Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

Myasthenia gravis (MG) is a disease characterized by typical clinical and immunopathogenic pe-culiarities, which correlate with age and sex/gender. Accordingly, MG patients show thymic al-terations and auto-antibodies productions, that can be the expression of a different pathogenetic mechanism related to age and gender. This determines, in relation to age at and sex/gender, a dif-ferent MG onset, prognosis, and outcome. Therefore, diverse MG forms can be identified, classi-fied, and characterized in relation to their different features, and precisely there are early onset and late-onset forms of MG. It has been hypothesized that the cause of appearance the two diverse forms of MG can be ascribed mainly to the diverse genetic and epigenetic factors. In this narrative review, we will analyze and discuss about the interplay of age- and sex-related factors (i.e. genet-ic and epigenetic factors) related to two different MG forms and how they contribute to their di-verse pathogenesis.

Health-Related Quality of Life (HRQoL) encompasses the comprehensive evaluation of an indi-vidual's health and well-being across multiple dimensions. Mindfulness, recognized as a scientifi-cally supported strategy for anxiety management, plays a role in enhancing both physical and mental health. The Gut-Brain Axis (GBA) serves as the bidirectional communication link between the gastrointestinal system and the central nervous system. This study aims to explore the associa-tion between Mindfulness and factors influencing the GBA in both healthy individuals and those with Inflammatory Bowel Diseases (IBD). A cross-sectional investigation involved 338 adults, in-cluding 50 IBD patients, utilizing validated Greek scales for Mindfulness (MAAS-15), Mediterra-nean Diet (14-MEDAS), and HRQoL (EQ-5D-5L). The questionnaire gathered demographic, an-thropometric, and lifestyle data. Among healthy participants, EQ-5D-5L showed a moderate cor-relation with the MAAS-15 scale (r=0.389, p

Objective To investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise regularly. Furthermore, the study examined the correlations between capillary function and other health-related indicators. Design A single- center pilot trial Setting Faculty of Health, Tsukuba University of Technology, Japan Participants hypertensive community-dwelling elderly people Intervention Microcirculation was observed before and 1 min after arm-curl exercise by means microscopy of capillary with non-exercised limb. Additionally, we examined other health-related indicators. Outcome measures: Acute effects of reperfusion on nailfold density, flow, and diameters. Secondary outcomes included the correlations between microvascular parameters and other health-related indicators. We hypothesized that brief exercise could enhance microcirculation reperfusion and correlate with other health-related parameters.　 Results: There were 20 participants with a mean (SD) age of 67.1 (5.8) years. The capillary flow rate changed from 2.3±6.7 to 2.7±0.2 log µm/s (P

The predatory mirids Macrolophus pygmaeus Ramber and Nesidiocoris tenuis Reuter (Heteroptera: Miridae) are used for the biological control of Tuta absoluta Meyrick (Lep.: Gelechiidae) and other pests in tomato greenhouses. The functional response of 1 (young) and 10 (old) days old adult females and males of M. pygmaeus and N. tenuis on eggs of T. absoluta, was determined on tomato at two temperatures (20° and 25°C) and LD 16:8 and found to be Type II. M. pygmaeus females exhibited higher predation efficiency, than males at both tested temperatures. Young M. pygmaeus females had a higher efficiency than old ones, whereas males had a low efficiency irrespective of age. The predation efficiency of N. tenuis was high (but lower than M. pygmaeus) in both young females and males, although old females had a higher efficiency than the respective males. Our results show that the two predatory species have different functional response characteristics to their prey depending mainly on sex and age which may affect their role as biological control agents.

The production of municipal solid waste incineration bottom ash (MSWIBA) is very massive and has the potential to replace cement despite the problems of complex composition, uneven particle size distribution, and low reactivity. This paper adopts sodium silicate activation of MSWIBA-slag to improve the reactivity to prepare composite cementitious materials. It explores the hydration performance study of the composite cementitious materials by isothermal calorimetric analysis, Fourier Transform Infrared (FTIR) spectroscopy, XRD physical diffraction analysis, and SEM/EDS tests. SEM/EDS tests will be used to explore the hydration properties of the composite gelling. The results showed that with the increase of MSWIBA doping, the porosity between the materials increased, the degree of Hydration decreased, and the compressive strength decreased with the rise of MSWIBA. When sodium silicate increased from 25% to 35%, too much alkaline material occurred over the alkaline effect, which inhibited the Hydration of the particles, and the degree of hydration reaction decreased, and the compressive strength decreased accordingly; the exothermic process of Hydration can be mainly divided into five stages, quartz and calcite did not participate in the hydration reaction completely, and sexual aluminum participated in the hydration reaction. The vibrational peaks of Si-O-Ti (T = Si and Al) were present in the material. The vibrational peaks of XRD, FTIR, and SEM-EDS all indicate the presence of silica-aluminate network structures in the hydration products, mainly N-A-S-H and C-A-S-H gels.

Abstract: Dispersal strategies of a species can affect its invasion success. Investigation into the dispersal strategies of invasive species in relation to different factors helps our understanding of the invasion mechanisms and provides knowledge for population management and invasion evaluation. Tetranychus ludeni Zacher (Acari: Tetranychidae) is an invasive species, which is native to Europe but now cosmopolitan. Here, we examined the effects of age and density on dispersal in mated females. Our results show that older females with more eggs were more likely to disperse and moved longer distances than younger ones with fewer eggs. Older females spread most of their eggs out of the natal habitats and over longer distances, which reduced competition and increased offspring fitness. Females significantly increased dispersal probability and distance with the increase of population density to avoid crowding. The synchronization of dispersal and reproduction, along with the positive density-dependent dispersal strategy, may facilitate habitat colonization and invasion speed of T. ludeni.

This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during mature and aged stages. Dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. Microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups, as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (P < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (P < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5 – 7 years (P < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (P < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (P < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (P < 0.05). Interestingly, the skin antioxidant capacity and oxidative damage exhibited significant positive and negative correlations, respectively, with the population of active secondary hair follicles (P < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

Although migraine belongs to the main causes of disability worldwide the mechanisms of its pathogenesis are poorly known, which is among the reasons that this disease is underdiagnosed and undertreated. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective markers of its occurrence and severity. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. Migraine patients displayed lower urinary levels of 5-HIAA and KYNA, but KYN and QA were enhanced as compared with the controls. Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios. Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score, monthly migraine, and monthly headache days. A negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be an easy-to-determine marker of migraine occurrence and severity and may contribute to the identification of migraine patients with depression.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Multiple myeloma (MM) accounts for about 10 to 15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60-minute workouts 3 times a week was conducted. Body mass and composition and the levels of: vitamin D, calcium and phosphorus, beta2-microglobulin and albumin were examined before and after completion of training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN) and Tartrate-resistant acid phos-phatase 5b (TRACP 5b). There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumines was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p=0.001 and p=0.022, re-spectively). The change in the concentration of this vitamin negatively correlated with the con-centration of TRACP 5b (r=-0.413, p=0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p=0.026, time vs. group: p=0.033) and TRACP 5b (time: p

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

The analysis and simulation of water quality in distribution networks is a complex issue of great concern today. The analysis of the evolution of water age, as a simple indicator of water quality in the network, is of great interest in both design and operation phases. Understanding the factors that have the strongest influence on water quality is key to developing adequate strategies aimed at preserving it. This paper firstly analyses the factors with biggest influence in the tanks water age, to support the selection of the most appropriate configuration from the point of view of water quality during design phases. Then, the main considerations when modelling tanks following the different mixing models considered in Epanet have been presented. Also, a real tank behaviour has been characterised through field measurements and Epanet simulations in order to determine the best fitted mixing model.

Lower limb exoskeletons have the potential to reduce the prevalence of work-related musculoskeletal disorders; however, they often lack user-oriented control strategies. Human-in-the-loop (HITL) controls can adapt an exoskeleton’s assistance in real-time, to optimize the user-exoskeleton interaction. This study presents a HITL control for a knee exoskeleton to minimize the users’ physical effort, a parameter innovatively evaluated by their interaction torque with the exoskeleton (a muscular effort indicator) and metabolic cost. This work innovates by estimating the user’s metabolic cost within the HITL control through a machine-learning model. The regression model was able to estimate the metabolic cost, in real-time, with a root-mean-squared error of 0.66 W/kg and a mean absolute percentage error of 26%, making faster (10s) and less noisy estimations than a respirometer (K5, Cosmed) device. The HITL reduced the user’s metabolic cost and interaction torque by 7.3% and 32.3%, respectively, when compared to a zero-torque control. The developed HITL control surpassed both a non-exoskeleton and a zero-torque condition regarding the user’s physical effort, even for a simple task such as slow walking. Furthermore, the user-specific control enabled a lower metabolic cost than the non-user-specific assistance. This proof-of-concept demonstrated the potential for HITL controls in assisted working.

Gold occurrence Maljavr, located in amphibolite metamorphosed rocks in the Uragubsky greenstone belt, is the first gold prospect connected with conglomerates of Archean age, found in the Fennoscandian Shield. Gold mineralization is controlled by a series of lenses of altered rocks in biotite gneiss-metaconglomerate. The age of zircon from biotite gneiss in the zone of alteration is 2665±22 Ma, this is considered as the time of alteration processes. Biotite gneiss and altered rocks were later intruded by tourmaline granite pegmatite at 2508±7Ga, the pegmatite caused recrystallization of sulfide minerals in the altered rocks. Visible gold in association with bismuth minerals native bismuth, ehrigite (the second finding in the world), maldonite, bismuthinite, joseite-B, hedleyite was found exceptionally in polymineral inclusions in recrystallized arsenopyrite and löllingite. The age of pegmatite 2508±7Ma we regard as the time of formation of gold-bismuth mineralization. Geological position of the Maljavr occurrence, the linkage of gold mineralization with pegmatite, geochemical association Au-As-Se-Te-Bi in the mineralized rocks – all these characteristics correspond to intrusion-related gold deposits. Biotite gneiss-metaconglomerate, hosting the mineralized altered rocks, was the probable primary source of arsenic and gold for mineralization.

In the context of artificial intelligence's pervasive integration across sectors, the rigorous examination of methodologies used in constructing mathematical models is imperative. This study delves into facial recognition models, particularly in their ability to extract features such as age. We address the prevalent practice of training models with unbalanced datasets and its implications for model performance and bias introduction. Utilizing 27,305 facial images, we investigate the influence of dataset imbalance on age prediction based on ethnicity. Employing preprocessing and oversampling techniques, we equalize sample sizes across ethnicities. A Convolutional Neural Network trained on the balanced dataset serves as our baseline, while three additional models undergo training with a 50% sample size reduction for each group to assess accuracy degradation. Our findings reveal a notable decline in accuracy for ethnic groups with reduced representation. The Asian group experiences a 67.94% accuracy deterioration, followed by a 51.60% drop for the Black group, and a 38.46% decline for the White group. These results underscore the sensitivity of certain ethnic groups to underrepresentation, highlighting the nuanced impact on age prediction accuracy. While a 50% reduction in representation does not uniformly result in a 50% accuracy decline, it unquestionably influences predictive accuracy for affected groups.

