Primary ciliary dyskinesia (PCD) is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. Low nasal NO (nNO) is a biomarker for diagnosis in patients with features of PCD; but the reason why it is low is unclear. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33- mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Variants in genes underlying the function of cilia, can be associated with poor lung function, even in the absence of PCD. Single nucleotide polymorphisms in PCD – related genes can be associated with increased asthma severity. The role of cilia and antigen stasis is the pathophysiology of asthma is an important area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma and asthma-like symptoms.

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.

The purpose of this research is to analyze the structural changes in primary energy production across European countries over the period from 1990 to 2022, with a focus on understanding the shifts in energy sources and their implications for energy security and sustainability. By applying clustering methods, the study categorizes European nations into distinct groups based on their primary energy production profiles, revealing significant transitions from fossil fuel-based systems to those increasingly dominated by renewable energy sources. The analysis demonstrates that while some countries have achieved substantial progress in integrating renewable energy, others remain heavily dependent on traditional energy sources such as coal and natural gas. Additionally, the study highlights the growing importance of natural gas as a transitional fuel and the relatively stable role of nuclear energy in certain regions. A key finding of this research is the disparity between energy production and consumption across Europe, with many large economies facing a persistent deficit in domestic energy production, leading to a high reliance on energy imports, particularly of natural gas and oil. This reliance poses significant challenges for energy security, especially in light of recent geopolitical disruptions and fluctuations in global energy markets. The paper also explores the environmental implications of these energy production trends, emphasizing the critical role of renewable energy in meeting the European Union’s decarbonization targets and combating climate change.

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

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.

Lomami National Park, located in the Democratic Republic of Congo, is renowned for the integrity of its forest ecosystems, safeguarded by the absence of agricultural activities and limited road access. However, these ecosystems remain under-researched, particularly regarding forest cover dynamics. This research gap poses a significant challenge to establishing rigorous monitoring, which is essential for ensuring the long-term preservation of these valuable ecosystems. This study evaluates land cover dynamics within Lomami National Park through supervised classification of Landsat images from 2008, 2016, and 2024. Seven spatial structure indices were calculated to highlight the dynamics of landscape composition and configuration, distinguishing between the park's core and buffer zones. The underlying spatial transformation processes were identified using a decision tree approach. The results highlight a striking contrast in forest cover stability between Lomami National Park and its surrounding periphery. Within the park, forest cover has not only been preserved but has also shown a modest increase, rising from 92.60% to 92.75%. In contrast, the peripheral zone experienced a significant decline in forest cover, decreasing from 79.32% to 70.48% over the same period. This stability within the park goes beyond simply maintaining forested areas; it includes the preservation and strengthening of the spatial structure of forest ecosystems. For instance, edge density, which is a key indicator of forest edge compactness, remained stable in the park, fluctuating between 8 m/ha and 9 m/ha. However, in the peripheral zone, edge density exceeded 35 m/ha, suggesting that forest edges in the park are considerably more cohesive and intact than in the surrounding areas. Furthermore, the spatial transformation processes within each area underscore these contrasting dynamics. In the park, the main process was aggregation of primary forest patches, which reflects a trend toward continuous and connected forest landscapes. By contrast, the peripheral zone experienced dissection, indicating fragmentation and breakdown of forest patches. Together, these findings underscore the park's role in maintaining both the extent and the structural integrity of forest ecosystems, setting it apart from the more degraded periphery. These findings highlight not only the resilience of forest ecosystems in the face of limited anthropogenic pressures but also the crucial importance of effective land management and rigorous conservation strategies in addressing the challenges of urbanization and surrounding rural expansion. They further emphasize that well-adapted conservation measures, combined with specific demographic and socio-economic conditions, can play a pivotal role in long-term forest preservation and ecological stability.

Background: Acute ischemic stroke treatment has been thoroughly studied to identify strategies to reduce treatment times. However, many centers still do not meet the benchmark time metrics. Additionally, smaller centers often face longer treatment times, yet studies focus primarily on larger, more advanced centers. Objectives: The aim of this study is to analyze existing literature to understand the strategies implemented in primary and comprehensive stroke centers to reduce their treatment times, and categorize the studies based on methods used to improve their processes Results: Three main categories of improvements were identified in the literature: 1) standardization of processes, 2) resource management, and 3) data collection. Both primary and comprehensive stroke centers were able to reduce treatment times through standardization of processes. However, challenges such as variations in resources between hospitals and difficulties in integrating data collection software into workflow were highlighted. Additionally, many strategies to optimize resource management and data collection were conducted in comprehensive stroke centers, which can benefit primary stroke centers. Conclusions: Many existing strategies to improve treatment times are viable for both primary and comprehensive stroke centers. However, while data collection is recognized as crucial for process improvement, challenges persist in integrating data collection methods into clinical workflow. Proposed solutions include the development of easy-to-use software tailored to clinician needs.

Ambiguity exists over treatment and surveillance strategies after endoscopic submucosal dissec-tion (ESD) for esophageal squamous cell neoplasia (ESCN) with unfavorable histologic features. This study investigated the long-term outcomes of ESD in high-risk ESCN patients. We retro-spectively included early ESCN patients treated with ESD at two medical centers in Taiwan be-tween August 2010 and December 2023. Demographic, endoscopic, and pathological data were collected. Among 146 patients (mean age 59.17 years) with 183 lesions, 73 (50%) had a history of head and neck cancer (HNC). En bloc and R0 resection were achieved in 100% and 95.6% of the lesions, respectively. The 5-year overall survival (OS), disease-specific survival (DSS) and local recurrence rates were 42.7%, 94.7% and 11%. R0 resection was significantly associated with re-currence in univariate analysis (adjusted OR: 0.23, 95% CI: 0.05-0.99, P=0.05). Alcohol abstinence was independently associated with lower recurrence (adjusted OR: 0.20, 95% CI: 0.08-0.48, P

The term “conservation,” as it relates to biodiversity in a Western context, has a storied past 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 empirically quantify the efforts of the conservation sector. This presents an avoidable hindrance to the systematic planning of the conservation field. To help remedy this situation, we provide an outcome separation framework that is based on the expected degree of separation between an action’s proximate outcome, from its intended, ultimate outcome for a habitat and/or 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. A distillation of this tiered framework also provides a new definition of biodiversity conservation that is more rigorous and adaptable to future conceptual evolutions of the field.

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.

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 insulin-regulated aminopeptidase (IRAP; oxytocinase) is part of the M1 aminopeptidase family and is highly expressed in many tissues, including the neocortex and hippocampus of the brain. IRAP is involved in various physiological functions and has been identified as a receptor for the endogenous hexapeptide Angiotensin IV (Ang IV). Binding of Ang IV inhibits the enzymatic activity of IRAP and has proven to enhance learning and memory in animal models. The macrocyclic compound 9 (C9) is a potent synthetic IRAP inhibitor developed from the previously reported inhibitor HA08. In this study, we have examined compound C9 and its effects on cognitive markers drebrin, microtubule-associated protein 2 (MAP2), and glial fibrillary acidic protein (GFAP) in primary hippocampal and cortical cultures. Cells from Sprague Dawley rats were cultured for 14 days before treatment with C9 for 4 consecutive days. The cells were analysed for protein expression of drebrin, MAP2, GFAP, glucose transporter type 4 (GLUT4), vesicular glutamate transporter 1 (vGluT1), and synapsin I using immunocytochemistry. The gene expression of related proteins was determined using qPCR, and viability assays were performed to evaluate toxicity. The results showed that protein expression of drebrin and MAP2 was increased, and the corresponding mRNA levels were decreased, after treatment with C9 in the hippocampal cultures. The ratio of MAP2 positive neurons and GFAP positive astrocytes was altered in both hippocampal and cortical cultures, and there were no toxic effects observed. In conclusion, IRAP inhibitor compound C9 enhance the expression of pro-cognitive markers drebrin and MAP2 which further confirms IRAP as a relevant pharmaceutical target and C9 as a promising candidate for further investigation.

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.

