Search Results (6,174)

Background: Metabolic control in phenylketonuria (PKU) is known to deteriorate with age, but national-level data describing blood phenylalanine (Phe) control across the United Kingdom (UK) are limited. Objective: To characterise blood Phe control in individuals with PKU attending UK metabolic centres. Methods: Sixteen UK centres (nine paediatric, six adult, one mixed) retrospectively extracted blood Phe results collected between 2012 and 2018. Demographic, phenotypic and monitoring-related variables were analysed. Written consent for data collection was obtained from all patients or their caregivers. Results: Data were available for 871 individuals (55% female), of whom 744 (85%) were classified as follows: classical PKU, 75%, mild PKU, 22% and hyperphenylalaninaemia, 3%. Mean blood Phe concentrations were significantly higher in adults than children (491 ± 308 vs. 303 ± 199 µmol/L; p < 0.001), and the proportion of samples within target range declined steadily with age, from 78% in children <2 years to 36% in adults ≥41 years. Individuals with classical PKU had higher mean Phe concentrations and lower target attainment than those with HPA (386 vs. 300 µmol/L; 61% vs. 78%; p < 0.001), while mild PKU and HPA showed comparable control. Females generally demonstrated better metabolic control than males. More frequent dried blood spot sampling for blood Phe was strongly associated with improved metabolic control: weekly (254 ± 175 µmol/L; 82% within target), fortnightly (319 ± 207 µmol/L; 70%), monthly (397 ± 231 µmol/L; 61%), and less than monthly (624 ± 349 µmol/L; 44%). Nearly half of the blood Phe samples (47%) with recorded timing were taken in a non-fasting state. Conclusions: Achieving lifelong metabolic stability on a Phe-restricted diet alone remains challenging. These national data highlight the need for broader therapeutic options to support individuals with PKU across the lifespan. Full article

Red blood cells (RBCs) are sensitive biomarkers of human health, influenced by urbanization and agricultural exposures. Using scanning electron microscopy (SEM) within an exposome framework, we examined RBC morphology in residents of an industrialized area of Thessaloniki, Greece, and in a rural population primarily exposed to agricultural stressors. Blood samples and questionnaires covering demographics, lifestyle, and environmental factors were statistically analyzed. SEM revealed moderate morphological alterations without significant differences between groups. Observed features were associated with longer residence duration and suboptimal nutrition, suggesting subclinical cellular stress. Integrating these findings into exposome research may clarify cumulative industrial and agricultural impacts on RBC morphology. Full article

Arthrogenic muscle inhibition (AMI), neurophysiological suppression of voluntary quadriceps activation triggered by joint effusion and inflammation, is consistently initiated within hours of any form of knee surgery. If not actively counteracted during the first two postoperative weeks, AMI may drive a cascade of neuromuscular, morphological, and biomechanical deficits that can persist for years, substantially increasing the risk of post-traumatic osteoarthritis, reinjury, and long-term functional disability. Emerging evidence indicates that preoperative patient-related factors, including baseline quadriceps strength, age, body mass index, and physical fitness, further modulate the rehabilitation response and should be considered in planning early postoperative protocols. This narrative review, which was not designed as a systematic review or meta-analysis and therefore does not include formal quality assessment or pooled statistical analysis, evaluates evidence for seven early-phase (0–2 weeks postoperative) knee muscle activation interventions: neuromuscular electrical stimulation (NMES), isometric quadriceps exercise, blood flow restriction (BFR) training, electromyographic (EMG) biofeedback, open and closed kinetic chain (OKC/CKC) exercise, cryotherapy, and continuous passive motion (CPM). Findings are synthesized against six clinically relevant dimensions, safety in the 0–2 week window, home-based usability, capacity to overcome AMI, requirement for volitional effort, objective monitoring capability, and progressive resistance, to characterize a consistent pattern: no single existing modality simultaneously meets all combined requirements for home deployment, volitional engagement, objective monitoring, and progressive resistance from postoperative day one. This collective unmet need provides direction for future device development and clinical research. Full article