Abstract: Exercise has been repeatedly shown to be safe and beneficial for cancer survivors. However, there is no normative guideline for exercise prescription, and it is under exploration. Therefore, this literature review aims to provide some advice for the formulation of exercise prescriptions for patients with breast cancer-related lymphedema (BCRL) from the perspective of reducing lymphedema severity. A review of relevant studies published before November 2023 was conducted using three scientific databases PubMed, Embase, and Scopus. A total of 2696 articles were found. Eventually, 13 studies fulfilled the inclusion criteria and were included in this literature review. We concluded daily, or nearly daily exercise at home can be recommended. Moreover, reduced lymphedema severity may not be maintained after ceasing the exercise program, so exercise should be a lifelong practice.

In this case series, we examine the impact of the Titan-iR Pro® deep spectrum biotherapeutic device on brain function in healthy individuals. Here we present 15 participants, aged 26-68 years, who enrolled in this open-label study, designed to assess the effect of a single 15-minute course of deep spectrum biotherapy on brain function. Although symptom-free upon enrollment, participants had diverse medical histories with some displaying early signs of cognitive decline. As part of the evaluation, all participants engaged in electroencephalogram (EEG) recording sessions that focused on assessing event-related potential (ERP) evaluations, including audio P300 amplitudes and latencies (speeds), neurocognitive testing, and physical reaction times. Following the Titan-iR Pro intervention an improvement in EEG-based cognitive markers was observed. These results underscore the importance of further investigation into the potential of advanced and deep spectrum photobiomodulation in the prevention and treatment of cognitive decline and other neurological disorders.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

Smoking is a pervasive global health concern associated with a myriad of diseases, but its impact on cellular aging, particularly in relation to telomeres, is increasingly recognized. Telomeres, protective caps at the ends of chromosomes, play a crucial role in maintaining genomic integrity. This review critically examines the existing evidence on the association between smoking and telomere atrophy, exploring the molecular mechanisms involved and the implications for accelerated aging and heightened disease risk. The comprehensive analysis encompasses both cross-sectional and longitudinal studies, elucidating potential gender and age disparities. Insights into the molecular pathways linking smoking to telomere shortening are discussed, along with the broader implications for public health. The review concludes by outlining potential interventions and suggesting future research directions in this critical area.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

The recent availability of commercial platforms for behavioral analysis in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor response (VMR). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood. In this work we have analyzed in 143 larvae the influence of age (5-8 days post-fertilization), time of day (8:00, 10:00, 12:00, 14:00; 16:00, 18:00, and 20:00 h), and experiment (three experiments performed at different days) on BLA and VMR results (4,004 analyses for each behavior). Results from both behaviors were adjusted to a Random-Effects linear regression model using generalized least squares (GLS), including in the model the effect of the three variables, the second-way interactions between them and the three-way interaction. The results presented in this manuscript show a specific effect of all three intrinsic factors and their interactions on both behaviors, supporting the view that the most stable time period for performing these behavioral assays is from 10:00 am to 04:00 pm, with some differences depending on age of the larva and the behavioral test.

The outstanding occurrences of red wood ant nests (RWA; Formica rufa-group) at two study sites in the Oberpfalz, NE Bavaria, Germany, could be confirmed by the 2023 re-inventory (a total of 5,393 nests and an increase by ≈8 %). RWA nests preferred mature and medium mature pine-dominated forests. Standing and downed dead wood do not negatively influence nests. Nest counts with woodpecker cavities and the diversity of the herb layer increased. The highly clustered nests in NW-SE direction suggests a strong interaction between nests distributions and the tectonic environment. Our developed (re-)inventory approach in combination with the comprehensive photo database is a valuable tool for a) monitoring the entire forest habitat including woodpecker cavities and dead wood in, at and around nests, and b) identifying GeoBio-Interactions. Such a comprehensive approach leads to more accurate and realistic counts of RWA nests during (re-)inventories and provides scientific evidence of the status quo of RWA occurrence. Our results disproved the unfounded and scientifically unsubstantiated blanket statement by laymen of the ASW Landesverband Bayern e.V. that RWA nest numbers in the Oberpfalz or even in the entire Bavaria are in sharp decline. We suggest seven to eight years as a suitable time interval for re-inventories.

Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7,738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method. We further applied Cochran’s Q statistical analysis, MR-Egger intercept, and MR-PRESSO for heterogeneity and pleiotropy assessment, alongside a Bonferroni correction ((P

The COVID-19-medical emergency has ended worldwide, yet there is still a need to evaluate the psychological impact of these years of unprecedented changes on students’ life. Methods: This study aims to assess and compare COVID-19-related stressors (Relationships-and-Academic-Life; Isolation; Fear-of-Contagion) and psychophysical symptoms reported by university students in April-2020, April 2021, and April 2022. The predictive role of COVID-19-related stressors on psychophysical symptoms within each time was also tested. Data were collected among 637 university students in April-2020 (n = 197), April-2021 (n = 200), April-2022 (n = 240). Results: In April-2022, perceived Isolation and Fear-of-Contagion decreased from the peak registered in April-2021, but stress related to Relationships-and-Academic-Life remained noteworthy high. A sharp and ongoing increase in psychophysical symptoms was found, with more than 50% of students reporting clinical levels of Sleep-Disorders, Depression, Psychoticism, and Interpersonal-Sensitivity. In April-2022, students still perceiving stress related to Relationships-and-Academic-Life and Isolation were at risk for Anxiety, Somatization, and Sleep-Disorders, while those still perceiving stress related to Fear-of-Contagion were also at risk for Depression, Obsessive-Compulsive, and Psychoticism. Conclusion: Findings emphasized the long-lasting detrimental effects of the COVID-19-related stress. Interventions must pinpoint the complex post-pandemic adjustment process and their effects on university students' psychophysical health.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

This research challenges the traditional perspective on consumer behavior, which focuses on external factors shaping the sequential stages of decision-making. Instead, it proposes a paradigm shift by treating the decision-making process itself as an independent variable, exploring its impact on various outcomes like purchasing behavior, brand loyalty, and post-purchase satisfaction. This novel approach offers deeper insights into the intricacies of consumer behavior, particularly in the digital age. By uncovering the reciprocal relationships between the decision-making process and other variables, the research provides a more nuanced understanding of how consumers navigate today's complex landscape. It further delves into how variations in the decision-making process across diverse consumer groups influence various outcomes, recognizing the unique characteristics and needs of different demographics. The research also acknowledges the interplay of psychological, social, and contextual factors that shape both the decision-making process and its downstream effects, offering a comprehensive understanding of the multifaceted influences on consumer behavior. Ultimately, by studying the decision-making process as an independent variable, this research aims to equip businesses and researchers with valuable insights, enabling them to better navigate the ever-evolving world of consumer behavior.

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer became the leading cause of death in several countries. Our objective was the determination of whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study is a nationwide analysis performed in Hungary. Study population was divided into a group with type 2 diabetes mellitus and into a non-diabetic group. The primary outcome was the risk related to overall cancer incidence. A key secondary outcome was the overall incidence of cancer in distinct study years. Further outcomes were the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, P&lt;0.0001) in patients with diabetes as related to controls. The odds ratio was higher in males than in females. The highest risk was found in the 18-39-year-old subgroup. The annual cancer incidence rate declined in controls, but not in patients with diabetes. Several types of cancer showed a decreasing tendency in non-diabetic controls.; (4) Conclusions: type 2 diabetes is associated with a higher risk of cancer. High risk in young patients with type 2 diabetes suggests that these young individuals should be considered as a risk group.

INTRODUCTION: With an increase in the aging population, the application of evidence-based practice in geriatric education can strengthen knowledge, skills, and clinical experience for healthcare students caring for older adults. Age Friendly Health Systems (AFHS) is one of the frameworks founded on providing evidence-based and low-risk care centered on what matters most to older adults, their families, and caregivers. Virtual Reality (VR) platforms are gaining popularity due to their ability to provide an immersive, hands-on learning experience resembling an actual medical practice or care setting. Immersive learning enhances students’ sensory perceptions, promoting an innovative and engaging way of acquiring concepts that are difficult to teach in real life. This study aimed to design, develop, implement, and evaluate a case-based training module highlighting AFHS and educating medical students on the 4Ms approach in geriatric care (What Matters, Medication, Mentation, and Mobility). METHODOLOGY: The project was a feasibility study completed in two phases. Phase one included planning and development of a case-based scenario incorporating 4Ms of AFHS. Phase two included implementing and evaluating the VR training module into the geriatric curriculum for medical students. RESULTS: The final VR case displays a hospital and post-acute setting where an elderly patient is admitted for a hip fracture. Students learn how to triage and treat patients from admission to discharge while demonstrating their knowledge of AFHS. Approximately 10% of students completed the evaluation survey, and preliminary results indicate significant knowledge change in pre-post scenario-based training on AFHS. CONCLUSION: The VR education platform and embedded scenario promise an innovative adaptation of technology in learning the concepts of the 4Ms of AFHS. However, future studies should explore VR education with clinical assessment evaluation to ensure competence in providing Age-Friendly care.

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

Assessment of health-related quality of life (HRQoL) after pediatric traumatic brain injury (TBI) has been limited in children and adolescents due to a lack of disease-specific instruments. To fill this gap, the Quality of Life after Traumatic Brain Injury for Children and Adolescents (QOLIBRI-KID/ADO) was developed for the German-speaking population. Reference values from a comparable general population are essential for comprehending the impact of TBI on health and well-being. This study examines the validity of the German QOLIBRI-KID/ADO in a general pediatric population in Germany and provides reference values for use in clinical practice. Overall, 1997 children and adolescents aged 8-17 years from the general population and 300 from the TBI population participated in the study. The questionnaire was tested for reliability and validity. A measurement invariance (MI) approach was used to assess the comparability of the HRQoL construct between both samples. Reference values were determined by percentile-based stratification according to factors that significantly influenced HRQoL in regression analyses. The QOLIBRI-KID/ADO demonstrated strong psychometric properties. The HRQoL construct was measured largely equivalently in both samples, and reference values could be provided. The QOLIBRI-KID/ADO was considered reliable and valid for assessing HRQoL in a general German-speaking pediatric population, allowing for clinically meaningful comparisons between general and TBI populations.

Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems, complicating the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In this review, the clinical usefulness and remaining problems of anti-HBc antibody and HBcrAg were summarized.

(1) Background/Objectives: Accurate determination of chronological age is crucial in legal dental identification. This study aimed to compare the effectiveness of different formulas in estimating the age of a Brazilian subpopulation by analyzing the pulp/tooth ratio of the maxillary canine and mandibular second premolar in panoramic and periapical radiographs. (2) Methods: The sample consisted of panoramic and periapical radiographs of 247 individuals. The file of each radiograph was opened in the Adobe Photoshop CS4® program to outline and obtain values in pixels for calculating the pulp/tooth ratio. Statistical analysis was conducted using the SPSS program, with a significance level set at 5%. (3) Results: The interclass correlation coefficient demonstrated excellent intra-observer agreement (0.990 – 0.999). The determination coefficients (R2) suggested that only 30-35% of the actual age results could be explained by the pulp/tooth ratio. Smallest differences were observed with Cameriere's formula for the mandibular second premolar on panoramic radiographs (+4.1 years). The greatest differences were found with the formulas for the mandibular second premolar in panoramic radiographs of the Korean (+12.5 years) and Portuguese (-12.1 years) populations. (4) Conclusions: The equations employed allowed for estimating the age of a Brazilian subpopulation and showed little agreement between the actual age and the estimated age.