This article provides a literature review on tubal carcinoma to offer an updated insight into its preventative strategies, diagnosis, treatment, and oncological surveillance. In addition to the search string utilized, the authors' focus extended to key scientific studies, consensus statements, guidelines, and relevant case reports essential for the proper clinical management of the disease, providing a methodologically well-structured literature review combined with the practical expertise in the oncological field. The article also includes two emblematic clinical cases that emphasize the importance of understanding the physiopathology and the current state of the art in the anatomopathological advancements of tubal/ovarian/peritoneal carcinoma, often assimilated into a single clinical entity.

Mesoscale eddies wield a significant influence on primary productivity in marine ecosystems by regulating nutrient availability, vertical mixing, and phytoplankton growth dynamics. In this study, we tracked and analyzed the effects of mesoscale eddies on net primary productivity (NPP) across the Bay of Bengal (BoB) using remote sensing data. Dividing the Bay into six zones based on mesoscale eddy frequency and distribution, our analysis identified 1880 anticyclonic eddies and 1972 cyclonic eddies during January 2010–March 2020 monitoring period. Cyclonic eddies predominantly occurred in the western part of the bay - along the east coast of the Indian Peninsula; while anticyclonic eddies were also observed, albeit in lesser proportions. Among eddies lasting one-week, anticyclonic eddies comprised approximately 48.81%, while cyclonic eddies constituted approximately 51.19% of the total. Analysis of the NPP distribution across the months revealed intriguing patterns. Mean values of NPP fluctuated throughout the year, with the highest value observed in August (748.51 mg C/m2/day) and the lowest in May (519.26 mg C/m2/day). The findings indicate a complex relationship between eddy distribution and NPP, with Zones 1 and 2 exhibiting a higher occurrence of cyclonic eddies, correlating with greater NPP and its variability. Conversely, Zones 3 and 5 display increased eddy activity despite fewer cyclonic eddies and lower NPP levels. Zone 6 shows reduced eddy activity and NPP, while Zone 4 presents moderate eddy activity alongside lower NPP. In contrast, Zones 3 to 5 exhibit lower NPP levels despite exhibiting heightened eddy activity. This study contributes valuable insights into the dynamics of ocean circulation and the impacts of eddies on NPP, which can inform fisheries management strategies, advances climate resilience measures, expands scientific knowledge, and guides policies related to conservation and sustainable resource utilization.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

The global issues of overweight and sedentary lifestyles demand comprehensive responses from health systems, yet health education still needs to be more cohesive and less sporadic. This study focuses on primary school children as a specific target for instilling healthy habits, employing ac-tive learning strategies to address healthy diet and physical activity. Through Problem-Based Learning projects, the study engaged fourth-grade primary students in acquiring healthy habits. The study was carried out over four consecutive years at a school with two lines, allowing the employment of an opportunity sample and evaluating intervention and control groups by com-paring their corresponding scores. Control groups integrated a total of 54 students, while the in-tervention group included a total of 159 students. A pre-test and post-test questionnaire were used for data collection. Evaluation differential scores revealed statistically significant higher scores in the intervention groups: 3.62 points in control groups and 6,94 in intervention groups, particu-larly in attitudinal competences. These strategies not only facilitated the development of crucial skills such as information search, synthesis, representation, analysis, decision-making, teamwork, and intrapersonal awareness but also significantly broadened the knowledge acquired in aspects related to healthy habits. This approach proved effective in helping children comprehend the im-portance of healthy choices and encouraged integrating such habits into their daily lives.

Cerebral cavernous malformations (CCM) or familial cavernomatosis is a rare, autosomal dominant, inherited disease characterized by the presence of vascular malformations consisting of blood vessels with an abnormal structure in the form of clusters. Based on the altered gene (CCM1/Krit1, CCM2, CCM3) and its origin (spontaneous or familial), different types of this dis-ease can be found. In this work we have isolated and cultivated primary endothelial cells (ECs) from peripheral blood of a type 1 CCM patient. Differential functional and gene expression pro-file of these cells were analyzed and compared to primary ECs from a healthy donor. The muta-tion of the familial index case consisted of a heterozygous point mutation in the position +1 splicing consensus between exons 15 and 16, causing failure in RNA processing and in the final protein. Furthermore, gene expression analysis by quantitative PCR revealed a decreased ex-pression of genes involved in intercellular junction formation, angiogenesis, and vascular ho-meostasis. Cell biology analysis showed that CCM1 ECs were impaired in angiogenesis and cell migration. Taken together, the results obtained suggest that the alterations found in CCM1 ECs are already present in the heterozygous condition, suffering from vascular impairment and someway predisposed to vascular damage.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by resistance to targeted and immunotherapies and combinations ob both. We have reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemically-modified antisense oligonucleotides induces proliferative arrest and apoptotic death in tumor cells from many human and mouse cancer types. These studies have been mostly performed in vitro and in vivo on commercially-available cancer cell lines and have shown that, in mouse models, tumor growth is stunted by the treatment. The present work was performed on cells derived from primary and metastatic ccRCC tumors. We established primary cultures fom primary and metastatic ccRCC tumors, which were subjected to knockdown of ASncmtRNAs in vitro and in vivo in an orthotopic xenograft model in NOD/SCID mice. We found that these primary ccRCC cells are affected in the same way as tumor cell lines and, in the orthotopic model, tumor growth was significantly reduced by the treatment. This study on patient-derived ccRCC tumor cells represents a model closer to actual patient ccRCC tumors and shows that knockdown of ASncmtRNAs poses a potential treatment option for these patients.

One of the most common subgroups of cutaneous T-cell lymphomas is the that of primary cutaneous CD30 positive lymphoproliferative disorders. The group includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL), as well as some borderline cases. Recently, significant progress has been made in understanding the genetics and treatment of these disorders. This review article summarizes the clinical evidence supporting the current treatment options in these diseases. Recent years have seen the introduction of novel agents into clinical practice; most of these target CD30, such as anti-CD30 monoclonal antibodies and conjugated antibodies (brentuximab vedotin), bispecific antibodies and cellular therapies, particularly anti-CD30 CAR-T cells. This paper briefly reviews the biology of CD30 that makes it a good therapeutic target, and describes the anti-CD30 therapies that have emerged to date.

This study evaluates the accessibility of primary care physicians (PCPs) in Eastern Quebec using an enhanced two-step floating catchment area (E2SFCA) methodology. The E2SFCA methodology considers both the population supply of PCPs and the travel time between PCPs and dissemination areas, and was found to be effective in identifying possibly underserved areas. The availability of primary care services is contingent upon the presence of adequate road infrastructure, and populations residing in areas with limited access to main road networks may experience compromised access to primary care. The study concludes that the E2SFCA methodology can facilitate the identification of areas experiencing a shortage of PCPs, and this information can be used to inform the development of regional medical workforce programs and support the establishment of rural residency initiatives.

In the Emergency Department (ED), pain is one of the symptoms that is most frequently reported, making it one of the most significant issues for the emergency physician, but is frequently under treated. Intravenous (IV), oral (PO), and intramuscular (IM) delivery are the standard methods for administering acute pain relief. Firstly, we compared the safety and efficacy of IN analgesia to other conventional routes of analgesia to assess if IN analgesia may be an alternative for the management of acute pain in ED. Secondary, we analyzed the incidence and severity of adverse events (AEs) and rescue analgesia required. We performed a systematic review-based keywords in Pubmed/Medline, Scopus, EMBASE, the Cochrane Library and Controlled Trials Register finding only twenty randomized Clinical trials eligible in the timeline 1992-2022. A total of 2098 patients were analyzed and compared to intravenous analgesia showing no statistical difference in adverse effects. In addition, intranasal analgesia also has a rapid onset and quick absorption. Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while providing effective pain relief. IN is simple to administer, non-invasive, rapid onset and quick absorption; it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management. Analgesia needs to be tailored to each patient's features and type of pain: IN Fentanyl and Ketamine look promising and may be administered easily and safely while providing effective pain relief.

