck, for predicting the risk of Type 2 Diabetes Mellitus. A mathematical model is used, which classifies the risk of Type 2 Diabetes Mellitus for a group of patients with intervention and for a comparative group, using Fuzzy Classification and Decision Trees. The proposed application allows the health professional to monitor patients through the history stored in a database, allowing a representation of the evolution of patients and indication of medications. Therefore, this proposal aims to carry out the diagnosis in the initial phase of the disease and help in the prescription of more effective treatments and in the proposition of public policy strategies in epidemiology and screening.

Smoker’s paradox usually refers to the common observation of a favourable outcome of smoker patients in acute myocardial infarction. The interpretation of this phenomenon is still controversial and not fully explained. We aimed at assessing whether smoking could be associated with mortality in a large cohort of prospectively enrolled patients with ST segment elevation myocardial infarction (STEMI) referred to primary percutaneous coronary intervention (pPCI). From April 2006 to December 2018 a population of 2456 STEMI patients treated with primary PCI were prospectively enrolled in the MATRIX registry. Ischemic time, clinical, demographics, angiographic data and 1-year follow-up were collected. Among 2546 patients admitted with STEMI 1007 (41%) were current smokers. Smokers were 10 years younger and had lower crude in-hospital and 1-year mortality (1.5% vs 6%, p&lt;0.0001 and 5% vs 11%, p&lt;0.0001), shorter ischemic time (203 [147-299] vs 220 [154-334] minutes, p=0.002) and shorter decision time (60 [30-135] vs 70 [36-170] minutes, p=0.0063). After propensity-matching, age, cardiogenic shock and low TIMI score were associated with in-hospital mortality, while smoking habit was still associated with reduced mortality. Smoking was also associated with reduced death rate at 1-year follow-up (HR 0.54, 95% CI [0.37 - 0.78]; p&lt;0.001). Our data show a protective link between smoking status and mortality in patients with STEMI, the so called “smoker’s paradox”. This could be explained not only by the shorter ischemic time and younger age of the smoking population but also by a specific pathogenetic effect of smoking underlying the onset of STEMI and response to therapies.

This study investigates effective strategies for second language education in primary schools, analyzing the efficacy of immersive and interactive methods, digital literacy tools, and mixed-method approaches. The findings reveal significant improvements in language proficiency and student engagement through these methodologies, with immersive and interactive strategies showing substantial benefits in oral proficiency and engagement, digital tools enhancing accessibility and engagement, and mixed-method approaches yielding the highest overall effectiveness. The study underscores the importance of a balanced, flexible approach to language education, integrating traditional and modern methods to cater to diverse learner needs. These strategies not only advance linguistic skills but also contribute to the broader cognitive and emotional development of young learners, emphasizing the critical role of effective language education in preparing students for a globalized world.

Milroy's disease (MD), also known as hereditary lymphedema type I, is a rare autosomal dominantly inherited primary lymphedema. It accounts for approximately twenty percent of all primary lymphedemas. MD typically presents clinically with bilateral lower extremity lymphedema. Our case report is about a rare case of MD presenting with unilateral lymphedema in both upper and lower extremities in a patient admitted to our clinic. A 24-year-old woman who had been under observation for lymphedema since she was 8 years old was diagnosed with MD by physical examination, venous Doppler ultrasound, whole body lymphoscintigraphy, and molecular genetic testing in our clinic, and partial improvement was achieved with Complete Decongestive Therapy, the gold standard treatment for lymphedema. Genetic counseling services may be especially useful for the patient and family. Although MD is rarely seen in the literature, many more studies are needed to identify carrier variants in the community.

The preservation of biodiversity has become a major concern in contemporary society. It is essential to understand teachers' representations of biodiversity to effectively guide educational efforts because of the significant role of education in raising awareness and promoting sustainable behavior. Through a survey of a sample of 118 teachers, we adopted a mixed-method approach combining both a closed questionnaire and interviews. We used these methods to explore teachers' representations of the concept of biodiversity as an integral part of the school curriculum, as well as to gather their views on certain features of its teaching. The results state that the majority of teachers perceive biodiversity as a whole and in its most complex relationships. During their professional experience, they have developed a biocentric and anthropocentric conception of biodiversity. This study provides valuable information to guide future pedagogical practices and educational policies in sustainable education.

Low nasal nitric oxide (nNO) is a typical feature in Primary Ciliary Dyskinesia (PCD). nNO is part of the PCD diagnostic algorithm due to its discriminative power against other lung diseases such cystic fibrosis (CF). However, the underlying pathomechanisms are elusive. To better understand NO dysregulation in PCD, the L-arginine/NO (Arg/NO) pathway in patients with PCD (pwPCD) and CF (pwCF) and in healthy control (HC) subjects was investigated. In a prospective, controlled study, we measured in 24 pwPCD, 25 age-matched pwCF, and 14 HC the concentrations of the NO precursors Arg and homoarginine (hArg), the arginase metabolite ornithine (Orn), the NO inhibitor asymmetric dimethylarginine (ADMA), and the major NO metabolites (nitrate, nitrite) in sputum, plasma and urine by validated methods. In comparison to HC, the sputum contents (in µmol/mg) of L-Arg (PCD 18.43 vs. CF 329.46 vs. HC 9.86, p &lt; 0.001) and of ADMA (PCD 0.055 vs. CF 0.015 vs. HC 0.010, p &lt; 0.001) were higher. In contrast, the sputum contents (in µmol/mg) of nitrate and nitrite were lower in PCD compared to HC (nitrite 4.54 vs. 9.26, p = 0.023; nitrate 12.86 vs. 40.33, p = 0.008), but higher in CF (nitrite 16.28, p &lt;0.001; nitrate 56.83, p = 0.002). The metabolite concentrations in urine and plasma were similar in all groups. The results of our study indicate that PCD, unlike CF, is associated with impaired NO synthesis in the lung, presumably due to mechano-chemical uncoupling.

The elastic wave equation with the seismic tensorial force is solved in a homogeneous and isotropic medium (the Earth). Spherical-shell waves are obtained, which are associated to the primary P and S seismic waves. It is shown that these waves produce secondary waves with sources on the plane surface of a half-space, which have the form of abrupt walls with a long tail, propagating in the interior and on the surface of the half-space. These secondary waves are associated to the seismic mainshock. The results, previously reported, are re-derived by using Fourier transformations and specific regularization procedures. The relevance of this seismic motion for the ground motion, the seismographs' recordings and the effect of the inhomogeneities in the medium are discussed.

Depression is estimated to be a leading contributor to the global mental health-related burden. The determinants of this huge prevalence lie in the fact that depressive symptoms may be comorbid in a wide variety of disorders, thus complicating and exacerbating their clinical pictures. This makes the treatment of depressive symptoms even more difficult since many pharmacological and pharmacokinetic interactions should be considered by physicians approaching the therapy. Hence, depression still represents a challenge for both psychiatrists and the other clinicians, in terms of its high rates of relapse and resistance despite well-established protocols. It is also complicated by the well-known latency in its complete response to current antidepressant treatments. In this context, the search for new strategies in antidepressant treatment is mandatory; even including revising the use of “old” pharmacotherapies by considering their specific features may help to perfecting the treatment of depression, both in its standalone psychiatric manifestation and in the framework of other clinical conditions. The results of a consensus of experts regarding the possible use of trazodone as a valuable strategy for addressing the “real world” unmet needs of depression treatment is herein reported. This is based on the unique characteristics of this drug possibly delivering a rapid antidepressant action as compared to other selective serotonin reuptake inhibitors (SSRIs) as well as on its pharmacodynamic malleability and pharmacokinetic tolerability when used in the milieu of other drugs in treating comorbid depressive symptoms.

Coumarin is an effective treatment for primary lymphoedema, as well as lymphoedema related to breast cancer radiotherapy or surgery. However, its clinical use is limited in several countries due to the possible occurrence of hepatotoxicity, mainly in the form of mild to moderate transaminase elevation. Noteworthy, only few cases of severe hepatotoxicity have been described in literature, with no reported cases of liver failure. Data available on coumarin absorption, distribution, metabolism and excretion have been reviewed, focusing on hepatotoxicity studies carried out in vitro and in vivo. Finally, safety and tolerability data from clinical trials have been thoroughly discussed. On the basis of these data, coumarin-induced hepatotoxicity seems to be restricted to a small subset of patients, probably due to the expression of specific alleles of CYP450 isoform not yet well characterized. In summary, more research is needed in order to identify patients at risk of developing hepatotoxicity following coumarin treatment, in order to improve the risk/benefit ratio of the product and allow more patients to benefit from its therapeutic properties.

(1) Background: Several agencies in the United States play a primary role in ensuring food safety, yet foodborne illnesses result in about 3,000 deaths and cost more than $15.6 billion each year. The study objectives included analyzing local health departments’ (LHDs) level of engagement in food safety and other related services, and LHDs’ characteristics associated with those services. (2) Methods: We used data from 1,496 LHDs that participated in the 2019 National Profile of Local Health Departments Survey, administered to all 2,459 LHDs in the United States. Logistic regression analyses were performed to model multiple dichotomous variables. (3) Results: An estimated 78.9% of LHDs performed food safety inspections, 78.3% provided food safety education, 40.7% provided food processing inspections, and 48.4% engaged in policy and advocacy. The odds for LHDs to directly provide preventive nutrition services were 20 times higher if the LHD had one or more nutritionists on staff (Adjusted Odds Ratio or AOR=20.0; Confidence Interval, CI=12.4-32.2) compared to LHDs with no nutritionists. Other LHD characteristics significantly associated with the provision of nutrition services (p&lt;.05) included population size, state governance (rather than local), and LHD having at least one registered, licensed, practical, or vocational nurse. The odds of providing food processing services were lower for locally governed than state governed LHDs (AOR=0.5; CI=0.4-0.7). The odds of performing food safety inspections varied by LHD’s population size, whether a nutritionist was on staff or not, state governance (vs. local), and having completed a community health assessment (CHA) within 5 years. (4) Conclusions: LHDs play a critical role in ensuring safe food for Americans, yet variations exist in their performance, based on their specific characteristics. Adequate funding and a competent workforce are essential for LHDs to utilize evidence-based practices and engage in policymaking and advocacy concerning food safety.

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.

Background: The concept of Quality of Work Life (QWL) has been built multidimensionally through social reproduction; it is impacted by the perceptions of each individual and by the relationship between workers and the work environment. Objective: to analyze the Work Process and QWL of assisting nurses in public health. Methods: Research in a critical paradigm, descriptive, exploratory with a qualitative approach. The population corresponds to Nurses who work in care work. Semi-structured guiding questions were applied and were analyzed with content analysis. Results: seven participants declared female; all Chilean; seven are young adults; six singles; only one has children, and one has a person dependent on her care; six are heads of household, and five receive help with housework. All have a nursing degree, five have a diploma, but none have a postgraduate. Work Process has three subcategories: work object, instrument, organization, and work conditions; the QWL category has six subcategories: definition and perception of QWL, QWL potentiating factors, QWL exhausting factors, QWL improvement strategies, the emotional burden associated with QWL, and Health problems. Conclusions: In this way, the lifestyle built by the assistance in the health area has repercussions on the quality of life and health in general.

