In some cases, the human impact on ancient landscapes has been so profound that local soils still remain significantly affected even after hundreds and thousands of years after ending impact. We studied the Late Bronze Age Muradymovo settlement located in Urals, Russia, aiming to estimate the consequences of the ancient people activity for environment. Despite the present humid climate, the modern soils inside the cultural layer of the study site contain more than 27% of gypsum at a depth of just 10 cm from the surface, and a microrelief of the study site is typical of a gypsum desert. The nearby background Chernozems are gypsum-free to a depth of 2 meters. According to the archaeological data, the ancient people belonged to the ‘Srubno-Alakul’ archaeological culture (1750–1350 yrs BC cal) and had a tradition of building their houses from gypsum rocks. At the present time, this area is still unsuitable for human settlement. The properties of modern soils inside the cultural layer of the study site are directly affected by the Late Bronze Age human activities. It has been identified on soil morphology, micromorphology and chemical properties of soils developed inside the cultural layer of the settlement.

Age-related diseases (ARDs) are the leading cause of death worldwide, and contribute to 90% of mortality in developed countries. Interestingly, the mortality rates of individual ARDs increase exponentially with age. Processes described by the exponential growth function typically involve a branching chain reaction or, more generally, a positive feedback loop. Here I propose that each ARD is mediated by one or several positive feedback loops (vicious cycles). I then identify critical vicious cycles in five major ARDs: atherosclerosis, hypertension, diabetes, Alzheimer’s and Parkinson’s. I also propose that the progression of ARDs can be halted by selectively interrupting the vicious cycles and suggest the most promising targets. An evolutionary perspective is also offered.

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.

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

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.

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.

Purpose The objective of this study was to eliminate any ambiguity by examining the correlation between gut microbiota and both AMD and glaucoma. Methods Mendelian randomization studies were conducted utilizing the data sourced from the GWAS database for the gut microbiome, AMD, and glaucoma. SNP estimates were summarized through five MR methods. We utilized Cochran's Q statistic to evaluate the heterogeneity of the instrumental variables. Additionally, we employed a "leave-one-out" approach to verify the stability of our findings. Results IVW suggests that Eubacterium (oxidoreducens group) and Parabacteroides had a protective effect on AMD. Both weighted median and IVW suggests that Lachnospiraceae (NK4A136 group) and Ruminococcaceae (UCG009) had a protective effect on AMD. However, both weighted median and IVW suggests that Dorea had a risk effect on AMD. Similarly, The IVW of Eubacterium (ventriosum group) showed a risk effect on AMD. The weighted median of Eubacterium (nodatum group), Lachnospiraceae (NC2004 group), and Roseburia had a risk effect on glaucoma. IVW suggested that Ruminococcaceae (UCG004) had a risk effect on glaucoma. Reverse MR analysis found a causal link between Eubacterium (nodatum group) and glaucoma. No causal relationships were found between AMD or glaucoma and the other mentioned bacterial groups. No significant heterogeneity or evidence of horizontal pleiotropy was detected. Conclusions This study found that certain gut bacteria had protective effects on AMD, while others may be risk factors for AMD or glaucoma. Besides, reverse MR found that glaucoma led to increased abundance of certain gut bacteria. Further trials are needed to clarify the specific mechanisms involved.

This trial was carried out to find out the effects of the parent flocks and the hatching time of broiler chickens on the production traits and bacteriota development of animals. Two times 730 hatching eggs were collected from two different parent flocks with age of 22-23 and 65-66 weeks. In the hatchery both groups were divided into two subgroups, when the day-old chickens were separated according to their hatching time. A feeding trial was carried out afterwards, using the 4 treatments in 6 replicate floor pens, feeding commercial starter, grower, and finisher diets, that contained all the nutrients according to the breeder’s recommendations. The day-old chickens of the parent older flock and those hatched later were heavier and this advantage of the birds remained until end of the production period. The different age and origin of parent flocks failed to modify the microbiological parameters of the chicken’s ceca. However, the hatching time significantly influenced the different bacteriota diversity indices. The late hatched chickens showed higher Bacteroidetes and Actinobacteria and lower Firmicutes abundances at day 11. These treatments resulted differences in the main families, Ruminococcaceae, Lactobacillaceae, Bacteroidaceae. These differences could not be found at day 39.

The coombs (in Catalan comes) form an integral part of the landscape. These are small valleys, with the deepest and flattest part cultivated for agriculture. They are predominantly found in the most arid regions of Catalonia, particularly around the cities of Tarragona and Lleida. They are generally dry land areas. We propose that these coombs gained significance in the early centuries of the Middle Ages, a period marked by intense erosion. It is important to identify their locations and establish connections with medieval written documents, the settlements that thrived throughout the Middle Ages, archaeological sites such as necropolises, and the valuable data derived from to-ponymy studies. We think that understanding these coombs can greatly contribute to under-standing how the territory was organized in the Middle Ages, the extent of cultivated lands that were established, and the distribution of many settlements. Ultimately, this knowledge can aid in acquiring better understanding of the current landscape.

Background: Current European guidelines support transcatheter aortic valve implantation (TA-VI) in intermediate to low-risk patients ≥75 years-old but its prognostic relevance is unknown. Methods: Intermediate-to-low-risk (Society of Thoracic Surgeon score <8%) patients enrolled in the HORSE registry were included. We compared the population with less versus more than 75 years old. The primary endpoint was all-cause mortality. Results: A total of 2685 patients were included, 280 (8.6%) <75 and 2405 ≥75 years. Through a mean follow-up of 437 ± 381 days, 198 (8.2%) and 23 (8.2%) patients died in the two arms, without statistically significant differences (log-rank p=0.925). At Cox regression analysis, age did not predict the occurrence of all-cause death, neither as a continuous variable (HR 1.01, 95% CI 0.99-1.04, p=0.294) nor dichotomizing according to the prespecified cutoff of 75 years (HR 0.97, 95% CI 0.63-1.51p=0.924). Time-to-event ROC curves showed low accuracy of age to predict all-cause mortality (area under the curve of 0.54 for both 1-year and 2-year outcomes). Conclusions: TAVI has comparable benefits across age strata in intermediate-to-low risk patients. The age cut-off suggested by current guidelines is not predictive of the risk of adverse events during hospital stay, neither of all-cause mortality through a mid-term follow-up.

Delve into the ebb and flow of human ingenuity as the researcher traces the evolution of writing from papyrus to pixels. Discover how humble instruments like quill pens and typewriters have propelled human into the digital frontier, forever reshaping the art of expression in the modern age. This article examines the evolution of writing tools from traditional pen and paper to digital writing in the modern age. It explores the development of writing materials such as papyrus, parchment, and paper, as well as the invention of writing tools including quill pens, fountain pens, and typewriters. The rise of digital writing tools, including word processing software and smartphones, is also discussed, along with their benefits such as increased efficiency and productivity, enhanced collaboration and sharing capabilities, and greater accessibility and flexibility. However, the article also highlights the challenges of writing in the digital age, including the impact of digital distractions on writing focus and quality, the issue of online plagiarism and copyright infringement, and the potential loss of traditional writing skills. The article concludes with recommendations for educators, school administrators, students, and researchers to strike a balance between digital and traditional writing practices, to embrace digital writing tools while preserving traditional writing skills, and to understand the importance of the evolution of writing. The theoretical frameworks of Social Construction of Technology (SCOT) Theory, Media Ecology Theory, and Activity Theory are also discussed in relation to the evolution of writing tools. Overall, this article provides valuable insights into the history, benefits, and challenges of writing in the digital age, as well as suggestions for navigating the future of writing and its tools.

Colorectal cancer remains one of the most commonly diagnosed cancers. Advanced rectal cancer patients receive neoadjuvant radiochemotherapy as well as surgery and suffer under reduced health-related quality of life due to various side effects. We were interested in the role of the COVID-19 pandemic and how it affected those patients’ quality of life. A total of 489 advanced rectal cancer patients from the University Hospital Erlangen in Germany were surveyed between May 2010 and March 2022 and asked to fill out the EORTC QLQ-C30 and QLQ-CR38 questionnaire over eight different time points: in the beginning, during and after radiochemotherapy, right before surgery and in yearly intervals after surgery for up to four years. Answers were converted to scores to compare the COVID-19 period to the time before March 2020 focusing on the follow-ups, the developments over time – including by sex and age - and the influence of the TNM cT-stage. Overall, a trend of impaired functional and symptom scores was found across all surveys with few significances (body image -10.6 percentage points (pp) after one year; defecation problems +13.5 pp, insomnia +10.2 pp and weight loss +9.8 pp after three years; defecation problems +11.3 pp after four years). cT4-stage patients lost significantly more weight than their cT1-3-stage counterparts (+10.7 to 13.7 pp). Further studies should be conducted to find possible causes and develop countermeasures for future major infectious diseases.

OCTA is an imaging modality used in the assessment of the retinal vasculature. It operates on the principle of coherence tomography used in standard OCT with the addition of delineating the retinal vascular. This provides a modern non-invasive retinal vascular imaging method compared to conventional dye-based imaging. High quality depth resolution of the superficial and deep capillary networks is possible on OCTA whereas this was not possible prior. OCTA may be limited by image quality degradation from factors such as motion artefact or media opacities, and therefore may not be the investigation of choice for all patient groups. There are multiple potential clinical applications for OCTA in retinal and choroidal vascular disease. Ongoing research is necessary to substantiate the more widespread use of OCTA due to its significant cost burden compared to current modalities.

This paper discusses the preliminary results of archaeological surveys conducted in the Juuku Region of north-central Kyrgyzstan on the south side of Lake Issyk kul. Our goal was to document ancient and contemporary agropastoral systems over a four millenia time period. During the surveys about 350 loci were identified as settlements, burial mounds, graves, single artifact finds, and artifact scatters (ceramic). The areas of Juuku Valley survey included two discrete polygons: Polygon 1, Lower Juuku at 1750 to 1950 m asl in elevation and Polygon 2, Chak Juuku or Upper Eastern Branch Juuku Valley at 2060 to 2100 m asl in elevation. Three radiometric dates and preliminary archaeobotanical studies were conducted at three exposed profile cuts. The methods included here are: (1) pedestrian surveys; (2) use of digital maps (Google Earth, Encarta); (3) placing archaeological loci within known chronological time periods; (4) AMS dating of charcoal samples collected from profile deposits; and (5) preliminary identification of plant remains found from archaeobotanical samples. The results of our research represent the first step toward inventorying and interpreting archaeological data in the Juuku Valley derived from field studies.

Abstract: The aim of the present study was to identify the age and sex-related associations between marital status with PA and TV time. We used data from Vigitel, an annual telephone survey started in 2006 in Brazil. We applied a complex sample logistic regression model to estimate the odds for PA and TV time comparing marital statuses according to age and sex subgroups, independent of obesity, hypertension, diabetes, self-assessed poor health, and smoking. Our sample included 561,837 individuals with a TV time &gt; 3 h/day (prevalence = 25.2%) and PA &gt; 150 min/week (prevalence = 35%). Compared to single individuals, married men and women were less likely to watch TV more than 3 h/day in participants &gt; 30 years old. When compared to single, married participants were less likely to do more than 150 min of PA/week at younger age groups. Married women older than 40 years were more likely to do more than 150 min of PA/week than the single ones, while there were no differences among married men by age group. In conclusion, married individuals are less likely to spend more than 3 hours a day watching TV than single individuals. Single men and women were more likely to do more than 150 min of PA/week at younger age groups and married women older than 40 years were more likely to do 150 min of PA/week than single women.