The aims of the review were to elucidate the spatial variation in sea ice algae primary production rates and biomasses (Chl a) in the Canadian Arctic – Greenland region, characterized by comparable physical settings. A database was compiled from 30 studies of sea ice algae primary production rates, biomasses (Chl a), snow and ice thicknesses, ice types, nutrient (Si(OH)4, PO4, (NO3+NO2), and (NH4) concentrations in ice and below ice from the region. Production rates were significantly high (463 mg C m-2 d-1) in Resolute Bay and in Northern Baffin Bay (317 mg C m-2 d-1) both in Canadian Arctic, as compared to a rate of 0.2 mg C m-2 d-1 in northeast Greenland. The biomasses reached 340 mg Chl a m-2 in Resolute Bay in comparison to a 0.02 mg Chl a m-2 in southwest Greenland. Primary production at other Canadian and Greenland sites were comparable but sea ice Chl a was higher (15.0 ± 13.4 mg Chl a m-2) at Canadian sites as compared to Greenland (0.8 ± 0.5 mg Chl a m-2). Resolute and Northern Baffin Bays production rates were significantly higher when compared to other Arctic Ocean sites outside the studied region. The review concludes that high production rates and biomasses in Resolute and Northern Baffin Bay’s were related to inflow and mixing of nutrient rich waters of Pacific origin. A conceptual model with drivers and inhibitors of sea ice algae primary production is projected, and the database compiles a dataset of published data for further studies.

Migraine is a primary headache disorder characterized by unilateral throbbing, pulsing headache, which lasts for hours to days, and the pain can interfere with daily activities. It exhibits various symptoms, such as nausea, vomiting, sensitivity to light, sound, and odors and physical activity consistently contributes to worsening pain. Despite the intensive research, little is still known about the pathomechanism of migraine. It is widely accepted that migraine involves activation and sensitization of the trigeminovascular system. It leads to the release of several pro-inflammatory neuropeptides and neurotransmitters and causes a cascade of inflammatory tissue responses including vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Convincing evidence obtained in rodent models suggests that neurogenic inflammation is assumed to contribute to the development of a migraine attack. Chemical stimulation of the dura mater triggers activation and sensitization of the trigeminal system and causes numerous molecular and behavioral changes; therefore, this is a relevant animal model of acute migraine. This review article discusses the emerging evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology of migraine, presenting the most recent advances in preclinical research and the novel therapeutic approaches to the disease.

In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans, TTC8 is also implicated in Bardet-Biedl syndrome (BBS). To investigate if the affected dogs only exhibit a non-syndromic PRA or develop a syndromic ciliopathy similar to human BBS, we recruited ten affected dogs to the study. The progression of PRA for two of the dogs was followed for two years, and a rigorous clinical characterization allowed a careful comparison with primary and secondary characteristics of human BBS. In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia. We used Oxford Nanopore long-read cDNA sequencing to characterize retinal full-length TTC8 transcripts in affected and non-affected dogs, the results of which suggest that three isoforms are transcribed in the retina, and the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet-Biedl syndrome with heterogeneous clinical signs.

Background and Objectives: Multiple primary malignant tumors represent a small percentage of the total number of oncological cases and can involve either metachronous or synchronous development and represent challenges in diagnosis, staging, and treatment planning. Our purpose is to present a rare case of bladder adenocarcinoma in a female patient with multiple primary malignant tumors and to provide systematic review of the available literature. Materials and Methods:A 67-year-old female patient who was admitted altered general condition, and anuria. The past medical history of the patient included malignant melanoma (2014), cervical cancer (2017), colon cancer (2021), obstructive anuria (2023), liver metastasectomy (2023). Transurethral resection of bladder tumor was performed for bladder tumors. Results: Contrast CT highlighted multiple pulmonary metastases, a poly nodular liver con-glomerate, retroperitoneal lymph node, II/III grade left ureterohydronephrosis, and no digestive tract tumor masses. The pathological result of the bladder resection showed an infiltrative adenocarcinoma. Conclusions: The difference between primary bladder adenocarcinoma tumor and metastatic colorectal adenocarcinoma is the key for the future therapeutic strategy. Identification and assessment of risk factors such as viral infection, radiotherapy, chemotherapy, smoking, genetics are pivotal in understanding and managing multiple primary malignant tumors. Personalized prevention strategies, screening programs may facilitate the early detection of this tumors, synchronous or metachronous one. The use of multicancer early detection (MCED) blood tests for early diagnosis appears promising. However, additional research is needed to standardize these techniques for cancer detection.

A homogenization of billets from Al-Cu-Li-Mg-Sc-Zr alloys should be accomplished at high annealing temperatures exceeding 500 °C. This type of aluminum alloy is susceptible to the depletion of surface layers from Li. Therefore, choosing a suitable homogenization temperature and duration is a crucial step in assuring a homogeneous distribution of alloying elements and optimal exploitation of the potential of the alloy. In-situ heating in an electron microscope was performed on a twin-roll cast Al-Cu-Li-Mg-Sc-Zr alloy to understand the peculiarities of the homogenization process. Four types of primary phase particles rich in Cu, Li, Mg, and Fe were identified in the as-cast material. They appear as coarse particles at the boundaries of eutectic cells. Their partial dissolution occurs at temperatures above 450 °C. They are almost fully dissolved at 550 °C, except for complex phases containing Fe and Cu. Small dimensions of eutectic cells in the range of 10 µm assure a homogeneous distribution of main alloying elements within the matrix after 20 min of annealing. Direct comparison with the same material prepared by mold-casting indicates that such short annealing times result in the dissolution of main primary phase particles but do not assure a homogeneous distribution of alloying elements in the whole volume of the specimen.

Combining the Job Demands-Resourses model and the Work Adjustment theory, this research aims to create a theoretical model that considers Leader-Member Exchange (LMX) and Work Adjustment as protective factors, capable of reducing job exhaustion and turnover intention. A convenience sample of 257 Italian employees filled an online self-report questionnaire. A sequential mediation model was tested, which showed that the relationship between LMX and turnover intention is mediated by Work Adjustment and Job Exhaustion. The results show that the higher the LMX, the higher the work adjustment of the workers and the less they will perceive job exhaustion and, consequently, intent to leave the organisation. With a view to primary prevention, the aim was to investigate possible protective factors at work and the risk factors to look out for in order to move in the direction of preventing a malaise phenomenon before it develops with the aim of promoting wellbeing in organisations.

This cross-country four-year longitudinal study investigated the development of processing speed throughout primary school education. The analyses were conducted on data collected from 441 schoolchildren in Grades 1, 2, 3 and 4 (aged 6.42 to 11.85 years) in the Kyrgyzstan and Russia. Mixed effects growth modeling was applied to estimate average and individual growth trajectories for processing speed at two cross-country samples. Latent class growth modeling was conducted to identify different types of growth trajectories for processing speed and to compare the distribution of the types within the analyzed samples. According to the results, processing speed significantly increases across primary school years. The trajectory is characterized by nonlinear changes with more intensive growth between Grades 1 and 2, which later slows down until Grade 4. There were no significant cross-country differences in the initial score of processing speed or developmental changes in processing speed across primary school years. The development of processing speed is described by a model with three quadratic growth types but minimally differs. It is concluded that in both samples, the development of processing speed may be characterized by homogeneity, with the most intensive growth from Grade 1 to Grade 2 and subsequent linear improvement until Grade 4.

The COVID-19 pandemic had a significant impact on the mental health of individuals globally, and primary healthcare (PHC) nurses play a critical role in providing mental healthcare services. However, limited research has explored the experiences of PHC nurses in providing mental healthcare services during the COVID-19 pandemic. This study explored the experiences of PHC nurses in providing mental healthcare services during the pandemic in Durban, South Africa. The aim was to identify the challenges faced by healthcare providers and the potential for innovative approaches to improve access to care. A qualitative, exploratory design guided the study, and data were collected through in-depth interviews with twelve PHC nurses purposively selected. Thematic analysis was used to analyse the data. Findings from interviews with primary healthcare nurses reveal that the pandemic exacerbated existing challenges, including medication adherence issues, fear and uncertainty among patients, vaccine hesitancy, decreased clinic visits, and the mental and emotional toll on both patients and healthcare workers. PHC nurses adapted their services by increasing outreach efforts, prioritising patient care, and utilising technology and non-governmental organisations’ (NGO) support. Challenges included reduced patient visits, complexities in healthcare provision, and lack of adequate support. Positive changes observed include increased mental health awareness among healthcare professionals and younger generations. Recommendations include implementing outreach and awareness campaigns, providing accurate information about COVID-19 and vaccinations, and promoting cultural sensitivity in mental healthcare provision.