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.

The process of international migration causes a situation of vulnerability in people's health and greater difficulty in coping with disease. Furthermore, the adversities suffered during migration can trigger reactive signs of stress and cause anxious, depressive, confusional and somatic symptoms. This article studies the relationships between psychosocial risk, psychological distress and somatization in immigrants from 4 communities: Maghrebis, Sub-Saharans, South Americans and South Asian. A cross-sectional study was carried out with questionnaires on 602 immigrants who were surveyed in the Primary Care Centres of an urban area of Catalonia. The instruments used were the Demographic Psychosocial Inventory (DPSI), the Brief Symptom Inventory (BSI) and the Somatic Symptom Inventory (SSI). The average psychosocial risk obtained was 0.35, with the highest values in the sub-Saharan community. Psychological distress showed a mean value of 0.66, with the sub-Saharan community scoring the lowest in all dimensions except depression. The average somatization values were 1.65, with the sub-Saharan community scoring the least. The female gender is a risk factor for somatization and psychological distress. Perceived psychosocial risk is a predictor of psychological distress, but not somatization, suggesting that the use of more adaptive coping strategies could minimize the effect of the migration process on somatizations.

This study aims at improving the forecast accuracy of primary energy consumptions in China, Japan and South Korea and verifying the correlation in primary energy consumptions among the neighboring countries. Considering the diversity of primary energy composition, this study selects 6 components of primary energy, including oil, coal, natural gas, nuclear energy, hydropower and renewable energy as characteristic variables. A collaborative prediction model based on SVR for primary energy consumption prediction is proposed to explore the correlation of primary energy consumption among three countries in China, Japan and South Korea. The results show that there is a strong correlation between primary energy consumption when multiple countries make collaborative prediction, among which the primary energy consumption of South Korea has the largest impact on the primary energy consumption of China and Japan. In the primary energy cooperation of China-Japan-South Korea, a primary energy cooperation system with the South Korea as the link should be established through regional coordination to alleviate the shortage of traditional fossil energy.

As a universal pathogen leading to neonatal defects and transplant failure, Human cytomegalovirus (HCMV) has strict species specificity that the inability to using this virus in animals has hampered its pathogenesis study. However, the mechanism of cross-species barrier remains elusive that no non-human cell model has been established to fill this knowledge gap. We observed that primary dermis fibroblasts (TSDF) isolated from the Chinese tree shrew (Tupaia belangeri chinensis), a small laboratory animal with close affinity to primates, were permissive to HCMV replication. In TSDF infected with GFP-expressing HCMV, the green fluorescence and cytopathic effect were observed and the expression of 3 kinetic genes and replication of viral genome were detected. The cell-free viruses produced in TSDF reached 103 pfu/mL at 96 hpi, which were 10-fold lower than in primary human foreskin fibroblasts. Our results demonstrated that TSDF supported low level of lytic replication of HCMV. The TSDF model provides a useful platform for the mechanism study of species barrier of HCMV.

Children’s motor competence (MC) has declined in the past decades, while sedentary behavior (SB) has increased. This study examined the association between MC and physical activity (PA) levels among primary schoolchildren. Demographics, body height and weight, MC (Athletic Skills Track) and PA levels (ActiGraph, GT3X+) were assessed among 595 children (291 boys, mean age = 9.2 years, SD = 1.1). MC was standardized into five categories: from very low to very high. PA levels were classified into sedentary behavior (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Mixed model analyses were conducted with PA levels as dependent variables and MC as the independent variable, while adjusting for age, gender, and BMI z-score on the individual level. Additional moderation analyses between covariates and MC and PA levels were also conducted. A negative association between MC and SB (β = -3.17) and a positive association between MC and MVPA (β =1.41) were found. The strength of both associations increased as children expressed lower or higher levels of MC. Increased age and being a girl were significant predictors of higher levels of SB and lower levels of MVPA. Non-overweight children spent significantly more minutes in MVPA compared with overweight children. No moderating effects of BMI, gender, and age were found on the association between MC and PA levels. MC is an important correlate of both SB and MVPA, particularly for children with very high or low MC. Developing and improving children’s MC may contribute to spending less time in SB and more time in MVPA, particularly for high-risk groups, i.e. children with low MC. Moreover, addressing MC development and PA promotion simultaneously might create positive feedback loops for both children’s MC and PA levels.

The current clinical model for genetic-testing is based on clinical-criteria/family-history(FH) and a pre-defined mutation probability threshold. It requires people to develop cancer before identifying unaffected individuals in the family to target prevention. This process is inefficient, resource intense and misses >50% of individuals/mutation carriers at risk. Population genetic-testing can overcome these limitations. It is technically feasible to test populations on a large scale; genetic-testing costs are falling and the acceptability/awareness is rising. MEDLINE/EMBASE/Pubmed/CINAHL/PsychINFO databases were searched using a free-text and MeSH terms; reference lists of publications retrieved screened; additionally web-based platforms, Google, and clinical-trial registries were searched. Quality of studies were evaluated using appropriate check-lists. A number of studies have evaluated population-based BRCA-testing in the Jewish-population. This has been found to be acceptable, feasible, clinically-effective, safe, associated with high satisfaction rates and extremely cost-effective. Data support change in guidelines to population-based BRCA-testing in the Jewish-population. Population panel-testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 gene mutations is the most cost-effective genetic-testing strategy in general-population women and can prevent thousands more breast/ovarian cancers than current clinical-criteria based approaches. A few ongoing studies are evaluating population-based genetic-testing for multiple cancer susceptibility genes in the general-population but more implementation studies are needed. A future population-testing programme could also target other chronic diseases.

Soil extracellular enzyme activity (EEAs) and enzymatic stoichiometry (ES) can provide a crucial indication of changes in soil ecosystem's nutrient availability and the microbial resource limitations. However, the changing characteristics of soil EEAs and ES at different stages of the native succession process and their key drivers are unclear. In order to investigate the soil EEAs, ES and driving factors of soil under vegetation at different succession stages, we adopted the "spatio-temporal substitution" method to collect the surface soil of bryophyte community, herbaceous community, shrub community and tree community in the new volcanic lava platform of Wudalianchi Volcanic Nature Reserve. We measured seven soil EEA, including carbon(C)-acquiring enzyme (β-1,4-glucosidase (BG)), N-acquiring enzymes (β-N-acetyl-glucosaminidase (NAG) and leucine aminopeptidase (LAP)) and phosphorus (P)-acquiring enzyme (acid phosphatase (AP)) activities. The length and angle of vectors defined by ratios of enzyme activities (BG/(NAG + LAP) vs. BG/AP) were used to indicate relative microbial investments in C- (length), and N- and P- (angle) acquiring enzymes. Our results showed that the contents of TC, TN, TP, MBC, DOC and NO3-N in shrub community soil were significantly higher than those in bryophyte, herb and tree communities, and increased by 441%, 246%, 137%, 5570%, 12% and 484%, respectively. The highest soil EEA of C-, N- and P-acquiring were found in shrub community, and the soil EEAs/MBC of C-, N- and P-acquiring were the highest in bryophyte community. Enzyme C:N, C:P and N:P ratios increased progressively in the order of bryophyte, herb and shrub community, but the enzyme C:N, C:P and N:P ratios of tree community were both far less than shrub community. Vector lengths increased progressively in the order of bryophyte (1.16), herb (1.27), tree (1.29) and shrub (1.40), and Vector angles decreased progressively in the order of bryophyte (49.15°), herb (45.65°), Tree (45.31°) and shurb (44.54°), suggested that as succession progresses, soil microbial nutrients transforms from P limitation (angle＞45°) to N limitation (angle＜45°). Redundancy analysis showed that TC, TN, EC and C:N were important drivers of variation in soil EEAs and ES in vegetation at different succession stages. Our findings highlight that the primary succession process cause nutrient limitation transformation. Soil ES might be a sensitive indicator mediated by soil microorganisms to the relative resource limitation at different stages of the primary succession process.

Scholars and policymakers see sustainability as depending on the interrelationships between the three pillars of the environment, society and the economy. However, it remains less clear how key stakeholders with a responsibility for educating the next generation perceive the concept of sustainability and act accordingly. In order to gain new insights, this research scrutinises participant perceptions on sustainability and climate change in two eco-schools in England for primary children (aged 5-11 years). Our case study involved individual interviews with classroom teachers and headteachers, group interviews with fourth- and fifth-year students (ages 10-12 years), and in-class observations. We also analysed data from student exercise books and photographs of school grounds to understand participants’ self-reported knowledge and perceptions of sustainability and climate change. Within a framework drawing on theories of science communication and transformative learning (a learning approach based on having challenging experiences), the results show that the integration of sustainability into the curriculum was limited and problematic. That is despite the fact that all students and teachers were aware of the environmental dimensions of sustainability, like climate change and the overuse of natural sources. These findings suggest that schools are no different to other institutional settings when it comes to dealing with the challenges of integrating sustainability into daily practice. We conclude that there is a need for in-service teacher education programmes to enable and motivate teachers to provide richer teaching-learning environments so as to enable effective learning in schools about sustainability and climate change.

The aim of the study was to compare the standard baseline imaging, with extended radiological staging. To assess our hypothesis, we performed a prospective, single-centre study which included 132 participants recruited between October 2015 and March 2020. Descriptive statistics, the Friedman and chi-squared tests were performed and p &lt; 0.05 was considered significant. Patients were grouped into two cohorts, CT scan cohort (n=87) and PET-CT cohort (n=43). In the first group the originally determined disease stage changed in 36.8 % of cases, in second group in 51.2 %. The consistency between assessment of axillary lymph nodes by imaging (cN) and the postoperative pathology report (pN) was evaluated. In most cases, clinical and pathological evaluation of involved nodes was consistent, for CT scan the result was χ2(1) = 18.98; p &lt; 0.001, for PET-CT the result was χ2(1) = 6.41; p = 0.03. Highly customized radiation therapy defined as dose boost within the involved lymph nodes, not covered by surgeon, was applied in nine patients.

