Search Results (3,562)

Background/Objectives: Typically, studies aiming to assess the ability of canine parvovirus (CPV) vaccines to immunise puppies with maternally derived antibody (MDA) are undertaken using group-housed puppies. Since live attenuated vaccine virus is invariably shed in the faeces, this can result in repeated oral re-exposure and puppies which failed to respond to the initial vaccination may respond instead to shed vaccine virus in the environment, thus artificially enhancing the efficacy of the vaccine. This problem can be avoided by adopting a pair-housed study design where one vaccinated pup is housed with one unvaccinated sentinel. Using this design, we examine the capability of four commercially available canine parvovirus vaccines to immunise MDA-positive pups. Methods: Thirty-four 6-week-old puppies born to vaccinated dams were divided into four vaccine groups with similar MDA ranges. Within each group puppies were paired based on matching MDA titres, and each pair was housed in separate biocontainment accommodation. In each pair, the pup with the highest MDA was vaccinated and the other left as an unvaccinated sentinel. All vaccinates were given a single dose of one of the vaccines. Vaccinates and sentinels were then bled every 2–4 days and CPV antibody was measured. Daily rectal swabs were also collected from all pups to identify any shed vaccinal CPV. Results: All the pups vaccinated with Nobivac DP PLUS seroconverted, with significantly higher antibody titres compared to the pups in other vaccine groups, all shed vaccine virus, and all bar one of the sentinel pups seroconverted. In the other groups, only vaccinated pups with lower levels of MDA seroconverted and shed vaccine virus but none of the sentinel pups seroconverted. Conclusions: Different canine parvovirus vaccines differ in their ability to replicate in and immunise puppies with MDA, the levels of which may vary widely between individuals. The shedding of vaccinal CPV is an important consideration when designing studies to demonstrate efficacy in MDA-positive puppies. Full article

Preeclampsia with severe features presents major anesthetic challenges, particularly in category 1 cesarean sections, in which rapid, safe, and hemodynamically stable induction is critical. Neuraxial techniques may be controversial due to neurological symptoms, making general anesthesia a viable option. However, traditional general anesthesia may exacerbate hypertension and increase maternal and fetal risks. Two primigravida patients with elevated blood pressure and neurological symptoms underwent category 1 cesarean delivery under TIVA-TCI with propofol, using the Marsh model. Hemodynamic stability, drug dosing, and maternal–neonatal outcomes were monitored. Sufentanil was administered for analgesia; neuromuscular blockade was achieved with rocuronium and reversed with sugammadex. No BIS or TOF monitoring was available. Both patients maintained stable hemodynamics and oxygenation throughout surgery. Intubation was successfully performed at an effect-site concentration of 3.5 µg/mL. Neonatal Apgar scores were within acceptable limits. No major complications occurred intraoperatively or postoperatively. TCI allowed individualized dosing and smooth emergence. TIVA-TCI with propofol appears to be a viable alternative to volatile-based general anesthesia in category 1 emergencies for cesarean sections for patients with preeclampsia with severe features, especially when neuraxial anesthesia is controversial. It offers hemodynamic stability and controlled depth of anesthesia, though its use requires experience and may not be optimal in cases requiring ultra-rapid induction. Full article

Background/Objectives: Pica, the compulsive ingestion of non-nutritive substances, has long been observed in patients with iron deficiency anemia (IDA). This behavior is particularly noted in adults, including pregnant women, and poses both diagnostic and management challenges. We conducted a review of studies from the past decade to evaluate the epidemiology and nature of pica in adult IDA patients and the outcome of various treatment strategies on anemia and pica behaviors. Methods: We searched PubMed, Scopus, and Cochrane Library for peer-reviewed articles (including observational studies, clinical trials, and reviews) published in English between 2015 and 2025. Inclusion criteria targeted studies of adult populations with IDA that reported on pica prevalence, characteristics, or treatment outcomes. We also reviewed clinical guidelines and meta-analyses on IDA treatment in adults for recommended management approaches. Results: Pica was found to be a prevalent symptom among individuals with IDA, but was readily treatable with appropriate iron deficiency treatment. Among treatment options, both oral and parenteral iron supplementation were found to be effective in resolving iron deficiency and pica. Choice of treatment depends on tolerance to oral iron, speed of resolution required, and comorbid conditions. Conclusions: Pica is closely intertwined with IDA; our review highlighted the prevalence of pica among individuals with IDA, which serves as both a clinical clue to underlying anemia and a potential source of complications. Crucially, the treatment of IDA is also effective for pica. We recommend oral iron therapy on alternate-day dosing as first-line therapy to minimize side effects, alongside dietary optimization. If IDA and pica are resistant to oral iron supplementation or oral iron cannot be tolerated, parenteral iron therapy can be considered. Full article

Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual cannabinoids affect fracture repair and spinal arthrodesis. Methods: PubMed, Web of Science and Scopus were searched from inception to 31 May 2025 with the terms “cannabinoid”, “CB1”, “CB2”, “spinal fusion”, “fracture”, “osteoblast” and “osteoclast”. Animal studies, in vitro experiments and clinical reports that reported bone outcomes were eligible. Results: CB2 signaling was uniformly osteogenic. CB2-knockout mice developed high-turnover osteoporosis, whereas CB2 agonists (HU-308, JWH-133, HU-433, JWH-015) restored trabecular volume, enhanced osteoblast activity and strengthened fracture callus. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with CB2 bias, accelerated early posterolateral fusion in rats and reduced the RANKL/OPG ratio without compromising final union. In contrast, sustained or high-dose Δ⁹-tetrahydrocannabinol (THC) activation of CB1 slowed chondrocyte hypertrophy, decreased mesenchymal-stromal-cell mineralization and correlated clinically with 6–10% lower bone-mineral density and a 1.8–3.6-fold higher pseudarthrosis or revision risk. Short-course or low-dose THC appeared skeletal neutral. Responses varied with sex, age and genetic background; no prospective trials defined safe perioperative dosing thresholds. Conclusions: CB2 activation and CBD consistently favor bone repair, whereas chronic high-THC exposure poses a modifiable risk for nonunion in spine surgery. Prospective, receptor-specific trials stratified by THC/CBD ratio, patient sex and ECS genotype are needed to establish evidence-based cannabinoid use in spinal fusion. Full article

This study investigated pesticide residues in 580 vegetable samples collected from markets in Serbia, encompassing potatoes, carrots, celery, radishes, horseradish, ginger, onions, and leeks. In total, 33 distinct pesticides were detected using validated HPLC-MS/MS and GC-MS/MS analytical methods. Multiple residues were identified in 19 samples, while 29 samples exceeded established maximum residue levels (MRLs). Acute and chronic dietary risks were assessed for both adults and children. Although individual hazard quotients (HQs) for adults and children remained below the threshold of concern (HQ < 1), the cumulative acute risk reached up to 63.1% of the Acute Reference Dose (ARfD) for children and 51.1% ARfD for adults, with ginger and celery posing the highest risks. Similarly, cumulative chronic risks remained below the safety threshold, with the Acceptable Daily Intake (ADI) percentages reaching a maximum of 5.9% ADI for adults and increased vulnerability of 11.0% ADI among children. Monte Carlo simulations were applied to account for variability and uncertainty in chronic exposure estimates. The hazard index (HI) results showed that adverse health effects for both population groups remained within acceptable safety limits (HI < 1), although higher susceptibility was observed in children. Sensitivity analysis identified body weight and vegetable consumption rates as the most influential factors affecting chronic risk variability. Full article

The use of chemical pesticides in agriculture has led to the development of resistant pest populations, posing a challenge to long-term pest management. This review aims to evaluate the scientific literature on the individual and combined use of baculoviruses with conventional chemical and biological insecticides to combat Plutella xylostella, Spodoptera exigua, and Spodoptera frugiperda in broccoli, tomato, and maize crops. Notable findings include that both individual Plutella xylostella nucleopolyhedrovirus (PxNPV) and the combination of Plutella xylostella granulovirus (PxGV) and azadirachtin at a low dose effectively control Plutella xylostella; both combinations of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) with emamectin benzoate and chlorfenapyr reduced resistance in Spodoptera exigua and increased the efficacy of the insecticides; and the combination of Spodoptera frugiperda nucleopolyhedrovirus (SfMNPV) and spinetoram is effective against Spodoptera frugiperda. Integrating baculoviruses into pest management strategies offers a promising approach to mitigate the adverse effects of chemical pesticides, such as resistance development, health risks, and environmental damage. However, there remains a broad spectrum of research opportunities regarding the use of baculoviruses in agriculture. Full article

