Search Results (11,463)

Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article

Erythrocyte (RBC) aging involves significant structural and nanomechanical alterations crucial to their function. This study aims to bridge the gap between analyses based on statistical morphometric parameters, e.g., membrane roughness, and those based on point-dependent nanomechanical properties, e.g., stiffness or Young’s modulus. Using Atomic Force Microscopy, we investigated morphology, membrane roughness, and nanomechanical properties on the very same RBCs under dehydrated (air) and hydrated (physiological buffer) conditions. The cells were studied at different stages of in vitro aging: one, seven, and 12 days. Our results quantitatively show that across dehydration, as well as along the aging pathway, RBCs become progressively more rigid while their membrane roughness decreases, a trend observed in both environments. Notably, the differences between the hydrated and dehydrated states were large in young cells but diminished when erythrocytes aged. Despite these parallel trends, high-resolution mapping on the nanoscale revealed that roughness and Young’s modulus do not correlate, indicating that these parameters are linked to different properties. In conclusion, this work provides a comprehensive protocol for a biophysical description of RBC aging and establishes that the simultaneous measurement of membrane roughness and nanomechanical properties offers a complementary approach, yielding a more complete characterization of cellular properties. Full article

This study describes and validates a novel method for assessing anterior crystalline lens curvature along vertical and horizontal meridians using radial measurements derived from Scheimpflug imaging. The aim was to evaluate whether pupil diameter (PD), anterior lens curvature, and anterior chamber depth (ACD) change during accommodation and whether these changes are age-dependent. A cross-sectional study was conducted on 104 right eyes from healthy participants aged 21–62 years. Sixteen radial images per eye were acquired using the Galilei Dual Scheimpflug Placido Disk Topographer under four accommodative demands (0, 1, 3, and 5 dioptres (D)). Custom software analysed lens curvature by calculating eccentricity in both meridians. Participants were analysed as a total group and by age subgroups. Accommodative amplitude and monocular accommodative facility were inversely correlated with age. Both PD and ACD significantly decreased with higher accommodative demands and age. Relative eccentricity decreased under accommodation, indicating increased lens curvature, especially in younger participants. Significant curvature changes were detected in the horizontal meridian only, although no statistically significant differences between meridians were found overall. The vertical meridian showed slightly higher eccentricity values, suggesting that it remained less curved. By enabling detailed, meridionally stratified in vivo assessment of anterior lens curvature, this novel method provides a valuable non-invasive approach for characterizing age-related biomechanical changes during accommodation. The resulting insights enhance our understanding of presbyopia progression, particularly regarding the spatial remodelling of the anterior lens surface. Full article

Hydrogen sulfide (H₂S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H₂S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health conditions, it may also contribute to inflammatory responses and gut barrier dysfunction. Controlling H₂S production in the GIT is important for maintaining a healthy gut microbiome. However, research on this subject is limited due to the gaseous nature of the chemical and the difficulty of accessing the GIT in situ. In the present ex vivo experiment, we used a single-dose sodium sulfide preparation (SSP) as a H₂S precursor to test the effect of H₂S on the human gut microbiome across different age groups, including breastfed infants, toddlers, adults, and older adults. Metagenomic sequencing and metabolite measurements revealed that the development of the gut microbial community and the production of short-chain fatty-acids (SCFAs) were age-dependent; that the infant and the older adult groups were more sensitive to SSP exposure; that exogeneous SSP suppressed SCFA production across all age groups, except for butyrate in the older adult group, suggesting that H₂S selectively favors specific gut microbial processes. Full article

Platelet-rich plasma (PRP) is widely applied in veterinary regenerative medicine due to its rich composition of growth factors that promote tissue repair. However, the direct pro-angiogenic function of canine PRP (cPRP) has not been thoroughly validated through controlled in vitro and in vivo experimentation. Human umbilical vein endothelial cells (HUVECs) were used to assess cell proliferation, migration, and tube formation after exposure to cPRP. In addition, a rabbit corneal micropocket assay was employed to evaluate in vivo angiogenic responses. Treatment with 20% cPRP significantly enhanced HUVEC proliferation and migration and induced robust tube formation. In the in vivo model, we observed dose-dependent neovascularization, with the earliest vascular sprouting seen on day 1 in the 40% group. Both models consistently demonstrated that cPRP stimulates vascular development in a concentration-dependent manner. This study provides novel evidence of cPRP’s capacity to induce neovascularization, supporting its therapeutic value for treating nonhealing wounds in dogs, especially in cases involving chronic inflammation, aging, or immune dysregulation. These findings offer a scientific foundation for the broader clinical application of cPRP in veterinary regenerative practice. Full article