Despite Vitamin B12's recognized importance for the nervous system, there's still a lack of research on the association between Vitamin B12 and sleep, especially in primary care settings. We assessed Vitamin B12 levels in adult primary health care users and investigated correlations with sleep quality, insomnia and sleepiness. In this cross-sectional study, 512 consecutive participants were included. Information regarding anthropometrics, socio-demographics, and medical history was obtained. The Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), and Pittsburg Sleep Quality Index (PSQI) were used to quantify excessive daytime sleepiness (EDS), insomnia symptoms, and sleep quality, respectively. Median Vitamin B12 was 342 (266, 446) pg/mL. After adjustments, Vitamin B12 levels&lt;342 pg/mL showed significant associations with insomnia symptoms [OR (95% CI) 2.434 (1.331–4.452), p=0.004], especially in elderly, non-obese and female participants, with EDS only in obese participants [OR (95% CI) 3.996, (1.006-15.876), p=0.039]. Nonetheless, there was no significant association between B12 levels and poor sleep quality (OR 1.416, 95% CI 0.678-2.958, p=0.354). In conclusion, our results show that lower Vitamin B12 was associated with insomnia symptoms and sleepiness in specific groups of participants. However, further research with objective measurements of sleep is crucial to assess the relationship between sleep and Vitamin B12.

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nasal nitric oxide measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF) based on the latest literature. CONCLUSION: nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis, acute and chronic rhinosinusitis.

Angiotensin II (Ang II) plays a role in several inflammatory diseases and is capable of inducing the release of inflammatory mediators in several cell types. The objective was to investigate the potential of Ang II to induce mRNA expression of inflammatory mediators by cultured primary human periodontal cells. A synergistic effect of a co-treatment with Ang II and IL1β on mRNA expression of inflammatory mediators was also explored. Primary cultures of human fibroblast-like cells isolated from gingival and periodontal ligament tissues from 3 subjects were established using explant techniques. Immunophenotyping of STRO-1, Ang II type 1 receptor (AT1R) and Ang II type 2 receptor (AT2R) was performed by flow cytometry analysis. Cell cultures were challenged with Ang II (1M) for 3, 6 and 24h with or without a co-treatment with IL1β (0.1ng/mL) for 24h. mRNA expression of inflammatory mediators was performed by real time quantitative polymerase chain reaction (RT-qPCR). We present, for the first time, a precise quantification for AT1R and AT2R on human gingival and periodontal fibroblast-like cell types; the percentage of positive immunostaining compared to the total population of cells varied from 3.35% through 5.29% for AT1R and 2.97% through 4.57% for AT2R. Ang II slightly upregulated mRNA expression of IL6 and CCL2/MCP1 in gingival cells and IL8 and PTGS2/COX2 in periodontal ligament cells. IL1β induced upregulation of IL8, IL6 CCL2/MCP1, PTGS2/COX2 and IL1β mRNA in both cell types. Co-treatment with Ang II and IL1β did not show a synergistic effect under these experimental conditions. Ang II shows a low potential to induce mRNA upregulation of inflammatory mediators in cultured primary human gingival and periodontal ligament cells, most likely due to the low percentage of Ang II receptors in such cells, and no synergistic effect with the co-treatment with IL1β.

Background: Disorders of immunity are poorly recognised in some rare multisystem genetic con-ditions. We aim to describe syndromic features and immunological defects in children with syn-dromic primary immunodeficiencies (sPIDs). Methods: This is a retrospective descriptive study of children aged 0-18 years with sPIDs under the care of the paediatric immunology service at the Bristol Royal Hospital for Children, United Kingdom from January 2006 to September 2021. Results: sPIDs were identified in 36 patients. Genetic diagnoses which are not commonly associ-ated with PIDs and not included in the International Union of Immunological Societies classifica-tion were present in 7/36 (19%): Trisomy 22, Arboleda-Tham syndrome, 2p16.3 deletion syn-drome, supernumerary ring chromosome 20 syndrome, Myhre syndrome, Noonan syndrome, trichothiodystrophy/Cockayne syndrome complex. Recurrent and/or severe infections were the commonest clinical features (n=33, 92%). Approximately half had combined immunodeficiency or antibody deficiency. Commonest extra-immunological manifestations include dysmorphism (72%), disorders of nervous (78%), musculoskeletal (69%), haematology/lymphatic (58%), and gastrointestinal, hepatic/pancreatic (58%) systems. Conclusions: Patients with sPIDs often have multiorgan involvement and some are non-immunologically mediated. There should be low threshold to clinically assess and investi-gate for disorders of immunity in any patients with syndromic features especially when they pre-sent with recurrent/severe/opportunistic infections, features of immune dysregulation, autoin-flammation or lymphoproliferation.

Angiotensin II (Ang II) plays a role in several inflammatory diseases and is capable of inducing the release of inflammatory mediators in several cell types. The objective was to investigate the potential of Ang II to induce mRNA expression of inflammatory mediators by cultured primary human periodontal cells. A synergistic effect of a co-treatment with Ang II and IL1β on mRNA expression of inflammatory mediators was also explored. Primary cultures of human fibroblast-like cells isolated from gingival and periodontal ligament tissues from 3 subjects were established using explant techniques. Immunophenotyping of STRO-1, AT1 and AT2 receptors was performed by flow cytometry analysis. Cell cultures were challenged with Ang II (1M) for 3, 6 and 24h with or without a co-treatment with IL1β (0.1ng/mL) for 24h. mRNA expression of inflammatory mediators was performed by real time quantitative polymerase chain reaction (RT-qPCR). We present, for the first time, a precise quantification for AT1 and AT2 receptors on human gingival and periodontal fibroblast-like cell types; the percentage of positive immunostaining compared to the total population of cells varied from 3.35% through 5.29% for AT1 and 2.97% through 4.57% for AT2. Ang II slightly upregulated mRNA expression of IL6 and CCL2/MCP1 in gingival cells and IL8 and PTGS2/COX2 in periodontal ligament cells. IL1β induced upregulation of IL8, IL6 CCL2/MCP1, PTGS2/COX2 and IL1β mRNA in both cell types. Co-treatment with Ang II and IL1β did not show a synergistic effect under these experimental conditions. Ang II shows a low potential to induce mRNA upregulation of inflammatory mediators in cultured primary human gingival and periodontal ligament cells, most likely due to the low percentage of Ang II receptors in such cells, and no synergistic effect with the co-treatment with IL1β.

The primary cilium plays critical roles in homeostasis and development of neurons. Recent studies demonstrate that cilia length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilia length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilia length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilia length increased significantly during neurons maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilia length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilia length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.

Background: A plethora of data supports HPV-based screening to be the preferred strategy for cervical cancer prevention. The shift to a more sensitive firstline test brings the need of effective triage up for discussion. Currently, most algorithms apply cytology as triage of HPV-DNA positive women. This study compared the performance of a 7-type HPV-mRNA test to cytology. Methods: From 2019-01-01, until 2021-12-31, cervical samples from 58,029 women were examined at the University Hospital of North Norway. 30.5% (17,684/58,029) fulfilled the criteria for HPV-DNA primary screening. All positive samples were triaged by cytology and followed-up according to national guidelines through 2022. Additionally, a 7-type HPV-mRNA test was applied. Study endpoint was histologically confirmed high grade lesion (CIN2+). Results: 5.6% (990/17,684) had positive HPV-DNA test, 97.2% (962/990) with valid HPV-mRNA results. 55.5% (534/962) had abnormal cytology (ASC-US+) and 35.1% (338/962) had positive HPV-mRNA test. 13.9% (134/962) had CIN2+. Sensitivity (CIN2+) of cytology versus the HPV-mRNA test was 76.1% (102/134)) versus 73.1% (98/134)), p=0.67. The specificity was 47.8% (396/828) versus 71.0% (588/624), p<0.001. PPV was 19.1% (102/534) and 29.0% (98/338), p<0.001 respectively. The number of colposcopies per CIN2+ detected by cytology and HPV-mRNA test was 5.2 and 3.1. Conclusion: The 7-type HPV mRNA test was significant more specific than cervical cytology in triage of HPV-DNA positive women. Using this biomarker as threshold for colposcopy may better balance the benefits and harms of screening.

Background: Occupational accidents contribute 46-65% of hepatitis B virus (HBV) infections among healthcare workers (HCWs). Vaccine against HBV infection offers protection of more than 90%. Despite availability of the vaccines in Tanzania, it’s uptake among HCWs in primary health facilities remains understudied. This study explored HBV vaccine uptake and associated factors among HCWs in rural and urban settings of north western Tanzania. Methodology: A cross-sectional analytical study was conducted between June and July in 2022 among HCW in Misungwi and Ilemela districts. Data were collected using a self-administered questionnaire and analyzed using IBM SPSS® version 25. Results: A total of 402 HCWs were recruited, their mean age was 34.9±7.77 years. Approximately half (54.7% (220/402) of HCWs had received at least one shot of HBV vaccine with only (18% (76/402) being fully vaccinated. Ilemela showed significantly higher uptake (χ2=23.64, df=1, p=0.00) of HBV vaccine as compared to their counterparts in Misungwi. Being male (aOR=2.38, 95% CI 1.28-4.45, p=0.006), working in urban (aOR=5.75, 95% CI 2.91-11.35, p=0.00) and employment duration of more than two years (aOR=3.58, 95%CI 1.19-10.74, p=0.023) were significantly associated with higher odds of HBV vaccination. Moreover, high perceived susceptibility to HBV infection (aOR=2.20, 95% CI1.02-4.75, p=0.044) and history of needle prick injuries (aOR=6.87, 95%CI 3.55-13.26, p=0.00) were also significantly associated with higher odds of HBV vaccination. Conclusion: There was low uptake of HBV vaccine among HCW in primary health facilities with a noteworthy difference between rural and urban settings.. Therefore, advocacy campaigns as well as resource mobilization towards promotion of HBV vaccination in primary health facilities are pivotal.

Primary and middle school teachers are a critical part of China’s foundational education; teacher turnover heavily affects the stable development of foundational education. In this study, interviews with 20 teachers found that relatively low income, high work pressure, unfair distribution, and difficulty in achieving promotion to higher professional titles are the main reasons for teacher turnover intention. This study investigates 485 primary and middle school teachers from Zhejiang and Jiangsu provinces. We found that primary and middle school teachers reported intense feelings of unfairness about their distribution of income. Their salary satisfaction was low, and the ratio of turnover intention was high. The main reasons for teachers’ high turnover intentions were low income, high pressure from work, unfair distribution, and the difficulty of achieving professional title promotion. To lower teachers’ turnover intentions, China should raise teachers’ income appropriately and increase the number of teachers with high professional titles. Schools should improve procedural, distributive, and interactive justice. Teachers should adjust their income references and perceptions of fairness. This situation can be effectively resolved only if all parties work hard to make positive changes.