This narrative review provides a thorough examination of medication-related osteonecrosis of the jaw (MRONJ), encompassing its etiology, the role of drug holidays, and contemporary treatment approaches. By systematically analyzing literature from 2022 to 2023, this paper synthesizes the latest findings and trends in MRONJ research. The study emphasizes the importance of a holistic understanding of MRONJ, beginning with its etiological factors, assessing the therapeutic implications of drug holidays, and evaluating the efficacy of current treatment modalities. This review aims to offer clinicians and researchers a consolidated resource, highlighting the intricacies of MRONJ management and proposing directions for future research. Through this comprehensive approach, the paper seeks to advance the understanding and treatment of MRONJ, ensuring an evidence-based, patient-centric approach in clinical practice.

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declined responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Seventeen eyes with PNV that underwent half-fluence PDT with adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9–18 mm from the fovea. The <9- and 9–18-mm subfields were divided into four quadrants. Choroidal thickness in each subfield decreased significantly after half-fluence PDT (P<0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9x9-mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. In conclusion, half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

To investigate the associated mechanisms concerning collagen and the expression of apoptosis-related proteins in porcine skin injuries induced by laser exposure, pig skin was treated with a 1064 nm laser. The healing process of the laser-treated areas, alterations in collagen structure, and changes in apoptosis were continuously observed and analyzed from 6 hours to 28 days post-irradiation. On the 28th day following exposure, wound contraction and recovery were notably sluggish in the medium-high dose groups, displaying more premature and delicate type III collagen within the newly regenerated tissues. The collagen density in these groups was roughly 37-58% of that in the normal group. Between days 14 and 28 after irradiation, there was a substantial rise in apoptotic cell count in the forming epidermis and granulation tissue of the medium-high dose group, in contrast to the normal group. Notably, the expression of proapoptotic proteins bax, caspase-3, and caspase-9 surged significantly 14 days after irradiation in the medium-high dose groups and persisted at elevated levels on the 28th day. During the later stage of wound healing, the augmented apoptotic cell population and insufficient collagen generation in the newborn skin tissue of the medium-high dose groups were closely associated with delayed wound recovery.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

Keywords: Addis Ababa; dietary factors; nutritional status; school-age children

Digital transformation systems generate a substantial volume of data, creating opportunities for potential innovation, particularly those driven by artificial intelligence. This study focuses on the intricate relationship between artificial intelligence and innovation as foundational elements in the digital transformation framework for sustained growth and operational excellence. This study provides a holistic perspective on the cultivation and pillars of AI-powered innovation, highlighting their pivotal role in revolutionizing industries, including healthcare, education, finance, manufacturing, transportation, and agriculture. The work emphasizes the key pillars essential for fostering AI-powered innovation, including monitoring performance measurement to use the power of the present, continuous learning and innovation, data analytics and insights, predictive analytics, and innovative product development. This study investigates how these pillars serve as the foundation for groundbreaking advancements, driving efficiency, enhancing decision-making processes, and fostering creativity within organizations. This study explores the significance of continuous learning, interdisciplinary collaboration, and industry partnerships in nurturing a thriving AI-powered innovation ecosystem. By understanding and harnessing these fundamental elements, businesses can navigate the complexities of the digital age, fostering innovation that not only optimizes processes but also enhances the overall human experience, ushering in a new era of technological excellence and societal progress.

The growth of the wind power sector has been marked by environmental, economic, and political drivers. Its starring role is also visible in the emergence of the so-called “green jobs”. Notwithstanding, its evolution ought not to compromise issues related to occupational risks. This exploratory study examines psychosocial risks in the operation and maintenance of onshore wind turbines in a leading Portuguese company. We conducted interviews with main stakeholders (Human Resources, OHS professionals, and team leaders); developed an “activity diary” for the operation and maintenance technicians to describe their activity and perceived impacts on health, complemented with collective interviews; and applied the Work and Health Survey. The results revealed particular risks and health impacts: working under adverse weather conditions; working at heights and in confined spaces; spending long work hours inside of the nacelles to achieve an optimum balance between favorable wind slots to intervene and avoiding additional trips up and down the wind turbines without lifts (70m-120m); and the feeling of early ageing. At a time when these workers are striving for recognition of their profession as a “rapid wear profession”, it is a key moment to discuss these results to guarantee sustainable conditions for future generations of workers.

Age-related macular degeneration (AMD) is an eye disease and the most common cause of vision loss in the Western World. In its advanced stage, AMD occurs in two clinically distinguished forms: dry and wet, but only wet AMD is treatable. However, the treatment based on repeated injections with vascular endothelial growth factor A (VEGFA) antagonists may at best stop the disease progression and prevent or delay vision loss but without an improvement of visual dysfunction. Moreover, it is a serious mental and financial burden for patients and may be linked with some complications. The recent first success of intravitreal gene therapy with ADVM-022, which transformed retinal cells to continuous production of aflibercept, a VEGF antagonist, after a single injection, has opened a revolutionary perspective in wet AMD treatment. Promising results obtained so far in other ongoing clinical trials support this perspective. In this narrative/hypothesis review, we present basic information on wet AMD pathogenesis and treatment, the idea of gene therapy in retinal diseases, update evidence on completed and ongoing clinical trials with gene therapy for wet AMD, and perspectives on the road to the clinic of “one and done” therapy for wet AMD to replace a lifetime of injections. Gene editing targeting the VEGFA gene is also presented as another gene therapy strategy to improve wet AMD management.

Free-Living Amoebae (FLA) are widely distributed protozoa in both nature and artificial environments such as drinking water. Besides the ability of all FLA to transport various pathogenic microorganisms, certain species, Acanthamoeba spp. or Balamuthia mandrillaris, have intrinsic pathogenic abilities and cause severe cerebral infections. Previous work has shown an enrichment of FLA cysts in biofilm developed in upper levels of Drinking Water Storage Towers (DWST), suggesting that differences in densities of FLA cysts may play a role in their unequal distribution in the water column. To evaluate this hypothesis, a model of a water column was created for this study and used to analyze the vertical distribution of cysts of the FLA Acanthamoeba castellanii, Vermamoeba vermiformis and Balamuthia mandrillaris from 0 to 23 weeks. Interestingly, our data showed that the cysts of both A. castellanii and V. vermiformis were enriched in upper water levels during their aging. However, B. mandrillaris cysts were equally distributed in the water column during the entire study. These results showed that, besides the role of the water level variation in the DWST, some FLA cysts can become less dense during their aging, which contributes to their enrichment in upper water, and thus biofilm levels.

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

Human resources management (HRM) development aims at career sustainability. Work-related flow, as originated and defined by Csikszentmihalyi, is a process experienced by those optimally challenged by their work, considered the optimal work-related experience. Happiness is a judgment-dependent state of a pleased satisfaction with one’s current experience that one hopes will continue. PERMA (Positive Emotions, Engagement, Relationships, Meaning, and Accomplishment) represents five measurable factors of positive psychology that constitute well-being. As the optimal work-related experience, flow determines career sustainability compared with either happiness or PERMA factors. HRM development programs focused on happiness or PERMA factors thus represents risk factors regarding an inability to develop career sustainability. Established from this publisher’s founding ongoing concern with sustainability, articles published in MDPI journals with the keywords “flow, Csikszentmihalyi, work” were searched, excluding those pertaining to education, health, leisure, marketing, non-workers, and spirituality. Of 628 results returned, 28 reports were included for potential assessment. Although current studies on flow represented only three, the results regarding flow position it as the best indicator of career sustainability, contrasted to either happiness or PERMA. Consequently, HRM is advised to concentrate on developing practices for assessing and encouraging employees’ engagement with work-related flow in its aim of career sustainability.

The COVID-19 pandemic has led to a substantial revolution in the incorporation of digital solutions in healthcare. This systematic review investigates the enduring physical and psychological consequences individuals experience up to two years post-recovery. Additionally, it focuses on examining the influence of mHealth interventions on these effects. Significantly, 41.7% of survivors experience lingering symptoms that have not been addressed, while 14.1% encounter difficulties in returning to work. The presence of anxiety, compromised respiratory functioning, and persistent symptoms highlight the immediate requirement for specific therapies. Telehealth, particularly telerehabilitation, presents itself as a possible way to address these difficulties. The study thoroughly examines 10 studies encompassing 749 COVID-19 patients, investigating the efficacy of telerehabilitation therapies in addressing various health markers. Telerehabilitation-based breathing exercises yield substantial enhancements in functional performance, dyspnea, and overall well-being. The results emphasize the potential of telerehabilitation to have a favorable effect on patient outcomes, however more research is needed to strengthen the existing evidence basis as one of the most important limitation is the limited number of trials and the evaluation of varied therapies. The analysis highlights the significance of digital solutions in post-COVID care and calls for ongoing research to improve comprehension and implementation of telehealth interventions in a swiftly changing healthcare environment.

To investigate factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The main outcome was an extension of the treatment interval after 6 months, and factors related to the success or failure of the extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes of 43 patients. Extended dosing intervals of more than 2 weeks were identified in 14 eyes (32.6%). A short dosing interval before the switch, the absence of polypoidal lesions, and a thin central choroidal thickness before the switch were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend from existing dosing intervals.

This study addresses the influence of working conditions on Work-Related Quality of Life (WRQOL) among Spanish healthcare professionals. The research seeks to elucidate the mediating roles of job engagement and burnout, and the moderating effects of resilience and self-efficacy, in this relationship. Methods: The study included 374 healthcare workers from Spain, encompassing physicians, nurses, and nursing assistants. It employed a methodological approach using validated instruments to assess psychosocial risks, work-life quality, job engagement, burnout, and resilience. Data were gathered through self-reported questionnaires. Results: Key findings indicate a negative association between working conditions and WRQOL. Job engagement and burnout significantly mediated this relationship, accounting for 19% to 33% of the variance in WRQOL. Notably, lack of support emerged as a strong negative factor for work-related quality of life. Additionally, resilience moderated the relationship between lack of support and burnout. Conclusions: The study concludes that improving working conditions could increase WRQOL. Interventions aimed at enhancing engagement and addressing burnout may be effective. The moderating role of resilience suggests that strategies to enhance resilience could also be beneficial. These findings hold significant implications for policy formulation and human resources planning in healthcare, emphasizing the need for enhanced workplace support and the development of resilience among health workers.