(1) Background: Although the rhesus macaque (Macaca mulatta) is widely maintained in captive populations for translational research, reliable molecular tools for monitoring their physiological status remain limited—a gap that directly affects population management and health monitoring. In particular, no validated panel of housekeeping genes (HKGs) is currently available for expression analysis at the mRNA level in peripheral blood of the species. (2) Methods: Peripheral blood samples from healthy male rhesus macaques aged 4–7 years were used. The expression stability of candidate HKGs was evaluated using RefFinder based on cycle threshold (Ct) values obtained from real-time PCR. (3) Results: A panel of 29 candidate HKGs was compiled. After multistage bioinformatic and experimental selection, 22 genes were excluded. Expression stability analysis of the remaining seven genes (AHSA1, B4GALT3, CYB5R1, HPCAL1, PSMD6, SSR2, and VPS72) identified B4GALT3 and PSMD6 as the most stable. (4) Conclusions: This study presents the experimentally validated set of HKGs for expression studies in Macaca mulatta. Based on the results of expression stability analysis, the B4GALT3 and PSMD6 genes can be recommended as reference genes for studying changes in gene expression in peripheral blood. Full article

Blood-based biomarkers offer a promising “biochemical imaging” approach for acute ischemic stroke (AIS) management, providing objective and accessible tools to complement conventional neuroimaging. This narrative review synthesizes recent advances in biomarkers derived from multiple neurovascular unit (NVU) compartments, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neuron-specific enolase (NSE), neurofilament light chain (NfL), matrix metalloproteinase-9 (MMP-9), Claudin-5, Occludin, brain-derived neurotrophic factor (BDNF), interleukin-33 (IL-33), tumor necrosis factor-alpha (TNF-alpha), PARK7/DJ-1, glycogen phosphorylase BB (GP-BB), and circulating microRNAs. We focus on their stage-specific clinical utility across three scenarios: (1) ultra-early differentiation between ischemic stroke and intracerebral hemorrhage in prehospital and emergency settings; (2) dynamic prediction and monitoring of hemorrhagic transformation after reperfusion therapies; and (3) assessment of infarct burden, neurorepair potential, and long-term functional outcomes. Despite their promise, clinical translation remains hindered by assay platform heterogeneity, lack of standardized cut-off values, limited cost-effectiveness data, and insufficient prospective validation adjusted for key covariates such as age and renal function. We further discuss multi-marker panel construction, including strategies to address biomarker collinearity and overfitting. Future directions emphasize stage-specific panels, point-of-care testing devices, and artificial intelligence algorithms to advance precision medicine in stroke care. Full article

Theranostics is a novel approach that integrates diagnostic and therapeutic efficacy on a single platform, holding great promise for precision medicine by enabling real-time monitoring of disease progression and therapeutic response. Despite significant advances, the successful development and delivery of theranostic systems are critically limited by multiple biological barriers present at systemic, tissue, cellular, anatomical, and immunological levels. These barriers restrict bioavailability, target accessibility, and therapeutic efficacy, while often increasing off-target accumulation and adverse effects. This review provides a comprehensive overview of the major biological barriers encountered in theranostic development, including physiological barriers such as plasma protein binding, renal clearance, and hepatic metabolism; anatomical barriers like endothelial linings, the blood–brain barrier (BBB), and the tumor microenvironment; cellular barriers involving membrane permeability, intracellular trafficking, and endo-lysosomal entrapment; and immunological barriers such as immune recognition, inflammatory responses, and complement activation. Special emphasis is placed on the BBB, highlighting its structural complexity, transport mechanisms, and strategies such as molecular Trojan-horse technology, receptor-mediated and adsorptive-mediated transcytosis, and nanocarrier-based approaches to enhance central nervous system delivery. The review further discusses targeted delivery challenges, including receptor heterogeneity and multidrug resistance, and critically evaluates current strategies to overcome these barriers through surface functionalization, stimuli-responsive systems, biomimetic carriers, and controlled-release mechanisms. Finally, recent advances, clinical challenges, and future perspectives—including personalized theranostics, artificial intelligence—assisted design, and next-generation barrier-penetrating systems—are explored. Overall, this review aims to provide a structured understanding of biological barriers in theranostics and highlight innovative approaches to improve their translational potential. Full article

