Search Results (348)

Psychiatric disorders affect nearly one billion people worldwide and remain a major therapeutic challenge due to frequent treatment resistance. Pharmacogenetics provides a precision-informed approach by accounting for interindividual variability in drug metabolism and response, and population-specific data offer valuable information for therapeutic considerations. This study analyzed 3011 Greek individuals to assess 24 pharmacogenetic variants across 13 genes. Genotyping was performed using TaqMan OpenArray^® assays, and metabolic phenotypes were predicted based on established genotype-to-phenotype translation guidelines. Allele frequencies were compared with those in European, African, and East Asian populations. Population structure and genetic differentiation were evaluated using Principal Component Analysis (PCA), K-means clustering, fixation index (F_ST), and STRUCTURE analysis. Results indicated that most allele frequencies in Greeks aligned with those in European populations, while several CYP2D6 and CYP2C19 variants differed significantly from those in African and East Asian cohorts. PCA and clustering confirmed strong European affinity, supported by low F_ST values, whereas STRUCTURE revealed minimal non-European admixture. Predicted metabolic phenotypes showed that 36%, 57.7%, and 41.6% of individuals exhibited altered CYP2D6, CYP2C19, and CYP2C9 activity, respectively. These findings highlight clinically actionable variation in the Greek population and emphasize the use of population-specific pharmacogenetic data to inform optimized strategies in precision psychiatry. Full article

Non-invasive glucose monitoring remains a persistent challenge in the scientific literature due to the complexity of biological samples and the limitations of traditional optical methods. Although advances have been made in the use of near-infrared (NIR) spectrophotometry, the direct application of the Lambert–Beer Law (LBL) to such systems has proven problematic, particularly due to the non-linear behavior observed in complex organic solutions. In this context, the objective of this work is to propose and validate a methodology for the determination of the extinction coefficient of glucose in blood, taking into account the limitations of the LBL and the specificities of molecular interactions. The method was optimized through an iterative process to provide consistent results over multiple replicates. Whole blood and plasma samples from two individuals were analyzed using spectrophotometry in the 700 nm to 1400 nm. The results showed that glucose has a high spectral sensitivity close to 975 nm.The extinction coefficients obtained for glucose (${\alpha }_g$) ranged from −0.0045 to −0.0053, and for insulin (${\alpha }_i$) from 0.000075 to 0.000078, with small inter-individual variations, indicating strong stability of these parameters. The non-linear behaviour observed in the relationship between absorbance, glucose and insulin concentrations might be explained by the changes imposed by both s and p orbitals of organic molecules. In order to make the LBL valid in this context, the extinction coefficients must be functions of the analyte concentrations, and the insulin concentration must also be a function of glucose. A regression model was found which allows to differentiate glucose from insulin concentration, by considering the cuvette thickness and sample absorbance at 965, 975, and 985 nm. It can also be concluded from experiments that wavelength of approximately 975 nm is more suitable for blood glucose calculation by using photometry. The final spectra are consistent with those reported in mid-infrared validation studies, suggesting that the proposed model encompasses the key aspects of glucose behavior in biological media. Full article

Background: The anatomical variability of the nasal cavity affects intranasal drug delivery, especially to the olfactory region for nose-to-brain treatments. While previous studies used average models or 2D measurements to account for inter-individual variability, 3D shape variation of the region crossed by drug particles that target the olfactory area, namely the region of interest (ROI), remains unexplored to our knowledge. Methods: A geometric morphometric analysis was performed on the ROI of 151 unilateral nasal cavities from the CT scans of 78 patients. Ten fixed landmarks and 200 sliding semi-landmarks were digitized, using Viewbox 4.0, and standardized via Generalized Procrustes Analysis. Shape variability was analyzed through Principal Component Analysis. Morphological clusters were identified using Hierarchical Clustering on Principal Components, and characterized with MANOVA, ANOVA, and Tukey tests. Results: Validation tests confirmed the method’s reliability. Three morphological clusters were identified. Variations were significant in the X and Y axes, and minimal in Z. Cluster 1 had a broader anterior cavity with shallower turbinate onset, likely improving olfactory accessibility. Cluster 3 was narrower with deeper turbinates, potentially limiting olfactory accessibility. Cluster 2 was intermediate. Notably, 31.5% of patients had at least one cavity in cluster 1. Conclusions: Three distinct morphotypes of the region of the nasal cavity that potentially influence accessibility were identified. These findings will guide future computational fluid dynamics studies for optimizing nasal drug targeting and represent a practical step toward tailoring nose-to-brain drug delivery strategies in alignment with the principles of personalized medicine. Full article