Humans are often exposed to various environmental contaminants, among which phthalates are prevalent due to their extensive use as plasticizers in various consumer goods. Di(2-ethylhexyl) phthalate (DEHP), a widely used phthalate, is recognized as an endocrine disruptor chemical (EDC). DEHP is reported to affect various organs. Few studies have addressed the effects of phthalates on bone. However, the effects of DEHP on the bone forming cells (osteoblasts) are obscure. The present study was peformed to determine the cytotoxic effects of DEHP on human osteoblasts in vitro and to delineate the mechansims. In this study, we exposed the human osteo-blastic cell line MG-63 to various concentrations of DEHP (1, 25, 50 and 100 µM) for 24, 48 and 72 h. Cell viability was assessed by MTT assay. Total RNA and protein were collected after 48 h treatment with 1 and 100 µM DEHP and determined for the mRNA and/or protein expression of alkaline phosphatase (ALP), sex steroid receptors (androgen and estrogen receptors), receptor activator of nuclear factor kappa-Β ligand (RANKL), runt-related transcription factor 2 (RUNX2) and peroxisome proliferator-activated receptor alpha (PPARα). The mRNA expression was stud-ied by real-time RT-PCR analysis and the protein expression was determined by western blot analysis. Statistical analyses were done by one-way analysis of variance (ANOVA) followed by the Students–Newman–Keuls (SNK) test. The exposure of MG-63 cells to DEHP caused a signifi-cant decrease in osteoblast viability in all the treatment groups and at all the time points stud-ied. Interestingly, DEHP exposure decreased the mRNA expression of ALP, a bone formation marker. DEHP had differential effects on estrogen receptor alpha (ERα) mRNA and protein ex-pression. However, DEHP treatment downregulated the mRNA and protein expression of ERβ, and androgen receptor (AR). Surprisingly, DEHP downregulated the RANKL mRNA expression. DEHP decreased the protein expression of RUNX2, the key transcription factor and master regu-lator of bone formation. Furthermore, DEHP increased the PPARα protein expression in the os-teoblasts. Importantly, DEHP increased the reactive oxygen species (ROS) molecules and thus oxidative stress in osteoblasts, as observed by increased hydrogen peroxide, hydroxyl radical levels and lipid peroxidation. On the other hand, it decreased the enzymatic and non-enzymatic antioxidant levels namely catalase, superoxide dismutase, glutathione peroxidase activity and reduced glutathione. Our study demonstrated that in vitro exposure to DEHP reduces the osteo-blast viability possibly through alterations in the oxidant-antioxidant system and modulation of the key genes involved in bone formation, highlighting the cytotoxic effects of DEHP on bone forming cells.

Introduction: Obstructive sleep apnea (OSA) is not only common in the general population but even more so in patients with tumors of the head and neck region. Untreated, it leads to reduced quality of life, increased daytime sleepiness, and other comorbidities. The aim of this study was to determine the difference in the occurrence of OSA in the patient population with head and neck tumors compared to the general population as represented by the Trend cohort of the Study of Health in Pomerania (SHIP) , and to assess the influence of tumor treatment. Methods: Between July 2018 and December 2021, preoperative polysomnography was conducted in 47 patients with histologically confirmed squamous cell carcinoma in the oropharynx, hypo-pharynx, or larynx. A follow-up polysomnography was performed in 23 patients 2-11 months af-ter completing treatment. The collected data was correlated with tumor treatment and tumor size. Results: Of the included patients, 43 were male and four were female. Age ranged from 54 to 90 years. The pretherapeutic measurement found no significant difference in the prevalence of a pathologically elevated apnea-hypopnea index (AHI) in our patients compared to the SHIP-Trend cohort. In the follow-up measurement after treatment completion, a significant deterioration in AHI was observed. Initially, 70 % of patients had an AHI > 5, after therapy this increased to 87 %. The effect was particularly pronounced in the group of patients with advanced tumor stages who had received primary chemoradiation. Conclusion: OSA is a relevant condition in patients with head and neck cancer. Tumor treatment can lead to an increased occurrence of sleep-related breathing disorders, especially in patients with advanced tumor stages undergoing primary chemoradiation. Additional studies are neces-sary to better understand the exact mechanism involved.

UNESCO highlights socio-emotional, cognitive, and behavioral learning as critical for advancing sustainability. As major events, sports generate significant social, economic, and environmental impacts. This study analyzed how academic background, gender, age, sport type, and modality influenced elite Colombian Olympic and Paralympic athletes' socio-emotional competencies. Methods: Colombian elite athletes who were members of the “Support to the Excellence Coldeportes Athlete” participated in the study. The total population studied included 334 Colombian elite athletes: mean age 27.10 ± 6.57 years old with 13.66 ± 6.37 years practicing his/her sports modality. The socio-emotional competencies of the participants were assessed using the Socio-emotional Competencies Scale (SECS). Results: Men scored higher in interpersonal regulation, self-awareness, conflict resolution, and emotional regulation. Younger athletes (≤25 years) had higher self-consciousness. Individual versus team sports did not differ. Paralympians showed higher motivation, self-awareness, teamwork, and emotional regulation. University educated athletes scored higher in motivation, self-awareness, teamwork, and empathy. All competencies positively correlated. Conclusion: Individualized interventions targeting improved socio-emotional performance are vital for sustainability and should account for differences across gender, age, education, and disability status.

In recent years, there has been a growing interest in the prediction of facial age due to its diverse applications in fields such as security, entertainment, and healthcare. The current scourge of underaged voting in Nigeria is a problem and this research delves into the realm of facial age prediction by employing four well-known convolutional neural network (CNN) architectures, namely VGG16, ResNet50, Mobile Net, and VGG19 to predict chronological ages from facial pictures of person. The objective is to achieve precise age estimation from facial images, utilizing two datasets: UTKFace and CASIA African Facial Datasets. The results of this investigation are noteworthy. Specifically, the VGG16 model which demonstrated remarkable performance, yielding a Mean Absolute Error (MAE) of 1.76 when applied to the UTK-Face dataset. Additionally, when utilizing Mobile-Net, an unprecedented MAE of 1.10 was achieved for the Casia Africa Face Dataset. Notably, this marks the first instance of employing the dataset for facial age detection with CNNs, and this approach outperformed previous works, yielding the lowest MAE among all the studies reviewed.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

Survival models have become popular for credit risk estimation. Most current credit risk survival models use an underlying linear model. This is beneficial in terms of interpretability but is restrictive for real-life applications since it cannot discover hidden nonlinearities and interactions within the data. This study uses discrete time survival models with embedded neural networks as estimators of time to default. This provides flexibility to express nonlinearities and interactions between variables, and hence allows for models with better overall model fit. Additionally, the neural networks are used to estimate Age-Period-Cohort (APC) models so that default risk can be decomposed into time components for loan age (maturity), origination (vintage) and environment (e.g., economic, operational and social effects). These can be built as general models, or as local APC models for specific customer segments. The local APC models reveal special conditions for different customer groups. The corresponding APC identification problem is solved by a combination of regularization and fitting the decomposed environment time risk component to macroeconomic data, since the environmental risk is expected to have a strong relationship with macroeconomic conditions. Our approach is shown to be effective when tested on a large publicly available US mortgage data set. This novel framework can be adapted by practitioners in the financial industry to improve modelling, estimation and assessment of credit risk.

Chemo-resistance is a substantial challenge in the realm of cancer treatment that requires exploring new therapeutic approaches for effective mitigation. Achieving this goal requires examination of the molecular mechanisms involved in both tumor growth and therapeutic interventions. The potential of NRF2 (Nuclear factor E2-related factor 2) in addressing resistance to chemotherapy across diverse cancer types highlights its value as a promising therapeutic approach based on cancer characteristics. Manipulating the NRF2 signaling pathway has a dual impact, offering promise for both preventing and treating cancer, as well as inhibiting carcinogenesis. The influence of the NRF2/KEAP1 pathway on the progression of tumor formation and resistance to drugs has been well-documented. The interplay between the NRF2 signaling pathway and processes such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy plays a crucial protective role. A deeper understanding of NRF2's role in the modulating these pathways is necessary to develop novel approaches for improving chemotherapeutic efficacy. This article discusses the significance of the NRF2-KEAP1 pathway in preventing/promoting cancer and resistance mechanisms to various chemotherapeutic agents, with a focus on the complementary effects of antioxidants via NRF2-mediated signaling pathways. This study aims to provide a molecular basis for targeting NRF2 via inhibitors/activators as promising therapeutic strategies to overcome chemo-resistance.

In this article, you will get acquainted with ancient settlements in the Bukhara region and settlements found at the foot of the Zarafshan River. In addition, the settlements of urbanized peasant and artisan families belonging to the ancient Sugdian culture are also covered. Just as Egypt was called "the gift of the Nile" in ancient times, Buhoro oasis can also be called the gift of the Zarafshan river. Because this land on the banks of the river itself, first of all, as a result of thousands of years of Zarafshan was created due to the turbidity that flowed. The innumerable streams, lakes and ponds formed by its floods played a major role in the formation of the nature of the oasis and its development. It is known that when the ice age ended and the weather started to warm, the thick glaciers and eternal snows that covered the mountain ranges of Turkestan, Khisor and Zarafshan melted, and huge floods formed from them, roared down the Zarafshan river. His depicted floods of those times reminded of the legendary "Noah's flood". At that time, Zarafshan flowed over a very wide area in its valley. Its right bank washes the Payarik and Khatirchi hills in the present Samarkand region, and the left bank washes the Pastdargom and Kattakurgan hills. Not a single drop of this large stream was wasted in the upper and middle parts of the Zarafshan valley and was used for farming and agriculture, it broke through the narrow Khazora dar band near the present city of Navoi and flowed into the cone-shaped Bukhoro oasis. Ancient Khitfar (Vobkent-Darya), Rudnzor (Shakhrud) in Bukhara oasis. Korakuldaryo, Mokhondaryo and Taikir formed several branches and flowed along the entire voka. At that time, the valley part of Bukhoro region was formed from the lakes and swamps formed by the flood waters of Zarafshan.They are covered with thick bushes, thickets and orchards. A wealth of information has been collected on the history of the ancient nature of the people of the country and the development of its unique culture, as well as the formation of self-interested cattle breeding and farming farms, as well as the emergence of large and small villages and cities. The data serve as the main source not only for the history of the emergence of the city of Bukhara, but also for the study of the emergence of the process of urbanization in the Zara Valley and its specific characteristics.

Osteoporotic vertebral fracture is the most common fracture from osteoporosis, and are largely undiagnosed due to the mostly asymptomatic nature of the condition. It increases the risk of subsequent fractures and contributes to societal burden. Risk factors for osteoporotic fractures are found in the WHO fracture risk assessment model and used as a tool for monitoring bone health. Vertebral fractures are diagnosed from anteroposterior and lateral spine radiographs and are confirmed with an approximate loss of 20% vertebral height as compared to adjacent vertebrae. One of the most used grading for vertebral fractures is the SQ grading. Mild vertebral fractures could easily be misdiagnosed due to some peculiarities of the vertebral column. CT scan is useful for planning surgical intervention while an MRI scan can provide information about the recency of the fracture and rule out cancer-related fractures. Management depends on the severity of the fracture which could range from conservative management to surgical vertebral augmentation and decompression. Bisphosphonates are used to treat osteoporosis in acute and long-term management of fractures. Osteoimmunological therapies such as denosumab and romosozumab are new therapeutic interventions for osteoporosis while there are many other potential treatment options. Precision medicine provides an individualized treatment approach while regenerative medicine utilizes mesenchymal stem cells for fracture repair.

