Search Results (577)

The present study examines the effect of viruses on forest insects depending on the virus dose. Two model approaches are used to quantify the effect of viruses on insect survival. Both approaches describe the processes of virus exposure to insects within the framework of the second-order phase transition model, which is well known in theoretical physics. The first approach examines the temporal dynamics of larval survival at a given dose of virus exposure. This dependence is characterized by the time–effect curve. In this case, the lethal time of exposure LT100 is the time required for the death of all larvae in the experiment at a given dose D of exposure. The second approach describes the relationship between the proportion q_r of larvae that survived a fixed time T_c after the start of the experiment and the dose D of virus exposure. This dependence is characterized by the dose–effect curve. The experiments tested the effect of two different viruses—nucleopolyhedrovirus (NPV) and cypovirus (CPV)—on such insect species as Lymantria dispar L., Manduca sexta L. and Loxostege sticticalis L. It was shown that the proposed models of second-order phase transitions very accurately (with coefficients of determination of the models close to R² = 0.95) describe experiments on studying the effect of different virus strains on insect survival. The proposed models turned out to be useful for assessing the effectiveness of different virus strains against insect pests. Since the parameters of the second-order “dose–time” and “dose–effect” phase transition models are related to each other, it is possible to reduce the number of measurements of virus–insect interaction due to the relationship between these parameters, and instead of n observations of insect dynamics over time depending on the dose of exposure, the basic parameters characterizing the “virus–insect” interactions can be accurately estimated using only one measurement. It appears that the proposed model can be used to calculate the effect of toxic agents on the population of victims for a wide variety of toxicant species and populations. A sharp reduction in the labor intensity of experiments to assess the toxicity of certain toxicants on animal populations will simplify and reduce the cost of testing the response of living objects to toxicants. Full article

Background: Fixed-dose combination medications (FDCs) are recognized methods of increasing adherence to polytherapy in chronic diseases. However, the role of FDCs in patients with benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) remains uncertain. We designed this study to assess persistence, adherence, and patient satisfaction with FDCs recently introduced to the Polish pharmaceutical market, which contain tamsulosin (an α1-adrenergic receptor antagonist) in combination with solifenacin (a muscarinic receptor antagonist) or dutasteride (a 5-α reductase inhibitor). Methods: The analysis included 50,435 men (67.8 ± 8.8 years old) managed by urologists for BPH-associated LUTS, who had been on combination therapies for at least 3 months. Two study visits, with an interval of 2.1 ± 1.4 months, were conducted between February and December 2024. Results: Single-component drugs (83.1%) were more common forms of therapy compared to FDCs (16.9%). ARAs (α1-adrenergic receptor antagonists) with 5-α reductase inhibitors comprised 70.2%, while ARAs with muscarinic receptor antagonists or β3-adrenergic agonists comprised 29.5%. Persistence with therapy across two visits was 82.0% for single-component drugs and 93.6% for FDCs (p < 0.001); OR = 1.31 (95% CI: 1.02–1.63). Similarly, adherence was better in patients treated with FDCs (96.6% vs. 91.0% at visit 1, p < 0.001; 99.3% vs. 97.9% at visit 2, p < 0.05). Patients prescribed FDCs were satisfied with therapy more often than those prescribed single-component drugs (62.6% and 76.8% vs. 50.6% and 67.5% at visits 1 and 2, respectively; p < 0.001). Conclusions: 1. Combination therapies are still more commonly administered as separate tablets than FDCs in patients with BPH-associated LUTS. 2. The use of FDCs increases short-term satisfaction and persistence with therapy, with a mild effect on adherence. Full article

Background: Drug combinations with complementary mechanisms of action are able to achieve effective analgesia at lower doses, thereby reducing the risk of adverse effects (AEs). This study evaluated the analgesic efficacy and tolerability of two fixed-dose combinations (FDCs) of ibuprofen/tramadol (IBU/TRA) compared with tramadol and a placebo. Methods: This multicenter, randomized, double-blind, dose-finding, pilot clinical trial compared IBU/TRA (400/37.5 mg and 400/75 mg) with 100 mg of tramadol and a placebo in patients with moderate-to-severe pain following dental surgery. The primary endpoints were pain intensity at 6 h (PI_6h) and the pain intensity difference from baseline to 6 h (PID_6h). PID_7h, the sum of pain intensity differences from baseline to 7 h (SPID_0–7h), pain relief (PAR_7h), total pain relief (TOTPAR_7h), the use of rescue medication and AEs were also assessed. Results: Seventy-two patients were randomized and evaluated. Both FDCs showed superiority over the placebo for PI_6h and PID_6h (p < 0.05) but were not significantly different from 100 mg of tramadol. The statistical superiority of FDCs over the placebo was observed for PID_7h, SPID_0–7h, PAR_7h and TOTPAR_7h. The percentage of patients receiving rescue medication was higher in the placebo (94.1%) and tramadol (52.6%) groups than the FDC groups (35.3% and 36.8% for 400/37.5 mg and 400/75 mg, respectively). A post hoc analysis showed that the FDCs had a superior analgesic efficacy to 100 mg of tramadol in the SPID_0–4h (p < 0.005). The incidence of AEs was comparable between treatment groups. Conclusions: Both FDCs of IBU/TRA provided superior analgesic efficacy compared to the placebo. We propose using SPID_0–4h as the preferred variable for evaluating the efficacy of this type of drug combination. Full article