Background/Objectives: Hyperlipidemia is a major risk factor for cardiovascular disease and atherosclerosis. Polyphenols found in polyphenol-rich extra virgin olive oil (EVOO) have been shown to possess strong antioxidant, anti-inflammatory, and cardioprotective properties. The present study aimed to assess the effects of two types of EVOO with different polyphenol content and dosages on the lipid profile of hyperlipidemic patients. Methods: In this single-blind, randomized clinical trial, 50 hyperlipidemic patients were randomized to receive either a higher-dose, lower-phenolic EVOO (414 mg/kg phenols, 20 g/day) or a lower-dose, higher-phenolic EVOO (1021 mg/kg phenols, 8 g/day), for a period of 4 weeks. These doses were selected to ensure equivalent daily polyphenol intake in both groups (~8.3 mg of total phenols/day), based on chemical analysis performed using NMR spectroscopy. The volumes used (8–20 g/day) reflect typical daily EVOO intake and were well tolerated by participants. A group of 20 healthy individuals, separated into two groups, also received the two types of EVOO, respectively, for the same duration. Primary endpoints included blood levels of total blood cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, lipoprotein-a (Lpa), and apolipoproteins A1 and B. Measurements were performed at baseline and at the end of the 4-week intervention. Linear mixed models were performed for the data analysis. Results: The higher-phenolic, lower-dose EVOO group showed a more favorable change in total blood cholesterol (p = 0.045) compared to the lower-phenolic, higher-dose group. EVOO intake was associated with a significant increase in HDL (p < 0.001) and reduction in Lp(a) (p = 0.040) among hyperlipidemic patients in comparison to healthy individuals. Conclusions: EVOO consumption significantly improved the lipid profile of hyperlipidemic patients. Higher-phenolic EVOO at lower dosages appears to be more effective in improving the lipid profile than lower-phenolic EVOO in higher dosages. 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

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

Greenhouses have positively impacted plant production by allowing the cultivation of different crops per year. However, the accumulation of agricultural plastics, potentially contaminated with agrochemicals, raises environmental concerns. This work evaluates the combined effect of Bordeaux mixture and low-density polyethylene (LDPE) microplastics (<5 mm) on the growth of lettuce (Lactuca sativa L.) and soil microbial communities. Different levels of Bordeaux mixture (0, 100 and 500 mg kg⁻¹), equivalent to Cu(II) concentrations (0, 17 and 83 mg kg⁻¹), LDPE microplastics (0, 1% and 5%) and their combination were selected. After 28 days of growth, biometric and photosynthetic parameters, Cu uptake, and soil microbial responses were evaluated. Plant germination and growth were not significantly affected by the combination of Cu and plastics. However, individual Cu treatments influenced root and shoot length and biomass. Chlorophyll and carotenoid concentrations increased with Cu addition, although the differences were not statistically significant. Phospholipid fatty acid (PLFA) analysis revealed a reduction in microbial biomass at the highest Cu dose, whereas LDPE alone showed limited effects and may reduce Cu bioavailability. These results suggest that even at the highest concentration added, Cu can act as a plant nutrient, while the combination of Cu–plastics showed varying effects on plant growth and soil microbial communities. Full article