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers expression in low (LGG) and high-grade gliomas (HGG). In 39 glioma cases, we assessed protein expression of autophagy markers LC3B, p62, and DRAM by immunohistochemistry (IHC) and mRNA expression of autophagy genes; PI3K, AKT, m-TOR, PTEN, ULK1, ULK2, UVRAG, Beclin 1 and VPS34 using RT-qPCR. Livak’s method was used to analyze the relative changes in gene expression and multi-variate Anova test and Spearman's correlation tests were performed for statistical significance. LC3B, p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases respectively. The expression of LC3B and p62 was notably higher in HGG compared to LGG. VPS34 exhibited a significant differential expression and increased fold change and demonstrated strong positive correlations with Beclin1 (rs=0.768), UVRAG (rs=0.802), and ULK2 (rs=0.786) in HGG compared to LGG, thus highlighting the potential link between autophagy and glioma progression. We Provide preliminary data for functional analysis of autophagy using cell culture model and to identify potential targets for therapeutic interventions

Keywords: Demographics, Diversity, Gender, Race, Age, Professionals, Built Environment, Construction Industry, South Africa

Slave Province in Canada is an Archean granite-supracrustal terrane at the northwestern corner of the Canadian Shield. It is bordered by the Thelon–Taltson orogen (2.0 to 1.9 Ga) to the south-east and the Wopmay orogen (1.9 to 1.8 Ga) to the west. Acasta gneisses exposed in the western-most Slave province and the Wopmay rocks close to the gneisses were collected systematically for K-Ar and laser step-heating 40Ar /39Ar analyses of the biotite and amphibole. The K-Ar biotite ag-es of the four Wopmay samples range from 1816 ± 18 Ma to 1854 ± 26 Ma, which is within the reported U-Pb zircon age range of the Wopmay orogen. The K-Ar biotite ages of the fifteen Acasta gneisses range from 1779 ± 25 Ma to 1877 ± 26 Ma, except for a younger sample (1711 ± 25 Ma). The 40Ar/39Ar biotite analyses of the three samples from the Wopmay orogen give the plateau ages of 1826 ± 21 Ma, 1886 ± 13 Ma, and 1870 ± 18 Ma. On the other hand, the 40Ar/39Ar analyses of the biotite crystals from the Acasta gneiss show a variety of ages. Three samples show the plateau ages of 1877 ± 8 Ma, 1935 ± 14 Ma, and 1951 ± 11 Ma. These plateau ages are a little older than the total gas ages. The 40Ar/39Ar analyses of the amphibole crystals show more varied age rela-tions. The two samples show consistent age relations between the plateau ages (1814 ± 22 Ma and 1964 ± 12 Ma) and the total gas ages (1789 ± 23 Ma and 1967 ± 11 Ma), respectively. Some sam-ples have the apparent old age of 2000 Ma in the middle temperature fractions. These old frac-tions are due to that the originally existed amphibole crystals formed in Archean were affected by the thermal events during the Wopmay orogeny. but did not fully reset. The results suggest that the K-Ar system ages of the biotite and amphibole of the Archean Acasta gneiss that is aged from 4200 to 2600 Ma of zircon U-Pb ages were rejuvenated in the Paleo–Proterozoic ages. The heat source that rejuvenated the K-Ar system ages may have arisen due to the asthenospheric intrusion into the wedge mantle, which took place because of the subduction rollback.

This in-depth review navigates the intricate relationship between gender, hormonal influences, and the progression of autosomal dominant polycystic kidney disease (ADPKD), highlighting the limited literature on this crucial topic. The study explores the impact of female sex hormones on liver and renal manifestations, uncovering gender-specific differences in disease progression. Actually hormonal therapy in women with ADPKD remains a challenging issue and is a source of concern regarding its potential impact on disease outcomes, particularly at the hepatic level. Notably, women with ADPKD exhibit a slower renal disease progression compared to men, attributed to hormonal dynamics. The review sheds light on the role of estrogen in regulating pathways of the renin-angiotensin-aldosterone system, revealing its complex interplay and implications for cardiovascular and renal health. Therapeutic considerations for fertile women with ADPKD, including contraception options, are discussed, emphasizing the necessity for personalized approaches. In the postmenopausal phase, the review evaluates the role of hormonal replacement therapy, considering its potential benefits and risks in the context of ADPKD. The review concludes by underscoring the imperative need for tailored treatment approaches for ADPKD patients, considering individual risks and benefits. The scarcity of literature underlines the call for further research to enhance our understanding of optimal hormonal therapies in the context of ADPKD, ultimately paving the way for innovative and personalized therapeutic interventions.

Both scleroderma and immunoglobulin G4-related disease (IgG4-RD) are systemic fibro-inflammatory diseases characterised by lymphoplasmacytic infiltrates. IgG4-RD and systemic Sclerosis (SSc) may share common pathophysiological mechanisms, but no examples of co-occurrence of the diseases have been found. Autologous haematopoietic stem cell transplantation (AHSCT) is implemented in selected rapidly progressive SSc with high risk of organ failure. However, existing guidelines are based on clinical trials that do not represent the entire patient population and exclude critically ill patients with no therapeutic alternatives. Examples of AHSCT in IgG4-RD are absent. We report the case of AHSCT in a female patient with overlapping progressive diffuse SSc and sinonasal IgG4-RD. Despite immunosuppressive therapy, IgG4-RD developed and clinically manifested shortly before AHSCT. Lacking therapeutic alternatives, after 11 years of SSc therapy, the 44-year-old successfully underwent AHSCT. The 63-month follow-up showed regression of symptoms. Only after surgical treatment (bilateral ethmoidectomy, sphenoidotomy, intranasal buccal antrostomy) the initially progressive clinical course of IgG4-RD remained indolent.

The assessment of Health-Related Quality of Life (HRQoL) in Thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of Transfusion-Dependent Thalassemia (TDT) patients in Greece. This was a multicentre, cross-sectional study conducted in 2017, involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower, compared to the general population in Greece. The mean summary score of TranQol was relatively high (71±14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment in a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

Electroencephalography (EEG) enabled earbuds represent a promising frontier in evaluating brain activity beyond traditional laboratory settings. However, these devices need more comprehensive characterization before widespread health related usage. A toolbox was developed to facilitate and expand the assessment of ear-EEG devices. The first component of this toolbox is a desktop application (“EaR-P Lab”) that integrates EEG validation paradigms. This application is designed to be used with EEG amplifiers compatible with the Lab Streaming Layer (LSL) protocol. The second element of the toolbox introduces an adaptation of the phantom testing concept, to the domain of ear-EEG by using 3D ear scans of the tested individuals, allowing controlled assessment of ear-EEG devices. The EEG paradigms were validated for scalp acquisitions and applied on ear-EEG measurements, under wet ear electrode conditions. The ear-EEG phantom was successful in measuring useful metrics in EEG system characterization, highlighting performance differences within the electrodes on the tested earpieces. This knowledge was factored in to select an optimal electrode reference which resulted in increased response power on the auditory steady-state response (ASSR). Through this work, an ear-EEG evaluation toolkit is made available with the intention to enable future and systematic assessment of novel ear-EEG devices from the hardware to the neural signals.

The advent of AI in medicine has transformed various medical specialties, including orthodontics. AI has shown promising results in enhancing the accuracy of diagnoses, treatment planning, and predicting treatment outcomes. With the growing number of AI applications and commercially available tools, there is an increase in their usage in orthodontic practices worldwide. This review aims to explore the principles of artificial intelligence (AI), its applications in the diagnostic process of modern orthodontic practices, and concerns associated with the implementation of AI algorithms in clinical practice. A comprehensive review of the literature was conducted, focusing on five categories where AI has been applied in orthodontics: dental diagnostics, cephalometric evaluation, skeletal age determination, temporomandibular joint (TMJ) evaluation, and extraction decision making. AI has demonstrated high efficacy in all those fields. However, variations in performance and the necessity of manual supervision indicate that AI should be used cautiously in clinical settings. Nevertheless, the high complexity and potential unpredictability of AI algorithms call for cautious implementation and regular manual validation of results. Continuous AI learning, proper governance, and addressing privacy and ethical concerns are crucial for the successful integration of AI into orthodontic practice.

In the heterogeneous wireless networked control system (WNCS), age of information (AoI) of the actuation update and actuation update cost are important performance metrics. To reduce the monetary cost, the control system can wait for the availability of WiFi network of the actuator and then conduct the update by using WiFi network in an opportunistic manner, but it leads to the increased AoI of the actuation update. To assess this problem, this paper proposes a priority-aware actuation update scheme (PAUS) where the control system decides whether to deliver or delay the actuation update to the actuator by considering the control priority (i.e., robustness of AoI of the actuation update). For the optimal decision, we formulate a Markov decision process model and derive the optimal policy based on Q-learning. Simulation results demonstrate that PAUS outperforms the comparison schemes in terms of the expected reward.

Background: Delayed graft function (DGF) is common after kidney transplantation from de-ceased donor and may significantly affect post-transplant outcomes. This study aimed to evaluating whether an innovative approach, based on the administration of intravenous prostaglandin-analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. Methods: This prospective, randomised (1:1), place-bo-controlled study enrolled all consecutive patients who received a kidney transplantation from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin-analogue iloprost at 0.27 μg/min through elastomeric pump (treatment group) or placebo (control group). Results: A total of 476 patients were included : DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that donor’s age > 70 years (OR 2.50, 95% Confidence Interval (CI) 1.40-3.05, p < .001), cold ischemia time > 24 h (OR 2.60, 95 CI 1.50-4.51, p < .001), donor’s AKI (OR 2.71, 95% CI 1.61-4.52, p = .021) and, above all, recipient’s arterial hypotension (OR 5.06, 95% CI 2.52-10.1, p < .0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p< .001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.58.3 v s13.46.7, days, p= .016). Conclusions: This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased donor kidneys, allowing a better graft functionality as well as a better graft survival.