Cardiac arrhythmia is a leading cause of sudden cardiac death. Its early detection and continuous monitoring hold significant clinical value. Photoplethysmography (PPG) signals, owing to their non-invasive nature, low cost, and convenience, have become a vital information source for monitoring cardiac activity and vascular health. However, the inherent non-stationarity of PPG signals and significant inter-individual variations pose a major challenge in developing highly accurate and efficient arrhythmia classification methods. To address this challenge, we propose a Fusion Deep Multi-domain Attention Network (Fusion-DMA-Net). Within this framework, we innovatively introduce a cross-scale residual attention structure to comprehensively capture discriminative features in both the time and frequency domains. Additionally, to exploit complementary information embedded in PPG signals across these domains, we develop a fusion strategy integrating interactive attention, self-attention, and gating mechanisms. The proposed Fusion-DMA-Net model is evaluated for classifying four major types of cardiac arrhythmias. Experimental results demonstrate its outstanding classification performance, achieving an overall accuracy of 99.05%, precision of 99.06%, and an F1-score of 99.04%. These results demonstrate the feasibility of the Fusion-DMA-Net model in classifying four types of cardiac arrhythmias using single-channel PPG signals, thereby contributing to the early diagnosis and treatment of cardiovascular diseases and supporting the development of future wearable health technologies. Full article

Platelet-rich plasma (PRP) is increasingly used in orthopedics, with its regenerative potential attributed to platelet-derived cytokines and growth factors. However, variability in PRP composition hampers standardization and reproducibility, contributing to inconsistent outcomes. Since platelet counts in whole blood follow circadian rhythms, we investigated whether blood collection time affects PRP composition. Venous blood was collected from 25 healthy individuals at 8:00 a.m., 12:00 p.m., and 4:00 p.m. Whole blood was analyzed, and leukocyte-poor PRP (LP-PRP) was prepared for quantification of erythrocytes, leukocytes, and platelets. Platelets were lysed by freeze–thaw cycles, and protein levels of PDGF-BB, IGF1, HGF, IL6, and IL10 were measured via ELISA. Whole blood exhibited diurnal variation in platelet counts. In contrast, LP-PRP was consistently depleted of leukocytes and erythrocytes and showed stable platelet enrichment (PRP/whole blood ratio 2.1 ± 0.3). Protein concentrations in LP-PRP did not differ across collection times. Despite marked interindividual variability, no time-dependent differences were observed in platelet or protein composition. These results demonstrate that LP-PRP is temporally stable, independent of blood sampling time. This robustness supports flexible clinical use and contributes to efforts toward PRP standardization in therapeutic practice. Full article