Sarcopenia is a progressive age-related musculoskeletal disorder characterized by loss of muscle mass, strength, and physical performance, contributing to functional decline and increased risk of disability. Emerging evidence suggests that vitamin D (Vit D) plays a pivotal role in skeletal muscle physiology beyond its classical functions in bone metabolism. This review aims to critically analyze the relationship between serum Vit D levels and sarcopenia in older adults, focusing on pathophysiological mechanisms, diagnostic criteria, clinical evidence, and preventive strategies. An integrative narrative review of observational studies, randomized controlled trials, and meta-analyses published in the last decade was conducted. The analysis incorporated international diagnostic criteria for sarcopenia (EWGSOP2, AWGS, FNIH, IWGS), current guidelines for Vit D sufficiency, and molecular mechanisms related to Vit D receptor (VDR) signaling in muscle tissue. Low serum 25-hydroxyvitamin D levels are consistently associated with decreased muscle strength, reduced physical performance, and increased prevalence of sarcopenia. Although interventional trials using Vit D supplementation report variable results, benefits are more evident in individuals with baseline deficiency and when combined with protein intake and resistance training. Mechanistically, Vit D influences muscle health via genomic and non-genomic pathways, regulating calcium homeostasis, mitochondrial function, oxidative stress, and inflammatory signaling. Vit D deficiency represents a modifiable risk factor for sarcopenia and functional impairment in older adults. While current evidence supports its role in muscular health, future high-quality trials are needed to establish optimal serum thresholds and dosing strategies for prevention and treatment. An individualized, multimodal approach involving supplementation, exercise, and nutritional optimization appears most promising. Full article

Background: Despite decades of high childhood vaccination coverage, pertussis has re-emerged in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia. We aimed to describe the temporal, seasonal, and age-specific patterns of pertussis in AP Vojvodina and to analyze trends by vaccination status in order to highlight changes in epidemiology and potential gaps in vaccine-induced protection. Methods: We retrospectively analyzed 2796 pertussis cases reported between January 1997 and December 2024, examining temporal, seasonal, and age-specific trends, stratifying by vaccination status across four consecutive periods (1997–2003, 2004–2010, 2011–2017, and 2018–2024). Results: Throughout the 28-year period, after low and sporadic cases in the pre-2012 period, a dramatic rise was observed in 2014, 2017, and 2018, culminating in the highest annual number of reported cases in 2024 (1011 cases). Throughout this period, primary vaccination coverage with the DTwP/DTaP three-dose series ranged between 91% and 98%, while first booster coverage gradually declined from 98% in the early 2000s to 83% in 2024. Regarding seasonality, a sharp increase in cases began in 2012, peaking in November 2023 (>350 cases) and early 2024 (312 in January, 268 in February), with a seasonal shift from summer peaks in the 2011–2017 period to higher incidence rates during colder months more recently. Adolescents aged 10–14 years had the highest cumulative incidence (1149.4/100,000), followed by infants under 12 months (978.5/100,000), despite the latter representing fewer absolute cases. The proportion of pertussis in fully vaccinated individuals rose from 6.3% (1997–2003) to 49.7% (2018–2024). Conclusions: These findings suggest that booster immunization in adolescence and routine maternal vaccination during pregnancy could reduce transmission, particularly to infants. Enhanced surveillance and updated immunization policies are critical to mitigating future pertussis outbreaks. Full article

Background and Objectives: Emerging evidence indicates that individuals exposed to adverse childhood experiences (ACEs) face elevated risks for various chronic illnesses. However, the association between ACEs and osteoporosis risk remains underexplored, particularly regarding potential modifications by genetic susceptibility. This prospective cohort study aims to examine the relationship of ACEs with incident osteoporosis and investigate interactions with polygenic risk score (PRS). Materials and Methods: This study analyzed 124,789 UK Biobank participants initially free of osteoporosis. Cumulative ACE burden (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) was ascertained through validated questionnaires. Multivariable-adjusted Cox proportional hazards models assessed osteoporosis risk during a median follow-up of 12.8 years. Moderation analysis examined genetic susceptibility interactions using a standardized PRS incorporating osteoporosis-related SNPs. Results: Among 2474 incident osteoporosis cases, cumulative ACEs showed dose–response associations with osteoporosis risk (adjusted hazard ratio [HR]_{per one-unit increase} = 1.07, 95% confidence interval [CI] 1.04–1.11; high ACEs [≥3 types] vs. none: HR = 1.26, 1.10–1.43). Specifically, emotional neglect (HR = 1.14, 1.04–1.25), emotional abuse (HR = 1.14, 1.03–1.27), physical abuse (HR = 1.17, 1.05–1.30), and sexual abuse (HR = 1.15, 1.01–1.31) demonstrated comparable effect sizes. Sex-stratified analysis revealed stronger associations in women. Joint exposure to high ACEs/high PRS tripled osteoporosis risk (HR = 3.04, 2.46–3.76 vs. low ACEs/low PRS) although G × E interaction was nonsignificant (P-interaction = 0.10). Conclusions: These results suggest that ACEs conferred incremental osteoporosis risk independent of genetic predisposition. These findings support the inclusion of ACE screening in osteoporosis prevention strategies and highlight the need for targeted bone health interventions for youth exposed to ACEs. Full article