AbstractIntroduction: Increasing knowledge of obstetric danger signs (ODS) and encouraging birth preparedness and complication readiness (BPCR) practices are strategies to increase skilled maternal health service utilization in low-income countries. One of the methods to increase mothers' knowledge about ODS and promote BPCR practice is through health education intervention (HEI). However, the effect of context-specific community-based health education led by women's groups on these outcomes has not been comprehensively studied, and the existing evidence is inconclusive. Thus, we aimed to evaluate the effect of a context-specific community-based HEI led by women's groups on mothers' knowledge regarding ODS and BPCR practices in southern Ethiopia.Methods: An open-label, two-arm parallel group cluster-randomized controlled trial was conducted from January to August 2023 on pregnant women from 24 clusters (kebeles) (12 interventions and 12 controls) in the northern zone of the Sidama region. The Open Data Kit smartphone application was utilized to collect data. The intention-to-treat analysis was used to compare outcomes between groups. We fitted multi-level mixed-effects modified Poisson regression with robust standard error to account for between and within cluster effects. Results: One thousand and seventy pregnant women (540 in the intervention and 530 in the control clusters) responded to this study, making the overall response rate 95.02%. Excessive vaginal bleeding (94.3% in the interventional group vs. 88.7% in the control group) was the commonest ODS mentioned during childbirth. Overall, 68.7% of women in the intervention group and 36.2% of mothers in the control group had good knowledge of ODS (P-value < 0.001). Saving money and materials (97.1% in the interventional group vs. 92.7% in the control group) was the most frequently practiced BPCR plan. Overall, 64.3% of women in the intervention group and 38.9% of mothers in the control group practiced BPCR (P-value < 0.001). HEI significantly increased overall knowledge of ODS (adjusted risk ratio [ARR]: 1.71; 99% CI: 1.14-2.57) and improved overall BPCR practice (ARR: 1.55; 99% CI: 1.02-2.39). Conclusions: A community-based HEI led by women's groups improved mothers' knowledge regarding ODS and BPCR practices in a rural setting in southern Ethiopia. Interventions designed to increase women's knowledge of ODS and improve BPCR practice must implement context-specific, community-based HEI that aligns with World Health Organization recommendations. Trial registration: NCT05865873

AbstractBackground: Maternal health service (MHS) use is a key strategy to reduce maternal mortality. However, the existing evidence is scarce to design efficient intervention strategies in Ethiopia. Thus, we aimed to explore community members and health care providers' perceptions of MHS, and barriers, and facilitators of MHS use in southern Ethiopia. Methods: A phenomenological qualitative study was conducted from November 14-30, 2022, in the northern zone of the Sidama region. Sixteen in-depth interviews, nine focus group discussions, and 15 key informant interviews were done with 112 study participants. A maximum variance sampling method was used to select study participants. Data coding and analysis were done using MAXQAD 2020 software and presented in narratives. Results: Communities have positive perceptions and good practices of skilled antenatal care (ANC) and health facility delivery (HFD), but lack awareness of postnatal care (PNC) services and schedules. Some have experienced negative interactions with health care providers, health facilities, and ambulance drivers. The main identified barriers to ANC use were lack of awareness of ANC benefits, distance from a health facility, costs associated with ANC use, long waiting time, lack of access to road, and women being busy with different household chores. Distance from health facility, costs associated with HFD use, unpredicted labour, lack of an ANC visit, lack of a birth preparedness plan, and non-dignified care were the main barriers to HFD. The major identified barriers to PNC use were home delivery, lack of awareness of PNC service and schedule, and socio-cultural beliefs. The main identified facilitators of MHS use were previous experience and fear of obstetric complications, health extension workers and women’s development teams, and pregnant women's forum.Conclusions: Rural women still encounter several challenges when using MHS, even though communities have positive perceptions and good practices of skilled MHS. Bad experiences mothers faced in health facilities, challenges associated with the costs of MHS use, poor awareness of service, and unpredictable labour continued to be basic barriers to MHS use. Intervention approaches should consider inter-sectoral collaboration to address barriers at the community and health facility levels. The programs must emphasize the transportation arrangements during unpredictable labour, the needs of poor mothers, and women who have poor awareness of MHS at the community level.

Breast cancer-related lymphedema (BCRL) affects approximately 20% of women after breast cancer therapy. Advances in treatment have increased life expectancy, thus the prevalence of BCRL will continue to rise with the number of cancer survivors. Hence the need to develop strategies to prevent this condition. We provide a systematic review of the literature on primary prevention of BCRL by prophylactic lymphatic surgery (PLS). Between June and August 2022, we conducted a search of PubMed, Google Scholar and Cochrane. In the end a total of eighteen papers were selected. The eleven studies without a control group reported only 15 of 342 patients who developed lymphedema at least six months after PLS (4.59%). The seven studies with a control group included 569 patients, 328 cases and 241 controls. Among the cases, 36 (10%) developed lymphedema. In contrast, the incidence of lymphedema in controls was 40% (98 of 241 patients). Formulation of definite recommendations in favour of PLS is hindered by low-quality studies. There is no consensus on which technique should be preferred, nor on whether adjuvant radiotherapy might affect the efficacy of PLS. Randomized controlled trials are mandatory to conceive evidence-based recommendations.

Online transportation services, initially presented as an innovative employment approach by categorizing workers as 'independent contractors', have come to be recognized for their exploitative nature. The notion of 'flexibility' suggests that workers have the autonomy to tailor their hours and location according to their income goals. However, this disguises the true situation for informal workers who lack rights and protections. This study delves into these issues from a psychological standpoint to uncover the mental and emotional interplay between the motivations and exploitation experienced by online drivers affiliated with multiple platforms. The study adopts a qualitative methodology with a phenomenological lens. Data was gathered through thorough interviews, observations, and document analysis, with Interpretative Phenomenological Analysis (IPA) employed as the data analysis technique. The study's participants were five male multi-platform online drivers from the Special Region of Yogyakarta, ranging in age from 18 to 64, and had been associated with at least two platforms for more than a year. The findings highlight two primary themes: firstly, the decision to join multiple platforms is chiefly driven by economic reasons, including a decline in orders, daily earnings, bonus incomes, and the conclusion of the initial profitable phase. Secondly, the exploitative conditions are linked to the platforms' algorithms, which exert control and influence the psychological state of the drivers. Nonetheless, the participants have developed effective strategies to manage fatigue, anxiety, and stress.

This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.

Tritordeum is an amphiploides species resulting from the hybridization between durum wheat (T. durum) and wild barley (H. chilense). This new cereal is considered a natural crop as it is obtained by traditional breeding techniques. Given its appreciable organoleptic characteristics, agronomic features, presence of interesting components, and good technological properties, tritordeum is of promising interest for the development of health-oriented foods. In this study, we evaluated two registered tritordeum cultivars, Bulel and Aucan. T. durum (Provenzal) was employed as the positive control. The extracted proteins were digested by gastric /pancreatic proteases and their biological effects on Caco-2 differentiated on transwell inserts were determined. Changes in cell viability, monolayer permeability, organization of F-actin microfilaments, and ER stress, triggered by protein-digested samples (DPs) were inspected. Our results showed that exposure to Provenzal-DPs promptly disrupted the tight junction barrier. Conversely, Aucan-DPs did not enhance monolayer permeability; whereas, Bulel-DPs exerted only slight effects. Provental-DPs-induced toxicity was also confirmed by changes in cell viability and by the deep reorganization of the enterocyte cytoskeleton. In contrast, Aucan-DPs and Bulel-DPs did not affect monolayer viability and cytoskeleton structure. Overall, our findings suggest that both tritordeum cultivars could be potential candidates for mitigating the toxicity of wheat flour.

In hepatocellular carcinoma (HCC), recurrence usually occurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce recurrence rates. In this report, the in vivo mouse effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance was evaluated. A phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in HCC recurrence in patients who have undergone curative surgery for HBV-related HCC. In animal modeling, HBV suppression was significantly greater with rmIFN-α and anti-PD1 sequential combination treatment than with their treatment alone. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks at the dose of 450 µg for six doses, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease or clearance of HBV surface antigen was observed in two patients. Dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was determined. Currently no HCC recurrence has been observed. The treatment modality was well tolerated. The data support further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

Better understanding of the quality of life among nursing home residents with dementia is im-portant for developing interventions. The objectives of this cross-sectional study were to examine factors associated with poor health-related quality of life in older adults with dementia living in nursing homes in Hanoi, Vietnam. In-person interviews were conducted with 140 adults 60 years and older with dementia and information about their quality of life was obtained using the Quality of Life in Alzheimer’s Disease scale (QOL-AD). A number of sociodemographic and clinical factors associated with poor health-related quality of life (lowest tertile) were assessed through the results of physical tests, interviews with nursing home staff, and review of medical records. The average age of the study sample was 78.3 years, 65% were women, and their av-erage QOL-AD total score was 27.3 (SD = 4.4). Malnutrition, total dependence in activities of daily living, and urinary incontinence were associated with poor quality of life after controlling for multiple potentially confounding factors. Our findings show that Vietnamese nursing home residents with dementia have a moderate quality of life and interventions based on comprehen-sive geriatric assessment remain needed to modify risk factors associated with poor health-related quality of life.

Aging is a major risk factor for the higher incidence and prevalence of chronic conditions, such as cancer, cardiovascular and metabolic diseases, and neurodegenerative diseases. Closely linked with the onset of all these age-related diseases is immunosenescence, a condition defined as progressive reconfiguration of the immune functions leading to an increased susceptibility to infectious diseases, poorer response to vaccination, increased prevalence of cancer, rheumatoid arthritis, and other chronic diseases characterized by a pro-inflammatory state named inflammaging. Given that immunosenescence frames age-related diseases, it is natural to ask how these illnesses are related under the context of innate and adaptative components of the immune system. Knowledge processing by Formal Concept Analysis (FCA) of age-related diseases framed in an immunosenescence multivalued context shows that a hierarchy among these diseases emerges with a subconcept-superconcept nested structure, with two clusters, first made of metabolic diseases, cancer, and cardiovascular diseases. Second metabolic and neurodegenerative diseases and rheumatoid arthritis. Metabolic diseases seem to be a pivot illness and they must be a primary target given their global incidence and prevalence and their cost-effective treatments like regular physical activity, weight loss, healthy diet, stopping smoking, and reducing or managing stress. Another implication of the ontological analysis of age-related diseases is about the nature of immunosenescence, suggesting that initial symptoms of age-related diseases are mainly related to innate immune mechanisms, and developing of severe symptoms of age-related diseases like cancer, cardiovascular or neurodegenerative diseases depends on the activation of acquired immunity processes.

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors like folate, B12, osteocalcin, and more. Not only do these biomarkers serve as indicators of senescence, but they actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual's life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

Chronological frameworks based on artefact typologies are essential for interpreting the archaeological record, but they inadvertently treat transitions between phases as abrupt events and disregard the temporality of transformation processes within and between individual phases. This study presents an absolute chronological investigation of a dynamic material culture from Early Iron Age urnfields in Denmark. The chronological framework of Early Iron Age in Southern Scandinavia is largely unconstrained by absolute dating, primarily due to it coinciding with the so-called ‘Hallstatt calibration plateau’ (c.750 to 400 cal BC), and it is difficult to correlate it with Central European chronologies due to a lack of imported artefacts. This study applies recent methodological advances in radiocarbon dating and Bayesian chronological modelling, specifically a statistical model for wood-age offsets in cremated bone and presents the first large-scale radiocarbon investigation of regional material culture from Early Iron Age in Southern Jutland, Denmark. Dated material is primarily cremated bone from 111 cremation burials from three urnfields. The study presents absolute date ranges for 16 types of pottery and 15 types of metalwork, which include most of the recognised metalwork types from the period. This provides new insights into gradual change in material culture, when certain artefact types were in production and primary use, how quickly types were taken up and later abandoned, and distinguishing periods of faster and slower change. The study also provides the first absolute chronology for the period, enabling correlation with chronologies from other regions. Urnfields were introduced at the Bronze-Iron Age transformation, which is often assumed to have occurred c.530-500 BC. We demonstrate that this transformation took place in the 7^th century BC, however, which revives the discussion of whether the final Bronze Age period VI should be interpreted as a transitional phase to the Iron Age.