Background: Osteoarthritis is the most common degenerative joint disease resulting in pain and altered joint function. Objective: We investigated the possible association between serum interleukin-6 and symptoms of knee osteoarthritis with regard to pain, stiffness, physical function, assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We also examined the connections between serum interleukin-6 and radiographic severity in primary knee osteoarthritis patients. Methods: In this case-control study, fifty primary knee osteoarthritis patients and fifty age and sex matched controls were randomly recruited. Serum interleukin-6 levels were immunoassayed in patients’ and controls’ serum. Patients’ knee pain, stiffness and physical function were assessed by the respective subscales of the WOMAC Index. Standing anteroposterior radiographs of the knee joint were performed and graded with the Kellegren-Lawrence grade. Results: The mean serum IL-6 level was significantly higher in osteoarthritis patients (110.22 ± 46.98pg/ml) than controls (46.04 ± 12.34 pg/ml) (p=0.001). The WOMAC Index in patients ranged from 0 – 95 and the Kellegren-Lawrence score mean was 2.7 ± 0.76. There was a significant correlation between serum IL-6 levels and pain (r=0.595 p=0.001), physical function score (r=0.666, p=0.001)), and the radiographic score (r=0.799, p=0.001). Regression analysis showed that IL-6 level had a greater impact on both the WOMAC Index (p=0.005) and the Kellegren-Lawrence score (p=0.01). Conclusion: Serum IL-6 level is increased in primary knee osteoarthritis patients. Also, serum interlukin-6 is significantly related to osteoarthritis symptoms and radiographic severity.

School Feeding Programmes are social safety net interventions providing educational and health benefits to vulnerable children in developing countries. This study assessed the impact of Osun Elementary School Feeding and Health Programme (O-MEALS) on the enrolment and retention of rural primary schools in Osun State. Multi stage sampling technique was used to select 188 respondents while data was collected through interview schedule. Percentages, Chi-square, PPMC and T-test were used for data analysis. Findings revealed that over half (51.6%) of the respondents were male, aged 9.38 ± 1.84 years and majority (83.0%) had a family size of 6-10 people. Food incentives (=1.25), health challenge (=0.69), and peer influence (=0.67) were major factors affecting school attendance. More than half (53.2%) of the respondents had unfavourable perception towards the school feeding programme. Results showed a significant difference between pupils’ enrolment (t = 5.332, p = 0.006) and retention rate (t = 58.386, p = 0.000) before and after the commencement of O-MEALS. Furthermore, pupils’ enrolment and retention (r = 0.993, p = 0.001) after the commencement of O-MEALS was significantly related. Food incentive was a major factor affecting school attendance, which fostered an improvement in the poor enrolment and retention previously experienced. Since a good number of the pupils possessed unfavourably perception towards the school feeding programme, it was recommended that effective monitoring be established to checkmate food vendors’ activities in delivering quality and satisfactory services. Likewise, the Government’s policies on school restructuring and levy, which had proved counterproductive, should be reviewed.

This study aimed to evaluate whether primary school classroom teachers reported changes in physical education teaching self-efficacy (SE-PE) and work engagement (WE) during the first COVID-19 wave. Six-hundred-twenty-two classroom teachers filled in an online questionnaire on SE-PE and WE, referring to before and during the lockdown, and on perceived digital competence. While controlling for perceived digital competence, a mixed between-within Repeated Measures Multivariate Analysis of Covariance (RM-MANCOVA) was performed, with a two-time (before vs. during the lockdown) and three age-categories (≤40 vs. 41-50 vs. ≥51 years) factorial design. The RM-MANCOVA revealed that perceived digital competence significantly adjusted teachers’ SE-PE and WE values (p&lt;0.001). The analysis yielded a significant multivariate main effect by time (p&lt; 0.001) and by time × age-categories (p=0.001). Follow-up univariate ANCOVA showed significant differences by time in teachers’ SE-PE (p&lt;0.001) and WE (p &lt; 0.001), with a reduction of both values from before to during the lockdown. A Bonferroni post hoc pairwise comparisons showed teachers’ SE-PE significantly decreased in all age categories (p&lt;0.001). The present findings confirm the importance of promoting SE-PE among primary school teachers, regardless of the crisis due to the COVID-19 pandemic. Teachers’ self-efficacy and WE are essential to master the challenges of PE teaching.

The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematous, celiac disease and Sjögren syndrome, and lymphoma has been widely demonstrated by several epidemiologic studies. By a not yet entirely elucidated mechanism, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to persistent stimulation of both of B- and T-cells, and to the onset of different types of lymphoma in such patients. Specifically, patients affected by may develop lymphomas may years after the original diagnosis. Several epidemiologic, hematologic and histological factors may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly diffuse large B-cell and extranodal marginal zone lymphomas is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma and predictive factors still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57 y.o. patient. The diagnostic work-up, including radiograms, core needle biopsy and histological examination are discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.

Teachers’ time resources are becoming increasingly scarce and time poverty will have a direct impact on the long-term sustainability of their professional development. However, the current state of teachers’ time poverty and its potential harmful consequences are unclear. Therefore, this research conducts two cross-sectional studies to investigate the current situation and group differences in time poverty among Chinese teachers (Sample 1), as well as the influence of teachers’ time poverty on job burnout (Sample 2). The results indicate that: (1) there is a high level of time poverty among teachers; (2) there is no significant difference in gender, teaching years, or teaching section, and there is a significant difference in teaching responsibilities; (3) time poverty could positively and significantly predict job burnout, and job burnout could positively and significantly predict mental health; (4) mental health factors (including depression, anxiety and stress) play the mediating role in the relationship between teachers’ time poverty and job burnout. To create a sustainable development environment for teachers, it is suggested that teachers improve time management skills and establish a self-regulation mechanism; schools should clarify the boundaries of teachers’ work and respect their right to rest; and society should provide positive and adequate spiritual support.

Noninvasive brain stimulation technique can be used for modulation of motor behaviors such as reaction time (RT). The main aim of this study was to investigate whether RT during a sequential visual isometric pinch task (SVIPT) can be affected by anodal transcranial direct current stimulation (a-tDCS) over three different stimulation sites such as dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1) or posterior parietal cortex (PPC). We also aimed to assess if stimulation of these cortical sites affect the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: 1) left M1, 2) left DLPFC, 3) left PPC and 4) sham. A-tDCS was applied concurrent with SVIPT in which the participants were precisely controlled their forces to reach seven different target forces from 10 to 40% of maximum voluntary contraction (MVC) presenting on a computer screen with right dominant hand. Four test blocks were randomly performed at baseline and 15 min after the intervention including sequence and random blocks with either hand. Our results showed significant differences between a-tDCS groups on ratio RT in the sequence blocks of both the right trained (P = .041) and left untrained hands (P = .023) for target forces of 15% and 30 % of MVC, respectively. In sequence blocks, M1 showed significant elongation in ratio RT for the target force of 15% and 30 % MVC compared to PPC and Sham groups in the right hand. In sequence blocks with left hand, this negative effect were found between M1-DLPFC and M1-Sham groups. In random blocks, no significant differences were found among four groups at each target forces for the left hand while there were significant differences for 15% (P =. 04) and 40% MVC (P =. 035) in the right hand. Our findings suggest that three different stimulation sites (DLPFC, M1 or PPC) were differentially affected by a single session of a-tDCS at some target forces during SVIPT. The effects of a-tDCS on ratio RT were transferred in the left untrained hand for sequence blocks but not random blocks. Further research is needed to understand fundamental aspects of these main areas of the brain on temporal processing in a precision control task such as SVIPT.