Improving access to sexual health services is critical in light of rising sexually transmitted infections (STIs). We evaluated a Hub and Spoke model for improving access to sexual health services in three general practices in Victoria, Australia. The primary outcome was the impact on HIV and STI (chlamydia, gonorrhoea, syphilis) testing. Segmented linear regression analysis was conducted to examine the trends in the total HIV/STI tests before (from January 2019 to June 2020) and post-implementation (from July 2020 to July 2021). We evaluated the feasibility and acceptability of integrating this model into the general practices using semi-structured individual interviews. There was a statistically significant rise in testing for HIV and STIs in all general practices: post-implementation, there was an increase of an average of 11.2 chlamydia tests per month (p=0.026), 10.5 gonorrhoea tests per month (p=0.001), 4.3 syphilis tests per month (p=0.010), and 5.6 HIV tests per month (p=0.010). Participants reported increases in knowledge level and confidence in offering STI testing and managing more variety of sexual health cases. This study demonstrated the feasibility of implementing a hub and spoke model to enable GPs to deliver sexual health care with support from a sexual health specialist service.

Artificial Intelligence are creating a paradigm shift in health care, being phenotyping patients through clustering techniques one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data in Electronic Health Records (EHR). Subjects and methods: 2854 subjects more than 25 years old with diagnose of HF and LVEF measured by echocardiography were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. Performance of the algorithm developed were tested in heart failure patients from Primary Care. To select the most influencing variables, LASSO algorithm setting was used and to tackle the issue of one class exceed the other one by a large proportion we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. Results: Full XGBoost model obtained the maximized accuracy, a high negative predictive value and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence FE value. Applied in the EHR data set with a total 25594 patients with an ICD-code of HF and no regular follow-up in Cardiology clinics, 6170 (21.1%) were identified as those pertaining to the reduced EF group. Conclusion: The algorithm obtained is able to rescue a number of HF patients with reduced ejection fraction that can be take benefit for a protocol with strong recommendation to succeed. Furthermore, the methodology can be used for studies with data extracted from the Electronic Health Records.

Background and Objectives The socioeconomics working group of the European ME/CFS Research Network (EUROMENE) has conducted a review of the literature pertaining to GPs’ knowledge and understanding of ME/CFS. Materials and Methods A MEDLINE search was carried out. The papers identified were reviewed following the Synthesis Without Meta-analysis (SWiM) methodology, and were classified according to the focus of the enquiry (patients, GPs, database and medical record studies, evaluation of a training programme, and overview papers), and whether they were quantitative or qualitative in nature. Results 33 papers were identified in the MEDLINE search. The quantitative surveys of GPs demonstrated that a third to a half of all GPs did not accept ME/CFS as a genuine clinical entity and, even when they did, they lacked confidence in diagnosing or managing it. Patient surveys indicated that a similar proportion of patients was dissatisfied with the primary medical care they had received. These findings were consistent with the findings of the qualitative studies that were examined, and have changed little over several decades. Conclusions Lack of knowledge and understanding of ME/CFS among GPs is widespread, and the resultant diagnostic delays constitute a risk factor for severe and prolonged disease. Failure to diagnose ME/CFS renders problematic attempts to determine its prevalence, and hence its economic impact.

Globalization has had an impact on the education system in the UAE, where increased use of bilingual curriculum (Arabic-English) is held in high regard. Nevertheless, literacy among Emirati children and teenagers remains low. This study uses a 15-item, open-ended questionnaire completed by Emirati parents and an 8-item, open-ended questionnaire completed by Emirati primary school children from 8 to 11 years of age, and compares the translation of The Little prince into Modern Standard Arabic (MSA) and into the Emirati dialect. The results suggest that not only the Emirati dialect, but any Arabic dialect (in its respective Arab country) could be used in primary schools to motivate children to read in Arabic and bridge the gap between their spoken language (dialect) and formal written Arabic. Not only must an Arab child learn how to read, but also, they have to understand a very formal language system that they are not used to speaking at home, i.e., Modern Standard Arabic (MSA). Having books in their own dialects may make children more interested in reading, as they can understand them more easily.

Beta-glucan-stimulated mammalian macrophages show an increased responsiveness to secondary stimulation in a nonspecific manner. This phenomenon is known as trained innate immunity. Our study aimed to explore training of primary chicken monocytes. We hypothesized that primary chicken monocytes, similar to their mammalian counterparts, can be trained with β-glucan resulting in increased responses of these cells to a secondary stimulus. Primary blood monocytes of white leghorn chickens were primary stimulated with β-glucan microparticulates (M-βG), LPS, recombinant chicken interleukin-4 (IL-4) or combinations of these components for 48 h. On day 6, the primary stimulated cells were secondary stimulated with LPS. Nitric oxide (NO) production levels were measured as an indicator of pro-inflammatory activity. In addition, the cells were analysed by flow cytometry to characterize the population of trained cells and to investigate the expression of surface markers associated with activation. After the secondary LPS stimulation, surface expression of CSF1R and the activation markers CD40 and MHC-II was higher on macrophages that were trained with a combination of M-βG and IL-4 compared to unstimulated cells. This increased expression was paralleled by enhanced NO production. In conclusion, this study showed that trained innate immunity can be induced in primary chicken monocytes with β-glucan, which is in line with previous experiments in mammalian species. Innate immune training may have potential to improve health and vaccination strategies within the poultry sector.

Ovarian hypofunction or primary ovarian insufficiency (POI) is a common cause in the etiology of female infertility. It is a heterogeneous disorder, affecting approximately 1% of women before the age of 40. The characteristics of POI are menstrual disorders, including amenorrhea and delayed menstruation, accompanied by a raised gonadotrophin level and decreased estradiol level. In recent years, electrophysiology (EP) technology has been advancing rapidly in the diagnosis and treatments of numerous diseases. According to studies, bioelectrical stimulation (BES) therapy is an electrophysiology technology that plays significant roles in numerous diseases, including on the thin endometrium in patients with POI. In this review, the overall research progress of this electrophysiological technology has been discussed in relation to the advancement of primary ovarian insufficiency.

In Taiwan, colorectal cancer is ranked second and third in terms of mortality and cancer incidence, respectively. In addition, medical expenditures related to colorectal cancer are considered to be the third highest. While advances in treatment strategies have provided cancer patients with longer survival, potentially harmful second primary cancers can occur. Therefore, second primary colorectal cancer analysis is an important issue with regard to clinical management. In this study, a novel predictive scheme was developed for predicting the risk factors associated with second colorectal cancer in patients with colorectal cancer by integrating five data mining classification techniques, including support vector machine, random forest, multivariate adaptive regression splines, extreme learning machine, and extreme gradient boosting. In total, 4,287 patients in the datasets provided by three hospital tumor registries were used. Our empirical results revealed that this proposed predictive scheme provided promising classification results and the identification of important risk factors for predicting second colorectal cancer based on accuracy, sensitivity, specificity, and area under the curve metrics. Collectively, our clinical findings suggested that the most important risk factors were the combined stage, age at diagnosis, BMI, surgical margins of the primary site, tumor size, sex, regional lymph nodes positive, grade/differentiation, primary site, and drinking behavior. Accordingly, these risk factors should be monitored for the early detection of second primary tumors in order to improve treatment and intervention strategies.

The aim of this study was to determine the impact of information technology in management of risks in the capital market-listed company is in Tehran Stock Exchange. The purpose of the present study is an applied descriptive approach. The target population for the survey, companies that from 2009 to the first half of 2015 have been a member of the Tehran Stock Exchange, through Cochranʼs sample size of 140 companies, respectively. We used cluster sampling method. In order to collect data from two questionnaires: risk management questionnaire Foakeh (2013) has 38 items and a standard questionnaire Chanvyas (2006) has 40 items, the whole five-item Likert scale questionnaire is above has been used. Data gathered through the questionnaire, sign the application was 21spss. For inferential analysis of the variables and to analyze the data from different statistical tests and regression was used Kolmogorov-Smirnov test. The results showed that information technology on risk management and its dimensions (primary market risk, market risk and the risk of secondary non-financial) impact.

In order to explore the grassland ecosystem productivity and landscape ecological patterns of main pastoral grasslands in China, it provides a theoretical basis for the efficient implementation of ecological engineering and rational management of grassland resources in the region. This study analyzed the changes in grassland area, landscape index (LSI), and net primary productivity (NPP) in seven major pastoral areas in China in 1985, 1995, 2005, and 2015. Results showed that (1) the sizes of the grassland study area in 1985, 1995, 2005, and 2015 were 248.34, 243.93, 245.80, and 244.660 km2 respectively. (2) The dominance of grassland in the landscape pattern increased from 2005 to 2015 as compared with that in 1985–1995 and 1995–2005. The degrees of spatial heterogeneity were reduced. (3) The grassland NPP showed spatial and temporal differences. The average NPP of grassland increased by 21.30%, 16.47%, and 36.17% during 1985–1995, 2005–2015, and 1985–2015, respectively. From 1995 to 2005, the average NPP decreased by 5.05 gC/m2, which is equivalent to -3.61% of the average NPP in 1995. The total amount of grassland NPP in the study area was the greatest in 2015, showing increments of 36.37% and 16.61% compared with those in 1985 and 2005, respectively.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in 70% of Puerto Rican patients, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the framework for PCD evaluation and diagnosis, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.

As breast cancer continues to take a devasting public health toll, most primary prevention approaches are targeted at individual actions. We have proposed, instead, developing systemic, population approaches to preventing the disease. We used a combined qualitative-quantitative methodology, Group Concept Mapping (GCM), to identify Importance and Feasibility ratings of systemic interventions across a wide spectrum of approaches and stakeholders. Participants (n=351) from across the state of California sorted 84 potential interventions into topical piles, and then rated each intervention on perceived Importance and Feasibility. Multidimensional scaling and cluster analysis identified eleven clusters or themes of interventions. Participants rated interventions on Importance and Feasibility differently depending on the region of the state in which they lived. The results of this study underscore the importance of sharing health information with and seeking public health solutions from community partners in general and from beyond the urban areas usually studied.

The healthcare domain is increasingly adopting IoT and Electronic Health Record (EHR) systems, generating vast volumes of healthcare data. This shift is driven by the growing need of delivering the right information to the right individuals, at the right time. The latter underscores the importance of adopting a comprehensive strategy for efficiently collecting, utilizing, and analyzing health-related data to not only enhance overall healthcare management but also for the provision of timely and personalized prevention strategies. The latter is of highest importance especially in scenarios where lack of effective treatments or poor survival rates (such in pancreatic cancer) renders typical healthcare strategies ineffective. In this article, we introduce an innovative and integrated platform that is specifically designed and developed for accessing, processing, and analyzing data in challenging healthcare scenarios, such as dealing with pancreatic cancer. This platform, called iHelp, combines multidisciplinary technologies and provides healthcare professionals reliable risk modelling, analysis, and prediction techniques so that individuals (at risk of developing pancreatic cancer) can be provided with timely, reliable, and personalized prevention and intervention measures. A key innovation in the iHelp platform is the standardized data management approach called Holistic Health Records (HHRs) that facilitate the capturing of all health determinants in a standardized and well-structured way for processing towards the provision of health risk detection and personalized healthcare decision support. In the development of iHelp platform, the HHRs are evaluated through different real-world healthcare datasets, including datasets coming from hospital systems, data from wearables, questionnaires, and mobile applications.