We report the first correction by Prime editing of a mutation in the RYR1 gene, paving the way to gene therapies for RYR1-related myopathies. The RYR1 gene codes for a calcium channel named Ryanodine receptor 1, which is expressed in skeletal muscle fibers. The failure of this channel causes muscle weakness in patients, which degenerates into motor disabilities. Currently, there are no effective treatments for these diseases, which are mainly caused by point mutations. Prime editing allows the modification of precise nucleotides in the DNA. Our results showed a 59% correction rate of the T4709M mutation in the RYR1 gene in human myoblasts by RNA delivery of the Prime editing components. It is to be noted that the T4709M is recessive, and thus, persons having a heterozygous mutation are healthy. These results are the first demonstration that it is possible to correct mutations in the RYR1 gene.

This study addressed algorithmic bias in predictive policing, focusing on the Chicago Police Department's Strategic Subject List (SSL) dataset. We specifically focused on identifying and mitigating age-related biases, a notably underexplored area in prior research. Our research introduced Conditional Score Recalibration as a bias mitigation strategy alongside the well-established Class Balancing technique. Conditional Score Recalibration involved reassessing and adjusting risk scores for individuals initially assigned moderately high-risk scores in the dataset. This recalibration marked such individuals as low risk if they met three conditions, namely: no prior arrests for violent offenses, no previous arrests for narcotic offenses, and having never been involved in shooting incidents. These fairness strategies were implemented on the Random Forest model, and the fairness metrics employed included Equality of Opportunity Difference, Average Odds Difference, and Demographic Parity. The results showed a significant improvement in model fairness, particularly for age biases, without compromising the model's accuracy. These findings challenged the often-assumed trade-off between fairness and accuracy, underscoring the feasibility of achieving fairness without compromising accuracy.

The evolutionary theory of aging, particularly antagonistic pleiotropy (AP), provides an account of the ultimate origins of aging. What remains unclear is the nature of the proximate mechanisms by which AP gives rise to diseases of aging, like cardiovascular disease and Alzheimer’s disease. Damage-centric theories focusing on loss of genetic and cellular function have been proposed, as well as programmatic theories focusing on unwanted gene and cellular function. The latter include the hyperfunction and developmental theory that view aging as the futile continuation, or run-on, of growth and developmental programmes into later life. Yet neither type of theory has performed well in explaining late-life disease aetiology, particularly with respect to disease onset, presentation and progression. What is proposed here in this review is a new programmatic theory of aging. We argue that the emergence of many specific diseases may involve quasi-programmes that are not the result of run-on, but rather are triggered by other factors in late life. Such triggers may be non-programmatic (e.g. infection, mechanical injury) or programmatic. Moreover, the consequent pre-pathological and pathological changes may in some cases trigger further changes, leading to futile and destructive cascades of quasi-programmes and pathology. The origins of triggered quasi-programmes can be traced to biological constraint i.e. the inability of organisms to optimise all functions at once. And, to some extent, the new theory presented here revises the understanding of AP. That is, because any gene can be triggered in an erroneous manner, every gene is potentially an AP gene that risks pathology, though level of risk varies according to constraint. To help validate the theory, we test it against several complex diseases of aging. The new model in this review attempts to provide a blueprint understanding that, to a certain extent, closes the gap in the causal chain of events between evolutionary causes of aging and the aetiology of age-related diseases. It also helps to explain why certain disorders mimic accelerated aging and how interventions, such as the suppression of IIS and mTOR retard many aspects of aging; notably, though, unlike prior programmatic theories, the new theory is not mTOR-centric. Finally, it provides new perspectives on possible treatment of aging.

The Vitamin D Receptor (VDR) mediates the actions of vitamin D, which has important roles in bone homeostasis, growth/differentiation of cells, immune functions and reduction of inflammation. Emerging evidences suggest that epigenetic modifications of the VDR gene, particularly DNA methylation, may contribute to the onset and progression of many human disorders. This review aims to summarize the available information on the role of VDR methylation signatures in different pathological contexts, including autoimmune diseases, infectious diseases, cancer and others. The reversible nature of DNA methylation could enable the development of therapeutic strategies, offering new avenues for the management of these worldwide diseases.

Pregnancy at advanced maternal age is considered a risk factor for adverse maternal, fetal, and neonatal outcomes. Here we investigated whether maternal age could be associated with differences in the blood levels of newborn screening (NBS) markers for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP). Population-level NBS data from screen-negative singleton infants were examined, which included blood metabolic markers and covariates such as gestational age, birth weight, age at blood collection, infant sex, parent-reported ethnicity, and maternal age at delivery. Marker levels were compared between maternal age groups (age range: 15-44 years) using effect size analyses, which controlled for group size differences and potential confounding from other covariates. Our results showed that 13% of the markers had maternal age-related differences including newborn metabolites with either increased (C14, C16, C18, C18:1, C3DC) or decreased (C5OH) levels at advanced maternal age group (≥35 years, absolute Cohen’s d ≥ 0.2). The increased C3DC levels in this group correlated with a higher false-positive rate in newborn screening for malonic acidemia (p-value < 0.001), while no significant difference in screening performance was seen for other markers. Maternal age at delivery is associated with inborn metabolic differences and should be considered together with other clinical variables in genetic disease screening.

Aging induces numerous physiological alterations, with immunosenescence emerging as a pivotal factor. This phenomenon has attracted both researchers and clinicians, prompting pro-found questions about its implications for health and disease. Among the contributing factors, one intriguing actor in this complex interplay is human cytomegalovirus (CMV), a member of the herpesvirus family. Latent CMV infection exerts a profound influence on the aging immune system, potentially contributing to age-related diseases. This review delves into the intricate relationship between immunosenescence and CMV, revealing how chronic viral infection im-pacts the aging immune landscape. We explore the mechanisms through which CMV can im-pact both the composition and functionality of immune cell populations and induce shifts in in-flammatory profiles with aging. Moreover, we examine potential role of CMV in such pathol-ogies as cardiovascular diseases, cancer, neurodegenerative disorders, COVID-19, and Long COVID. This review underlines the importance of understanding the complex interplay be-tween immunosenescence and CMV. It offers insights into the pathophysiology of aging and age-associated diseases, as well as COVID-19 outcomes among the elderly. By unraveling the connections between immunosenescence and CMV, we gain a deeper understanding of aging's remarkable journey and the profound role that viral infections play in transforming the human immune system.

Appropriate diagnosis, treatment and care contributes to better service engagement, improvements to wellbeing, cost savings, reductions in morbidity and mortality for people with Alcohol Related Brain Damage. In the North-East of England large amounts of alcohol are consumed, reflected in the number of alcohol-related deaths in the region. However, the pathway for people with Alcohol Related Brain Damage to receipt of diagnosis, treatment and care is unknown and could be unwittingly influenced by stigma. Qualitative in-depth semi-structured interviews were completed with 25 health and social care professionals from organisations involved with people with Alcohol Related Brain Damage recruited via snowball-sampling. Interviews were recorded, transcribed verbatim, coded, and analysed. People with Alcohol Related Brain Damage were stigmatised both by society and professionals which inhibited entry into services therefore Alcohol Related Brain Damage remained underdiagnosed and misdiagnosed. There was no dedicated service but silos with revolving doors and underfunded generic care with long waiting lists typically excluding those with alcohol or neurological problems. Professionals need to be challenged on the assumption that Alcohol Related Brain Damage is self-inflicted via training aimed at challenging unconscious bias. Reducing stigmatising processes associated with Alcohol Related Brain Damage could counteract professionals’ reluctance to provide care.

Pathologic angiogenesis is responsible for much of the vision loss that stems from several chorioretinal vascular diseases including neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Because vascular endothelial growth factor (VEGF) serves as a pivotal angiogenic molecule, it has emerged as the primary target for therapeutic drugs. Current anti-VEGF therapy is dominated by bevacizumab, ranibizumab, and aflibercept, all of which have been available for more than a decade, but new drugs, both biosimilars (Byooviz and Cimerli) and drugs whose primary aim is to decrease treatment burden (brolucizumab, faricimab, and the ranibizumab port delivery system), have been approved. Recent failures (conbercept, abicipar, and KSI-301) emphasize the complexity of drug development and the difficulties faced by innovators. Most therapies under development, including tyrosine kinase inhibitors and gene therapy, include VEGF-A blockade as their primary function and aim to extend durability rather than increase peak efficacy. But even as many new drugs look to extend durability, cost containment with mandated use of biosimilars serves to balance the therapeutic landscape.

We compared the functional and morphologic effects in the loading dose between patients with treatment-naïve neovascular age-related macular degeneration treated with either intravitreal aflibercept (IVA) or intravitreal faricimab (IVF) injection in clinical settings. This retrospective study included 30 eyes from 28 patients who started IVA treatment between June and September 2022 and 30 eyes from 29 patients who started IVF treatment between October 2022 and March 2023. The mean best corrected visual acuity (BCVA) significantly improved from pre-treatment after loading dose in the IVA group (from 0.46 ± 0.46 to 0.36 ± 0.37, p=0.0047) and not in the IVF group (from 0.46 ± 0.41 to 0.44 ± 0.45, p=0.60). The mean central retinal thickness (CRT) significantly improved in both groups. The proportion of eyes with residual exudative change was greater in the IVF group than in the IVA group at 2 months after the first treatment. (p=0.026) We further analyzed the patients who obtained complete resolution of exudative changes after the loading dose. The IVA group had a significant improvement in BCVA, whereas the IVF group did not p=0.0047 and 0.20, respectively) Although IVA and IVF significantly improved the CRT, the BCVA improved significantly in IVA group and not in IVF group.

The ongoing conflict in Syria and Iraq has caused many residents of these countries to flee. This study explored how these refugees cope with traumatic experiences from pre-migration to post-migration phases and how they develop resilience experiences at the individual, familial, and community levels. Data were collected through individual interviews and analyzed using Interpretative Phenomenological Analysis. A discussion of the findings revealed (1) a cumulative effect of prolonged adversity from pre-migration to resettlement phases; (2) the impacts of post-migration context as it facilitates refugees’ adjustment or leads to re-traumatization through increased marginalization; and (3) finally, an overview of refugees’ ongoing survival. Clinical implications are presented along with policy implications and future directions for research.

Healthcare workers' stress, burnout, and job dissatisfaction were exacerbated by the Covid-19 pandemic, whose mid-term negative effects are still present. The aim of this study was to investigate in healthcare workers the effect of the dimensions of burnout (Psychophysical exhaustion, Relational deterioration, and Professional inefficacy) on Career satisfaction. These relationships were evaluated by considering the direct and mediated effects of Disillusion. For these purposes, the Link Burnout Questionnaire (LBQ) and the Career Satisfaction Scale (Occupational Stress Indicator - OSI) were administered to 295 healthcare professionals working at three Italian public hospitals in Cagliari, Italy. The analyses were conducted using the Partial Least Square Structural Equation Model (PLS-SEM) method. Findings highlight that healthcare workers were in a condition of work distress, high risk of burnout, and career dissatisfaction. Also recognized was the direct negative effect of burnout dimensions on career satisfaction. Finally, the mediated negative effect of Disillusion in the relationship between burnout and career satisfaction was identified. This study emphasizes the relevance of the dimension of Disillusion, and its “bright side” Fulfilment, in healthcare workers, specifically referring to the disregarded relationship between burnout and career satisfaction.