Anterior-tooth (ANT) contacts induce short latency reflex inhibition of human jaw-closing muscles. The jaw is a rigid class 1 lever for pinpoint-targeting muscle force into a single bite-point, the pivoting food particle. See-saw reflex movements around the food particle fulcrum multiply the food-crushing force. Unpredictable jolts of reaction force caused by food-crushing are subjected to the rostral ANT and caudally to the two articulate ends of the jaw triangle. Compression/distraction strains of food-crushing must be monitored and inhibited by withdrawal reflexes. The mesencephalic ganglion (Vmes), neural myelin sheath, and muscle stretch receptors evolved subsequently to the advent of jaws to improve the velocity of proprioceptive and withdrawal reflexes. In mammalians, the spindles of the taut motor units, stretched by the food-fulcrum send excitatory monosynaptic feedback for the efferent neurons of the respective ipsilateral muscle units, via Vmes. In the Vmes, the spindle-input-mediating afferent neurons are coupled with another source of afferent feedback, which is also excitatory, from the back-tooth (BAT) mechanoreceptors. The two sources of excitatory pulses are summated and targeted for the efferent neurons to boost the stretched and taut motor units. Likewise, the afferent feedback from ANT mechanoreceptors is also coupled in the Vmes with concomitant feedback from spindles. The ANT output, however, is inhibitory to negate the excitatory feedback from the stretched jaw-muscle units. The inhibitory feed from ANT temporarily blocks the excitatory potential of masticatory motor efferent neurons to protect the ANT and jaw-joints from inadvertent strains. The inhibitory inputs from ANT alternate with the excitatory inputs from BAT to determine which jaw-closing muscle units are activated or inhibited at any given instant of food-crushing. The Vmes exists in all jawed vertebrates, and its’ evolution was probably motivated by demands for the control of bite force. The monosynaptic unilateral food-crushing excitatory and inhibitory reflexes (UFCR) override the coexisting bilaterally executed feed for jaw muscles from the central nervous system. Hypothesis: The Vmes-mediated UFCR combine neural inputs from tooth contacts with concomitant feedback from muscle stretch receptors for the control of mammalian food-crushing bite force.

Cannabinoids, mainly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the pathogenesis of numerous chronic inflammatory disorders, including coronavirus disease 2019 (COVID-19), which results in the accumulation of pro-inflammatory cytokines. Therefore, we hypothesized that CBD and THC reduce the levels of pro-inflammatory cytokines by inhibiting key inflammatory signalling pathways. The nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signalling has been implicated in a variety of chronic inflammatory diseases, which results in the release of pyroptotic cytokines, interleukin-1β (IL-1β) and IL-18. Likewise, the activation of the signal transducer and activator of transcription-3 (STAT3) causes increased expression of pro-inflammatory cytokines. We studied the effects of CBD and THC on lipopolysaccharide (LPS)-induced inflammatory response in human THP-1 macrophages and primary human bronchial epithelial cells (HBECs). Our results revealed that CBD and, for the first time, THC, significantly inhibited NLRP3 inflammasome activation following LPS + ATP stimulation, leading to a reduction in the levels of IL-1β in THP-1 macrophages and HBECs. CBD attenuated the phosphorylation of nuclear factor-κB (NF-κB) and both cannabinoids inhibited the generation of oxidative stress post-LPS. Our multiplex ELISA data revealed that CBD and THC significantly diminished the levels of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) after LPS treatment in THP-1 macrophages and HBECs. In addition, the phosphorylation of STAT3 was significantly downregulated by CBD and THC in THP-1 macrophages and HBECs, which was in turn, attributed to the reduced phosphorylation of tyrosine kinase-2 (TYK2) by CBD and THC after LPS stimulation in these cells. Overall, CBD and THC were found to be effective in alleviating the LPS-induced cytokine storm in human macrophages and primary HBECs, at least via modulation of NLRP3 inflammasome and STAT3 signalling pathways. The encouraging results from this study warrant further investigation of these cannabinoids in vivo.

The three-armed cluster-randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance) aimed to foster appropriate antibiotic use and reduce overprescribing in German ambulatory care to counter antibiotic resistance. Multi-faceted interventions targeted primary care physicians, teams and patients. This study examined effectiveness of the implementation program. ARena was conducted in 14 primary care networks with 196 practices. All arms received data-based feedback on antibiotics prescribing and quality circles. Arms II and III received different add-on components each. Primary outcome examined is the prescribing rate for systemic antibiotics for cases with non-complicated acute infections (upper respiratory tract, bronchitis, sinusitis, tonsillitis, otitis media). Secondary outcomes refer to prescribing of quinolones and guideline-recommended antibiotics. Based on pseudonymized quarterly claims data, mixed logistic regression models examined pre-post intervention antibiotic prescribing rate changes and compared to matched standard care. A significant rate reduction (arm I 11.7%; arm II 9.9%; arm III 12.7%) and significantly lower prescribing rates were observed for all arms (20.1%, 18.9% and 23.6%) compared to matched standard care (29.4%). Fluoroquinolone prescribing was reduced in all intervention arms and rates for recommended substances generally increased. No significant post-interventional difference between intervention arms was detected. Findings indicate implementation program impact compared to standard care. Trial registration: ISRCTN, ISRCTN58150046

The streptavidin and biotin interaction is one of the strongest non-covalent interactions in nature. As a result, this non-covalent interaction has been of great interest when it comes to biochemical assays, diagnosis of diseases, and cell-targeted drug delivery. Past research has proven that biotin-streptavidin is useful in biosensor development to improve the detection of a system when conjugated to nanoparticles. This study aims to prove that streptavidin-coated nanoparticles can be conjugated with biotinylated antibodies using the primary-secondary method to non-invasively detect adenocarcinoma in-vitro. While the use of nanoparticles is not uncommon to the diagnostics area of scientific research, the technique this research aims to investigate is a non-invasive one, utilizing the primary-secondary method. Specifically, the increased stability of fluorophores when bound to antibodies as opposed to nanoparticles directly can be indicative of the particles conjugated through the primary-secondary method’s ability to specifically bind to overexpressed transferrin receptors in the A549 cell line. In this paper, streptavidin-coated nanoparticles were conjugated with biotinylated anti-transferrin receptor antibodies and AlexaFluor-488 secondary antibodies were used to enable fluorescence-based detection. The efficiency of these particles were observed quantitatively through a plate reader and qualitatively through a fluorescence microscope. I demonstrated that these nanoparticles are able to specifically bind to the target proteins in this study. These findings contribute to the field of nanoparticle diagnostics and can be extended to different diseases caused by overexpression of proteins in the future. While this was conducted in-vitro, conjugates can be prepared to detect cancer in-vivo and can be tested with magnetic relaxometry in the future.

Chronic diseases, such as type 2 diabetes (T2D), are difficult to manage because they demand continuous therapeutic review and monitoring. Beyond achieving the target HbA1c, new guidelines for the therapy of T2D have been introduced with the new groups of antidiabetics (GLP-1ra and SGLT2-in). Despite new guidelines, clinical inertia, that can be caused by physicians, patients or healthcare system, results in T2D not being effectively managed. This opinion paper explores the shift in T2D treatment, challenging assumptions and evidence-based recommendations, particularly for family physicians, considering the patient's overall situation in decision-making. We looked for the possible reasons of clinical inertia and poor application of guidelines in the management of T2D. Guidelines for antidiabetic drugs should be more precise, providing case studies and clinical examples to define clinical contexts and contraindications. Knowledge communication can improve confidence and should include clear statements on areas of decision-making not supported by evidence. Precision medicine initiative in diabetes aims to identify subcategories of T2D patients (including frail patients) using clustering techniques from data science applications, focusing on CV and poor treatment outcomes. Clear, unconditional recommendations for personalized T2D management may encourage drug prescription, especially for family physicians dealing with diverse patient contexts and clinical settings.

Transcranial direct current stimulation (tDCS) over the left Inferior Frontal Gyrus (IFG) was found to improve apraxia of speech (AOS) in post-stroke aphasia, speech fluency in adults who stutter, naming and spelling in primary progressive (PPA). This paper aims to determine whether tDCS over the left IFG coupled with AOS therapy improves speech fluency in patients with PPA more than sham. Eight patients with non-fluent PPA with AOS symptoms received either active or sham tDCS, along with speech therapy for 15 weekday sessions. Speech therapy consisted of repetition of increasing syllable-length words. Evaluations took place before, immediately after, and two months post-intervention. Words were segmented into vowels and consonants and the duration of each vowel and consonant was measured. Segmental duration was significantly shorter after tDCS than sham for both consonants and vowels. tDCS gains generalized to untrained words. The effects of tDCS sustained over two months post-treatment in trained words. Taken together, these results demonstrate that the tDCS over the left IFG facilitates speech production by reducing segmental duration. The results provide preliminary evidence that tDCS can maximize efficacy of speech therapy in non-fluent PPA with AOS.