Background: Candidemia remains a significant public health challenge, with increasing resistance. Contemporary post-pandemic data from high-complexity Latin American hospitals are scarce. Methods: A retrospective study (2022–2023) was conducted in adults with candidemia at a high-complexity Colombian university hospital. Species identification and susceptibility were analyzed using VITEK^® 2 and Clinical and Laboratory Standards Institute (CLSI) criteria. Survival was estimated using Kaplan–Meier analysis. Results: Of 3483 blood cultures, 109 episodes were identified. The incidence was 1.13/1000 admissions (5.96/1000 in the Intensive care unit—ICU). Species other than Candida albicans predominated (61.5%), mainly C. tropicalis (22.9%) and C. parapsilosis (22.0%). Alarmingly, 28.6% of C. parapsilosis isolates were resistant to fluconazole. Consultation with an infectious diseases service was performed in 72.5% of cases, with a significantly higher rate among survivors (p < 0.05). Overall mortality was 52.3%, while 30-day mortality reached 42.2%. ICU patients had a cumulative mortality rate of 50% by day 30. Conclusions: Post-pandemic candidemia shows shifting species and high resistance. Key priorities include expert infectious disease consultation to optimize outcomes in non-neutropenic patients and strengthening laboratory capacity for identification and susceptibility testing to monitor rising resistance and guide effective institutional antifungal policies. Full article

Background and Objectives: Right heart failure is a life-threatening complication of pulmonary hypertension (PH), with limited treatment options. Although recombinant human brain natriuretic peptide (rhBNP) is widely used in left heart failure, its effectiveness in right heart failure associated with varying groups of PH (Groups 1, 2, and 4) is unknown. Materials and Methods: 763 patients with varying groups of PH (PH Groups 1, 2, and 4) were enrolled and received both conventional therapy and rhBNP treatment. Therapeutic efficacy and adverse event incidence were evaluated among the PH groups. Results: Significant reductions in variables reflecting cardiac congestion, including NT-proBNP, total bilirubin, and body weight, were observed in all PH subgroups (all p < 0.001). The median percentage changes were −47% (IQR −76 to −24), −21% (IQR −33 to −1), and −3% (IQR −7 to −1), respectively. Alanine transaminase levels presented a decreasing trend (p < 0.001), whereas creatinine levels remained unchanged (p > 0.05), with consistent trends across PH subgroups. The hemodynamic response was heterogeneous, with marked decreases in the mean arterial pressure in Groups 1 and 4 (p < 0.001) but not in Group 2. Improvement in dyspnea and edema of the lower limbs was observed in 49.9% and 66.6% of cases, respectively. The overall incidence of adverse events was 0.66%, with 0.26% (2/763) being serious, all of which were in Group 1 PH. Conclusions: Findings from this exploratory analysis indicated that rhBNP treatment was associated with favorable changes in congestive status and clinical symptoms across different PH subgroups, as well as stable end-organ function. Of note, all patients received comprehensive conventional background therapy; thus, these improvements cannot be exclusively attributed to rhBNP alone. Given the observed hemodynamic fluctuations, close blood pressure monitoring should be considered throughout the treatment course, particularly for patients in Groups 1 and 4, and most notably for high-risk PAH patients (Group 1 PH). Full article