Background: Patients with infectious complications related to the presence of cardiac implantable electronic devices (CIED) constitute a heterogeneous group, including local pocket infection (PI) and lead related infectious endocarditis (LRIE). The diagnosis of CIED-related infection is often difficult and requires complex imaging and microbiological tests. The aim of the current study was to evaluate the usefulness of new simple hematological parameters in detecting infectious complications in patients with CIED and assessing their extent. Methods: The retrospective analysis of clinical data of 2909 patients (36.37% with CIED-related infections), undergoing transvenous lead extraction (TLE) procedures in three high-volume centres in the years 2006-2020, was conducted. The sensitivity and specificity of new hematological markers were evaluated: the neutrophil to lymphocyte ratio (NLR), neutrophil to platelet ratio (NPR), and lymphocyte to platelet ratio (LPR) in the diagnosis of infectious complications, assessment of the spread of the infectious process and differentiation of additional structures related to the presence of leads. Results: In patients with CIED infections, compared to the non-infectious group, high inflammatory parameters were confirmed, and the highest specificity of the new markers in detecting the infectious process was demonstrated. (79.47% for NPR and 72.82% for NLR). Analysis of laboratory parameters in infectious and non-infectious patients with the presence of additional lead-related masses showed the highest specificity of NPR (82,78%) in predicting the diagnosis of vegetation. Comparison of laboratory parameters in patients with LRIE and PI showed higher NLR % (4.24 vs 2.56; p<0.001, area under curve (AUC) in a receiver operating characteristic (ROC) curve: 0.67 and 0.78 respectively) and higher NPR (0.03 vs 0.02; p<0.001; AUC: 0,51 and 0,55) in patients with LRIE. The highest sensitivity in the detection of coexistence LRIE with PI has been demonstrated for NLR (87.33%). Conclusions: Novel hematological markers may be helpful in the recognition of the inflammatory process in patients with CIED, differentiation of vegetation and vegetation-like masses, and the extent of infection in patients with PI.

: Healthcare workers are affected by mental health issues, burnout and turnover, and this burden is even greater during epidemics and pandemics, such as COVID-19. The purpose of this research is to provide an overview of the measures introduced or supported in the institutions of Quebec’s health and social services network during the COVID-19 pandemic with the aim of protecting healthcare workers’ mental health. An online questionnaire survey was administered in 2021 among human resources department personnel in health and social services network institutions involved in workplace mental health in Quebec. A total of 223 key informants representing 31 of the 34 public health and social services institutions in the province of Quebec in Canada responded to the questionnaire. Measures that focus on the needs of staff, involve all levels of authority and the ones that provide flexibility, support and recognition at work were more successful, according to the advisors surveyed. Future research into whether the same measures are considered effective or ineffective outside of a pandemic context is needed.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, and peaking around delivery.; (2) Methods: 80 Eighty thrombophilia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively studied, together with 80 eighty age- and para-matched control patients. Patients were admitted for delivery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis, in during both the 24 hours before and the 24 hours after labor—, extracted from the hospital’s medical records—, were calculated, and then correlated with uterine involution.; (3) Results: In pregnant patients treated for thrombophilia patients, the patients who did not manage to have close their uterine cavity closed with in the first 24-48 hours had significantly higher SII and AISI inflammation indexes SII and AISI , than the onesthose who did manage to have their uterine cavity closed their uterine cavity. In pregnant patients treated for thrombophilia patients, MLR is higher in patients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, PLR was significantly higher as compared to treated thrombophilia patients. In non-thrombophilia patients, MCVL increased with age and, before labor, while SII and AISI increased with age, postpartum. ; (4) Conclusions: There may be an underlying inflammation state that persisted despite treatment in some pregnant thrombophilia pregnant patients.

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting women worldwide. This study aimed to develop a rapid qPCR assay for accurate identification of VVC etiological agents and reduced azole susceptibility. One hundred and twenty nine vaginal samples from an outpatient clinic (Bilbao-Spain) were analyzed using culture-based methods and multiplex qPCR targeting fungal species, Candida albicans being the predominant species. Antifungal susceptibility tests revealed reduced azole susceptibility in three (3,48%) isolates. Molecular analysis identified several mutations in genes associated with azole resistance and novel mutations in TAC1 and MRR1 genes were also identified, which could contribute to drug resistance.

Akebia trifoliata is an economically important self-incompatible fruit tree in the family Lardiza-balaceae. Asexual propagation is the main strategy used to maintain excellent agronomic traits. However, the generation of adventitious roots during asexual propagation is very difficult. To study the important role of the WUSCHEL-related homeobox (WOX) transcription factor in fruit and adventitious root growth and development, we characterized this transcription factor family in the whole genome of A. trifoliata. A total of 10 AktWOXs were identified, with the fol-lowing characteristics: length (657~11328 bp), exon number (2~5), isoelectric point (5.65~9.03), amino acid number (176~361 AA), and molecular weight (20.500~40.173 kDa). 10 AktWOXs were classified into modern (6), intermediate (2), and ancient clades (2) and that all AktWOXs had undergone strong purifying selection during evolution. The expression profile of AktWOXs dur-ing A. trifoliata fruit development and adventitious root formation indicated that AktWOXs are widely involved in the development of the three fruit tissues, flesh, seeds and rind, and play an important role in the regulation of adventitious root development. Overall, this is the first study to identify and characterize the WOX family in A. trifoliata and will be helpful for further re-search on A. trifoliata fruit development and adventitious root formation.

Premenstrual syndrome (PMS) continues to impact the health outcomes and emotional well-being of reproductive-age women, globally. Several studies have provided conflicting evidence concerning the role of dietary approaches in improving PMS symptoms. Accordingly, this study aimed to evaluate the possible influence of a healthy diet and motivational strategies on PMS symptoms and health-related quality of life among Omani adolescents. This open-label, randomized, prospective controlled trial was conducted in two randomly selected secondary schools, in Al Seeb Willayah, in Muscat region. Adolescents with PMS symptoms, who were at grade 10 or 11, aged 16 years or above, had regular menstrual cycles and not known to have psychiatric disorder, were included in this study. Participants in the intervention group received an individual face-to-face dietary consultation and motivational phone consultation. The health outcomes, including the PMS symptoms in both groups, and quality of life, were recorded via a daily record of severity of problems questionnaire (DRSP) and the 14-item Self-Reporting-Based Perceived Stress Scale tools, respectively. The primary outcome was the differences in the mean premenstrual symptom scores between the two groups. Secondary outcomes included the quality of life and stress levels of participants. The study period was from 1 February and ended 30 June 2021. SPSS was used to analyze the data and intention-to-treat analysis was utilized.A total of 72 adolescents with PMS were randomized to the intervention and control groups (n=36 each). Both groups were similar at baseline (P-value&gt;0.05). No significant association was found between healthy-diet and PMS symptoms (P-value&gt;0.05). In addition, no significant association was found between healthy-diet and quality of life at follow-up (P-value=0.216). The outcomes of this study refuted any possible relationships between healthy diet and PMS symptoms. Accordingly, dietary consultations may not facilitate the clinical management of PMS symptoms in adolescent females.

Age estimation is an important tool when dealing with human remains or undocumented minors. Although the skull, the skeleton or the hand-wrist are used on age estimation as maturity indicators, they often present lack of good conditions for a correct identification or estimation. Few systematic reviews (SRs) have been recently published; therefore, this umbrella review critically assesses their level of evidence and provides a general comprehensive view. An electronic database search was conducted in four databases (PubMed, Cochrane, WoS, LILACS) up to December 2022, focusing on SRs of age estimation through forensic dentistry procedures. The methodological quality was analyzed using the measurement tool to assess SRs criteria (AMSTAR2). Eighteen SRs were included, five of critically low quality, six of low quality, three of moderate quality and four of high quality. The SRs posited that Willems’ method is more accurate and less prone to overestimation; most methods seem to be geographically sensitive; and 3D-Imaging and artificial intelligence tools demonstrate high potential. The quality of evidence on age estimation using dental approaches was rated as low to moderate. Well-designed clinical trials and high standard systematic reviews are essential to corroborate the accuracy of the different procedures of age estimation in forensic dentistry.

Background and Objectives: Chemokines have various biological functions and potential roles in the development or progression of neuroinflammatory diseases. However, the specific pathogenic roles of chemokines in age-related macular degeneration (AMD), the leading cause of blindness in older individuals, remain elusive. Chemokines interact with their receptors expressed in the endothelium and on leukocytes. The sulfation of tyrosine residues in chemokine receptors increases the strength of ligand–receptor interaction and modulates signaling. Therefore, in the present study, we aimed to construct a human recombinant sulfated CXCR3 peptide trap (hCXCR3-S2) and mouse recombinant sulfated CXCR3 peptide trap (mCXCR3-S2) to demonstrate in vivo effects in preventing choroidal neovascularization and chemotaxis. Materials and Methods: First, the effect of hCXCR3-S was validated in vitro. Interestingly, hCXCR3-S2 inhibited the migration and invasion of two human cancer cell lines. Subsequently, the in vivo efficacy of mCXCR3-S2 was investigated using a mouse model of neovascular AMD. Results: Intravitreal injection of mCXCR3-S2 attenuated choroidal neovascularization and macrophage recruitment in neovascular lesions. These in vitro and in vivo effects were significantly stronger with CXCR3-S2 than with wild-type CXCR3 peptides. Conclusion: These findings demonstrate that the sulfated form of the CXCR3 peptide trap is a valuable tool that could be supplemented with antivascular endothelial growth factors in AMD treatment.

Assessment of renal function is critical to diagnose and manage renal age-related decline, disease (KD), and failure, which are prevalent in the elderly population. Glomerular filtration rate (GFR) is widely used as an indicator of kidney function, but its direct measurement is challenging, as are its age and gender caveats. This makes difficult the differential diagnosis, between age-related physiological decline and KD and/or failure. Currently, the inflammation-based modified Glasgow prognostic score (mGPS) is emerging as promising biomarker of several inflammatory acute/chronic diseases. In this study, the large variability of eGFR with age and gender was evaluated, as the association of eGFR values with mGPS levels. A population of 57449 adult participants (age ≥18 years) was enrolled. Appropriate circulating biomarkers were measured to detect eGFR and mGPS values. The data obtained demonstrated a significant decrease of eGFR in men vs. women across the four selected age classes (18-40, 40-60, 60-80, 80-100 years), eGFR classes were significantly associated with mGPS (p<0.001), as age-classes and gender with mGPS categories. Accordingly, the percentage of people having a mGPS score= 2 significantly increased across the eGFR classes: with a 11% in the G1/eGFR class to achieve the 44% in G5/eGFR. Thus, the combination of mGPS with eGFR could represent the best benchmark risk model for differentiating age-related renal decline from a very KD, and for a better identification of different degrees of KD severity.