Biologics targeting tumor necrosis factor-α (TNFi), interleukin-12/23 (IL-12/23i), and interleukin-17 cytokine or receptor (IL-17i/IL-17Ri) have transformed psoriasis management. However, interindividual variation in response underscores the need for predictive biomarkers in guiding therapy selection. Patients treated with a biologic for psoriasis were genotyped for 67 single-nucleotide polymorphisms (SNPs) previously associated with response to biologics. Odds ratios (OR) with 95% confidence intervals (CI) for associations between SNPs and response to biologics were calculated using logistic regression models with an absolute Psoriasis Area and Severity Index (PASI) ≤2 after 3 months as treatment response. A p-value < 0.05 was considered statistically significant. In total, 373 patients with 574 treatment series were included. Twelve SNPs were associated with treatment response: four uniquely with response to TNF inhibitors (TNFi), two to IL-12/23i, and five to IL-17i/IL-17Ri, while one was associated with response to both TNFi and IL-17i/IL-17Ri. Notably, IRAK3 (rs11541076) and CD84 (rs6427528) were associated with response to TNFi (OR: 2.56 [95% CI: 1.22–5.37], p = 0.012 and OR: 0.53 [95% CI: 0.30–0.91], p = 0.023) and IL-17i/IL-17Ri (OR: 2.55 [95% CI: 0.70–9.22], p = 0.15), and OR: 0.50 [95% CI: 0.25–0.98], p = 0.045), with trends toward opposite associations for IL-12/23i (OR: 0.38 [95%CI: 0.08–1.72], p = 0.21 and OR: 1.64 [95%CI: 0.68–3.93], p = 0.26). This study replicates known genetic associations with biologic response in psoriasis. Variants in IRAK3 and CD84 show potential as stratification biomarkers, although they need confirmation in independent cohorts. Full article

Background: The annular ligament is a key secondary stabilizer of the elbow, but its biomechanical behavior during forearm rotation has not been objectively quantified. This study aimed to assess interindividual variability in annular ligament tension, validate prior arthroscopic observations, and explore associations with chondral lesions in the lateral elbow compartment. Methods: In this cross-sectional anatomical study, 25 cadaveric upper limbs were analyzed following standardized dissection, preserving ligamentous and muscular integrity. Ligament displacement was measured using a custom mechanical apparatus and high-precision digital micrometer in neutral, 60° pronation, and 60° supination positions under axial tractions of 1, 2, and 3 kg. Ulnar length and presence of chondral lesions were also recorded. Results: Maximal ligament displacement occurred in supination in 80% of specimens (mean: 1.23 mm at 3 kg; range: 0.30–2.87 mm), indicating considerable interindividual variation. Significant displacement differences were observed between all forearm positions across load levels (p < 0.001). Chondral lesions were identified in three specimens with marked ligament laxity and reduced radial head coverage. Conclusions: This study provides the first objective evidence of annular ligament tension variability during forearm rotation. Ligament laxity may contribute to lateral elbow instability and cartilage degeneration, supporting the ligament’s role as a secondary stabilizer. Full article

The genus Paphiopedilum (Orchidaceae) has high ornamental value due to its long flowering period, brilliant flower color, and peculiar floral morphology. Guangxi is the center of ecological diversity of Paphiopedilum, and therefore it is urgent to conduct rescue studies on the genetic resources and genetic structure of this genus in Guangxi. In this study, the genetic diversity of 39 populations from eight Paphiopedilum species in Guangxi was analyzed using ten selected EST-SSR primer pairs and fluorescent PCR amplification. The results show that genetic diversity varied among species, with large differences in expected heterozygosity (He). The highest genetic diversity was observed in P. barbigerum (I = 0.923; He = 0.480), while P. dianthum (I = 0.179; He = 0.098) showed the lowest diversity. From the genus perspective, molecular variance analysis (AMOVA) revealed that 57% of the genetic variation occurred among populations and 43% within populations, with inter-population variation being the main source of genetic variation. From a species perspective, genetic differentiation varied, with inter-individual differentiation ranging from 79% to 95%. The percentage of molecular variance indicated that genetic variation mainly occurred among individuals, which was the main source of total variation. According to the principle of maximum likelihood, the optimal K value was determined to be 6, and 760 Paphiopedilum samples were divided into six subgroups. The results of this study not only identify priority populations for conservation and establish a germplasm repository to preserve existing resources, but also provide references for research on asexual reproduction, seed propagation, and hybrid breeding of Paphiopedilum, thereby promoting the conservation and sustainable utilization of Paphiopedilum germplasm resources. Full article