Introduction: Marine recreational fishing (MRF) is a socially, economically, and ecologically important activity. However, the absence of systematic monitoring and research in Portugal has limited a comprehensive understanding of the sector and its broader implications. Addressing these gaps is essential to support evidence-based and adaptive recreational fisheries management. Objective: This work aimed to improve understanding of marine recreational fishing in Portugal by integrating social and biological perspectives across national, regional, and local scales. Methodology: A multidisciplinary approach was applied. At the national scale, online questionnaire data were combined with licencing information and regional effort estimates to quantify fishing effort, catches, release rates, catch composition, and direct trip expenditures. The same survey framework was also used to identify recreational fisher profiles based on motivations, behaviours, fishing practices, and attitudes toward management. At the local scale, shore angling surveys conducted before the implementation of the Natural Marine Park of the Algarve Reef were used to estimate fishing activity and establish a baseline for future monitoring. From a biological perspective, field-based catch-and-release experiments were conducted to assess post-release mortality and physiological disturbance, using indicators such as mortality, condition, capture and handling variables, and blood biomarkers of stress and recovery. Results: The national estimates documented substantial fishing effort, catches, and direct expenditure, confirming the relevance of MRF in Portugal at both ecological and socio-economic levels. Portuguese recreational fishers were also shown to be heterogeneous in their motivations, behaviours, and practices, reinforcing the need for management approaches that reflect this diversity. At the local scale, shore angling estimates from the Natural Marine Park of the Algarve Reef provided an important pre-protection baseline for the now established Marine Protected Area, enabling future comparisons and long-term assessment of management effects. Biological experiments showed that recreational fishing can generate measurable physiological disturbance in fish, with post-release condition influenced by capture and handling factors. Among the variables examined, hook location emerged as particularly important, with deep-hooked fish showing greater impairment and higher mortality risk. Conclusions: Together, these findings show that improving recreational fisheries management in Portugal requires integrating social patterns, fishery magnitude, and biological responses to capture and release. Long-term monitoring programmes, combined with management approaches adapted to different fisher profiles and fishing contexts, are essential to support more effective and sustainable recreational fisheries governance. Full article

Objectives: This study investigated the relationship between interstitial and blood glucose concentrations following ingestion of carbohydrate-containing drinks differing in carbohydrate amount, osmolarity, and glycaemic index. Methods: Ten healthy adults (nine male; age: 22 ± 1 y; height: 177 ± 12 cm; weight: 75 ± 14 kg) completed a double-blind, randomised cross-over study with seven beverage trials varying in carbohydrate (CHO) characteristics. Blood samples were collected at rest and over two hours, while interstitial glucose ([iG]) was recorded using a continuous glucose monitor (Supersapiens, Atlanta, USA). Glycaemic metrics and mean absolute relative difference (MARD) were calculated for hypoglycaemic, euglycaemic, and hyperglycaemic ranges. Data were analysed using repeated-measures ANOVA with Bonferroni correction and paired t-tests (p ≤ 0.05). Results: Interstitial and blood glucose concentrations were similar at baseline but diverged post-ingestion. MARD varied by glucose rate and direction, exceeding 20% during rapid declines (>2 mg/dL/min), where [iG] underestimated [BG] by −7.3 ± 27.1 mg/dL. Accuracy was highest during stable glucose (MARD = 10.5 ± 8.6%). Carbohydrate amount and glycaemic index influenced peak glucose, whereas beverage concentration (5–20%) had minimal effect when CHO amount was fixed, though variation in CGM agreement appeared during post-peak declines. Conclusions: CGM tracked blood glucose overall but showed reduced accuracy during rapid falls or hypoglycaemia. Carbohydrate properties influenced glycaemic response but not sensor agreement when CHO load was constant. Glucose rate and direction of change are key considerations for interpreting CGM data in research and applied settings. Full article