Understanding the processes that govern the transformation of the landscape through time is essential for exploring the evolution of a coastal area. Coastal landscapes are dynamic sites, with their evolution strongly linked with waves and sea-level variations. Geomorphological features in the coastal area, such as beachrock formations and dune fields, can function as indicators of the coastal landscape evolution through time. However, our knowledge of the chronological framework of coastal deposits on the Aegean coasts is limited. Optically stimulated luminescence dating techniques are deemed to be very promising indirect dating of the coastal sediments, especially when they are linked with archaeological evidence. The dating of the sediments from different sediment core depths, as they are determined by the method of luminosity, allows us to calculate the rate of sediment deposition over time. Additionally, the coastal evolution and stability were studied from 1945 until today, with the use of aerial photographs and satellite images. This paper presents the 6000 ka years evolution of a coastal landscape based on geomorphological, archaeological, and radio-chronological data. Based on the results, the early stages of the Ammoudara beach dune field appear to be formed ~9.0 – 9.6 ka BP, while the OSL ages from 6 m depth represented the timing of its stabilization (OSL ages ~5–6 ka). This indicates that the dune field appears to already have been formed long before the Bronze Age (5-10 ka BP) and became stabilized with only localized episodes of dune reactivation occurring, while high coastal erosion rates are found in modern times.

Wrist-worn fitness trackers and smartwatches are proliferating with an incessant attention towards health tracking. Given the growing popularity of wrist-worn devices across all age groups, a rigorous evaluation for recognizing hallmark measures of physical activities and estimating energy expenditure is needed to compare their accuracy across the lifespan. The goal of the study was to build machine learning models to recognize physical activity type (sedentary, locomotion, and lifestyle) and intensity (low, light, and moderate), identify individual physical activities, and estimate energy expenditure. The primary aim of this study was to build and compare models for different age groups: young [20-50 years], middle (50-70 years], and old (70-89 years]. Participants (n = 253, 62% women, aged 20-89 years old) performed a battery of 33 daily activities in a standardized laboratory setting while wearing a portable metabolic unit to measure energy expenditure that was used to gauge metabolic intensity. Tri-axial accelerometer collected data at 80-100 Hz from the right wrist that was processed for 49 features. Results from random forests algorithm were quite accurate in recognizing physical activity type, the F1-Score range across age groups was: sedentary [0.955 – 0.973], locomotion [0.942 – 0.964], and lifestyle [0.913 – 0.949]. Recognizing physical activity intensity resulted in lower performance, the F1-Score range across age groups was: sedentary [0.919 – 0.947], light [0.813 – 0.828], and moderate [0.846 – 0.875]. The root mean square error range was [0.835 – 1.009] for the estimation of energy expenditure. The F1-Score range for recognizing individual physical activities was [0.263 – 0.784]. Performances were relatively similar and the accelerometer data features were ranked similarly between age groups. In conclusion, data features derived from wrist worn accelerometers lead to high-moderate accuracy estimating physical activity type, intensity and energy expenditure and are robust to potential age-differences.

Increasing numbers of researchers are interested in the importance of dietary fiber for the gut microbiota, microbiotal metabolite SCFA, energy metabolism and gut health of the host. However, studies have demonstrated that long-term and longitudinal observation may be needed to evaluate the effect of dietary fiber better, and few such works have been made in chickens. Therefore, we successively fed low-fiber, high--fiber and low-fiber diets to two breeds of chickens during different growth periods (1—8, 9—20 and 21—50 weeks), aiming to longitudinally observe the long-term effect of altered dietary fiber on the gut microbiota, SCFA and development of cecum of chickens with age. The results showed that the composition and function of the gut microbiota, SCFA and the development of the cecum were different during different periods, which was largly affected by dietary fiber. However, the causes of some effects were different during the different periods. For example, compared with that in low-fiber chickens at 8 weeks, dominant fiber-degradation bacteria such as Bacteroidetes, Alloprevotella and SCFA-producing bacteria such as Faecalibacterium increased due to a high-fiber diet at 20 weeks, while due to a high feed intake in 50 weeks. Moreover, the concentration of SCFA in 20 weeks was significantly higher than in 8 weeks and 50 weeks, but the causes of this difference were also distinct. It was proposed that a long-term observation was needed to evaluate the effect of dietary fiber better on chickens. The metabolite pathways of ATP-binding cassette (ABC) transporters encoded by Firmicutes were enriched in 8 weeks, while a two-component system and β–glucosidase encoded by Bacteroidetes were enriched in 20 and 50 weeks. The trend was the same in two breeds of chickens except for Alloprevotella. In addition, the total content of SCFA in the contents of cecum was also affected by the size of the cecum. Surprisingly, the length of the cecum shortened from 20—50 weeks, maybe due to reduced dietary fiber.

Biophoton emission has been experimented for decades. The photo-genic origin of biophoton has also been attributed to the oxidative stress or free radical production. However, there are considerable gaps in quantitative understanding of biophoton emission. In this work, I propose an analytical hypothesis for interpreting a few patterns of steady-state biophoton emission of human, including the dependency on age, the diurnal variation, and the geometric asymmetry associated with serious asymmetrical pathological conditions. The hypothesis is based on an alternative form of energy state, termed vivo-nergy, which is associated with only metabolically active organisms that are also under neuronal control. The hypothesis projects a decrease of the vivo-nergy in human during growth beyond puberty. The hypothesis also proposes a modification of the vivo-nergy by the phases of systematic or homeostatic physiology. The hypothesis further postulates that the deviation of the physiology-modified vivo-nergy from the pre-puberty level is deteriorated by acquired organ-specific pathological conditions. A temporal differential change of vivo-nergy is hypothesized to proportionally modulate oxidative stress that functions as the physical source of biophoton emission. The resulted steady-state diffusion of the photon emitted from a photo-genic source in a human geometry simplified as a homogeneous spherical domain is modeled by photon diffusion principles incorporating an extrapolated zero-boundary condition. The age and systematic physiology combined determines the intensity of the centered physiological steady-state photo-genic source. An acquired pathology sets both the intensity and the off-center position of the pathological steady-state photo-genic source. When the age-commemorated, physiology-commanded, and pathology-controlled modifications of the steady-state photo-genetic sources are implemented in the photon diffusion model, the photon fluence rate at the surface of the human-representing spherical domain reveals the patterns on age, the temporal variation corresponding to systematic physiology, and the geometric asymmetry associated with significant asymmetric pathological condition as reported for spontaneous biophoton emission. The hypothesis, as it provides conveniences for quantitative estimation of biophoton emission patterns, will be extended in future works towards interpreting the temporal characteristics of biophoton emission under stimulation.

(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.

(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.

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 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.

Background: Urinary tract infection (UTI) is one of the commonest bacterial infections among reproductive age females. Untreated UTI in reproductive age female is associated with sexual dysfunction, cystitis, pyelonephritis and Pelvic inflammatory disease. At present, the antimicrobial resistance emergency has quadrupled worldwide and poses a serious threat to the treatment of patients. Thus, this study aimed to determine bacterial profile, antibiotic susceptibility pattern and associated risk factors of urinary tract infection among reproductive age females attending the Logbaba District Hospital Methods: A hospital-based cross-sectional study was conducted from January – July, 2023. Convenient sampling was employed to recruit 259 reproductive age females. Sociodemographic and risk factors information were obtained using a well-structured questionnaire. Mid-stream urine was collected and inoculated on cystine lactose electrolyte deficient media. Isolates were identified using API 20. Antibiotic sensitivity testing was performed using modified kirby-bauer susceptibility testing technique. Multivariate logistic regression model was used to assessed risk factors. A p-value < 0.05 was considered as statistically significant. Results: The overall prevalence of UTI among reproductive age females was 82/259 (31.66%). Symptomatic and asymptomatic patients reported a prevalence of 50/121(41.32%) and 32/138 (23.19%), respectively. Ages ranging from 21-30 years (AOR: 2.53 ,95% CI 1.32 – 4.43, p=0.006) and 31 – 40 years (AOR: 0.19 , 95% CI: 0.14- 0.54; p <0.0001), student (AOR: 1.8, 95% CI: 1.21 - 2.75; p = 0.010), history of UTI (5.34, 95% CI = 1.86 - 18.15; p = 0.03), symptomatic (AOR = 2.86, 95% CI1.78 - 4.67, p <0.0001) and secondary education (AOR: 0.13, 95% CI 0.08 - 0.32; p<0.0001) were predictors to UTI. Klebsiella Pneumoniae was the most frequent species 27 (32.9%), follow by E coli 22(26.8%), Staphylococcus aureus 16 (19.5%), CONS 8 (9.8%), Proteus mirabilis 6 (7.3 %) and Pseudomonas aeruginosa 3(3.7%). Majority of the isolates were sensitive to cefotaxime (87.80%), imipenem (85.7%), vancomycin (79.27%), Ofloxacillin (76.83%), Ceftriaxone (75.61%), Ciprofloxacin (74.39%), Gentamicin (71.95%) and Doxycycline (69.51%), and resistant to Amoxicillin (51.22%), cotrimoxazole (47.56%) and Azithromycin (31.71%) , All the isolates were multidrug drug resistant (100%) and Klebsiella Pneumoniae and E coli were the most multidrug drug resistant species Conclusion: In the present study, the prevalence of urinary tract infection among reproductive age females was high and considerably a high proportion of multidrug resistance was observed. This result will have a significant impact on the selection of appropriate antimicrobial agents for the treatment of urinary tract infection in the study area.

Intergenerational integration has given rise to a novel aging paradigm known as all-age communities, which is garnering international attention. In China, the aging population and the implementation of the three-child policy have resulted in increased demand for retirement and childcare services among residents in older neighborhoods. Consequently, there is a pressing need to retrofit these older neighborhoods to accommodate all-age living arrangements given the high demand they generate. Therefore, this study undertakes research interviews with residents and constructs an exploratory theoretical model rooted in established theory. To assess the significance of our model, we employ Smart PLS 3.0 based on 297 empirical data points. Our findings indicate that anxiety has a significant negative effect on payment behavior; objective perception, willingness to pay, and government assistance exert significant positive effects on payment behavior. By comprehensively analyzing the mechanisms underlying residents’ payment behavior, this study provides valuable insights to the government for promoting the aging process within communities and formulating effective transformation policies.

As the global aging trend continues to intensify, there will inevitably be more complex and diverse aging problems in the future. There is no doubt that designers have the responsibility to explore the possibilities of the future and solve the problems that will be faced in the future. Based on the Future Cone, the Double Diamond Model and the IDEO Method Cards, this study proposes a new model to guide the design practice of future aging issues in the context of aging. With the aim of validating and refining the framework, an ageing designer workshop was held where participants were asked to imagine, explore and express ideas about future ageing issues. The workshop was used to refine the proposed model. More specifically, the model includes a future concept, a design guidance process based on the Double Diamond Model, and tools that can be applied at all stages of design, which can help designers generate ideas and solutions for future aging problems, and collectively lead society to a more desirable future. Moreover, this study also explores broader directions for the development of the model and provides a reference for continued research on this topic in the future.