Background: This study aims to establish standardized reference values for myocardial T1 and T2 relaxation times in a clinically and imaging-defined real-world patient cohort, evaluating their variability in relation to age, sex, and comorbidities. By identifying key physiological and pathological influences, this investigation seeks to enhance CMR-based myocardial mapping for improved differentiation between normal and pathological myocardial conditions. Methods: This retrospective observational study analyzed T1 and T2 relaxation times using CMR at 1.5 Tesla in a cohort of 491 subjects. T1 and T2 times were measured using MOLLI and GRASE sequences, and statistical analyses assessed intra- and interindividual variations, including the influence of age, sex, and comorbidities, to establish reference values and improve myocardial tissue characterization. Results: T1 and T2 relaxation times were analyzed in 291 and 200 participants, respectively. The mean global T1 time was 1004.7 ± 49.8 ms, with no significant differences between age groups (p = 0.81) or sexes (p = 0.58). However, atrial fibrillation (AF) and mitral regurgitation (MR) were associated with significantly prolonged T1 times (p < 0.05). The mean global T2 time was 67.4 ± 8.6 ms, with age-related prolongation (p < 0.05), but no sex differences (p = 0.46). Comorbidities did not significantly influence T2 times, except for NYHA Class III–IV patients, who exhibited prolonged T2 values (p < 0.05). Conclusions: Standardized T1 and T2 reference values are essential to improve diagnostic accuracy and risk stratification in CMR-based myocardial tissue characterization. Future research should focus on multicenter validation, AI-driven analysis, and the development of age- and comorbidity-adjusted normative databases to enhance individualized cardiovascular care. Full article

Background: Tacrolimus is a cornerstone of immunosuppressive therapy following heart transplantation. Despite routine therapeutic drug monitoring (TDM), substantial interindividual variability in tacrolimus pharmacokinetics presents a persistent challenge. Pharmacogenetic profiling—particularly of CYP3A5 and CYP3A4 polymorphisms—offers a promising approach to individualize tacrolimus dosing and improve clinical outcomes. Case Presentation: We describe a 54-year-old male heart transplant recipient with persistently subtherapeutic tacrolimus trough concentrations despite escalating standard doses. Tacrolimus dosing initially started at 3.5 mg twice daily, escalated to 7.0 mg twice daily, with final maintenance dosing at 6.5 mg twice daily. TDM values were persistently subtherapeutic at 3–5 ng/mL for over a month before achieving therapeutic targets >10 ng/mL. Pharmacogenetic testing revealed a CYP3A5 expresser genotype (*1/*3) and normal CYP3A4 activity (*1/*1), suggesting enhanced metabolic clearance. In accordance with CPIC guidelines, tacrolimus dosing was intensified and supported by co-administration of diltiazem (60 mg twice daily, later adjusted to 90 mg twice daily), a CYP3A4 inhibitor. Subsequent TDM confirmed achievement of therapeutic levels. At nine months post-transplant, the patient exhibited stable graft function and excellent clinical status. Discussion: This case underscores the value of genotype-informed tacrolimus dosing in clinical scenarios where standard TDM is insufficient. Pharmacogenetic variation—particularly involving CYP3A5 expression—has been consistently associated with altered tacrolimus exposure and dose requirements. The literature supports routine genotyping in solid organ transplant recipients, although implementation remains limited. Additional considerations include drug–drug interactions, notably with CYP3A-modulating agents such as diltiazem and antifungals, which may further influence tacrolimus pharmacokinetics. Current evidence suggests that the utility of CYP3A4 genotyping may be phase-dependent, being more impactful during early post-transplant periods. Conclusions: Incorporating pharmacogenetic data alongside TDM facilitates more precise and individualized tacrolimus therapy, optimizing immunosuppressive efficacy and minimizing risk. This case, supported by literature review, advocates for broader integration of genotype-guided strategies in transplant pharmacotherapy. Full article