The management of adult spinal deformity (ASD) has evolved dramatically over the past century, transitioning from external bracing and in situ fusion to complex, technology-driven surgical interventions. This review traces the historical development of spinal deformity correction and highlights contemporary enabling technologies that are redefining the surgical landscape. Advances in stereoradiographic imaging now allow for precise, low-dose three-dimensional assessment of spinopelvic parameters and segmental bone density, facilitating individualized surgical planning. Robotic assistance and intraoperative navigation improve the accuracy and safety of instrumentation, while patient-specific rods and interbody implants enhance biomechanical conformity and alignment precision. Machine learning and predictive modeling tools have emerged as valuable adjuncts for risk stratification, surgical planning, and outcome forecasting. Minimally invasive deformity correction strategies, including anterior column realignment and circumferential minimally invasive surgery (cMIS), have demonstrated equivalent clinical and radiographic outcomes to traditional open surgery with reduced perioperative morbidity in select patients. Despite these advancements, complications such as proximal junctional kyphosis and failure remain prevalent. Adjunctive strategies—including ligamentous tethering, modified proximal fixation, and vertebral cement augmentation—offer promising preventive potential. Collectively, these innovations signal a paradigm shift toward precision spine surgery, characterized by data-informed decision-making, individualized construct design, and improved patient-centered outcomes in spinal deformity care. Full article

Pyridoxine-dependent epilepsy (PDE) represents a group of rare developmental and epileptic encephalopathies. The most common PDE is caused by biallelic pathogenic variants in ALDH7A1 (PDE-ALDH7A1; OMIM #266100), which encodes α-aminoadipate semialdehyde (α-AASA) dehydrogenase, a key enzyme in lysine catabolism. Affected individuals present with seizures unresponsive to conventional anticonvulsant medications but responsive to high-dose of pyridoxine (vitamin B6). Adjunctive lysine restriction and arginine supplementation have also shown potential in improving neurodevelopmental outcomes. Given the significant benefit of early intervention, PDE-ALDH7A1 is a strong candidate for newborn screening (NBS). However, traditional biomarkers are biochemically unstable at room temperature (α-AASA and piperideine-6-carboxylate) or lack sufficient specificity (pipecolate), limiting their utility for biomarker-based NBS. The recent identification of two novel and stable biomarkers, 2S,6S-/2S,6R-oxopropylpiperidine-2-carboxylate (2-OPP) and 6-oxo-pipecolate (oxo-PIP), offers renewed potential for biochemical NBS. We evaluated the feasibility of incorporating 2-OPP, oxo-PIP, and pipecolate into routine butylated FIA-MS/MS workflows used for biochemical NBS. A total of 9402 dried blood spots (DBS), including nine confirmed PDE-ALDH7A1 patients and 9393 anonymized controls were analyzed using a single multiplex assay. 2-OPP emerged as the most sensitive biomarker, identifying all PDE-ALDH7A1 patients with 100% sensitivity and a positive predictive value (PPV) of 18.4% using a threshold above the 99.5th percentile. Combining elevated 2-OPP (above the 99.5th percentile) with either pipecolate or oxo-PIP (above the 85.0th percentile) as secondary marker detected within the same multiplex FIA-MS/MS assay further improved the PPVs to 60% and 45%, respectively, while maintaining compatibility with butanol-derivatized method. Notably, increasing the 2-OPP threshold above the 99.89th percentile, in combination with either pipecolate or oxo-PIP above the 85.0th percentile resulted in both 100% sensitivity and 100% PPV. This study supports the strong potential of 2-OPP-based neonatal screening for PDE-ALDH7A1 within existing NBS infrastructures. The ability to multiplex 2-OPP, pipecolate and oxo-PIP within a single assay offers a robust, practical, high-throughput and cost-effective approach. These results support the inclusion of PDE-ALDH7A1 in existing biochemical NBS panels. Further prospective studies in larger cohorts are needed to refine cutoffs and confirm clinical performance. Full article