Stand biomass in boreal forests has attained recognition for its crucial role in carbon cycling. In this study, we examined the effect of stand age on above- and belowground biomass allocation in downy birch (Betula pubescens Ehrh.) in three drained peatland sites in Central Finland. We used allometric equations to estimate individual-tree above-ground biomass and its various components, including stem wood, stem bark, living branches, leaves, and dead branches. The above-ground biomass ranged from 10.5 t ha-1 to 276.0 t ha-1 and foliage biomass from 0.009 t ha-1 to 0.6 t ha-1. We found that stand age had a strong correlation with above-ground biomass, but foliage biomass appeared to peak at the middle-aged (50 years) stand compared to the young (10 years) or mature (80 years) stands. We observed coarse root biomass production of 45, 250, and 110 g m-2 in the 0–50 cm peat layer for young, middle-aged, and mature stands, respectively. Most coarse root biomass occurred in the top 20-cm layer (77%). These findings improve our understanding of how biomass allocation patterns – specifically those in foliar biomass– change over time, and the impact on litter inputs into the soil.

Purpose: Cardiovascular disease (CVD) is a major risk factor for mortality in patients with osteoarthritis, and comorbidities increase postoperative complications after total knee arthroplasty (TKA). Arteriosclerosis plays a major role in hemodynamic dysfunction and CVD; however, arteriosclerosis has not been preoperatively evaluated before TKA using the cardio–ankle vascular index (CAVI). In this study, we evaluated the degree of preoperative arteriosclerosis using the CAVI in patients undergoing TKA, as well as its correlations with several preoperative patient factors. Methods: Arteriosclerosis was evaluated in 209 consecutive patients (251 knees) with osteoarthritis who underwent TKA at our institution between May 2011 and June 2022. The CAVI was measured in the supine position 1 day before TKA, and the correlations between the CAVI and several clinical factors were analyzed. A p value of <0.05 was considered statistically significant. Results: The CAVI was normal in 62 knees (25%), borderline in 71 knees (28%), and abnormal in 118 knees (47%). Univariate analysis revealed a moderate positive correlation between preoperative CAVI and age (r = 0.451, p < 0.001) and a weak negative correlation between preoperative CAVI and body weight (r = −0.306, p < 0.001) and body mass index (BMI) (r = −0.319, p < 0.001). Multivariate analysis showed that age (β = 0.349, p < 0.001) and BMI (β = −0.235, p < 0.001) were significantly correlated with preoperative CAVI. Conclusion: Arteriosclerosis should be carefully managed intraoperatively and postoperatively in patients with osteoarthritis undergoing TKA, particularly in older patients and patients with a low BMI.

For a long time, there has been interest in the relationship between personality traits and life satisfaction. However, many previous studies suffer from small sample sizes or selective sampling, sometimes leading to biased or imprecise results. The current study, which focuses on the trait of extraversion, attempts to overcome these limitations by using a large-scale German survey of more than 40,000 individuals aged 10 to 72. As the descriptive and regression results clearly show, there is a statistically significant relationship between extraversion and several dimensions of current life satisfaction. Depending on the type of satisfaction, the unstandardized regression coefficients range from 0.18 to 0.33. To gain further insight, age is added as an explanatory variable to test whether these associations change as a person ages. The results show that the effect sizes sometimes differ by age but remain robust and statistically significant. In conclusion, the study adds to the literature by providing convincing evidence that extraversion and life satisfaction are positively associated, at least in Western and industrialized countries, and that there are interaction effects with age.

The Huayangchuan uranium deposit, located in the west of the Xiaoqinling belt on the southern margin of the North China Craton, is a polymetallic deposit dominated by U, Nb, Pb, and rare earth elements. The Huayangchuan uranium deposit, discovered in the 1950s, has long been known as a carbonatite-type uranium deposit. Recently, new geological work has found uranium mineralisation in many granitic pegmatite veins in the Huayangchuan deposit and adjacent areas. Here, we report a systematic investigation of the petrography, whole-rock geochemistry, zircon U-Pb ages, and in situ Lu-Hf isotopic characteristics of newly discovered U-rich granitic pegmatite veins in the west of Huayangchuan deposit. The petrological results showed that the lithology of the samples is equivalent to that of granite. The U-Pb ages of zircon were 1826.3 ± 7.9 and 1829 ± 11 Ma. Microscopically, the symbiotic characteristics of zircon, betafite, and uraninite exist in the intergranular fissures of K-feldspar and quartz, reflecting metallogenic phenomena in the rock formation process. Almost all whole-rock samples were rich in SiO2 (64.37–70.69 wt.%), total alkalis (K2O+Na2O = 8.50–10.30 wt.%), and Al2O3 (12.20–14.41 wt.%), but poor in Ti2O (0.23–0.73 wt.%), MgO (0.38–0.90 wt.%), P2O5 (0.14–0.83 wt.%), MnO (0.04–0.57 wt.%). Additionally, they showed enrichment of LILEs (such as Rb, Ba, Th, U, and K), depletion of HFSEs (such as Ta, Nb, P, Ti, and Hf), no alkaline dark minerals, and the characteristics are typical of intraplate A1-type granite. The A1-type granite displayed low zircon εHf(t) values (-19.42– -15.02) with zircon two-stage Hf model aged 3.10–2.76 Ga, indicating that the U-rich granitic pegmatite was derived predominantly from partial melting of the ancient continental crust (such as the early Taihua group formed in Archean-Neoarchean). Combined with the above results and regional geological data, the U-rich granitic pegmatite discovered in the Huayangchuan deposit was related to granite magma activity that formed in a post-collisional regime after the Luliang movement in the late Palaeoproterozoic. This study suggests that future uranium prospecting work in this area should focus on late Palaeoproterozoic U-rich granitic pegmatites.

Abstract. Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Fifty-five SARS-CoV-2 positive and 61 negative third trimester patients were randomly selected from Montefiore Medical Center (MMC), Bronx, NY. In addition, two positive cases from Yale New Haven Hospital, CT were included as controls. All 55 placentas delivered by SARS-CoV-2 positive mothers were uninfected by the virus, based on immunohistochemistry, in-situ hybridization, and qPCR analysis. However, placental villous infarcts, mild preeclampsia, shortened gestational periods and lower Apgar scores were observed in the infected cases. These findings suggest that even without entering the placenta, SARS-CoV-2 can affect various systemic pathways culminating in altered placental development and function, which may adversely affect the fetus, especially in a high-risk patient population such as ours. These results underline the importance of vaccination among pregnant women, particularly in low resource areas.

The evolution of digital media in adolescents has changed the patterns and motives of use and the impact on their communication choices in their social and family networks. The objectives of this study are to understand how peers communicate adopting a social network (SN) or by voice and their social desirability. After the informant consent signature, the adolescents completed a series of self-report questionnaires on the use of SN, on communication preferences, and on social desirability through online. Most of the adolescents belonged to the 17-19 age group (83.6%) and were female (68.9%). Adolescents spent more than 3 hours/day on Whatsapp and more than 2 hours/day on Instagram, while the use of Facebook was on average only 35 minutes/day. Females used digital media for longer than males. Adolescents aged 17-19 years choose more Facebook and voice modes compared to adolescents aged 14 and 16 years. The alternative modes of Whatsapp and voice were chosen more than the social networks in their communication strategies, especially for negative topics. Motives for use were, in addition to boredom, related to maintaining one's social sphere with peers. Some educative considerations were made based on these results.

Objectives: This study aimed to analyze the awareness of local residents regarding healthcare projects and to suggest some ideas for the revision of local ones. Methods: To delve into the opinions of local residents, the author of this study created a questionnaire composed of eight questions on the general characteristics of the respondents, eight questions on satisfaction with health centers, 16 questions on the awareness of healthcare projects, and 22 questions on local healthcare. The survey was conducted for 409 residents who visited public centers in Gimcheon from 15 March to 14 April 2021. Results: Data analysis revealed the following: The proportion of local residents who use health centers was 39.1%, and those users visit health centers, on average, 3.92 times a year. Among healthcare projects, the project known by the highest proportion of people was vaccinations (84.5%), which was also the project that was most used (38.1%). Among healthcare projects needed in the with-COVID-19 age, respondents awarded the highest score to vaccinations (4.15 points on a five-point Likert scale) and the second highest score to infectious disease management (4.12). Conclusions: For healthcare projects, central and local governments should focus on activating vaccinations, solving the problem of medical accessibility through untact remote treatment and establishing national infectious disease-specializing hospitals and local infectious disease management based on such national hospitals.

Background: Little is known about potential confounding factors influencing the humoral response in individuals having received the BNT162b2 vaccine. Methods: Blood samples from 231 subjects were collected before and 14, 28 and 42 days following COVID-19 vaccination with BNT162b2. Anti-Spike Receptor-Binding-Domain protein (anti-Spike/RBD) immunoglobulin G (IgG) antibodies were measured at each time-point. Impact of age, sex, childbearing age status, hormonal therapy, blood group, body mass index and past-history of SARS-CoV-2 infection were assessed by multivariable analyses. Results and Conclusions: In naïve subjects, the level of anti-Spike/RBD antibodies gradually increased following administration of the first dose to reach the maximal response at day 28 and then plateauing at day 42. In vaccinated subjects with previous SARS-CoV-2 infection, the plateau was reached sooner (i.e. at day 14). In the naïve population, age had a significant negative impact on anti-Spike/RBD titers at day 14 and 28 while lower levels were observed for males at day 42, when corrected for other confounding factors. BMI as well as B and AB blood groups had a significant impact in various subgroups on the early response at day 14 but no longer after. No significant confounding factors were highlighted in the previously infected group.

Learning disorders (LD) are diagnosed in children impaired in the academic skills of reading, writing and/or mathematics. Children with LD usually show a slower resting-state electroencephalogram (EEG), with EEG patterns corresponding to a neurodevelopmental lag. LD-children also show a consistent cognitive impairment in working memory (WM), including an abnormal task-related EEG with an overall slower EEG activity of more delta and theta power, and less gamma activity in posterior sites; task-related EEG patterns considered indices of an inefficient neural resource management. Neurofeedback (NFB) treatments aimed at normalizing the resting-state EEG of LD-children have shown improvements in cognitive-behavioral indices and diminished EEG abnormalities. Given the typical findings of a WM impairment in LD-children; we aimed to explore the effects of a NFB treatment in the WM of children with LD, by analyzing the WM-related EEG power-spectrum. We recruited 18 children with LD (8-10 years old). They performed a Sternberg-type WM-task synchronized with an EEG of 19 leads (10-20 system) twice in pre-post treatment conditions. They went through either 30 sessions of a NFB treatment (NFB-group, n= 10); or through 30 sessions of a placebo-sham treatment (Sham-group, n= 8). We analyzed the before-after treatment group differences for the behavioral performance and the WM-related power-spectrum. The NFB group showed faster response times in the WM-task post-treatment. They also showed an increased gamma power at posterior sites and a decreased beta power. We explain these findings in terms of NFB improving the maintenance of memory representations coupled with a reduction of anxiety.