Obesity is a global health challenge marked by substantial inter-individual differences in responses to dietary and lifestyle interventions. Traditional weight loss strategies often overlook critical biological variations in genetics, metabolic profiles, and gut microbiota composition, contributing to poor adherence and variable outcomes. Our primary aim is to identify key biological and behavioral effectors relevant to precision medicine for weight control, with a particular focus on nutrition, while also discussing their current and potential integration into digital health platforms. Thus, this review aligns more closely with the identification of influential factors within precision medicine (e.g., genetic, metabolic, and microbiome factors) but also explores how these factors are currently integrated into digital health tools. We synthesize recent advances in nutrigenomics, nutritional metabolomics, and microbiome-informed nutrition, highlighting how tailored dietary strategies—such as high-protein, low-glycemic, polyphenol-enriched, and fiber-based diets—can be aligned with specific genetic variants (e.g., FTO and MC4R), metabolic phenotypes (e.g., insulin resistance), and gut microbiota profiles (e.g., Akkermansia muciniphila abundance, SCFA production). In parallel, digital health tools—including mobile health applications, wearable devices, and AI-supported platforms—enhance self-monitoring, adherence, and dynamic feedback in real-world settings. Mechanistic pathways such as gut–brain axis regulation, microbial fermentation, gene–diet interactions, and anti-inflammatory responses are explored to explain inter-individual differences in dietary outcomes. However, challenges such as cost, accessibility, and patient motivation remain and should be addressed to ensure the effective implementation of these integrated strategies in real-world settings. Collectively, these insights underscore the pivotal role of precision nutrition as a cornerstone for personalized, scalable, and sustainable obesity interventions. Full article

Vitamin D (VD) plays a critical role in human health, with deficiencies linked to a range of adverse outcomes, including compromised immune function and increased disease risk. While environmental factors such as sunlight exposure and diet influence circulating VD levels, genetic variation is a significant and underappreciated contributor to interindividual differences in serum 25-hydroxyvitamin D [25(OH)D] concentrations. This review provides a comprehensive summary of genetic variants in key genes involved in VD synthesis (e.g., DHCR7, cyp2r1, cyp27b1), transport (GC), and metabolism (cyp24a1, cyp3a4), as well as in cholesterol transport proteins (SCARB1, CD36, NPC1L1). We examine how single-nucleotide polymorphisms (SNPs) and rare mutations in these genes affect enzyme activity, VD bioavailability, and overall 25(OH)D status. Importantly, we highlight evidence supporting gene-by-environment interactions and population-specific allele frequencies that further shape individual VD responses. In the context of clinical nutrition and precision health, these findings support the development of genomic risk scores (GRSs) to identify individuals at risk for deficiency or toxicity and guide personalized VD supplementation strategies. Regular monitoring of serum 25(OH)D alongside genetic screening may improve clinical outcomes by helping to achieve optimal VD immunosufficiency while minimizing the risk of adverse effects. Full article

Human milk bacteria contribute to gut microbiome establishment in breastfed infants. Although breastfeeding is recommended throughout infancy, temporal variation in the milk microbiome—particularly beyond solid food introduction—remains understudied. We analyzed 539 milk samples from 83 mother–infant dyads between 1 week and 12 months postpartum using full-length 16S rRNA gene sequencing. The microbiota was dominated by Streptococcus (34%), Cutibacterium (12%), and Staphylococcus (9%), with marked inter-individual variation. Microbiome profiles remained largely stable across lactation, with only six taxa showing temporal fluctuations, including increases in typical oral bacteria such as Streptococcus salivarius, Streptococcus lactarius, Rothia mucilaginosa, and Granulicatella adiacens. Richness and evenness were higher at 1 week compared to 1 month postpartum (p = 0.00003 and p = 0.007, respectively), then stabilized. Beta diversity also remained stable over time. Maternal pre-pregnancy BMI was positively associated with Gemella haemolysans (p = 0.016), while Haemophilus parainfluenzae was more abundant in milk from mothers with allergies (p = 0.003) and those who gave birth in autumn or winter (p = 0.006). The introduction of solid food was linked to minor taxonomic shifts. Overall, the milk microbiome remained robustly stable over the first year of lactation, with limited but notable fluctuations in specific taxa. This study supports the role of human milk as a consistent microbial source for infants and identifies maternal BMI, allergy status, and birth season as key variables warranting further investigation. Full article