Economic growth, especially in emerging economies, has altered the composition of international tourism. It is therefore essential to possess the skills necessary to understand the influence of culture on human behaviour, thereby enabling an appropriate response to the traveller. This research aims to develop a tool for identifying openness, flexibility, awareness, and intercultural preparedness. It focuses on the metacognitive and cognitive aspects of cultural intelligence that shape the development of empathy in customer service staff in hotels in Quintana Roo. The variables were validated and incorporated into a quantitative study using multivariate analysis and inferential statistics. A sample of 77 questionnaires was analysed using simple random sampling under a proportional design. Multiple Correspondence Analysis (MCA) was employed as a discriminatory technique to identify the most significant independent variables. These were subsequently entered as regressors into ordinal logistic regression (OLR), along with age and work experience, in order to estimate the probabilities associated with each level of the dependent variable. The results indicated that age had minimal influence on the metacognitive and cognitive variables, whereas years of experience among tourism staff exerted a significant effect. Full article

Postmenopausal osteoporosis is estrogen-dependent and results in an imbalance between bone formation and resorption. The approved therapy is intended to reduce the risk and consequences of fractures, but still has a number of contraindications and associated adverse effects. Recently, oxytocin has been shown to have an anabolic effect on bone tissue, increasing the production of osteoblasts and inhibiting the activity of osteoclasts. Thus, this study aimed to examine the potential of oxytocin as a biomarker and therapeutic agent for postmenopausal osteoporosis. A PubMed search yielded 16 articles upon analysis of the inclusion and exclusion criteria. The results showed that, compared to women in the same age group without bone loss, those diagnosed with osteoporosis exhibited lower blood oxytocin levels, possibly related to a greater tendency towards fractures. The administration of oxytocin could be a promising strategy to enhance bone quality and, consequently, to reduce the incidence of fragility fractures; however, no human studies have been conducted regarding its use as a possible treatment. Thus, it is essential to increase the number of clinical trials in women with ovarian dysfunction and bone loss, in which oxytocin could become a viable therapeutic alternative. Full article

The rapidly changing dynamics of the digital age reshape the addiction relationship that high school students establish with technology. While smartphones remove boundaries in terms of communication and access to information, their usage triggers a source of anxiety and nomophobia. The increase in students’ anxiety levels because of their over-reliance on mobile phone use leads to significant behavioral changes in their mental health, academic performance, social interactions and financial dependency. This study examined the nomophobia levels of high school students according to selected socio-demographic indicators. Using the relational screening model, the multistage sampling technique was used to select a sample of 884 participants: 388 from Science High School and 496 from Anatolian High School (459 female, 425 male, Mage = 16.45 ± 1.14 year). Independent sample test and One-way ANOVA were applied. Depending on the homogeneity assumption of the data, Welch values were considered, and Tukey tests were applied as a second-level test from post hoc analyses. Comprehensive analyses of nomophobia levels revealed that young individuals’ attitudes towards digital technology differ significantly according to their demographic and behavioral characteristics. Variables such as gender, physical activity participation, grade level and duration of smartphone use are among the main factors affecting nomophobia levels. Female individuals and students who do not participate in physical activity exhibit higher nomophobia scores. Full article

As the size of the elderly population increases, the need for an improved understanding of what leads to the age-related decline in physiological function continues to grow. SAMP8 mice were selected for their accelerated aging phenotype. The low levels of glyoxalase 1 (Glo1), the main enzyme that removes the reactive dicarbonyl methylglyoxal (MGO), in the cerebral cortex of SAMP8 mice prompted us to produce the first transgenic mice overexpressing Glo1 against the SAMP8 background, aimed at rescuing the accelerated aging phenotype. Selected health and biochemical endpoints were assessed in ten-month-old SAMP8 mice overexpressing Glo1. Glo1 overexpression increased median survival in males (21%) and females (4.6%), which was associated with better memory performance. Glo1 overexpression also increased synaptic markers (synaptophysin and SNAP25) as well as markers of mitochondrial function (NDUFB8, SDHB) and negative modulators of oxytosis/ferroptosis (NQO1, FTH1, and GPx4) in the cerebral cortex. For all parameters analyzed, the effect of Glo1 overexpression was more pronounced in males. Overall, the data support the beneficial effects of overexpressing Glo1 in multiple tissues, especially in SAMP8 males, suggesting a possible gender effect of MGO in aging. Both modulation of oxytosis/ferroptosis and mitochondrial metabolism warrant further investigation as potential mechanisms underlying the improved health span of Glo1 mice. Full article