Background: This paper investigates the statistical relationship between bilingualism and the Onset Age (OA) of AD and MCI across a clinical sample, consisting of 580 Alzheimer's Disease (AD) subjects and 1264 Mild Cognitive Impairment (MCI) subjects, via a statistical analysis conducted on the sample retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Method: To investigate whether bilingualism has any correlation with the OAs of AD or MCI subjects, our study leverages the full potential of the ADNI dataset, a dataset that covers both the OA and the bilingualism status of both the AD and MCI subjects. Prior to performing any meaningful statistical analysis, a regression model and a probabilistic model were developed in parallel to fill in the missing OA and bilingualism values. A simple least-square regression model that consists of an independent variable of registered age for Mini-Mental State Examination (MMSE) score was used to estimate the OA of the AD and MCI subjects in the ADNI dataset. After filling in the missing OA values, the number of subjects relevant for the statistical analysis increased from 816 (AD: 371, MCI: 445) to 1844 (AD: 580, MCI: 1264), which greatly enlarged the representation of the AD and MCI sample in the ADNI population. With increased sample size, a novel probabilistic classification model was introduced to infer an ADNI subject’s bilingualism when relevant demographic information and deterministic outcome were not readily available from the ADNI dataset. The weighted average OA for the bilinguals and the monolinguals was then computed, where the weights for the probabilistic labels were assigned based on the percentage of bilingualism in the general US population. Finally, a statistical analysis was performed to test whether any statistically significant correlation exists between the OA and the bilingualism of the AD and MCI subjects within the ADNI dataset. Findings: Our preliminary study demonstrates no significant statistical difference between the OA of the bilinguals and the monolinguals within the ADNI dataset. Thus, the monolingual speakers within the ADNI dataset do not statistically manifest earlier onset, as compared to the bilingual speakers, which is slightly inconsistent with some earlier statistical findings that bilingual speakers enjoy certain distinctive advantages, such as late onset of AD, as compared to monolingual counterparts.

Unification point of view, quantum cosmology must be given a priority and one should make a note that, Spin is a basic property of quantum physics and rotation is a very common experience. In this context, we have developed a quantum model of cosmology associated with Machian universe having Planck scale origin, total dark matter, light speed rotation and equality of gravitational self energy density and thermal energy density. We would like to appeal that, observed cosmic radius and age seem to be shortened by 146.3 times their actual magnitudes.

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.

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.

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.

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.

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.

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.

(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.

Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system which is crucial for memory, emotions, and learning. Though distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies.

This study examined the eye movement patterns of 317 elementary students across reading conditions (audio-assisted reading (AR) and reading-only (R)) and text types (fiction and non-fiction), and identified eye movement parameters that predict their literal comprehension (LC) and inferential comprehension (IC). Participants, randomly assigned to either reading condition and either text type, answered questions assessing their LC and IC. Average fixation duration (AFD), total fixation duration (TFD), and scanpath length were used as eye movement parameters. There were main effects of age on all parameters and interaction effects between age and reading condition on TFD and scanpath length. Controlling for age, TFD had a positive impact on LC of both text types in the AR, while under the R, it affected negatively on IC of both text types. Longer scanpaths predicted IC of fiction in the AR, LC and IC of non-fiction under the AR, and LC of non-fiction within the R. AFD influenced negatively on IC of fiction in the AR, LC and IC of non-fiction in the AR, and LC of non-fiction under the R. These eye movement patterns and predictors indicate children employ different reading strategies based on reading modality and text type.

The impact of early maternal age on several outcomes (e.g. mental health issues, delinquency, aggression, impulsivity, victimization and interpersonal difficulties) has been studied since the late 1980s. Research has demonstrated links between exposure to adverse childhood experiences (ACEs) and trauma related outcomes such as substance abuse, interpersonal and self-directed violence, and sexual risk-taking, to name a few. The current study analyzed the incidence of ACE exposure and mental health outcomes (e.g. suicidal behaviors or self-harm, psychiatric hospitalizations, and substance use) as related to early maternal age in youth known to have experienced trafficking or sexual abuse. General demographics and incidence of various experiences and clinical presentations (e.g. ACE exposure, age of mother at birth of youth and age at first birth), and history of self-harm, substance use and psychiatric hospitalization were examined in a sample of 225 youth referred for services subsequent to experiences of sex trafficking or exploitation. Relationships between ACE exposure and maternal age related to mental health outcomes was also examined. Trafficked and exploited youth reported rates of ACE exposure and poor mental health outcomes at far greater rates than the general population. Significant findings were related to early maternal age and engaging in self-harm or suicidal behaviors. Previously anticipated mediational analyses were not conducted due to the sample size and lack of correlations. Findings highlight the significant ACE exposure and high needs of exploited, trafficked and abused youth and related mental health outcomes, emphasizing the need for early and comprehensive preventive and therapeutic interventions.

Neovascular age-related macular degeneration (nAMD) leads to visual impairment if not treated timely. Intravitreal anti-VEGF drugs have revolutionized nAMD treatment in two decades. We evaluated visual outcomes of anti-VEGF treatment in nAMD. A real-life population-based cohort study. Data included parameters for age, sex, age at the diagnosis, laterality, chronicity, symptoms, visual outcomes, lens status, and history of intravitreal injections. A total of 1088 eyes (827 patients) with nAMD were included. Visual acuity was stable or improved in 984 eyes (90%) after an average 36±25 months follow-up. Bevacitzumab was the first-line drug in 1083 (99.5%) eyes. Vision improved ≥15 ETDRS letters in 377 (35%), > 5 ETDRS letters in 309 (28%) and was stable (±5 ETDRS letters) in 298 (27%) eyes after anti-VEGF treatment. The loss of 5-<15 ETDRS letters in 44 (4%) and ≥15 ETDRS letters in 60 (6%) eyes was noted. At the diagnosis of nAMD, 110 out of 827 patients (13%) fulfilled the criteria of visual impairment, whereas 179 patients (22%) were visually impaired after the follow-up. Improvement or stabilization in vision was noted in 90% of the anti-VEGF-treated eyes with nAMD. In addition, anti-VEGF agents are crucial in diminishing nAMD-related visual impairment.

This paper uses preliminary studies of archaeological sites (burial mounds and settlements) from the Iron Age through Medieval periods (ca. 800 BCE to 1200 CE) in the Juuku Valley on the South side of Lake Issyk-Kul to model land-use across vertical mountain zones. To do so, we have established a radiometric chronology, conducted test excavations of an Iron Age settlement and a Turkic period burial, undertaken preliminary archaeobotanical research, and pedestrian surveys. Seed remains of wheat (Triticum aestivum), barley (Hordeum vulgare), broomcorn millet (Panicum milaceum) and foxtail millet (Setaria italica) and legumes were recovered in very small quantities from an Iron Age upland settlement at 2100 m asl and a Turkic period burial mound at 1934 m asl. These preliminary archaeobotanical results are compared to the Talgar Iron Age settlements on the north side of the Tian Shan Mountain range in Kazakhstan studied earlier by Robert Spengler. Small samples of faunal remains found at the Turkic period kurgan and from a profile at the upland Iron Age settlement indicate livestock herding of sheep/goats, cattle, and horses in Juuku Valley. The goal of this paper is to test the hypothesis that pastoral transhumance and agropastoralism were economic strategies used by ancient societies during the Iron Age through Medieval periods in mountain-river valley areas between 750 m to 2500 m asl. These economic strategies that combined the pasturing of sheep, goats, cattle and horses with the cultivation of cereals were adapted to the use of different vegetational zones along a vertical gradient. This paper based on preliminary research of upland sites of the Juuku Valley in Kyrgyzstan, initiates a long-term research study of four millennia of settlements that ranged from pastoral transhumance, pastoral nomadism, and combined mountain agriculture using survey data and test excavations.

In the vaginal ecosystem there is a symbiotic relationship between the microbiota and the host, particularly Candida spp., which are considered commensals of the vaginal mucosa. During pregnancy there is an increase in hormonal secretion that alters the vaginal microbiota and favors the development of Candida infection. Several studies have shown the increased prevalence of Candida during pregnancy, as well as its association with perinatal complications and current clinical practice guidelines recommend fluconazole as the treatment of choice during pregnancy in case of infection by Candida albicans and non-albicans Candida. However, in the Mexican population, this association has not been studied. So in this study, an intentional search for colonization by Candida spp. in pregnant women who attended the obstetric triage of the Hospital Regional de Alta Especialidad de Ixtapaluca during the period from May to October 2019, and they were followed up until the end of the pregnancy. Data on age, number of pregnancies, gestational age, body mass index, and perinatal outcomes were analyzed. Of 83 patients included in the study, yeasts corre-sponding to C. albicans (12) and C. glabrata (4) were isolated in 16. In the group of patients with Candida, the maternal age range was from 15 to 36 years old, of which 7 were adolescents and 2 with advanced maternal age, with an average of 2 gestations, the range of body mass index was from 19.3 to 42.4, of which 4 were overweight and 7 obese. Perinatal complications were observed in three patients, one presented chorioamnionitis and in two the neonates were small for gestational age. No association was found between colonization by Candida spp. and the number of preg-nancies, gestational age, body mass index or perinatal results. However, it was found that age (adolescence) may be a risk factor for the development of vulvovaginitis during pregnancy.

In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th cause of death globally in males. In Mexico, PC epidemiology has been reported for a selected number of metrics and years, although without including the most up-to-date estimates. Herein, we describe and compare the burden and trends of PC in Mexico and its 32 states from 2000 to 2019. For this, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rate (ASR per 100,000 people) of incidence, mortality, and disability-adjusted life years (DALYs). In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6-36.0 thousand) incident cases, 9.2 thousand (7.7-12.7 thousand) deaths, and 161.5 thousand (122.7-219.5 thousand) DALYs in males of all ages in 2019. Among states, Sinaloa had the greatest ASR of incidence and Guerrero the highest values of deaths and DALYs. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest.

Digitalization is widely recognized as a transformative power for sustainable development. Careful alignment of progress made by digitalization with the globally acknowledged Sustainable Development Goals (SDGs) is crucial for inclusive and holistic sustainable development in the digital era. However, limited reference has been made in SDGs about harnessing the opportunities offered by digitalization capabilities. Moreover, research on inhibiting or enabling effects of digitalization considering its multi-faceted interlinkages with the SDGs and their targets is fragmented. There are only limited instances in the literature examining and categorizing the impact of digitalization on sustainable development. To overcome this gap, this paper introduces a new Digitainability Assessment Framework (DAF) for context-aware practical assessment of the impact of the digitalization intervention on the SDGs. The DAF facilitates in-depth assessment of the many diverse technical, social, ethical, and environmental aspects of a digital intervention by systematically examining its impact on the SDG indicators. Our approach draws on and adapts concepts of the Theory of Change (ToC). The DAF should support developers, users as well policymakers by providing a 360-degree perspective on the impact of digital services or products, as well as providing hints for its possible improvement. We demonstrate the application of the DAF with the three test case studies illustrating how it supports in providing a holistic view of the relation between digitalization and SDGs.