Background/Objectives: Heart failure with reduced ejection fraction (HFrEF) is associated with significant renal complications, affecting disease progression and patient outcomes. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have emerged as a key therapeutic strategy, offering cardiovascular and renal benefits in these patients. However, interindividual variability in response to dapagliflozin underscores the role of pharmacogenetics in optimizing treatment efficacy. This study investigates the influence of genetic polymorphisms on renal outcomes in HFrEF patients treated with dapagliflozin, focusing on variations in genes such as SLC5A2, UMOD, KCNJ11, and ACE. Methods: This prospective, observational cohort study was conducted at the National Heart Institute, Cairo, Egypt, enrolling 200 patients with HFrEF. Genotyping of selected single nucleotide polymorphisms (SNPs) was performed using TaqMan™ assays. Renal function, including estimated glomerular filtration rate (eGFR), Kidney Injury Molecule-1 (KIM-1), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels, was assessed at baseline and after six months of dapagliflozin therapy. Results: Significant associations were found between genetic variants and renal outcomes. Patients with AA genotype of rs3813008 (SLC5A2) exhibited the greatest improvement in eGFR (+7.2 mL ± 6.5, p = 0.004) and reductions in KIM-1 (−0.13 pg/mL ± 0.49, p < 0.0001) and NGAL (−6.1 pg/mL ± 15.4, p < 0.0001). Similarly, rs12917707 (UMOD) TT genotypes showed improved renal function. However, rs5219 (KCNJ11) showed no significant impact on renal outcomes. Conclusions: Pharmacogenetic variations influenced renal response to dapagliflozin in HFrEF patients, particularly in SLC5A2 and UMOD genes. These findings highlighted the potential of personalized medicine in optimizing therapy for HFrEF patients with renal complications. Full article

Menopause is characterized by a decline in estrogen levels, leading to symptoms such as vasomotor instability, osteoporosis, and increased cardiovascular and cognitive risk. Hormone replacement therapy (HRT) remains the gold standard for managing menopausal symptoms; however, concerns regarding its long-term safety, including elevated risks of cancer and cardiovascular events, have prompted interest in alternative therapies. Phytoestrogens, particularly the isoflavones daidzein and genistein, are plant-derived compounds structurally similar to 17β-estradiol (E2) and capable of binding estrogen receptors. Found abundantly in soybeans and red clover, these compounds exhibit selective estrogen receptor modulator (SERM)-like activity, favoring ERβ over ERα, which underlies their tissue-specific effects. In vitro, in silico, and in vivo studies demonstrate their ability to modulate estrogenic pathways, inhibit oxidative stress, and influence reproductive and neurological function. Clinical trials show that daidzein and genistein, especially in equol-producing individuals, can reduce vasomotor symptoms such as hot flashes and night sweats. While results across studies vary, consistent findings support their safety and modest efficacy, particularly for women unable or unwilling to use HRT. Pharmacokinetic studies reveal moderate bioavailability and interindividual variability due to gut microbiota metabolism. At dietary levels, these compounds are generally safe, although high-dose supplementation is discouraged in individuals with hormone-sensitive cancers. Emerging evidence suggests lifelong consumption of soy-based foods may reduce cancer risk. In conclusion, daidzein and genistein represent promising, well-tolerated natural alternatives to conventional HRT, offering symptom relief and additional health benefits. Further research is warranted to optimize dosing, improve clinical outcomes, and clarify long-term safety in diverse populations, particularly with genetic variations in isoflavone metabolism. Full article