The average body size (fork length) of juvenile salmonids in small streams varies across landscapes and can be influenced by stream temperature, density dependence, catchment size, and physical habitat. In this study, we compared sets of 16 mixed-effects linear models representing these four potentially influencing indicators for three species/age classes to assess the relative importance of their influences on body size. The global model containing all indicators was the most parsimonious model for juvenile coho salmon (Oncorhynchus kisutch; R²m = 0.4581, R²c = 0.5859), age-0 trout (R²m = 0.4117, R²c = 0.5968), and age-1 or older coastal cutthroat trout (O. clarkii; R²m = 0.2407, R²c = 0.5188). Contrary to expectations, salmonid density, catchment size, and physical habitat metrics contributed more to the top models for both coho salmon and age-1 or older cutthroat trout than stream temperature metrics. However, a stream temperature metric, accumulated degree days, had the only significant relationship (positive) of the indicators with body size in age-0 trout (95% CI 1.58 to 23.04). Our analysis identifies complex relationships between salmonid body size and environmental influences, such as the importance of physical habitat such as pool size and boulders. However, management or restoration actions aimed at improving or preventing anticipated declines in physical habitat such as adding instream wood or actions that may lead to increasing pool area have potential to ensure a natural range of salmonid body sizes across watersheds. Full article

Aim: To compare diabetic polyneuropathy (DPN) and cardiac autonomic neuropathy (CAN) between T1DM and T2DM patients. Methods: This study enrolled 66 T1DM and 79 T2DM patients. DPN was evaluated using three different methods: clinical examination, using neuropathy symptom score (NSS) and neuropathy disability score (NDS), current perception threshold (CPT) using Neurometer, and nerve conduction studies (NCSs). CAN was assessed by cardiovascular autonomic reflex tests (CARTs). Results: The prevalence of DPN did not differ between T1DM and T2DM (p > 0.05 for all), however, the proportion of DPN depended on the method used and was highest with CPT (53.0% vs. 46.8%), followed by NCSs (44.1% vs. 41.2%) and clinical examination (25.8% vs. 31.6%). T2DM vs. T1DM patients were more often diagnosed with painful DPN (51.9% vs. 27.3%, p = 0.004), reduced perception of vibration (72.2% vs. 48.5%, p = 0.006), and autonomic neuropathy (59.5% vs. 32.3%, p = 0.001), while NCSs revealed more prevalent motor nerve dysfunction in T1DM compared to T2DM (41.2% vs. 19.6%). Multivariate regression analysis showed increased DPN risk with age and CAN risk with worsening of eGFR in T1DM. No significant associations remained after multivariate adjustment for T2DM. Conclusions: The prevalence of DPN is highly varied and depends on the diagnostic method used. T2DM patients more often had symptoms and signs of diabetic neuropathy. However, stronger associations with risk factors were observed in T1DM. Full article

This article examines how digital innovation ecosystems have emerged as strategic institutions of power in contemporary world politics. It argues that, unlike Cold War technological rivalries driven by centralized, state-led control, today’s digital competition depends on states’ capacity to orchestrate scalable, multistakeholder ecosystems. Using a cultural–institutional framework, we explain how differences in strategic culture and institutional governance impact the ecosystem’s vitality and performance. A qualitative comparative analysis of the United States, China, and Russia reveals that constructive orchestration, aligning state institutions with generative, commercial-to-national innovation flows, enhances digital leadership, whereas rigid, obstructive governance limits it. This highlights ecosystem governance as a critical dimension of statecraft in the digital age. The findings underscore that the positions of great powers in the global technological hierarchy depend not only on resources or capabilities but also on the effectiveness of ecosystem governance as an evolving instrument of geopolitical power. Full article