The Mediterranean is one of the regions of the world where human-induced climate warming is expected to have large impacts on water and environmental resources. To predict shifts in the current climate system, more regional climate records, including seasonal-to-century scale variability spanning longer than the instrumental periods, are needed. To help fill this gap, we provide a reconstruction of autumn precipitation variations for the Central Pyrenees range since 1500 Common Era (CE) using the varved sediments of Lake Montcortès. To assess the suitability of the calcite sublayer width of the sediments of this lake as a proxy for precipitation anomalies, we performed an analysis and smoothing of the temporal structure of the width series, calibration of the new series with the available instrumental climate records, calculation of a transfer function and testing and comparison of the reconstructed series against available empirical data.The prediction model was statistically robust and showed that the climatic signal was captured in the calcite sublayers. The reconstruction provides the first estimations of regional autumn precipitation shifts in the Central Pyrenees at annual resolution, since 1500 CE. Pronounced interdecadal shifts in precipitation were noticeable; no increasing nor decreasing linear trends or periods of extreme precipitation events were identified. The reconstructed precipitation anomalies suggest a decrease in rainfall during the coldest phase within the coldest period of the Little Ice Age and also during the 20^th century, probably associated to current Global Warming. Correlations between autumn precipitation and the North Atlantic Oscillation, Western Mediterranean Oscillation and Southern Oscillation indices were weak to moderate. A potential relationship with the Atlantic Multidecadal Oscillation pattern is suggested. The reconstructed autumn precipitation trends are coherent with other palaeohydrological reconstructions in similar Mediterranean settings, and consistent at a regional level.

Novel strategies have been developed to reduce or to avoid the intravitreal injections (IVTs) of the antiangiogenic (ranibizumab; RBZ) and the anti-inflammatory (triamcinolone acetonide; TA) agents used to treat vitreoretinal diseases. One of the strategies include liposomes. In this study, it was evaluated the safety and efficacy of topical triamcinolone-loaded liposomes formulation (TALF) as an adjuvant to intravitreal RBZ therapy in treatment-naive patients with neovascular age related macular degeneration (nAMD). Subjects were randomly assigned to the RBZ-TALF or the RBZ-pro re nata (RBZ-PRN) group. Patients from the RBZ-TALF group were instructed to apply TALF for a 12-month period after a single dose of RBZ. Patients from the RBZ-PRN group received three monthly RBZ-IVTs. Retreatment with RBZ was considered in case of nAMD reactivation. Related to safety, non-ocular abnormalities were observed during TALF therapy. Owing to the efficacy, non-significant differences are identified in visual acuity or central foveal thickness when the RBZ-PRN and RBZ-TALF groups are compared. Importantly the average number of RBZ injections was significantly lower in the RBZ-TALF group (2.5 ± 1.4 vs 6.1 ± 1.3 IVTs; p=0004). Therefore, TALF used as an adjuvant to RBZ reduce the number of RBZ-IVTs retreatment with optimal visual and anatomic results.

Artificial Intelligence innovations, such as chatbots and specialized education suggestion tools, provide potential interactive and on-demand pedagogical engagement between non-Christians and Christians with Christianity. However, there is little empirical research on the readiness, acceptance, and adoption of A.I.'s involvement in religious education in a secular state, such as Vietnam. This research addresses the literature gap by providing an entrepreneurial analysis and customer perspectives on the ideas of A.I.'s involvement in religious education. Specifically, the study explores whether the Vietnamese across different ages and religious orientations accept and have enough skills to adopt A.I.'s religious education innovation. The interview sample is 32 participants, selected based on their religious orientation (Christians & Non-Christians) and age (Generation X, Generation Y & Generation Z). Most respondents are open to A.I. application in religious education except for the Church's personnel. However, only gen Z generations are fully prepared to adopt this innovation. Theoretically, the research customizes the Unified Theory of Acceptance and Use of Technology model into religious innovation context. Practically, this research acts as market research on the demand for A.I.'s religious innovation in Vietnam, an insight for future religious tech entrepreneurs.

Learning disorders (LD) are diagnosed in children whose academic skills of reading, writing or mathematics are impaired and lagged according to their age, schooling and intelligence. Children with LD experience substantial working memory (WM) deficits, even more pronounced if more than one of the academic skills is affected. We compared the task-related EEG power spectral density of children with LD (n= 23), with a control group of children with good academic achievement (n= 22), during the performance of a WM task. sLoreta was used to estimate the current distribution at the sources, and 18 brain regions of interests (ROIs) were chosen with an extended version of the eigenvector centrality mapping technique. In this way, we lessen some drawbacks of the traditional EEG at the sensor space by an analysis at the brain sources level over data-driven selected ROIs. Results: The LD group showed fewer correct responses at the WM task, an overall slower EEG with more theta activity in all ROIs, less upper-alpha power at posterior areas, and less high-frequency beta activity in frontal areas. We explain these EEG patterns in LD children as indices of an inefficient neural resource management related with a delay in the neural development.

COVID-19 emerged in Wuhan and is later declared as a pandemic by World Health Organization. Different-aged people have varying gender-wise immunity control properties that necessitates understanding COVID-19 impact on age and gender which does not exist, currently. In this paper, COVID-19 surveillance variables are extensively studied along with hospitalization, tests-performed, and recovery data. Dataset is curated from three sources; however, age and gender data belong to Belgium, particularly. Visualizations, frequencies, Pearson’s and polyserial correlation, student’s t-test, and Cramer’s V are used for enhanced analysis. Results show higher mortality rate in males and need of more ventilators to combat severe symptoms.

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.

Oiola archeological site, located in the mining complex of La Arboleda (Biscay, North Spain) was an important iron smelting center from the Roman Period to the Early Middle Ages and even in more current times (19th-20th centuries). Tap-slags and some plano-convex slags were identified as smelting slags. Samples were analyzed by optical microscopy, X-ray powder diffraction, scanning electron microscopy coupled with electron-dispersive spectroscopy and Raman microspectroscopy to perform a mineralogical and textural characterization. Additionally, thermogravimetric and thermodiffraction analyses were carried out to determine furnace operating temperatures. The mineral assemblage reflects furnace cooling rates and temperatures and the addition of quartz as the main flux to decrease the melting temperature of the iron ore. The comparison of slags from the Roman Period and the Early Middle Age allows to observe changes in the pyrometallurgical process through time.

In the paper, the results of an investigation into trace elements found in slag sulphides from 14 archaeological Bronze Age settlements of the Cis-Urals, Trans-Urals and North and Central Kazakhstan are presented. The study used Cu-(Fe)-sulphides as indicator minerals. Cu-(Fe)-S minerals in slags are primarily represented by covellite and chalcocite, as well as by rarer bornite and single chalcopyrite grains. Slag sulphides formed relic clasts and neogenic droplets of different shapes and sizes. Supergenic ores in the Bronze Age in Urals and Kazakhstan played a significant role in the mineralogical raw material base. In sulphides, the main indicator elements Fe, Co, Ni, As, Se, Te, Sb, Ag, Pb, and Bi are important markers of copper deposit types. Sulphides from olivine Cr-rich spinel containing slags of Ustye, Turganik, and Kuzminkovskoe 2 are characterised by As-Co-Ni assemblages and confined to copper deposits in ultramafic rocks. Olivine sulphide-containing slags from Kamenny Ambar, Konoplyanka and Sarlybay 3 are characterised by Co-Se-Te assemblage and confined to mafic rocks. Glassy sulphide-containing slags from Katzbakh 6, Turganik, Ordynsky Ovrag, Ivanovskoe, Tokskoe, Bulanovskoe 2, Pokrovskoe, Rodnikovoe, and Taldysay are characterised by Ag-Pb-(Ba)-(Bi) assemblage and confined to cupriferous sandstone deposits. High As, Sb, Sn and Ba contents found in slags can be seen as indicators of alloying or flux components in primary copper smelting. These include samples from Ustye, Katzbakh 6, Rodnikovoe, and Taldysay sites, where high Ba and As slag contents are identified. The compilation of a database with a broad sample of sulphide compositions from Bronze Age slags and mines in the Urals and Kazakhstan will permit the further identification of ore types and raw materials associated with a particular deposit.

Patterns of age and growth of a sedentary damsel fish Acanthochromis polyacanthus were tested over a latitudinal range of approximately 10 degrees (1,200 km) on the Great Barrier Reef, Australia. Within latitudes these patterns were also compared on reefs across a continental shelf that ranged in width from 52 to 128 km. Although variation in length-max, growth, age-max and the von-Bertalanffy metrics of L, and K were found within and among latitudes, greatest variation in some demographic characteristics were found across the shelf regardless of latitude. Fish were always smaller at inner shelf reefs and grew more slowly when compared to mid and outer shelf reefs. The oldest fish collected was 11 years old and, there were no consistent variation in age-max among distances from shore. On outer reefs, there was a linear relationship with age-max and latitude. This ‘tropical gradient’ of age only explained 34% of the variation, further this was not found when the oldest 10% of fish were considered. Fish only reached an age-max of 6 years on the southern-most reefs. There was a trend for a smaller L with latitude but, it was not significant and L did not vary predictably with water temperature. The sampling of MPAs did not confound the resultant patterns. Instantaneous mortality rates were 0.245-0.685, highest at inner reefs and showed no consistent MPA-related patterns. Our study suggested that the mid and outer shelf waters of the GBR appeared best suited for growth of A. polyacanthus. In conclusion, position on continental shelves and related local environmental conditions needs to be considered in spatial models of growth.

Background: Appendicular skeletal muscle (or lean) mass (ALM) estimated using dual-energy X-ray absorptiometry (DXA) is considered to be a preferred method for sarcopenia studies. However, DXA is expensive, has limited portability, and requires radiation exposure. Bioelectrical impedance analysis (BIA) is inexpensive, easy to use, and portable; thus BIA might be useful in sarcopenia investigations. However, a large variety of models have been commercially supplied by different companies, and for most consumer products, the equations estimating ALM are not disclosed. It is therefore difficult to use these equations for research purposes. In particular, the BIA equation is often age-dependent, which leads to fundamental difficulty in examining age-related ALM loss. The aims of the current study were as follows: (1) to develop and validate an equation to estimate ALM using multi-frequency BIA (MF-BIA) based on theoretical models, and (2) to establish sarcopenia cutoff values using the equation for the Japanese population. Methods: We measured height (Ht), weight, and ALM obtained using DXA and a standing-posture 8-electrode MF-BIA (5, 50, 250 kHz) in 756 Japanese individuals aged 18 to 86-years-old (222 men and 301 women as developing equation group and 97 men and 136 women as a cross validation group). The traditional impedance index (Ht²/Z₅₀) and impedance ratio of high and low frequency (Z₂₅₀/Z₅) of hand to foot values were calculated. Multiple regression analyses were conducted with ALM as dependent variable in men and women separately. Results: We created the following equations: ALM = (0.6947 × (Ht²/Z₅₀)) + (−55.24 × (Z₂₅₀/Z₅)) + (−10,940 × (1/Z₅₀)) + 51.33 for men, and ALM = (0.6144 × (Ht²/Z₅₀)) + (−36.61 × (Z₂₅₀/Z₅)) + (−9332 × (1/Z₅₀)) + 37.91 for women. Additionally, we conducted measurements in 1624 men and 1368 women aged 18 to 40 years to establish sarcopenia cutoff values in the Japanese population. The mean values minus 2 standard deviations of the skeletal muscle mass index (ALM/Ht²) in these participants were 6.8 and 5.7 kg/m² in men and women, respectively. Conclusion: The current study established and validated a theoretical and age-independent equation using MF-BIA to estimate ALM and provided reasonable sarcopenia cutoff values.