The WHO European Region defined the role of a new central professional for primary care, the Family and Community Nurse (FCN). The introduction of FCN in the framework of health policies highlight a key role of nurses in addressing the families’ and communities’ needs. A scoping review was conducted in order to identify and describe the available tools which has been adopted for the assessment of the community health needs by FNC. A comprehensive literature review on Embase, Cochrane Library, PubMed, CINAHL, Scopus and PsycInfo databases was conducted including all studies up to May 2021. A total of 1563 studies were identified and 36 of them were included. The literature review had made possible to identify studies employing twelve different community assessment's tools or modalities. Referring the WHO framework proposed in 2001 some common themes have been identified with an uneven distribution, as profiling the population, deciding on priorities for action and public healthcare programmes, implementing the planned activities, evaluation of health outcomes, multidisciplinary activity, flexibility and involving the community. To the best of our knowledge, this work is the first attempt to provide an overview of community assessment tools, keeping the guidance provided by the WHO as a reference.

Systemic hypertension has been recognized as a modifiable traditional cardiovascular risk factor and influenced by many factors such as eating habits, physical activity, diabetes and obesity. The objective of this study was to identify cardiometabolic factors that predict changes in blood pressure induced by a one-year lifestyle intervention in primary care settings involving a collaboration between family physicians, dietitians, and exercise specialists. Patients with metabolic syndrome diagnosis were recruited by family physicians participating in primary care lifestyle intervention among several family care clinics across Canada. Participants for whom all cardiometabolic data at the beginning (T0) and the end (T12) of the intervention were available were included in the present analysis (n=101). Patients visited the dietitian and the exercise specialist weekly for the first three months and monthly for the last nine months. Diet quality, exercise capacity, anthropometric indicators, and cardiometabolic variables were evaluated at T0 and at T12. The intervention induced a significant decrease in waist circumference (WC), systolic (SBP) and diastolic (DBP) blood pressure, and plasma triglycerides and an increase in cardiorespiratory fitness (estimated VO2max). Body weight (p<0.001), body mass index (BMI) (p<0.001), and plasma glucose (p=0.006) reduction and VO2max increase (p=0.048) were all related to changes in SBP. WC was the only variable for which changes were significantly correlated with those in both SBP (p<0.0001) and DBP (p=0.0004). Variations in DBP were not associated with changes in other cardiometabolic variables to a statistically significant extent. Twelve participants were identified as adverse responders in both SBP and DBP and displayed less favorable changes in WC. The beneficial effects of a lifestyle intervention on blood pressure were significantly associated with cardiometabolic variables, especially WC. These findings suggest that a structured lifestyle intervention in primary care can help improve cardiometabolic risk factors in patients with metabolic syndrome.

The primary distribution systems are comprised of power lines delivering power to utility feeders from substations. The inspection and maintenance of damaged and broken power system insulators are of paramount importance for continuous power supply and public safety. hence, to identify any faults and defects in advance a periodic inspection of power line insulators and other components be ensured beforehand. To automate the process and reduce operational cost and risk Unmanned Aerial Vehicles (UAVs) are being extensively utilized. As they present a safer and efficient way to examine the power system insulators and their components without closing the power distribution system ensuring continuous supply to the end-users. To achieve these objectives in this work a novel dataset is designed by capturing real images using UAVs and manually generated images collected to overcome the data insufficiency problem. Deep Laplacian pyramids based super-resolution network is implemented to reconstruct high-resolution training images. To improve the visibility of low light images a low light image enhancement technique is used for the robust exposure correction of the training images. Using computer vision-based object detection techniques to identify faults and classify them according to classes they belong. A different fine-tuning strategy is implemented for fine-tuning the object detection model to increase detection accuracy for the specific faulty insulators. To improve the faults detection several flight path strategies are proposed for efficient inspection. Such strategies overcome the shuttering effect of insulators along with providing a less complex, time, and energy-efficient approach for capturing video stream of the power system components. Performance of different object detection models is presented for selecting the suitable one for fine-tuning on the specific faulty insulator dataset. Our proposed approach gives a less complex and more efficient flight strategy along with better results. For defect detection, our proposed method achieved an F1-score of 0.81 and 0.77 on two different datasets. Our approach is based on real aerial inspection of in-service porcelain insulators by extensive evaluation of several video sequences showing robust faults recognition and diagnostic capabilities. Our approach is demonstrated on data acquired by a drone in Swat Pakistan.

HybridAC/DC microgrids(HMG) are emerging as an attracting method for integrating the AC/DC distributed energy resources(DERs) with the features of high-performance and low-cost. In the isolated hybrid AC/DC microgrid (IHMG), the key problem is how to balance the power variation and regulate the voltage and frequency. Various energy storage systems (ESS)and interlinking converter (IC) technologies are viable for this application. The present study proposes a novel unified power flow model to evaluate and compare the abilities of the ESS with different connection topologies and ICs with different control approaches to maintain the voltage and frequency stability of the IHMG. In order to investigate the performance of the proposed scheme, five operation modes of the IHMG are defined and explained. The classification is based on the connection topologies and control modes of the ESS/IC in the IHMG. Then, a set of generic PF equations are derived. Moreover, three binary matrices are applied in the construction of the unified power equations. These matrices are used for describing the running state of the IHMG. Finally, in order to verify the proposed scheme, it is applied to several case studies of the IHMG. The operation characteristics of multi-DC subgrids IHMG in different modes, particularly when an external disturbance occurs, are investigated.

The workforce crisis of primary care is reflected in the increasing number of general medical practices (GMP) with vacant general practitioner (GP) position, and the GPs’ ageing. Our study aimed to describe the association between this crisis and premature mortality. Age-sex-standardized mortality for 18-64 years old adults were calculated for all Hungarian GMPs annually in the period from 2006 to 2014. The relationship of premature mortality with GPs’ age and vacant GP position were evaluated by standardized linear regression controlled for list size, urbanization, geographical location, clients’ education, and type of the GMP. The clients’ education was the strongest protective factor (beta=-0175; p<0.001), followed by urban residence (beta=-0.149; p<0.001), and the bigger list size (beta1601-2000=-0.054; p<0.001; beta2001-X=-0.096; p<0.001). The geographical localization influenced significantly also the risk. Although, GMP with a GP aged older than 65 years (beta=0; p=0.995) did not affected the risk, GP vacancy was associated with higher risk (beta=0.010; p=0.033), but the corresponding number of attributable cases was 23.54 for 9 years. The vacant GP position is associated with significant but hardly detectable increased risk of premature mortality without considerable public health importance. Nevertheless, employment of GPs aged more than 65 does not impose premature mortality risk elevation.

The aim of this study was to examine oxidative stress and low level of alpha-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, alpha-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-LC-MS/MS from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Further, concentrations of anti-A1AT^50-63 IgG and anti-A1AT^50-63 HNE IgA were significantly lower in pSS patients than HCs. Our study suggests that elevated HNE-protein adduct, oxidative stress, level [odds ratio (OR) 4.877, p = 0.003], lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT^50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.

Background. The molecular mechanisms underlying de novo metastasis of luminal breast cancer (dnMBC) remain largely unknown. Materials & Methods. Newly diagnosed dnMBC patients (grade 2/3, ER+, PR+/-, HER2-), with available core needle biopsy (CNB), collected from the primary tumor, were selected from our clinical-pathological database. Tumors from dnMBC patients were 1:1 pairwise matched (n=32) to tumors from newly diagnosed patients who had no distant metastases at baseline (eBC group). RNA was extracted from 5 x 10µm sections of FFPE CNBs. RNA sequencing was performed using the Illumina platform. Differentially expressed genes (DEG)s were assessed using EdgeR, deconvolution was performed using CIBERSORTx to assess immune cell fractions. Paired Wilcoxon test was used to compare dnMBC and eBC groups, and corrected for false discovery rate (FDR). Results. Many regulatory DEGs were significantly downregulated in dnMBC compared to eBC. Also, immune-related and hypoxia-related signatures were significantly upregulated. Paired Wilcoxon analysis showed that CCL17 and neutrophils fraction were significantly upregulated, whereas the memory B-cell fraction was significantly downregulated in the dnMBC group. Conclusion. Primary luminal tumors of dnMBC patients display significant transcriptomic and immunological differences compared to comparable tumors from eBC patients.

Nutrient release from marine sediments in Osaka Bay has a significant impact on nutrient concentrations in seawater. A tsunami induced by the Nankai Trough earthquake may disturb marine sediments in the inner part of Osaka Bay. An incubation experiment to estimate the release rates of NH4-N and PO4-P was conducted to understand the present conditions and to quantify the changes caused by tsunamis. Two types of cores were created: a "control core" representing the current sediment, and a "redeposition core" representing the redeposition after the tsunami. The release rates have been decreasing since the year 2000 and have remained low. The experimental results suggest that the release rate after exposure to an aerobic environment by a tsunami may decrease to approximately 70% for NH4-N and 60% for PO4-P of the current level. In the past, the release rates were values experienced in the inner part of Osaka Bay. However, the reduction in the release rate by tsunamis may be more limiting for primary production under the current situation where the contribution of release for nutrients in seawater is significant.

Riverine particulates dominate the transport of vital nutrients like Si, Fe or P to the ocean mar-gins, where they may increase primary production by acting as slow release fertilizer. Further-more, the supply of particulate surface area to the ocean is considered to be a major control or-ganic carbon burial. Taken together, these observations suggest a close link between the supply of riverine particulate material and the organic carbon cycle. To explore this link, we conducted microcosm experiments to measure the growth of the marine diatom Thalassiosira weissflogii in the presence and absence of different types and concentrations of riverine particulate material. Results demonstrate a strong positive effect of riverine particulate material on diatom growth with increased total diatom concentrations and slowed post-exponential death rates with in-creasing particulate concentration. Moreover, SEM and optical microscope investigations con-firm that riverine particulates facilitates organic carbon burial through their role in the aggrega-tion and sedimentation of phytoplankton. The supply of riverine particulate material has been shown to be markedly climate sensitive with their fluxes increasing dramatically with increas-ing global temperature and runoff. This pronounced climate sensitivity implies that riverine particulates contribute substantially in regulating atmospheric CO2 concentrations through their role in the organic carbon cycle.