Background/Objectives: Accurately assessing the independence level of older adults using useful assessment tools is an important step toward providing them with the necessary care while preserving their dignity. These tools allow older adults to receive effective, personalized home care, which improves their quality of life. This study aimed to clarify the current prevalence of severe and complete functional dependence and associated factors among Kazakhstan’s older adults aged >60 years. Methods: This cross-sectional study was conducted in several polyclinics and geriatric service care centers in two cities of Kazakhstan from March to May 2024. Functional status was assessed by the Barthel Index. We combined the selection into two categories: total dependency and severe dependency in the category “dependent”, and moderate dependency, slight dependency, and total independence in the category “active patients”. Results: Among the 642 older people in this study, 43.3% were dependent patients, and 56.7% were active patients. The odds of severe and total functional dependence are significantly higher for frail participants (adjusted odds ratio (AOR) = 2.96, 95% confidence interval (CI) [1.70, 5.16], p < 0.001) compared to those that are not frail; eleven times higher for those at home (AOR =11.90, 95% CI [5.77, 24.55], p < 0.001) than those in nursing homes; two times higher for participants with sarcopenia (AOR =2.61, 95% CI [1.49, 4.55], p < 0.001) compared to those with no sarcopenia; and three times higher for participants with high risk of fracture (AOR =3.30, 95% CI [1.94, 5.61], p < 0.001) compared to those with low risk. The odds of having severe and total functional dependence are significantly higher for participants with low dynamometry (AOR =1.05, 95% CI [1.03, 1.07], p < 0.001) compared to those with normal dynamometry. Conclusions: Old age, low dynamometry (for men ≤ 29 kg, for women ≤ 17 kg), frailty, being at home, high risk of fracture and osteoporosis, and sarcopenia were associated with increased risk of severe and total functional dependence. Full article

This study aims to characterize short-wave infrared (SWIR) reflectance spectra at cranial (at the scalp overlying the frontal cortex and the temporal bone window) and extracranial (biceps and triceps) sites in patients with multiple sclerosis (MS) and age-/sex-matched controls. We sought to identify the diagnostic accuracy of wavelength-specific patterns in distinguishing MS from normal controls and spectral markers associated with disability (e.g., Expanded Disability Status Scale scores). To achieve these objectives, we employed a multi-site SWIR spectroscopy acquisition protocol that included measurements from traditional cranial locations as well as extracranial reference sites. Advanced spectral analysis techniques, including wavelength-dependent absorption modeling and machine learning-based classification, were applied to differentiate MS-related hemodynamic changes from normal physiological variability. Classification models achieved perfect performance (accuracy = 1.00), and cortical site regression models showed strong predictive power (EDSS: R²_CV = 0.980; FSS: R²_CV = 0.939). Variable Importance in Projection (VIP) analysis highlighted key wavelengths as potential spectral biomarkers. This approach allowed us to explore novel biomarkers of neural and systemic impairment in MS, paving the way for potential clinical applications of SWIR spectroscopy in disease monitoring and management. In conclusion, spectral analysis revealed distinct wavelength-specific patterns collected from cranial and extracranial sites reflecting biochemical and structural differences between patients with MS and normal subjects. These differences are driven by underlying physiological changes, including myelin integrity, neuronal density, oxidative stress, and water content fluctuations in the brain or muscles. This study shows that portable spectral devices may contribute to bedside individuation and monitoring of neural diseases, offering a cost-effective alternative to repeated imaging. Full article

Background: Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. Methods: High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues. Results: Nearly 10% of mature miRNAs showed a daily rhythm in expression. A peak of miRNAs’ levels was in most cases observed during the first half of the D phase of the LD cycle. The highest amplitude was detected in expression of miR-150-5p and miR-142-3p. In the L phase of the LD cycle, the maximum in miR-30d-5p expression was detected. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during the D phase influence apoptosis, angiogenesis, the immune system, and EGF and TGF-beta signaling. Rhythm in miR-150-5p, miR-142-3p, and miR-30d-5p expression was confirmed by real-time PCR. Oncogenes bcl2 and myb and clock gene cry1 were identified as miR-150-5p targets. miR-150-5p administration promoted camptothecin-induced apoptosis. Expression of myb showed a rhythmic profile in DLD1 cells with inverted acrophase with respect to miR-150-5p. miR-150-5p was decreased in cancer compared to adjacent tissue in CRC patients. Decrease in miR-150-5p was age dependent. Older patients with lower expression of miR-150-5p and higher expression of cry1 showed worse survival in comparison with younger patients. Conclusions: miRNA signaling differs between the L and D phases of the LD cycle. miR-150-5p, targeting myb, bcl2, and cry1, can influence CRC progression in a phase-dependent manner. Full article