With the increasing of copper consumption, the in-use stock of copper tends to increase. This paper used the “average use life method” to quantify the amount of copper in-use stock, and calculated the average age of in-use stock. It was indicated that the total in-use stock had an overall smooth trends, and reached its peak in 2007 was about 68.9 Mt (million tons), in addition, in-use stock per capita reached its peak ,234 kg/capita in 2001. The results demonstrated that during the period 1992-2002, the average age of copper in-use stock was continually decreased, but gradually increased since the year 2003. The fixed assets depreciation method used in this paper is applied to analyze depreciated copper in-use stock, and to analyze the relationship with economic indicator (GDP). It is demonstrated that it was inconsistent with the theory of Environmental Kuznets Curve (EKC) before 2000, this might be the demand for copper in the service sector is greater than the reduced strength of alternatives. Finally, scenario analysis of future copper in-use stock and depreciated copper in-use stock per capita in the U.S. were presented. The corresponding average age of the in-use stock will have a slight rise in the next decade.

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.

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.

Visual impairment and blindness are a growing public health problem, as they reduce the quality of life of millions of people. The management and treatment of these diseases represent a scientific and therapeutic challenge, since the different cellular and molecular actors involved in the pathophysiology are still being identified. The visual system components, particularly the retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune cells activated by insults contribute to biological events that culminate with vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and diseases such as retinitis pigmentosa, age-related macular degeneration, glaucoma and diabetic retinopathy are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cells degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiologic and molecular features, biochemical hallmarks and possible directions for novel treatments, aiming to assist as a guide for innovative research. The expansion of knowledge of the mechanistic bases of the pathobiology of eye diseases, including information on the complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors will allow the identification of new therapeutic strategies.

Farmers are continually looking for new reliable, objective and non-invasive methods for evaluation of ewe condition. Live weight (LW) and body condition score (BCS) are used by farmers as a basis to determine the condition of the animal. Body composition is an important aspect of monitoring animal condition. The body composition is the amount of fat, lean and bone; knowing the amount of each is important because the information can be used for better strategic management interventions. Experiments were conducted to establish the relationship between body composition and body parameters, at key life’s stages (weaning and pre-mating), using measurements automatically determined by an image processing ap-plication at Lincoln University sheep farm for 88 Coopworth ewes. Computerized Tomography technology was used to develop relationship with body parameters and a subset was used to validate the predicted model. Multivariate linear regression (MLR), artificial neural network (ANNs) and regression tree (RT) statistical analysis methods were evaluated to determine their efficacy to predict body fat, lean and bone. The results showed a correlation between fat, lean and bone determined by CT and the fat, lean, bone weight estimated by live weight and body parameters calculated using the image processing application with R2 values of 0.90 for fat, 0.72 for lean and 0.50 for bone using ANNs statistical model. From these results, farmers can utilize accurate measures of fat which will enhance nutritional and management practices.

Disrupted biological function, manifesting through the hallmarks of aging, poses as one of the largest threats to healthspan and risk of disease development, such as metabolic disorders, cardiovascular ailments, and neurodegeneration. In recent years, numerous geroprotectors, senolytics, and other nutraceuticals have emerged as potential disruptors of aging and may be viable interventions in the immediate state of human longevity science. In this review, we focus on the decrease of nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds to restore youthful NAD+ levels. Furthermore, these geroprotectors may enhance the efficacy of NMN supplementation while concurrently providing their own numerous health benefits. By analyzing the prevention of NAD+ degradation through inhibition of CD38 or supporting protective downstream agents of SIRT1, we provide a potential framework of the CD38/NAD+/SIRT1 axis through which geroprotectors may enhance the efficacy of NMN supplementation and reduce the risk of age-related diseases, thereby potentiating healthspan in humans.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress, decreased phagocytic activity, and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory drug developed for treating atopic dermatitis and known to inhibit toll-like receptor 4, on light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once a day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 protected against this decrease in retinal thickness and increase in ERG am-plitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregu-lation of C-C motif chemokine 2　by LPS stimulation was significantly inhibited by SIG-1451 treatment, and western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 protects photoreceptor cells by attenuating light damage progression through inhibiting inflammatory responses.

The age of information (AoI) metric was proposed to measure the freshness of messages obtained at the terminal node of a status updating system. In this paper, the AoI of discrete time status updating system with probabilistic packet preemption is investigated by analyzing the steady state of a three-dimensional discrete stochastic process. Assuming the queue used in system is Ber/Geo/1/2*/η, which represents that the system size is 2 and the packet in buffer can be preempted by fresher packet with probability η. Instead of considering system’s AoI separately, we use a three-dimensional state vector (n,m,l) to simultaneously track the real time changes of the AoI, the age of packet in server, and the age of packet waiting in buffer. We give the explicit expression of system’s average AoI, and show that the average AoI of system without packet preemption is obtained by letting η=0. When η is set to 1, the mean of AoI of system having Ber/Geo/1/2* queue is obtained as well. Combining the results we have obtained and comparing them with corresponding average continuous AoIs, we propose a possible relationship between average discrete AoI with Ber/Geo/1/c queue and the average continuous AoI with M/M/1/c queue. For each of two extreme cases where η=0 and η=1, we also determine the stationary distribution of AoI using the probability generation function (PGF) method. The relations between average AoI and the packet preemption probability η, as well as AoI’s distribution curves in two extreme cases are illustrated by numerical simulations. Notice that the probabilistic packet preemption may occur, for example, in an energy harvest (EH) node of wireless sensor network, where the packet in buffer can be replaced only when the node collects enough energy. In particular, to exhibit the usefulness of our idea and methods and highlight the merits of considering discrete time systems, in this paper we give much more explanations showing that how the results about continuous AoI is derived by analyzing the corresponding discrete time system, and how the discrete age analysis is generalized to the system with multiple sources. In terms of packet service process, we also propose our idea to analyze system’s AoI when the service time distribution is relaxed to be arbitrary.

The results of an LA-ICP-MS U-Pb dating and Hf isotope study of zircon crystals separated from small eclogite xenoliths found in Devonian kimberlites within the Prypyat horst, Ukraine, are reported. The studied area is located in the Central Belarusian Suture Zone, which represents a Paleoproterozoic belt extending along the boundary between the Sarmatian and Fennoscandian segments of the East European Platform. Four laser ablation sites on two zircon grains yielded Paleoproterozoic U-Pb ages between 1954 ± 24 Ma and 1735 ± 54 Ma. In contrast, three of four Hf sites revealed negative εHf values and Paleoarchean to Mesoarchean model ages, excluding the possibility that the eclogite xenoliths represent segments of a Paleoproterozoic subducted slab or younger mafic melts crystallized in the subcontinental lithospheric mantle. A single laser ablation Hf spot yielded a positive εHf value (+3) and a Paleoproterozoic model age. Two models for eclogite origin can be proposed. The first foresees the extension of the Archean lower-crustal or lithospheric roots beneath the Central Belarus Suture Zone for over 200 km from the nearest known outcrop of Archean rocks. The second model is that the Central Belarus Suture Zone represents a rifted-out fragment of the Kola-Karelian craton that was accreted to Sarmatia before the actual collision of these two segments of Baltica.

We present a new analytical method to find the asymptotic stable equilibria states based on the Markov chain technique. We reveal this method on the SIR-type epidemiological model that we developed for viral diseases with long-term immunity memory pandemic. This is a large-scale model containing 15 nonlinear ODE equations, and classical methods have failed to analytically obtain its equilibria. The proposed method is used to conduct a comprehensive analysis by a stochastic representation of the dynamics of the model, followed by finding all asymptotic stable equilibrium states of the model for any values of parameters and initial conditions.

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and its application in current clinical trials.

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global threat to human health and disease risk increases with advancing age. The regulation of the ACE2 gene that codes for COVID-19 host receptor ACE2 has been shown to be under epigenetic regulation. Here, we examined whether intensive DNA methylation profiling of the ACE2 gene differed by human host tissue and cell type, gender, and age. Results: Accessing four public datasets, we observed unique human cell-type-specific ACE2 DNA methylation patterns. In human lung tissues, gender differences in DNA methylation at 2 sites related to the ACE2 gene were identified. Further, in freshly isolated airway epithelial cells, DNA methylation near the transcription start site of the ACE2 gene associated with biological age. Conclusion: Epigenetic profiling of host tissue may permit discovery of age and gender-related potential risk factors for COVID-19. How perturbations in ACE2 methylation relate to clinical severity across the ages and gender needs to be determined to guide screening tools and potential epigenetic modification targeting to alleviate COVID-19 morbidity in the elderly.

Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways leads to the accumulation of lipofuscin and N-retinylidene-N-retinylethanolamine aggregates and chemically-modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as Age-related Macular Degeneration, Stargardt disease and Choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, a-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.

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.

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.

A recent study has suggested that the age profiles for deaths due to COVID-19 variants differs between variants and shows male/female specificity. This study demonstrates the age and sex dependency is common among human pathogens. The often-reported higher susceptibility to infections among the young and elderly is true in general but does not apply to individual pathogens. Even among different types of pneumonia there are subtle differences in the age profile. The gender ratio between pathogens likewise shows wide variation from as low as 10% female admissions for leptospirosis to around 90% for gonococcal admissions. The observed age/sex variation observed for mortality due to COVID-19 variants is an expression of a far wider phenomenon with implications to the age/sex response to vaccines. We propose that such differences are likely to be controlled by small noncoding RNAs which act as potent regulators of gene expression leading to altered cell morphology, metabolism, immune function, and response to vaccines.

Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.

Age-related mitochondrial markers may facilitate the prognosis of artificial reproductive technology outcomes. In this report, we present our study concerning the ratio of cf-mtDNA/cf-nDNA, namely the amount of cell-free mitochondrial DNA relative to cell-free nuclear DNA, in the follicular fluid (FF) of women undergoing IVF, aiming to generate a molecular fingerprint of oocyte quality. The values of this ratio were measured and compared among three groups of women (101 in total): (A)31 women with polycystic ovary syndrome (PCOS), (B) 34 women younger than 36 years, and (C) 36 women older than 35 years of age. Real-time quantitative PCR (qPCR) was performed to quantify the ratio by using nuclear- and mitochondrial-specific primers and analyzed for potential correlation with age and pregnancy rate. Our analysis showed that the level of FF-cf-mtDNA was lower in the group of advanced-age women than in the groups of PCOS and non-PCOS women. Moreover, a significant positive correlation between FF-cf-mtDNA and the number of mature (MII) oocytes was observed. Collectively, the data show that the relative ratio of cf- mtDNA to cf-nDNA content in human FF can be an effective predictor for assessing the corresponding oocyte’s age-related performance in IVF.