Noninvasive light-based measurements have recently been suggested for monitoring fracture healing and for the development of smart implants. The aim of this study was to collect the first exploratory longitudinal in vivo data from human distal fibular fractures. In this prospective observational pilot study, blood flow, oxygen saturation, and relative hemoglobin were noninvasively measured by using combined laser Doppler and white-light spectroscopy at depths of 3 mm and 10 mm. In patients with fibular fractures, measurements were performed at 1–3 days, 2 weeks, 6 weeks, 3 months and 6 months after surgery. Patients with fibular nonunion and healthy control participants underwent a single measurement. Fourteen longitudinal fracture patients, a nonunion patient, and 42 controls were included. In the longitudinal fracture group, oxygen saturation at a depth of 10 mm significantly decreased from baseline to 2 weeks (p < 0.001) and remained at a low plateau significantly below healthy control levels throughout the 6-month period. Blood flow and relative hemoglobin levels did not longitudinally change but remained significantly elevated compared with controls (p < 0.001). A single nonunion case demonstrated a markedly low oxygen saturation value (8.3%) combined with increased blood flow. Fibular fractures treated with plate fixation exhibit a prolonged low-oxygen saturation plateau, in contrast to the rapid recovery observed in tibial shaft fractures, possibly due to differences in anatomy or healing mechanisms. The low oxygen saturation observed in the nonunion requires further investigation, as it may have prognostic potential. Full article

The present study evaluated the effects of the prepartum administration of immunotropic preparations on the growth performance, physiological status, and metabolic profile of calves. Sixty pregnant Holstein cows were divided into three groups (n = 20 each): the first experimental group received a single intramuscular injection of sodium nucleinate (5 mL), the second experimental group received a single intramuscular injection of Ribotan (5 mL), and the control group received saline solution. All treatments were administered 3–9 days before calving. The obtained calves were monitored until 60 days of age. Clinical, growth, hematological, and biochemical parameters were assessed at days 1, 10, 30, and 60. Calves from the treated cows showed improved neonatal adaptation, including faster development of standing posture and the suckling reflex. Body weight was significantly higher in experimental groups at 30 and 60 days (p ≤ 0.05), with consistently greater average daily gains. Blood analysis revealed increased total protein, albumin, and γ-globulin levels, indicating enhanced protein metabolism and immune status. In contrast, cortisol concentrations were lower in treated groups, reflecting reduced physiological stress. Multivariate (PCA) and correlation analyses confirmed strong associations between growth performance, metabolic activity, and immune indicators, and demonstrated clear separation between control and treated groups. Ribotan exhibited the most pronounced biological effect, while sodium nucleinate showed moderate but consistent improvements. In conclusion, prepartum immunotropic treatment of cows enhances early-life adaptation, metabolic efficiency, and growth performance of calves and may represent a practical strategy for improving calf rearing outcomes in dairy farming systems. Full article

Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA in blood, has emerged across multiple cancers as a minimally invasive precision biomarker to detect minimal residual disease (MRD); predict recurrence; and monitor treatment response. This review’s objective was to summarize recent advances in ctDNA as a tool for therapeutic decision-making in MCC, contextualized by findings in other malignancies. Methods: A comprehensive literature review was performed, focusing on studies published between 2016 and 2026 that evaluate ctDNA in MCC and other cancers. Key prospective trials, observational studies, and case reports were identified through PubMed and relevant conference proceedings. Data on ctDNA assay methods (tumor-informed vs. tumor-agnostic), clinical sensitivity, lead time for recurrence detection, and predictive value for therapy response were extracted and synthesized. Results: Across cancers such as colorectal, lung, and melanoma, ctDNA positivity after curative treatment predicts relapse months in advance of imaging and can guide adjuvant therapy decisions. In MCC, recent studies demonstrate that ctDNA levels correlate with MCC tumor burden and exhibit high sensitivity and specificity for clinically evident disease. Stage I-III MCC patients who were ctDNA-positive within four months of treatment had a 7.4-fold higher recurrence risk within the subsequent 12–18 months of follow-up. Serial ctDNA monitoring may enable earlier intervention in otherwise asymptomatic ctDNA-positive MCC cases, helping distinguish responders from non-responders. Conclusions: ctDNA is an emerging precision biomarker that offers significant prognostic and surveillance utility in MCC. It enables earlier detection of recurrence, potentially allowing treatment to begin before clinical disease manifests. It also helps stratify patients by risk and treatment response, informing personalized surveillance intensity and therapeutic choices. Integrating ctDNA monitoring into MCC management could improve outcomes by guiding timely interventions, although prospective trials are needed to confirm that ctDNA-guided decisions translate to improved patient survival. Formal cost-effectiveness analyses have not yet been conducted and represent an important area for future investigation. Full article