Novel mechanism of ccRCC progression is essential, including PBRM1, BAP1, and SETD2 in histone-modifying and chromatin remodeling genes. The study aimed to investigate VHL, PD-1, PD-L1, PD-L2. BAP1, PBRM1, SETD2 expression in ccRCC primary cancers and metastatic tissues associated with the cancer dissemination. A total of 62 patients with RCC were enrolled in the study. Investigation of mRNA level of VHL, PD-1, PD-L1, PD-L2. PCR in real-time performed BAP1, PBRM1, SETD2 with the previous RNA isolation. Western Blotting analysis was used for detecting the p-VHL protein content in tissues. The VHL expression and p-VHL content determined the aggressive cancer behavior and elevated in disseminated tumors. The cancer dissemination was accompanied by an increase in both mRNA and VHL content. The PD-L2 prevalence in metastatic cancers is crucial in tumor progression. ccRCC progression in VHL overexpression is associated with the decrease in BAP1 gene expression. It is revealed the heterogeneity in molecular markers in primary tumors and metastases. The low mRNA level of BAP1, PBRM1, SETD2, PD-1, PD-L1, PD-L2 in metastases compared with primary tumors were found. We show a novel mechanism for VHL tumor progression and present a new instrument and factor targeting tumor-related pathologies with p-VHL/HIF altered function.

Background: During the COVID-19 pandemic some family physicians were overburdened and experienced difficulties reaching vulnerable patients and meeting the increased need for psycho-social support. This randomized controlled trial (RCT) tested whether a primary healthcare (PHC) based community health worker (CHW) intervention could tackle psychosocial suffering due to physical distancing measures in patients with limited social networks. Methods: CHWs provided 8 weeks of tailored psychosocial support to the intervention group. Control group patients received ‘care as usual’. The impact on feelings of emotional support, social isolation, social participation, anxiety and fear of COVID-19 were measured longitudinally using a face-to-face survey to determine their mean change from baseline. Self-rated change in psychosocial health at 8 weeks was determined. Results: We failed to find a significant effect of the intervention on the prespecified psychosocial health measures. However, the intervention did lead to significant improvement in self-rated change in psychosocial health. Conclusions: This study confirms partially the existing evidence on the effectiveness of CHW in-terventions as a strategy to address mental health in PHC in a COVID context. Further research is needed to elaborate the implementation of CHWs in PHC to reach vulnerable populations during and after health crises.

Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.

In zebrafish inner ear, hair cell orientation in anterior and posterior maculae of the embryonic otic vesicle is different (about 30–40 degrees): this is rather unusual in planar polarity mechanism of action, instead suggests that kinocilia may be rotationally polarized. In mice node, the innermost monociliated cells generate a left-ward fluid flow sensed by the immotile primary cilia of Left peri-nodal cells: the Nodal signaling pathway is then expressed asymmetrically, in the Left lateral plate mesoderm, breaking symmetry in visceral organs (situs solitus); however, Right peri-nodal cells also, if artificially excited by a right-ward flow, break symmetry and activate the Nodal cascade, though inverting visceral organ asymmetry (situs inversus); surprisingly, peri-nodal cells prove to be adept at distinguishing flow directionality. Recently, in the Kupffer vesicle (the zebrafish laterality organ), chiral primary cilia orientation has been described: primary cilia, in the left and right side, are symmetrically oriented, showing a mirror average divergence of about 15–20 degrees from the midline. This finding, taken together with the mirror behavior of mouse perinodal cells and zebrafish hair cells, champions the idea of primary cilia enantiomerism.

To evaluate the 2-year efficacy and safety of ab interno trabeculectomy with the Trabectome in Chinese primary open-angle glaucoma (POAG) patients. This was a multicenter, retrospective study and included POAG patients with or without visually-significant cataracts. The primary outcome was intraocular pressure (IOP) reduction. Secondary outcomes included reduction of glaucoma medications, surgical complications, and success at 2-years. Success was defined as: 1) IOP < 21 mmHg and at least 20% IOP reduction from baseline after 3 months at any two consecutive visits, and 2) no additional glaucoma surgery required. A total of 42 patients were enrolled; thirteen had a history of failed glaucoma surgery. Twelve patients underwent Trabectome surgery combined with phacoemulsification while the remainder underwent Trabectome surgery alone. Overall, the mean preoperative IOP was 21.4±1.23 mmHg. The Trabectome lowered IOP to 18.5± 0.94 mmHg at 2 years (P<0.05). The number of glaucoma medications also decreased from a baseline of 2.0±0.9 to 1.2± 0.21 at 2 years (P=0.04). The overall success was 78%, with patients undergoing combined surgery having a higher success than those with Trabectome surgery alone (100% vs. 76%). No major complications were seen. The Trabectome appears to be an efficient and safe procedure in Chinese POAG patients in the long-term.

Primary care pediatricians encounter a wide range of complex conditions in their daily clinical practice. It is not uncommon for their patients to get exposed to medical errors. Diagnostic errors, defined as missed, delayed, or wrong diagnosis, are of great importance as they may cause significant harm to the pediatric patient with severe disease. These errors often occur when the symptoms and signs of a disease are atypical or missing. Data on the most frequent misdiagnosed situations in pediatrics is scarce. One of these groups of conditions is that regarding cardiac diseases. The pediatric cardiology field has met rapid development over the past few decades. Primary care providers play a key role in diagnosis, management, and referral of children with heart disease, both congenital and acquired, because many common cardiac complaints are first addressed in the primary care setting. The scope of this review is to investigate the cardiac entities that are often missed by the general pediatricians. In particular, it aims to spot the most common of them, to describe their clinical presentation, their diagnostic options, red flags, and tips, and to provide the ways to avoid erroneous, delayed, or missed diagnosis.

More than 13.5 billion COVID-19 vaccine doses have so far been delivered between 2021 and 2023 through a mix of delivery platforms, with mass vaccination campaigns being the main approach. In 2022, with the most likely scenario of continued circulation of SARS-CoV-2 and the need for periodic booster doses, there was a need for countries to plan for more sustainable approaches to provide COVID-19 vaccination. In this context of uncertainty, a global tool for integrating COVID-19 vaccines into immunization programmes and primary health care was published jointly by WHO and UNICEF to respond to country needs. The guidance leveraged existing health system frameworks, proposed four steps for the COVID-19 integration journey, and identified investment areas. The development process maximized robust global stakeholder and country engagement, and the timeframe was aligned with donor funding windows to support the integration of COVID-19 vaccination. The rapid dissemination of guidance allowed its use by countries to ascertain their readiness for integrating COVID-19 vaccination and inform the development of national plans and funding applications. While progress has been made in specific areas (e.g., optimizing cold chain and logistics leveraging COVID-19 vaccination), in the context of decreasing demand for COVID-19 vaccines, reaching adult COVID-19 vaccine high-priority-use groups and engaging and coordinating with other health programmes (beyond immunization) remains a challenge. We share the learning that despite the uncertainties of a pandemic, guidance documents can be developed and used within a short timeframe. Working in partnership with stakeholders beyond immunization towards a common objective is powerful and can allow progress to be made on integrating health services and preparing better for future pandemics.

Consuming fish sustainably means consuming less and better, considering environmental, social, and economic impacts. This demands more knowledge to make informed decisions. In this study, the main goal was to understand how sustainability education can be used as a tool to raise awareness and promote new habits regarding the sustainable consumption of fish in 4th-grade students at primary school. During the COVID-19 pandemic, face-to-face and online learning methodologies were used in two different groups of students to understand whether the teaching method impacted learning. A sequential explanatory mixed methodology was applied, with a pre-test/post-test design, combined with focus group sessions. Between the pre and post-tests three learning modules were performed. The results showed that the students were unaware of many aspects related to fish sustainable consumption, but the developed activities significantly increased their knowledge of the subject and impacted students to change their consumption behaviours. It was also found that the construction of knowledge by the students after the activities was achieved either by face-to-face or online learning. Interviews from focus group sessions showed that students got to know new fish species, learned about the concept of minimum landing size and closure season and that fish are labelled like other types of food.

This paper utilizes a life cycle assessment to evaluate the energy resources and environmental impacts of three heating systems. In the first step, life cycle assessments (LCAs) are prepared for the renewable, conventional, and combined systems. The system boundary of the LCA method is "cradle to gate," which means it includes the entire life cycle of a product or process. This includes energy supply, transport, energy generation, and operational energy use. The system scenarios were compared based on ecological and energy loads in the second step. Primary energy, resources, emissions, and environmental potentials are calculated for the system scenarios using the life cycle assessment methods CML 2016 and ReCiPe 2016. Finally, models for environmental reliability and complex decision-support tools have been developed. This work addresses two main questions: how to characterize the environmental and energy impacts of the systems under study, and what is the optimal scenario for the system? The research results show that the gas boiler system has a greater environmental impact. The most significant differences between the systems relate to the degrada-tion of abiotic fossil fuels when using a gas boiler and the process of acidification when using an electric heat pump. The results can be used to develop sustainable heating systems with reduced environmental impacts and enhanced energy efficiency.

The term “conservation,” as it relates to biodiversity in a Western context, has had a contested history and as conservation science and societal values have evolved, consensus over its precise meaning has remained elusive. The broad scope of contemporary definitions hampers effective communication during a period of environmental crisis and is troublesome for any derivative concept which aims to quantify the efforts of the conservation community. This presents an avoidable hindrance to the systematic planning of the conservation field. To remedy this situation, we provide an outcome separation framework that is based on the expected degree of separation of the action’s proximate outcome from its intended, ultimate outcome for native habitat and/or native or ecological replacement species. Framing a definition of conservation through this lens of outcome separation allows for conservation-related actions to be clearly categorized into one of three discrete tiers (primary, secondary, and tertiary) based on both the proximate outcome’s degree of separation from its intended, ultimate outcome and the conservation status of native habitat and/or native or ecological replacement species. A distillation of this tiered framework also provides a fully inclusive, succinct definition of biodiversity conservation that is resilient to future conceptual evolutions of the field.

This study, which was supported by a quantitative research paradigm with two experiment and two control groups of 4x4 quasi-experimental design, aimed to find out the impact of a sustainable progressive STEAM (SP-STEAM Model) application model on 5th grade primary school students critical thinking dispositions and mathematic achievements in Northern Cyprus. The treatment model was applied to experimental groups for 14 weeks of time. Split-plot multiple group analysis of variance (Split-plot ANOVA) statistical technique was used to calculate between and within group significances regarding exogenous variable. SPSS24 software package was used for the analysis. Pre-test and post-test results derived from experiment and control groups revealed significant effect of SP-STEAM Model on 5th grade primary school students’ critical thinking dispositions as measured with CCTDI and mathematic achievements as measured with a dedicated ex-am. The results were discussed in detail under the light of related literature and suggestions for further studies were proposed.