Objectives: The aim of this study is to understand the rationale for the lack of interest to perform regular opportunistic oral cancer screening (OCS) by primary care providers (PCPs) and the challenges they have in incorporating OCS into their annual examination protocol. Method: Sequential exploratory mixed methods were used. Both qualitative and quantitative data from PCPs working at Nebraska Medicine were obtained. One-on-one in-depth interviews were performed to identify PCP's perceptions and challenges in performing OCS. The themes identified in the qualitative study were used as a guide in the development of survey questionnaires. The survey was emailed to all the PCPs (N=100), whose information was available on the Nebraska Medicine publicly accessible website. Results: The response rate was 34%. Approximately 60% of the participants mentioned that they currently perform oral cancer screening, but only 3.8% of the providers answered that they were performing comprehensive oral cancer screening every time. Forty-eight percent of the providers identified time as the biggest challenge. Over 35.3% of the providers answered that they perform screenings for patients with a history of tobacco (i.e., smoking) or alcohol use. Conclusion: Around half of the participants identified lack of time as their primary challenge in performing OCS and lack of knowledge as their second main obstacle. Very few provided comprehensive OCS and visual examination of the oral cavity is the only step performed often.

Background. Ovarian cysts are common in premenopausal women but can present with vague, non-specific symptoms, making discovery more challenging. Most are benign and resolve spontaneously; however, they can present, as in this case, as ovarian torsions, which is a gynecological emergency. Case presentation. A twenty-year-old female had presented over 3–4 times per year for the last 6 years to her primary doctor citing intermittent abdominal pain, irregular menstruation, dyspnea, and an enlarging abdomen circumference. The doctor stated, she was “just fat” and could, benefit from a “special camp to lose weight”, so she stopped mentioning her concerns. Upon presenting to the emergency department with acute onset abdominal pain, a computed tomography scan showed a large cyst lesion filling the abdominal and pelvic cavity. Its origin appeared to be from the left adnexa. Surgery was performed, and an acute ovarian torsion caused by a 36 cm craniocaudal left ovarian cyst was found and removed along with the left fallopian tube and 16 L of fluid. Conclusions. The value of respecting the “third presentation” rule indicates to health care providers that any patient who presents with any /or other symptoms or complaint needs to be thoroughly investigated. In this case the patient presented recurring pelvic/abdominal concerns, irregular menstruation, which warranted further investigation to safeguard fertility and prevent errors of omission. It is important to consider the differentials and be aware of vague symptoms that may lead to early recognition and effective management to prevent adverse consequences, complications, or even death.

This paper presents a method of fusion of identification (attribute) information provided by two types of sensors: combined primary and secondary (IFF) surveillance radars and ESM (Electronic Support Measures). In the first section, the basic taxonomy of attribute identification is adopted in accordance with the standards of STANAG 1241 ed. 5 and STANAG 1241 ed. 6 (draft). These standards provide the following basic values of the attribute identifications: FRIEND, HOSTILE, NEUTRAL, UNKNOWN and additional values: ASSUMED FRIEND and SUSPECT. The basis of theoretical considerations is Dezert-Smarandache theory (DSmT) of inference. The paper presents and practically uses for combining identification information from different ESM sensors and radars six information fusion rules proposed by DSmT - the Proportional Conflict Redistribution rules (PCR1, PCR2, PCR3, PCR4, PCR5 and PCR6). In the paper, rules of determining attribute information by ESM sensor equipped with the data base of radar emitters are presented. It was proposed that each signal vector sent by the ESM sensor contained an extension specifying a randomized identification declaration (hypothesis) - basic belief assignment (BBA). The paper also presents a model for determining the basic belief assignment for a combined primary and secondary radar. Results of the PCR rules of sensor information combining for different scenarios of radio-electronic situation (deterministic and Monte Carlo) are presented in the final part of the paper. They confirm the legitimacy of the use of Dezert-Smarandache theory into information fusion for primary radars, secondary radars and ESM sensors.

The effects of chemical composition and solidification rate on the solidification behavior of high-Cr white irons were investigated through directional solidification. Increasing the solidi-fication rate in hypoeutectic alloys caused the finer dendrite arm spacing as expected. The eutec-tic structure which formed in the interdendritic region comprised of M7C3 and austenite, how-ever, secondary dendrite arms of hypoeutectic alloys contained a few M7C3 particles that solidi-fied prior to the eutectic structure. The transition from cellular to dendritic solidification oc-curred at a solidification rate between 50 µm/s and 100 µm/s in a near eutectic alloy. In the near eutectic alloy with cellular solidification, a directionally arrayed in-situ composite of M7C3/austenite formed within the cell. Speckle-like feature appeared in the intercellular region due to M23C6 carbide precipitation during subsequent cooling after freezing. Like dendrite arm spacing in hypoeutectic alloys, the inter-speckle spacing and the inter-fibre spacing became finer with increasing solidification rate in the cellular solidification range.

Our skin epidermis constitutes the most important innate defense barrier against all pathogens. Therefore, even if skin lesions are common due to infections, scarring, genetic disorders, and other diseases, skin integrity is crucial for maintaining body homeostasis. Marine collagen peptides (MCPs) and Glycosaminoglycans (GAGs) have been described as potential wound healing (WH) agents. Recently, through an ex vivo clinical approach, we have demonstrated the nutricosmetic potential of fish cartilage hydrolysate (FCH), which presents a combination of collagen peptides and GAGs. Here, we coupled a clinical approach with in vitro experiments on human dermal fibroblasts (HDFs) and applied a Data Independent Acquisition - Parallel Accumulation Serial Fragmentation (diaPASEF) proteomic analysis, to assess the potential benefit of FCH in WH and its mode of action. Our results show that human serum enriched with circulating metabolites resulting from FCH ingestion, improved wound closure in scratch assays. In support, some proteins with anti-inflammatory and immunomodulatory properties or prone to promote hydration and extracellular matrix (ECM) stability showed increased expression in HDFs, after exposure to FCH-enriched serum. These findings suggest that FCH appears as a promising nutrient for WH and skin regeneration.

People from Black and Asian backgrounds are more likely to die from Covid-19 but less likely to be vaccinated, threatening to exacerbate health inequalities already experienced by ethnic minority groups. Literature suggests that mistrust rooted in structural inequality may be a key barrier to Covid-19 vaccine uptake. We need to better understand how structural inequalities influence vaccine confidence. Understanding and addressing these processes is likely to lead to longer-term impacts than information alone. We draw on health and sociological theories of structure and agency to inform our understanding of structural factors. We conducted qualitative interviews and focus groups with 22 people from London and surrounding areas in December 2021 to March 2022. Fifteen participants were members of the public from ethnic minority backgrounds and 7 were professionals working with the public to address concerns and encourage vaccine uptake. Our findings suggest that people from ethnic minority backgrounds make decisions regarding Covid-19 vaccination based on a combination of how they experience external social structures (including political authority, social positioning and racial inequality) and internal processes (what they believe and understand about Covid-19 vaccines). We may be able to support knowledge accumulation through the provision of reliable and accessible information, particularly through primary and community care. But we recommend a number of changes to research, policy and practice which address structural inequalities. These include working with communities to improve ethnicity data collection, increasing funding allocation to health conditions where ethnic minority communities experience poorer outcomes, greater transparency and public engagement in the vaccine development process, and culturally adapted research recruitment processes.

The theory of heterogeneous nucleation was initially developed as a part of condensed matter physics and later it was used as an important engineering tool to design metallurgical processes. The success leads to wide applications of the theory in metallurgical practice. For example, engineering heterogeneous nucleation in ductile iron has been used to reduce shrinkage defects, suppress cementite formation, and modify size and shape of micro-structural constituencies. This demonstrates how theoretical knowledge could benefit industry practice. This overview aims to summarize the authors’ published studies in co-authorship with colleagues and students, which covered different aspects of engineering heterogeneous nucleation in multiphase cast alloys. Several approaches for engineering heterogeneous nucleation using thermodynamic simulation and practical methods for improving efficiency of nucleation using co-precipitation technique and a local transient melt supersaturation were suggested. Automated Scanning Electron Microscopy Energy-Dispersive-X-ray (SEM/EDX) analysis and a high-resolution Transmission Electron Microscopy (TEM) were used to verify simulation predictions. Practical examples of controlling micro-porosity shrinkage in cast irons with spheroidal graphite are presented to illustrate the power of engineering heterogenous nucleation. The authors appreciate the great efforts that the co-authors have made on the original, overviewed articles here.