Excessive fluoride intake from drinking water remains a public health concern in geogenic high-fluoride regions, yet direct evidence linking environmental fluoride levels to internal exposure in remote high-altitude areas is limited. This study integrated environmental monitoring with human biomonitoring to assess fluoride exposure and health risks in the Taruo Lake region of the Tibetan Plateau. Surface water (n = 45 for Taruo Lake; n = 8 for its tributaries) and groundwater samples (n = 4) were collected and analyzed for fluoride concentrations, and blood ionic fluoride (BIF) levels were measured in 122 local residents (47 adults, 75 children). The results showed that fluoride concentrations in most surface water tributaries of Taruo Lake and groundwater sources were below China’s drinking water standard, whereas those in Taruo Lake exceeded this limit (routine monitoring mean 2.54 mg/L; multi-site mean 2.79 mg/L). BIF levels were significantly higher in adults (0.126 ± 0.041 mg/L) than in children (0.075 ± 0.032 mg/L) and showed a positive correlation with age (r = 0.533, p < 0.001). Notably, 23.4% of adults and 1.3% of children exceeded 0.15 mg/L, an empirical threshold typical for healthy populations in non-endemic areas. Based on the hazard quotient (HQ) model recommended by the US EPA, most drinking water sources posed acceptable non-carcinogenic risks (HQ < 1). In contrast, Taruo Lake water presented an elevated risk (HQ > 1) in 2024 primarily due to the regional geological background, and although not used for daily drinking, this finding offers an indicative reference for local water management and risk prevention. This preliminary monitoring and biomonitoring assessment provides baseline data for future studies and underscores the necessity of continuous surveillance and evaluation of total dietary fluoride intake to protect the health of this vulnerable high-altitude population. Full article

Adults with type 1 diabetes mellitus (T1DM) face elevated cardiovascular risk, and regular exercise is a key non-pharmacological mitigation strategy. However, safe prescription requires cardiovascular and glycemic monitoring, often unfeasible in real-world gyms. Low-cost psychophysiological tools (ratings of perceived exertion—RPE and enjoyment) may offer practical alternatives. This exploratory randomized crossover trial examined whether post-session RPE and enjoyment are associated with acute heart rate (HR) and capillary blood glucose (BG) responses to gym-based aerobic and resistance training. Twelve adults with T1DM (29.8 ± 7.8 years; HbA1c 7.7 ± 1.6%; LDL-c 119.5 ± 24.4 mg/dL) completed three ~30 min sessions: aerobic interval training (AE) and two resistance protocols (STA, STB). HR and BG were measured pre-, immediately post-, and 20 min post-exercise; RPE and enjoyment, post-session. Multiple linear regression, controlling for exercise session type, examined associations of RPE and enjoyment with resting HR, BG, and percentage of heart rate reserve (%HR). RPE was higher after STA and STB than AE (p < 0.001; η²p = 0.529), while enjoyment and %HR were similar across sessions. Neither variable was associated with resting HR or BG (all adjusted R² < 0; all p > 0.05). Controlling for exercise session type, RPE was a significant positive predictor of %HR (β = 0.44, p = 0.044), whereas enjoyment was not (β = −0.06, p = 0.719); however, the overall %HR model did not reach statistical significance (adjusted R² =0.119; F(4,31) = 2.183; p = 0.094). These exploratory findings suggest that RPE, but not enjoyment, may serve as a low-cost adjunct intensity marker to inform exercise prescription in adults with T1DM at elevated cardiovascular risk; however, replication in larger samples is needed before clinical recommendations can be drawn. Direct BG monitoring remains essential for safety. Full article