Public Health Officers' (PHO) experiences in reaction to the COVID-19 pandemic can be based on whether the PHO is passive or active. Therefore, the study’s objectives are to identify the types of experiences and analyse the predictors of proactive practical experiences in solving COVID-19 among PHOs in the upper southern region of Thailand. Methods: An explanatory mixed-methods approach was used to collect data, through questionnaires and online in-depth interviews. The study was conducted from August 4, 2020, to August 3, 2021. Results: The results included 60 PHOs from 60 PCUs in 6 provinces, with 41 (68.3%) females and an average age of 35.57 years (SD = 11.61). The PHOs’ knowledge, understanding, and participation experience aspects were mostly proactive rather than passive. Factors that significantly predicted proactive practical experiences included sex (ORadj = 1.52, 95% CI = 1.04–2.21), age (ORadj = 1.69, 95% CI = 1.16-2.48), married status (ORadj = 1.69, 95% CI = 1.16-2.48), education level (ORadj = 1.50, 95% CI = 1.02–2.20), and position for work (ORadj = 1.69, 95% CI = 1.16-2.48). Conclusions: PHOs’ knowledge, understanding, opinion, and participation experiences were significant predictors of practical experience. Primary health care systems should promote proactive experiences in all four aspects to increase proactive practical experiences.

Several noninvasive vascular biomarkers have been suggested for improving the risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment (L-LT) in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and free of diabetes and L-LT. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score =0 (OR 0.67; 95%CI 0.48-0.92, P=0.01), CAC score >100 (1.59; 1.08-2.39, P=0.01) and with high femoral IMT (1.89; 1.19-3.06, P<0.01), but not with other biomarkers. Our data confirm that in the presence of CAC score =0 in individuals at intermediate risk, L-LT can be avoided, while it should be used in those with CAC score >100. Femoral artery IMT could represent a useful biomarker for decision regarding L-LT, however the reference values according to sex and age should be established in a large healthy population

Older adults in low-and middle-income countries experience a disproportionate burden of non-communicable diseases (NCDs). Unintentional injuries are among the major NCDs, and falls are the second leading cause of these injuries and deaths worldwide, including in Thailand. We aimed to culturally adapt the CDC’s Stopping Elderly Accidents, Deaths, and Injuries (STEADI) for Thai older adults and explore the feasibility, appropriateness, and acceptability of using STEADI in primary care via trained community health workers (CHWs) and care managers (CMs). STEADI takes a coordinated care approach that consists of three steps: screening, assessing, and intervening. In Step a, CHWs screened fall risk in 20 community-dwelling older adults using three key questions and found that all of them had fall risk, then CHWs screened with a Stay Independent questionnaire (range 0-14) and found that 100% have high fall risk (total scores 9.7± 2.4). In Step b, CMs assessed balance, vision, footwear, postural hypotension, medications, and CHWs assessed home hazards. They found that 50% had poor balance, 70% took 4+ medications,75% fell on the walkway, and 70% had no bathroom modifications. In Step c, individual participants received fall prevention interventions to mitigate their specific fall risk factors. CHWs and CMs indicated high acceptability (19.20±.1.31 of 20 total), appropriateness (18.80± 1.79 of 20 total), and feasibility (18.60±1.67 of 20 total) of the Thai-STEADI intervention. Our study showed that the community-based multifactorial Thai-STEADI delivered by CHWs and CMs is feasible and acceptable to prevent falls in older adults with limited access to health care.

COVID-19 pandemic-related pressures on primary care may have driven inappropriate continuation of antibiotic prescriptions. Yet prescribing modality (repeat/non-repeat) has not previously been investigated in a pandemic context. Using the OpenSAFELY-TPP analytics platform, we analysed repeat/non-repeat prescribing frequency in monthly patient cohorts between Jan 2020–2022. In-depth analysis was conducted on Jan 2020 (“pre-pandemic”) and Jan 2021 (“pandemic”) cohorts. Per-patient prescribing and clinical conditions were determined by searching primary care record data using clinical code lists. Repeat prescribing was defined as >=3 prescriptions in a 6 month lookback period. Associations between demographics (e.g. age, sex, geography) and repeat/non-repeat prescribing were explored using unadjusted risk ratios. Antibiotic prescribing declined from May 2020; non-repeat prescribing declined more strongly than repeat prescribing (maximum declines -26% vs -11%, respectively). In the pandemic cohort, older patients were at higher risk of prescribing (especially repeat prescribing). The most common clinical conditions for repeat prescribing were COPD comorbidity and urinary tract infection. Comorbidities were more common among repeat vs non-repeat prescribed patients. In the pandemic cohort, vs pre-pandemic, repeat and non-repeat prescribing for comorbidities generally declined less compared with shorter-term conditions (infections, including COPD exacerbation/lower respiratory tract infection). Our findings inform ongoing development of stewardship interventions in England..

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

This article propose a didactic, through games, tool based on information and communication technologies, in order to eliminate possible communication barriers and to promote the inclusion of students with hearing impairment in Physical Education classes. To this end, a dossier of traditional games has been developed. These are structured in turn into objectives, materials, organisation, graphic description and a QR code for each game. These codes are linked to different videos hosted on the YouTube platform, in which the explanation of the games, mentioned above, can be visualised graphically using sign language. The whole creative process is described in the article, as well as possible pedagogical applications of the use of the tools created for this purpose in other educational contexts.

The emotional dimension in education has become increasingly important in recent decades. Enhancing the emotional dimension of prospective teachers in science subjects is higher education stuff responsibility. The implementation of active methodologies could modify the traditional student-teacher roles that are encouraged by the educational policies implemented in the Bologna Process. The principal aim of this work is to describe a Project Based Learning methodology and to introduce it as potential resource for the emotional and cognitive improvement of 19 prospective primary teachers enrolled in a scientific subject. This is a qualitative study with a transversal sustainability approach in the context of a research line focused on Higher Education for Sustainable Development. A questionnaire was designed and filled by the students at two different times, before and after implementation of the activity. The initial feedback from students was surprisingly enthusiastic by the fact that they were working with rockets, despite of this is not a common emotion in the science field. The results show the emotional improvement of prospective teachers after the implementation. It is concluded that a correct science education is necessary during the training of teachers taking into account their emotional dimension and the social repercussion due to the future transmission.

Background: Australia’s healthcare system is complex and fragmented which can create challenges in healthcare, particularly in rural and remote areas. Aboriginal people experience inequalities in healthcare treatment and outcomes. This study aimed to investigate barriers and enablers to accessing healthcare services for Aboriginal people living in rural and remote Australia. Methods: Semi-structured interviews were conducted with healthcare delivery staff and stakeholders recruited through snowball sampling. The communities were selected for their high proportion of Aboriginal people and geographical representation (coastal, rural, and border). Thematic analysis identified barriers and enablers. Results: Thirty-one interviews were conducted (n =5 coastal, n=13 remote, and n=13 border) and six themes identified: 1) Improved coordination of healthcare services; 2) Better communication between services and patients; 3) Trust in services and cultural safety; 4) Importance of prioritizing health services by Aboriginal people; 5) Importance of reliable, affordable and sustainable services; 6) Distance and transport availability. These themes were often present as both barriers and enablers to healthcare access for Aboriginal people. They were also present across the healthcare system and within all three communities. Conclusions: This study describes a pathway to better healthcare outcomes for Aboriginal Australians by providing insights into ways to improve access.

The primary cilium plays a pivotal role during embryonic development of vertebrates. It acts as a somatic signaling hub for specific pathways, such as sonic hedgehog signaling. In humans, mutations in genes that cause dysregulation of ciliogenesis or ciliary function lead to severe developmental disorders called ciliopathies. Beyond its obvious role in early morphogenesis, growing evidence points towards an essential function of the primary cilium in neural circuit formation in the central nervous system. However, very little is known about a potential role in the formation of the peripheral nervous system. Here, we investigated the presence of the primary cilium in neural crest cells and their derivatives in the trunk of the developing chicken embryo in vivo. We found that neural crest cells, sensory neurons, and boundary cap cells all bear a primary cilium during key stages of early peripheral nervous system formation. Moreover, we described differences in the ciliation of neuronal cultures of different populations from the peripheral and central nervous system. Our results offer a framework for further in vivo and in vitro investigations on specific roles that the primary cilium might play during peripheral nervous system formation.

Kaposi’s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the first in vivo model for a virally-induced lymphoma in zebrafish, whereby KSHV-infected PEL tumour cells engraft and proliferate in the yolk sac of zebrafish larvae. Using a PEL cell line engineered to produce the viral lytic switch protein RTA in the presence of doxycycline, we demonstrate drug-inducible reactivation from KSHV latency in vivo, which enabled real-time observation and evaluation of latent and lytic phases of KSHV infection. In addition, we developed a sensitive droplet digital PCR method to monitor latent and lytic viral gene expression and host cell gene expression in xenografts. The zebrafish yolk sac is not well-vascularized and using fluorogenic assays we confirmed that this site provides a hypoxic environment that may mimic the microenvironment of some human tumors. We found that PEL cell proliferation in xenografts was dependent on the host hypoxia-dependent translation initiation factor, eukaryotic initiation factor 4E2 (eIF4E2). This demonstrates that the zebrafish yolk sac is a functionally hypoxic environment and xenografted cells must switch to dedicated hypoxic gene expression machinery to survive and proliferate. The establishment of the PEL xenograft model enables future studies that exploit the innate advantages of the zebrafish as a model for genetic and pharmacologic screens.

This study aims to suggest a basis for the selection of technologies for developing high-performance buildings to reduce energy consumptions and greenhouse gas emissions. Energy-saving technologies comprising of 15 cases were categorized into passive, active, and renewable energy systems. EnergyPlus v8.8 was used to analyze the contribution of each technology in reducing the primary energy consumptions and CO₂ emissions in the Korean climate. The primary energy consumptions of the base model were 464.1 and 485.1 kWh/m²a in the Incheon and Jeju, respectively, and the CO₂ emissions were 83.4 and 87.4 kgCO₂/m²a, respectively. Each technology (cases 1–15) provided different energy-saving contributions in the Korean climate depending on their characteristics. The heating, cooling, and other energy-saving contributions of each technology indicate that their saving rates can be used when selecting suitable technologies during the cooling and heating seasons. Case 15 (active chilled beam with dedicated outdoor air system + ground source heat pump) showed the highest energy saving rate. In case 15, the Incheon and Jeju models were reduced by 189.4 (59.2%) and 206.2 kWh/m²a (57.4%) compared to the base case, respectively, and the CO₂ emissions were reduced by up to 32.7 (60.8%) and 35.6 kgCO₂/m²a (59.3%), respectively.