Drug functionalization through formation of hydrophilic groups is the norm in phase I metabolism of drugs for modification of drug action. The reactions involved are mainly oxidative catalyzed mostly by CYP isoenzymes. The benzene ring, as phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e. the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e. the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retaining, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues have been presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design and drug development.

This study evaluates the impact of a Project-Based Learning (PBL) intervention on post-pandemic educational recovery in rural Colombia, focusing on student competencies in mathematics, language, science, and 21st-century skills. Conducted in rural schools, the intervention aimed to address significant learning gaps exacerbated by the COVID-19 pandemic by providing teacher training and direct student support. A pretest-posttest single-group design was used to assess the effectiveness of the intervention, with standardized tests measuring academic competencies and an analytical rubric evaluating 21st-century skills. The results indicate significant improvements in math, language, and science test scores, with notable gains in problem-solving, collaborative work, communication, and critical thinking. However, a decline in creativity scores highlights the need for a stronger emphasis on fostering creativity within the PBL framework. Gender differences were observed, with female students generally outperforming males, suggesting the need for tailored instructional approaches. The study's limitations, including the absence of a control group, non-random sampling, and the use of subjective assessment methods, are acknowledged, with recommendations for future research to address these issues. Despite these limitations, the findings underscore the potential of PBL to enhance student learning outcomes in rural settings, offering valuable insights for educators and policymakers aiming to support educational recovery and development in similar contexts. Further research is recommended to explore the long-term effects of PBL and to refine the intervention for broader implementation.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today we are talking about a new paradigm - cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous hu-mour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side ef-fects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGF affects both the structural and functional changes in the outflow pathway and IOP is required to de-velop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study we evaluated the effects of TGF-1 and -2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are pre-sented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in net-works to control cellular pathways and processes, a pathway-centric view of miRNA ac-tion is also reported. Evaluating TGF-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

Aim: The purpose of this study is to evaluate the remineralization potential of primary teeth enamel after being exposed to different laser diode therapy. Methods: Ninety-six vestibular primary teeth enamel samples were divided into eight groups (n=12) with varying treatments: control (G1), CPP-ACP-fluoride varnish (G2), diode lasers at 980 nm (G3), 808 nm (G4), 450 nm (G5), 980 nm + CPP-ACP-fluoride varnish (G6), 808 nm + CPP-ACP-fluoride varnish (G7), and 450 nm + CPP-ACP-fluoride varnish (G8). Each sample was assessed using DIAGNOdent® at baseline, post-treatment, and post-pH cycle re-mineralization. SEM imaging was performed before and after treatment and following the pH cycle. Results: The results indicated that the 980 nm and 808 nm diode lasers, both alone and in combination with CPP-ACP-fluoride varnish, either maintained or increased the calcium (Ca) weight percentage (Wt%) in the enamel. The 980 nm diode laser combined with CPP-ACP-fluoride varnish (G6) showed a significant increase in Ca Wt%, suggesting a strong remineralization effect. Similarly, the 808 nm diode laser alone (G4) also promoted a substantial increase in Ca Wt%. In contrast, the 450 nm diode laser, whether applied alone or in combination with CPP-ACP-fluoride varnish, resulted in a lower Ca Wt% and an increase in phosphorus (P) Wt%. Most groups, except for the CPP-ACP-fluoride varnish alone (G2), demonstrated an increase in P Wt%, indicating a complex interaction between laser therapy and enamel remineralization. Conclusions: The combined use of laser therapy with CPP-ACP-fluoride varnish significantly enhanced the remineralization of temporary teeth enamel. The 980 nm diode laser + CPP-ACP-fluoride varnish showed the most pronounced improvement in remineralization, while the 808 nm diode laser alone also effectively increased calcium solubility. These findings suggest that higher wavelength diode lasers, particularly when combined with remineralizing agents, can effectively enhance the mineral content of primary teeth and promote enamel remineralization.

Cisplatin (CDDP) is a platinum-based drug effective against various cancers, including lung, bladder, prostate, ovarian, esophageal, stomach, and cervical cancer and malignant lymphoma. It plays a central role as the first choice in current anticancer therapy. However, CDDP causes serious side effects, such as neurological disorders, myelosuppression, and renal damage, because it is a small molecule indiscriminately distributed in normal tissues. Therefore, it is very important to prevent or attenuate CDDP toxicity. We hypothesized that liposomalization of CDDP could alleviate serious side effects. Therefore, this study aimed to evaluate the safety and efficacy of CDDP liposomes. A patient with multiple recurrent liver metastases from metastatic nasal carcinoma was administered CDDP liposomes with consent. Magnetic resonance imaging showed that the patient remained stable-diseased; however, no apparent side effects were observed, and blood draw data showed no worsening of renal function. Patients undergoing partial pancreatectomy and jejunoileal biliary anastomosis for biliary tract cancer who consented to receive CDDP liposomes demonstrated a partial response on angiographic computed tomography; however, they showed slight fatigue. To our knowledge, the present study is the first in Japan to suggest that liposomalization of CDDP may have anticancer effects while alleviating renal damage and bone marrow suppression.

To date, the patent foramen ovale (PFO) does not get the deserved medical attention. The PFO poses a serious threat to health and even life of mankind. The first respective case report in the medical literature dates back to the 19th century. It led to death. The fact that a PFO is present in roughly 25% of people underscores its overall potential to do harm. Yet at the same time by the sheer number, it discourages the medical community from screening for it and from treating it. About 5% of the population have particularly dangerous forms of PFOs. Such PFOs portray a high enough risk for clinical events, the likes of death, stroke, myocardial infarction, or ocular, visceral, and peripheral embolism, to justify screening for them. Highly significant health incidents being at stake, it appears obvious that PFO closure should be used for primary prevention. This is supported by the fact that closing a PFO is the simplest intervention in cardiology, with presumably the highest clinical yield. Being mainly a preventive measure, PFO closure represents a mechanical vaccination. When closing PFOs for one of the rarer therapeutic indications (migraine, platypnea orthodeoxia, etc.), patients automatically profit from the collateral benefit of getting at the same time mechanically vaccinated for life against paradoxical embolism. Vice versa, closing a PFO for prevention of paradoxical embolism not infrequently betters or cures migraine or exercise dyspnea, thereby improving quality of life as a collateral benefit.