It is unclear how maternal glycemic status and maternal iodine status influence birth weight in mild-to-moderate iodine deficiency (ID). We studied the association between birth weight and both maternal glucose levels and iodine intake in pregnant women with mild-to-moderate ID. Glucose values were assessed using a glucose challenge test (GCT), non-fasting glucose before delivery; iodine status was assessed using an iodine food frequency questionnaire, serum thyroglobulin (Tg) and urinary iodine concentrations (UIC). Thyroid antibodies and free thyroxine (FT4) were measured. Obstetric and an-thropometric data were also collected. Large for gestational age (LGA) was predicted using a Cox proportional hazards model with multiple confounders. Tg>13g/L was in-dependently associated with LGA (adjusted hazard ratio = 3.4, 95% CI: 1.4–10.2, p=0.001). Estimated iodine intake correlated with FT4 among participants reporting io-dine-containing supplements (ICS) after adjusting for confounders (β = 0.4 95 %CI: 0.0002-0.0008, p=0.001). Newborn weight percentiles were inversely correlated with maternal FT4 values (β=-0.2 95 %CI:-0.08 - -56.49, p=0.049). We conclude that in mild-to-moderate ID regions, maternal insufficient iodine status may increase LGA risk. Iodine status and ICS intake may modify the effect maternal dysglycemia has on offspring weight.

The human polyamines spermine and spermidine are essential for cell function, and their properties have been extensively studied. However, research results of experiments conducted without understanding the properties of polyamines have been evaluated and published by reviewers who appear to have little knowledge of the properties of polyamines. It is sad that some studies repeat what was done more than half a century ago before polyamines were characterized. First, I explain the basic properties of polyamines that researchers need to know. Then, the relationship between changes in polyamine levels in the body and age- and lifestyle-related diseases is discussed. In addition, the epigenetic mechanism of action of polyamines in relation to healthy longevity and, conversely, age- and lifestyle-related diseases and the progression of senescence are discussed. Spermine, which increases with a polyamine-rich diet, acts to suppress aberrant gene methylation and proinflammatory status associated with aging. Meanwhile, chronic inflammation associated with aging induces the enzyme activity of spermine oxidase, which breaks down spermine and produces acrolein, resulting in reduced spermine levels. Acrolein, a toxic aldehyde that increases with age- and lifestyle-related diseases, is thought to accelerate these diseases.

The main goal of this paper is to present results of preliminary archaeological research on the south side of Lake Issyk-Kul in Kyrgyzstan. We test the hypothesis that agropastoral land use changed over four millennia from the Bronze Age through the ethnographic Kirghiz period due to economic, socio-political, and religious changes in the prehistoric and historic societies of this region. Our research objectives are to: (1) describe and analyze survey results from Lower Kizil Suu Valley; (2) discuss the results of radiometric and archaeobotanical samples taken from three stratigraphic profiles from three settlements from the Juuku Valley, including these chronological periods: the Wusun period (200 to 400 CE), the Qarakhanid period (1100 to 1200 CE), and the ethnographic Kirghiz period (1700 to 1900 CE); and (3) conduct preliminary GIS spatial analyses on the Iron Age mortuary remains (Saka and Wusun period). This research emerges out of the first archaeological surveys conducted in 2019 - 2021 and includes the Lower Kizil Suu alluvial fan; it is an initial step toward developing a model for agropastoral land use for upland valleys of the Inner Tian Shan Mountains.

Dehydrolutein accumulates in substantial concentrations in the retina. The aim of this study was to compare antioxidant properties of dehydrolutein with other retinal carotenoids, lutein and zeaxanthin, and their effects on ARPE-19 cells. The time-resolved detection of characteristic singlet oxygen phosphorescence was used to compare the singlet oxygen quenching rate constants of dehydrolutein, lutein, and zeaxanthin. The effects of these carotenoids on photosensitized oxidation were tested in liposomes, where photooxidation was induced by light in the presence of photosensitizers, and monitored by oximetry. To compare the uptake of dehydrolutein, lutein, and zeaxanthin, ARPE-19 cells were incubated with carotenoids for up to 19 days, and carotenoid contents were determined by spectrophotometry in cell extracts. To investigate the effects of carotenoids on phototocytotoxicity, cells were exposed to light in the presence of rose bengal or all-trans-retinal. The results demonstrate that the rate constants for singlet oxygen quenching are 0.77x1010, 0.55x1010, and 1.23x1010 M-1s-1 for dehydrolutein, lutein and zeaxanthin, respectively. Overall, dehydrolutein is similar to lutein or zeaxanthin in protection of lipids against photosensitized oxidation. ARPE-19 cells accumulate substantial amounts of both zeaxanthin and lutein but no detectable amounts of dehydrolutein. Cells pre-incubated with carotenoids are equally susceptible to photosensitized damage as cells without carotenoids. Carotenoids provided to cells together with the extracellular photosensitizers offer partial protection against photodamage. In conclusion, the antioxidant properties of dehydrolutein are similar to lutein and zeaxanthin. The mechanism responsible for its lack of accumulation in ARPE-19 cells deserves further investigation.

The Early Paleozoic is a crucial period in the formation and evolution of the Eastern Kunlun Orogenic Belt (EKOB), which is of great significance for understanding the evolutionary history of the Proto-Tethyan Ocean. This paper presents new petrography, geochemistry, zircon U–Pb dating, and Lu–Hf isotopic research on the Yuejingshan gabbro from the eastern segment of the EKOB. Zircons U-Pb data suggests the gabbro formed in the Early Silurian (435 ± 2 Ma). All samples have relatively low TiO2 contents (0.45-2.97%), widely varying MgO (6.58-8.41%) and Mg# (58-65) contents, rich in large ion lithophile elements (LILE such as Rb, Ba, Th, and U) and light rare earth elements (LREE),which indicate it has a similar geochemical composition than island arc basalt. The major elements features indicate that the formation of this gabbro underwent fractional crystallization of clinopyroxene, olivine, and plagioclase. The depletion of high field strength elements (HFSE such as Nb, Ta, and Ti), and feature a slightly enriched Hf isotope composition (with εHf (t) ranging from 1.13 to 2.45) may be related to the partial melting of spinel-bearing peridotite, led by the slab fluid metasomatism. The significantly earlier than the metamorphic age (428 Ma) of the collision-related eclogite facies and the peak metamorphic age (427 Ma) of medium pressure (epidotization) amphibolite facies in the Eastern Kunlun Orogenic Belt indicates that its formation is still closely related to the subduction of the Eastern Kunlun oceanic crust. The gabbro likely represents magmatic records of the latest period of the Early Paleozoic oceanic crust subduction in the Eastern Kunlun. Therefore, the final closure of the Proto-Tethyan Ocean and the beginning of collisional orogeny, occurred before the Early Silurian.

Cognitive and behavioural disturbances are growing public healthcare issue for the modern society, as stressful lifestyle is becoming more and more common. Besides, several pieces of evidence state that environment is crucial in the development of several diseases as well as compromising healthy aging. Therefore, it is important to study the effects of stress on cognition and its relationship with aging. To address these queries, Chronic Mild Stress (CMS) paradigm was used in the senescence-accelerated mouse prone 8 (SAMP8) and resistant 1 (SAMR1). On one hand, we determined the changes produced in the three main epigenetic marks after 4 weeks of CMS treatment, such as a reduction in histone posttranslational modifications and DNA methylation, and up-regulation or down-regulation of several miRNA involved in different cellular processes in mice. In addition, CMS treatment induced reactive oxygen species (ROS) accumulation and loss of antioxidant defence mechanisms, as well as inflammatory signalling activation through NF-κB pathway and astrogliosis markers, like Gfap. Remarkably, CMS altered mTORC1 signalling in both strains, decreasing autophagy only in SAMR1 mice. We found a decrease in glycogen synthase kinase 3 β (GSK-3β) inactivation, hyperphosphorylation of Tau and an increase in sAPPβ protein levels in mice under CMS. Moreover, reduction in the non-amyloidogenic secretase ADAM10 protein levels was found in SAMR1 CMS group. Consequently, detrimental effects on behaviour and cognitive performance were detected in CMS treated mice, affecting mainly SAMR1 mice, promoting a turning to SAMP8 phenotype. In conclusion, CMS is a feasible intervention to understand the influence of stress on epigenetic mechanisms underlying cognition and accelerating senescence.

The Late Bronze Age on the territory of Southern Transurals is represented by two major archeological cultures: Srubnaya and Andronovskaya (Alakul culture and Fyodorovskaya – type). Their interaction of constitutes a special mix of material cultures which preserves common features of two independent, Srubnaya and Andronovskaya cultures, but also creates novel local material features. These cultural groups are also known to have brought to the region the technology of bronze production. This is evidenced, amongst others, by the proximity of the largest copper mining in the region, Kargaly mines Chernykh (2002). New methods to produce ceramics and to work bones were also developed, combining two traditions, coming from Srubnaya and Andronovskaya cultures respectively. Importantly, the features of these cultures are commonly encountered together in a single cultural horizon across the distribution ares. These diffusion processes took place in a vast area (more than 120,000 km²) andwere reflected in archeological micro-district of the Urshak river basin. We present here the most recent results of the scientific examination of the Late Bronze Age settlements in southern Transurals and attempt to address a peculiar cultural co-habitation of two distinct cultural groups in this region. We also discuss their synchronism based on absolute dates and elaborate on this cultural syncretism in the entire territory of the Volga-Ural region.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has gradually come to be regarded as an effective therapy, but the hospital mortality rate after ECPR is still high and unpredictable. The present study tested whether age-adjusted Charlson comorbidity index (ACCI) can be used as an objective selection criterion to ensure the most efficient utilization of medical resources. Methods: Adult patients (age ³ 18 years) receiving ECPR at our institution between 2006 and 2015 were included. Data regarding ECPR events and ACCI characteristics were collected immediately after extracorporeal membrane oxygenation (ECMO) setup. Adverse events during hospitalization were also prospectively collected. The primary endpoint was survival to hospital discharge. The second endpoint was short-term (2-year) follow-up outcome. Results: A total of 461 patients included in the study were grouped into low ACCI (ACCI 0–3) (240, 52.1%) and high ACCI (ACCI 4–13) (221, 47.9%) groups. The median ACCI was 2 (IQR: 1–3) and 5 (IQR: 4–7) for the low and high ACCI groups, respectively (P < 0.001). Cardiopulmonary resuscitation (CPR)-to-ECMO duration was comparable between the groups (42.1 ± 25.6 and 41.3 ± 20.7 min in the low and high ACCI groups, respectively; P = 0.754). Regarding hospital survival rate, 256 patients (55.5%) died on ECMO support. A total of 205 patients (44.5%) were successfully weaned off ECMO, but only 138 patients (29.9%) survived to hospital discharge (32.1% and 27.6% in low and high ACCI group, P = 0.291). Multivariate logistic regression analysis revealed CPR-to-ECMO duration and CPR cause of septic shock as significant risk factors for hospital survival after ECPR (P = 0.043 and 0.014, respectively), whereas age and ACCI were not (P = 0.334 and 0.164, respectively). The 2-year survival rate after hospital discharge for the 138 hospital survivors was 96% and 74% in the low and high ACCI groups, respectively (P = 0.002.)Conclusions: High ACCI before ECPR does not predict poor outcome of hospital survival. Therefore, ECPR should not be rejected solely due to high ACCI. However, high ACCI in hospital survivors is associated with a higher 2-year mortality rate than low ACCI, and patients with high ACCI should be closely followed up.