The annual demand for fibres continues to rise worldwide. Consequently, more and more fibres must be produced to meet this demand, most of which are melt-spun polymeric man-made fibres. [1] Smooth filaments made of polymers are mainly used for technical applications in industry. For use in clothing or home textiles, for example, a texturing process is used to give the filaments a crimp and thus a feel like that of natural fibres. In this state, they can be processed together with natural fibres and used in textiles. Partially oriented yarns (POY) are of great importance in tex-turing. The yarns are mainly crimped with the help of the so-called false-twist texturing process (FTTP). [2] Since POY accounts for about 60 % of the melt-spun filament yarn produced world-wide, the FTTP is the most important texturing process in the textile industry [3]. In this paper, the main components of false-twist texturing (FTT) machines are explained along with the state of the art and research for each component and its influence on the process. Relevant patents are dis-cussed as well as process optimisation techniques, innovative polymers and yarn types recently used in FTT, followed by a conclusion and an outlook for the process.

Abstract: The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRa and GRb), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e. GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have lower expression of GRb, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. Increased expression of GRb can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. Endogenous expression of GRb in the TM may relate to differences in the development of GC-OHT among the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease modifying therapies to better treat these two sight threatening forms of glaucoma.

The prognosis of patients with recurrent or metastatic of the head and neck squamous-cell carcinoma (HNSCC) refractory to platinum-based chemotherapy is severe and, consequently, the identification of therapeutic options for this category of patients is a priority. Nivolumab, an anti- programmed cell death protein 1 (anti-PD-1) monoclonal antibody, has been approved for the treatment of recurrent or metastatic HNSCC after platinum-based therapy progressing. We present the early experience of two academic center including diagnostic, clinical, biological, therapeutic and outcomes characteristics of head and neck cancer (HNC) patients treated with Nivolumab. The purpose of the study is to identify certain peculiarities and to report them compared to the data from the literature in order to generate some hypotheses that coud constitute criteria for the selection of cases with maximum benefit to immunotherapy. Analyzing the data obtained from 18 patients treated in Emergency County Hospital Craiova, "Saint Nectarie" Oncological Hospital Craiova and Euroclinic Oncological Center Iasi January 2020 and March 2023 it could be hypothesized that lower nadir values of neutrophil to lymphocyte ratio (<3.5) and the adition of intensive regimens of chemotherapy and radiotherapy could justify a favorable response in terms of progression free survival (PFS) during immunotherapy with Nivolumab. To our knowledge, the study included the first two cases of second primary malignancy (SPM) in the head neck region treated with Nivolumab. The reported data support a possible benefit of the sequential administration of radiotherapy, immunotherapy for SPM cases. Higher positive dynamic of neutrophil to lymphocyt ratio (NLR) could be associated with worst outcome during immunotherapy. All study observations including the role of infections and antibiotic treatment as well as the possible biomarker value of NLR variation during immunotherapy should be investigated in multicenter clinical trials.

Background. Cardiorespiratory fitness (CRF) is a predictor of chronic disease that is impractical to routinely measure in primary care settings. We used a new estimated cardiorespiratory fitness (eCRF) algorithm that uses information routinely documented in electronic health care records to predict abnormal blood glucose incidence. Methods: Participants were adults (17.8% female) 20-81 years old at baseline from the Aerobics Center Longitudinal Study between 1979 and 2006. eCRF was based on sex, age, body mass index, resting heart rate, resting blood pressure, and smoking status. CRF was measured by maximal treadmill testing. Cox proportional hazards regression models were established using eCRF and CRF as independent variables predicting the abnormal blood glucose incidence while adjusting for covariates. Results: Of 8,602 participants at risk at baseline, 3,580 (41.6%) developed abnormal blood glucose during an average of 4.9 years follow-up. The average eCRF of 12.03 ± 1.75 METs was equivalent to the CRF of 12.15 ± 2.40 METs within the 10% equivalence limit. In fully adjusted models, the estimated risks were the same (HRs = 0.96), eCRF (95% CIs = 0.93−0.99), and CRF (95% CI of 0.94−0.98). Each 1-MET increase was associated with a 4% reduced risk. Conclusion: Higher eCRF is associated with a lower risk of abnormal glucose. eCRF can be a vital sign used for research and prevention.

Covid-19 pandemic affected outcome in ST-elevation myocardial infarction (STEMI) patients in majority of countries. We aimed to assess retrospectively admissions, treatments, complications and mortality of STEMI patients in the northeast of Slovenia in the first (March-May 2020) and the second wave (October-December 2020) of Covid-19 pandemic and compare them with the data from 2019 (March-October). Comparing 2019 and both waves of Covid-19 pandemic we observed nonsignificant differences in the number of STEMI admissions, in baseline characteristics, in the use of primary percutaneous coronary intervention (PCI), either within the first 3 (40.5%* vs 30.2% vs 25%*, *p = 0.074) and 6 hours, nonsignificant differences in TIMI III flow after primary PCI and in hospital complications, except for significant increase in hospital heart failure (23.3% vs 42%, p = 0.015) and mitral regurgitation in the second wave (10% vs 26.9%, p = 0.008) of the pandemic with nonsignificant increase in hospital mortality (8.9% vs 9.4% vs 13.6%) in both waves of the pandemic. We conclude, that with increased severity of Covid-19 pandemic in the second wave there was a longer delay to primary PCI in STEMI patients, resulting in significantly increased hospital heart failure and nonsignificantly increased hospital mortality

Every day around 93% of children under the age of 15 (1.8 billion children) breathe outdoor air that is so polluted it puts their health and development at serious risk. Due to the pandemic, however, ventilation of buildings using outdoor air has become an important safety technique to prevent the spread of COVID-19. With the mounting ev-idence suggesting that air pollution is impactful to human health and educational out-comes, this contradictory guidance may be problematic in schools with higher air pol-lution levels, but keeping kids COVID-19 free and in school to receive their education is now more pressing than ever. To understand if all schools in an urban area are ex-posed to similar outdoor air quality and if school infrastructure protects children equally indoors, we installed research grade sensors to observe PM2.5 concentrations in indoor and outdoor settings to understand how unequal exposure to indoor and out-door air pollution impacts indoor air quality among high- and low-income schools in Salt Lake City, Utah. Based on this approach, we found that during atmospheric inver-sions and dust events, there was a lag ranging between 35 to 73 minutes for the out-door PM2.5 concentrations to follow a similar temporal pattern as the indoor PM2.5. This lag has policy and health implications and may help to explain the rising concerns re-garding reduced educational outcomes related to air pollution in urban areas. These data and resulting analysis show that poor air quality may impact school settings, and the potential implications with respect to environmental inequality.

(1) Background: In patients suffering from heart failure, the main causes of death are either he-modynamic failure, or ventricular arrhythmias. The only tool to significantly reduce arrhythmic sudden death is the implantable cardioverter defibrillator (ICD), but not all patients benefit to the same extend of these devices. (2) Methods: The primary outcome of this single center study was defined as cardiovascular death in patients with ischemic and non-ischemic heart failure who have benefited from ICD therapy. The secondary outcomes were death from any cause, sudden cardiac death, ICD-related therapies (appropriate antitachycardia pacing or shock therapy for ventricular tachycardia or fi-brillation) and recurrences of ventricular tachyarrhythmias. (3) Results: A total of 403 consecutive ICD recipients – symptomatic heart failure patients with ICD for the primary prevention of sudden cardiac death – were included retrospectively: 59% is-chemic cardiomyopathy (ICMP) and 41% non-ischemic cardiomyopathy (NICMP). Within a median follow-up period of 36 months, the incidence of cardiovascular mortality was not signif-icantly different in patients with NICMP and ICMP: the primary outcome had occurred in 9 pa-tients (5.4%) in the NICMP group and in 14 patients (5.9%) in the ICMP group (hazard ratio 1; 95%confidence interval [CI] 0.45 to 2.28; p =0.97). All-cause mortality occurred in 14 of 166 pa-tients (8.4%) in NICMP group and 18 of 237 patients (7.6%) in ICMP group. Sudden cardiac death occurred in 2 patients (1.2%) in the NICMP group and in 4 patients (1.7%) in the ICMP group (hazard ratio 0.71; 95% CI, 0.13 to 3.88; P=0.69). The rate of appropriate device therapies was comparable in both groups. (4) Conclusion: In this study, ICD implantation for primary prevention of sudden cardiac death in patients with symptomatic systolic heart failure was associated with similar rates of cardiovas-cular and all-cause mortality in patients with ischemic heart disease, and in patients with heart failure from other causes. NICMP and ICMP showed comparable rates of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

Low-cost miniature hyperspectral and thermal cameras onboard lightweight unmanned aerial vehicles (UAV) bring new opportunities for monitoring land surface variables at unprecedented fine spatial resolution with acceptable accuracy. This research applies hyperspectral and thermal imagery from a drone to quantify upland rice growth and water use efficiency (WUE) after biochar application in a Costa Rican dry region. The field flights were conducted over two experimental groups with bamboo biochar and sugarcane biochar amendments and one control group without biochar application. Rice canopy biophysical variables were estimated by inversion of a canopy radiative transfer model on hyperspectral reflectance. Variations in gross primary production (GPP) and WUE across treatments were estimated from the normalized difference vegetation index (NDVI), canopy chlorophyll content (CCC), and evapotranspiration. We found that GPP was increased by 41.9±3.4 % when using bamboo biochar and 17.5±3.4 % when using sugarcane biochar, which was probably due to higher soil moisture in the biochar-amended plots and led to significantly higher WUE by 40.8±3.5 % in bamboo biochar and 13.4±3.5 % in sugarcane biochar. This study demonstrated the use of hyperspectral and thermal imagery from drone to provide indicators for quantifying biochar effects on tropical dry cropland by integrating with ground point samples and physical models.

In this study, we evaluated chlorophyll fluorescence (CF) under two extreme illumination conditions at plant scale with a passive spectroradiometer. Fluorescence (F) was estimated by reading directly from radiance spectra of a variety of plants illuminated with light-emitting diode (LED) grow lights in the laboratory. Solar-induced fluorescence (SIF) was estimated from spectral measurements of the same plants under sunlight using the Fraunhofer Line Depth (FLD) method. Chlorophyll fluorescence yield (F_yield) and solar-induced fluorescence yield (SIF_yield) were calculated by normalizing F and SIF with absorbed photosynthetically active radiation (APAR). Two approaches to estimating APAR were compared: utilizing white reference spectra and reflected spectra versus white reference spectra combined with the fraction of absorbed photosynthetically active radiation (fPAR) derived from literature. Average F and SIF were different by a factor of approximately twenty-four (F = 0.110 ± 0.038 Wm⁻²μm⁻¹sr⁻¹ versus SIF = 2.60 ± 1.87 Wm⁻²μm⁻¹sr⁻¹). In contrast, the average normalized values F_yield and SIF_yield were within the margin of error of one another (F_yield = 0.022 ± 0.008 μm⁻¹sr⁻¹ and SIF_yield = 0.030 ± 0.020 μm⁻¹sr⁻¹). This study highlights the influence of APAR on CF and the importance of properly accounting for it when estimating yield and demonstrates the ability of two simple and portable experimental setups with a passive instrument to obtain fluorescence metrics.