Despite being a rare disease worldwide, rabies has the highest morbidity and mortality rates, with nearly all symptomatic cases leading to coma and death. Rabies represents an infectious disease caused by the Rabies virus (RABV), which is part of the Lyssavirus group and the Rhabdoviridae family, and it mainly spreads through the bite and scratch of an infected mammal, but particularly of wild animals, such as bats, foxes, wolves and racoons, and of domestic animals, such as dogs and cats, in rabies-prone areas of the world. Airborne transmission has been deemed as extremely rare, and no clinical case as such has been recorded worldwide yet, except in the enclosed environment, such as research laboratories and caves where infected bats are present. Domestic mammals, such as dogs and ferrets, represent other important reservoirs of disease transmission, and the human cases of Asia and Africa amount approximately 95% of all human cases worldwide. Infected animals most commonly start transmitting the virus once the first symptoms have occurred, and if they experience disease aggravation and death within 10 days, a case of rabies is registered, more easily if the incidence occurred in the urban area and then, any person or animal that had been potentially exposed are strongly recommended to receive the inoculation. It is rare for asymptomatic mammals to transmit the illness. Most First-World and several Second-World countries have recently been declared dog rabies-free by the World Health Organization. The disease can only be treated prophylactically, with three doses of a vaccine containing an inactivated form of RABV, or with five doses of the vaccine and two doses of anti-RABV immunoglobulins within 28 days if the patient is believed to have been exposed to the virus beforehand. It has been projected that, once the viral load reaches elements of the central nervous system, prophylactic approaches are no longer effective, even if symptoms have not begun yet, and this highlights the urgent trait of the medical condition, strongly recommending exposed people to receive the prophylactic doses immediately after the potential exposure to the virus. The pathogen first infects the bodily fluids, before reaching the peripheral nervous system, from where it will gradually move toward the spinal cord or the encephalon, at a speed of movement ranging from 1 to 40 cm per day. It was also found, in extremely rare circumstances, to infect the nasopharyngeal cavity and the lungs. The primary cause of a successful, gradual advance of the viral load toward the point of clinical no-return for the patient - the CNS - is a complex mechanism of induced innate immune evasion, with the interferon system being heavily targeted and silenced by RABV proteins. The ‘Milwaukee’ protocol is locally believed to decrease the mortality rate of the clinical illness to approximately 80%, although significantly more research is required in this sense. First-line immune evasion represents the central mechanism developed by viruses during their evolutionary process to gain control over human immunity, so it could be the development and adjustment of a counter-offensive to this evolutionary operating system that could address the core elements of the problem. Human recombinant Type I and Type III Interferons were found to be significant vaccine adjuvants and to considerably delay the clinical onset of the disease. Despite their central role in natural immunity-based prophylaxis, vaccine support and, in often cases, vaccination per se, a local administration of IFNs as such may not be enough to tackle the core problem of the endemic disease, and a specific and systemic treatment of potential host cells with IFN I and III, as well as IFN-stimulating proteins, may constitute a major research requirement in the coming years of disease investigation, as the inoculation efforts with the inactivated virus and immunoglobulin administration continue. The administration of a relatively low dosage of somatic Natural Killer cells, gamma-interferon and perhaps, of somatic helper CD4+ and somatic cytotoxic CD8+ T-lymphocytes treated with alpha-, beta- and lambda-interferon could be merged with the administration of a similar dosage of alpha-, beta- and lambda-interferon during the efforts to develop an effective and less costly prophylactic vaccine against rabies. A combination of a nasal substance containing a low dosage of IFN I and III with a reduced concentration of neutralized RABV copies, and/or with a low dose of anti-RABV IgA antibodies, could also be tested for humans for the purposes of pre- and post-exposure prophylaxis.

The concept of gray-zone lymphoma (GZL) has been progressively refined since its in-troduction in the literature in 1998. For several years, it was applied to a rather broad spectrum of conditions, posing the problem of the differential diagnosis between any type of Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma, with special reference to primary mediasti-nal forms (PMBL). Officially recognized as a provisional entity in the 4th and revised 4th editions of the WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues with the term “B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lym-phoma and classical Hodgkin lymphoma”, it was limited to tumours, which showed either morphologic features reminiscent of classical HL (CHL) but carrying a complete B-cell pheno-type or conversely provided with a PMBL morphology but revealing CHL phenotypic charac-teristics. The definition of GZL has been further revised in the recently published International Lymphoma Classification and 5th Edition of the WHO Classification of Haemato-lymphoid Tu-mours, which have limited it to mediastinal neoplasms based on emerging molecular evidences. The aim of this review is to critically discuss the issue of GZL, also in the light of the suboptimal response to current therapies.

Measures in the SARS-CoV-2 pandemic were based on rough ideas regarding transmission routes of pathogens. Quantified models of physical transmission routes are mostly lacking, a gap to be filled. Vaccines and medicines, important, are not studied here. We first survey main routes, from primary production in the alveoli and intestines to emissions, environmental routes, to exposure and alveolar infection. Next, specific routes are modelled, mostly at a preliminary state, open to systematic improvement. Starting from a standardized emitter, modelling results show extreme differences in potential exposure, in a range covering up to 4 orders of magnitude. The outcomes are pathogen-specific, already different between SARS-CoV-2 and influenza. Extreme exposures may result in smaller spaces; with lower ventilation rates; with a high density of emitting persons per m3; who stay there for several hours; and visitors staying more than a few minutes. In spaces where a build-up of concentrations is low, exposures are low, lowest in open air situations. A main conclusion for the next pandemic is that a quantified model can give strong guidance on where measures are primarily due. For SARS-CoV-2, ventilation can be improved short-term. Longer-term, effective ventilation rules and adaptation of buildings may reduce high exposures substantially.

Quantum mechanics could be studied through polynomial algebra, as has been demonstrated by a work (“An approach to first-principles electronic structure calculation by symbolic-numeric computation” by A. Kikuchi). We carry forward the algebraic method of quantum mechanics through algebraic number theory; the basic equations are represented by the multivariate polynomial ideals; the symbolic computations process the ideal and disentangle the eigenstates as the algebraic variety; upon which one canbuild the Galois extension of the number field, in analogy with the univariate polynomial case, to investigate the hierarchy of solutions; the Galois extension is accompanied with the group operations, which permute the eigenstates from one to another, and furnish the quantum system with a non-apparent symmetry. Besides, this sort of algebraic quantum mechanics is an embodiment of the class field theory; some of the important consequences of the latter emerge in quantum mechanics. We shall demonstrate these points through simple models; we will see the use of computational algebra facilitates such sort of analysis, which might often be complicated if we try to solve them manually.

Alkyl moieties—open chain or cyclic—are common in drug molecules and can be internal or terminal. The open-chain alkyls can be linear or branched; the cyclic alkyls may be substituted. Usually, the branches in open-chain alkyls and substituents in cycloalkyls influence both the pharmacokinetics and pharmacodynamics of a drug molecule. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some parent-drug equiactive hydroxy metabolites have been developed into metabolite ester prodrugs, while some of the parent-drug carboxy metabolites have been developed into metabolite drugs. In this review, we present and discuss the above state of affairs for a variety of drug classes, using selected drug members to show the effect on pharmacologic activity as well as dependence of the metabolic change on drug molecular structure. Some subtexts found to manifest from the hydroxy and carboxy functionalization of alkyl moieties in drug molecules are presented and discussed. The review provides basis for informed predictions of (i) structural features required for metabolic hydroxy and carboxy functionalization of alkyl moieties in existing or planned small drug molecules; and (ii) whether the resulting metabolites will possess pharmacologic activity or be devoid of it.

A new framework in quantum chemistry has been proposed recently ("An approach to first principles electronic structure calculation by symbolic-numeric computation'' by A. Kikuchi). It is based on the modern technique of computational algebraic geometry, viz. the symbolic computation of polynomial systems. Although this framework belongs to molecular orbital theory, it fully adopts the symbolic method. The analytic integrals in the secular equations are approximated by the polynomials. The indeterminate variables of polynomials represent the wave-functions and other parameters for the optimization, such as atomic positions and contraction coefficients of atomic orbitals. Then the symbolic computation digests and decomposes the polynomials into a tame form of the set of equations, to which numerical computations are easily applied. The key technique is Grröbner basis theory, by which one can investigate the electronic structure by unraveling the entangled relations of the involved variables. In this article, at first, we demonstrate the featured result of this new theory. Next, we expound the mathematical basics concerning computational algebraic geometry, which are necessitated in our study. We will see how highly abstract ideas of polynomial algebra would be applied to the solution of the definite problems in quantum mechanics. We solve simple problems in "quantum chemistry in algebraic variety'' by means of algebraic approach. Finally, we review several topics related to polynomial computation, whereby we shall have an outlook for the future direction of the research.

This literature review investigates the morphological and behavioral significance of the horns of Carnotaurus sastrei, a theropod dinosaur from the Late Cretaceous period. Through a comprehensive analysis of fossil specimens, comparative anatomy, and biomechanical modeling, this review explores the evolutionary adaptations and potential functions of these distinctive cranial structures. The horns of Carnotaurus are hypothesized to serve multiple roles, including species recognition, thermoregulation, and intraspecific combat. Our findings suggest that its cranial horns likely served a primary role in species recognition, intimidating rivals and signaling mating readiness. It also could have been used occasionally in head-butting contests, potentially as a display of dominance, but likely did not play a role in thermoregulation. Additionally, we examine the ecological context in which Carnotaurus lived, assessing how environmental factors could have influenced the development of such features. The implications of this study extend to broader discussions on the functional morphology and adaptive strategies of theropod dinosaurs, highlighting the complex relationship between form and function in the evolutionary history of predatory dinosaurs like Carnotaurus sastrei.