This study presents the validation process of the Questionnaire on Academic Stress in Secondary Education –QASSE-, designed to assess the wide variety of school sources and situations related to academic stress in adolescence, and their relationship with students’ physical and psychological well-being. Participants were 860 Spanish high school students (52.9% girls) with an average age of 14.62 years (SD = 1.8). Through a cross-validation process, EFA and CFA supported QASSE multifactorial structure with four first-order factors -academic overload, interaction with classmates, family pressure, and future-oriented perspective- and a second-order factor of academic stress, showing a significant and intense relationship with adolescents’ psychological and physical well-being. Results also highlight the effects of the gender*educational level interaction on the students’ stress, with girls showing higher levels of stress in the transition courses between educational phases (sophomore and junior years). The QASSE demonstrates good validity and reliability, showing potential for both research and educational application. The results show the high impact of the QASSE dimensions on psychological and physical well-being in adolescence, highlighting its special usefulness for designing and adjusting educational prevention and intervention actions in this area to the students’ specific characteristics and needs

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

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.

Introduction: The primary objective of researchers in the biology of ageing is to gain a comprehensive understanding of the ageing process while developing practical solutions that can enhance the quality of life for older individuals. This involves a continuous effort to bridge the gap between fundamental biological research and its real-world applications. Purpose: In this narrative review, we attempt to link research findings concerning the hormetic relationship between neurons and germ cells, and translate these findings into clinically relevant concepts. Methods: We conducted a literature search using PubMed, Embase, PLOS, Digital Commons Network, Google Scholar and Cochrane Library from 2000 to 2023, analyzing studies dealing with the relationship between hormetic, cognitive, and reproductive aspects of human ageing. Results: The process of hormesis serves as a bridge between the biology of neuron-germ cell interactions on one hand, and the clinical relevance of these interactions on the other. Details concerning these processes are discussed here, emphasizing new research which strengthens the overall concept. Conclusions: This review presents a scientifically and clinically relevant argument, claiming that maintaining a cognitively active lifestyle may decrease age-related degeneration, and improve overall health in ageing.

Despite the high prevalence of epilepsy in individuals with autism spectrum disorder (ASD) there is little information regarding whether seizure characteristics and treatment effectiveness change across age. Using an on-line survey, seizure characteristics, effectiveness of antiepileptic treatments, comorbidities and ASD diagnosis were collected from individuals with ASD and seizures. We previously reported overall general patterns of treatment effectiveness but did not examine the effect of seizure characteristics or age on antiepileptic treatment effectiveness. Such information would improve the personalized medicine approach to the treatment of seizures in ASD. Survey data from 570 individuals with ASD and clinical seizures were analyzed. Seizure severity (seizure/week) decreased with age of onset of seizures, plateauing in adolescence, with a greater reduction in generalized tonic clonic (GTC) seizures with age. Seizure severity was worse in those with genetic disorders, neurodevelopmental regression (NDR) and poor sleep maintenance. Carbamazepine and oxcarbazepine were reported to be more effective when seizures started in later childhood while surgery and the Atkin’s/Modified Atkin’s Diet (A/MAD) were reported to be more effective when seizures started early in life. A/MAD and the ketogenic diet were reported to be more effective in those with NDR. Interestingly, atypical Landau-Kleffner syndrome was associated with mitochondrial dysfunction and NDR, suggesting a novel syndrome. These interesting findings need to be verified in independent, prospectively collected cohorts, but none-the-less these data provide some insight into novel relationships that may assist in a better understanding of epilepsy in ASD and providing insight into personalizing epilepsy care in ASD.

Since 2020 COVID-19 has caused serious mortality around the world. Given the ambiguity in es-tablishing COVID-19 as the direct cause of death we first investigate the effects of age and sex upon all-cause mortality during 2020 and 2021 in England and Wales. Since infectious agents have their own unique age profile for death, we explore several methods to adjust single year of age deaths in England and Wales during 2019 (the pre-COVID-19 base year) to a pathogen-neutral single year of age baseline. This adjusted base year is then used to confirm the widely reported higher deaths in males for most ages above 43 years in both 2020 and 2021. During 2020 (+ COVID-19 but no vac-cination) both male and female population-adjusted deaths were significantly increased above age 35. A significant reduction in all-cause mortality among both males and females aged 75+ could be demonstrated in 2021 during widespread COVID–19 vaccination, however, below age 75 deaths progressively increased. This finding arises from a mix of vaccination and year of age profiles of deaths for the different SARS-CoV-2 variants. In addition, specific effects for age around puberty were demonstrated where females had higher deaths rather than males. There is evidence that year-of-birth cohorts may also be involved, indicating that immune priming to specific pathogen outbreaks in the past may lead to lower deaths for some birth cohorts. To specifically identify the age profile for the COVID-19 variants in 2020 to 2023, we employ the proportion of total deaths at each age which are potentially due to or ‘with’ COVID-19. The original Wuhan strain, and the Alpha variant show somewhat limited divergence in the age profile with the Alpha variant shifted to a moderately higher proportion of deaths below age 84. The Delta variant specifically targeted persons below age 65. The Omicron variants showed significantly lower proportion of overall mortality, with markedly higher relative proportion of deaths above age 65 steeply increasing with age to a maximum around 100 years of age. A similar age profile for the variants can be seen in the age-banded deaths in US states – although slightly obscured by using age bands rather than single year of age. However, the US data shows that higher male deaths are greatly dependent on age and the COVID-variant. Deaths determined as ‘due to’ COVID-19 (as opposed to ‘involving’ COVID-19) in England and Wales were especially over-estimated in 2021 relative to the change in all-cause mortality. This arose as a by-product of an increase in COVID-19 testing capacity in late 2020. Potential structure-function mechanisms for the year of age specificity of SARS-CoV-2 var-iants are discussed. The question is posed as to whether vaccines based on different variants carry the specific age profile through into the vaccine.

All vaccines exhibit both specific and non-specific effects. The specific effects are measured by the efficacy against the target pathogen, while the non-specific effects can be detected by the change in all-cause mortality . All-cause mortality data (gender, age band, vaccination history, month of death) between January 2021 and May 2022 was compiled by the Office for National Statistics. COVID–19 vaccination gave good protection on many occasions but less so for younger ages. Each gender and age group shows its own unique vaccination benefit/disbenefit time profile. Individuals are free to make vaccination decisions. For example, women aged 18-39 show a cohort who do not progress beyond the first or second dose. The all-cause mortality outcomes for the Omicron variant showed a very poor response to vaccination with 70% of sex/age/vaccination stage/month combinations increasing all-cause mortality, probably due to unfavorable antigenic distance between the first-generation vaccines and this variant, and additional non-specific effects. The all-cause mortality outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated, and virus vector appear better than the mRNA vaccines in this specific respect. The latter are seemingly more likely to increase all-cause mortality especially in younger age groups. An extensive discussion/literature review is included to provide potential explanations for the observed unexpected vaccine effects.

Child and adolescent sexual abuse (CSA) is an international public health problem. Despite the importance of the CSA, there is no consensus definition, and the lack of consensus is related to difficulties in conducting prevalence studies, as well as research in other areas. To establish a consensual definition, legal aspects such as the age of sexual consent and the difference in age or power between victim and aggressor, aspects related to sexual freedom and sexual indemnity must be considered. Therefore, the main goal of this research was to analyze the age of sexual consent in the legal systems of Spanish-speaking countries and to examine whether the Romeo and Juliet clause is established. To achieve the proposed aims, we employed the legal interpretation method, and we analyzed the current Criminal Codes of the 21 Spanish-speaking countries. From the results, it is found that the age of sexual consent varies between countries, establishing valid sexual consent between 13 and 18 years. In addition, only six countries have the Romeo and Juliet clause that protects sexual freedom in adolescents. Finally, we discussed the lack of consensus on the age of sexual consent and the limitations presented by the Romeo and Juliet clause.

In the design of multi-loop Networked Control Systems (NCSs) wherein each control system is characterized by heterogeneous dynamics and associated with certain set of timing specifications and constraints, appropriate metrics need to be employed for the synthesis of control and networking policies to efficiently respond to the requirements of each control loop. Majority of the design approaches for sampling, scheduling and control policies include either time-based or event-based metrics to perform pertinent actions in response to the changes of the parameters of interest. We specifically focus in this article on Age-of-Information (AoI) as a recently-developed time-based metric and threshold-based triggering function as a generic event-based metric. As the NCS model, we consider multiple heterogeneous stochastic linear control systems that close their feedback loops over a shared-resource communication network. We investigate the co-design across the NCS, and discuss the pros and cons with AoI and ET approaches in terms of asymptotic control performance measured by linear-quadratic Gaussian (LQG) cost functions. In particular, sampling and scheduling policies combining AoI and stochastic event-triggered metrics are proposed. It is argued that pure AoI functions that generate decision variables solely upon minimizing the average age irrespective of control systems dynamics may not be able to improve the overall NCS performance even compared with pure randomized policies. Our theoretical analyses are successfully validated through several simulation scenarios.

The current spreading novel coronavirus SARS-CoV-2 is highly infectious and pathogenic and has attracted global attention. Recent studies have found that SARS-CoV-2 and SARS-CoV share around 80% of homology and use the same cell entry receptor, ACE2. These inspired us to study other receptors of SARS-CoV, which may be used for SARS-CoV-2 binding as well. In this study, we screened the gene expression of three receptors (ACE2, DC-SIGN and L-SIGN) in four datasets of normal lung tissue from lung adenocarcinoma patients and two single-cell RNA sequencing datasets from normal lung and bronchial epithelial cells separately. No significant difference in gene expression of these three receptors were found between gender groups (male vs female). We found higher gene expression of DC-SIGN in elder with age>60 and higher gene expression of L-SIGN in Caucasian than Asian. Similar to ACE2, we observed significantly higher DC-SIGN gene expression in the lungs of smokers, especially former smokers. However, smokers upregulate ACE2 and DC-SIGN gene expression in different cell types. In the whole lung, ACE2 is actively expressed in remodeled Alveolar Type II cells of former smokers, while DC-SIGN is largely expressed in monocytes of former smokers and dendritic cells of current smokers. In bronchial epithelium, no obvious gene expression of DC-SIGN and L-SIGN was observed while ACE2 was found to be actively expressed in goblet cells of current smokers and club cells of non-smokers. In conclusion, our findings may indicate that smokers, especially former smokers, and people over 60 have higher risk and are more susceptible to SARS-CoV-2 infection. Also, this study provides hints on possible SARS-CoV-2 pathogenicity mechanisms in lung infection.

Emulsion stabilisation of base layers surfaced with chip seals often proves problematic with chips punching into the base and early distress. This can be aggravated by the use of modified binders that restricts the evaporation of moisture from pavement layers. The introduction of New-age (Nano) Modified Emulsion (NME) stabilisation has the advantage that water is chemically repelled from the stabilised layer resulting in an accelerated development of strength. A need was identified to evaluate the early life performance of selected chip seals, together with identified binders. Three different chip seal surfacings with unconventional modified binders were constructed and evaluated using Accelerated Pavement Testing (APT) with the MMLS3. The objectives of the experimental design and testing were to evaluate binder performance, early loss of chips before chip orientation at low temperatures, punching of the chips into the NME stabilised base, deformation characteristics of a Cape seal and the effect of the use of a standard normal modified binder. This paper contains details of the NME base layer, the binder and seal selection and the test results. It is shown that a cost-effective thin chip seal in combination with a suitable binder can be used on a NME stabilised base with confidence.

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.