Background/Objectives: Fixed-dose combination (FDC) antihypertensive medications containing olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide are widely used for the treatment of essential hypertension. Although effective, the use of racemic amlodipine, which contains both active S(−)-amlodipine and inactive R(+)-amlodipine, has been associated with dose-dependent adverse effects, such as peripheral edema. S-amlodipine, a pharmacologically active enantiomer, provides comparable antihypertensive efficacy at half the dose with a lower incidence of side effects. Methods: In this study, a modified FDC formulation was developed by replacing racemic amlodipine with S-amlodipine to enhance tolerability while maintaining therapeutic efficacy. Results: A bilayer tablet design was employed to minimize the formation of impurities and ensure formulation stability, which was confirmed under stress and accelerated conditions. In vitro dissolution testing demonstrated pharmaceutical equivalence with the marketed reference FDC, and an in vivo pharmacokinetic study confirmed bioequivalence. Conclusions: These results suggest that the newly developed S-amlodipine besylate-containing FDC tablet is a viable alternative to existing olmesartan/amlodipine/hydrochlorothiazide combinations, offering comparable efficacy and pharmacokinetic properties with the potential for improved safety and patient adherence in the management of hypertension. Full article

Background/Objectives: The aim of this study was to develop evaluation metrics for lower-limit vasopressor control, a strategy intended to prevent prolonged intraoperative hypotension under noninvasive blood pressure monitoring. Methods: Using general-purpose simulation software, we developed a blood pressure generation model with one-minute intervals and an automated vasopressor administration model with five-minute intervals. The latter delivered drugs according to predefined rules when systolic blood pressure (sBP) fell below a threshold. Four dosing strategies were constructed by combining bolus, repeated low-dose bolus, and continuous infusion approaches. Simulations were performed, and the following evaluation metrics were calculated: (1) proportion of time below threshold (PTBT), (2) mean value below threshold (MVBT), (3) average sBP, and (4) median performance error (MDPE) and median absolute performance error (MDAPE). Results: PTBT and MVBT analyses showed that incorporating continuous infusion reduced both the duration and severity of hypotension. Moreover, adding MVBT to the average sBP after subtracting the threshold quantified the extent to which sBP exceeded the threshold on average. In contrast, MDPE and MDAPE varied substantially with the assumed target pressure, highlighting their limitations in evaluating lower-limit control without a fixed target. Conclusions: For lower-limit control, metrics such as PTBT, MVBT, and average sBP offer useful insights into control stability and hypotension avoidance, whereas MDPE and MDAPE may be unsuitable for quantitative assessment when the primary goal is to exceed a threshold rather than achieve a fixed target pressure. Full article

Background/Objectives: As global aging accelerates, prevalence of mild cognitive impairment (MCI) continues to rise, challenging healthcare systems and diminishing older adults’ quality of life. There is great interest in better understanding the neuroprotective/anti-inflammatory properties of omega-3 polyunsaturated fatty acids but the results from many published studies in humans come to different conclusions. This review aims to clarify the efficacy of n-3 fatty acids as a preventive or therapeutic strategy for cognitive health and to inform future clinical recommendations within aging populations. Methods: Following PRISMA guidelines and a registered PROSPERO protocol, we reviewed systematic reviews (SRs) from 2014 to 2024 assessing exclusive n-3 fatty acid supplementation and cognitive outcomes via MMSE. Data were extracted on intervention details and cognitive scores. Meta-analyses used fixed and random-effects models, with Hedges’ estimating overall impact. Quality was assessed using AMSTAR-2, and statistical analyses were performed (SPSS 28). Results: A total of nine SRs incorporating 14 RCTs were included, representing 26,881 participants aged 40 years or older. The pooled random-effects meta-analysis showed a statistically significant but modest improvement in MMSE scores (effect size: 0.16; 95% CI: 0.01–0.32). Heterogeneity was moderate (I² = 42.8%), and no publication bias was detected. Further analyses revealed no significant associations between treatment duration or dosage and cognitive outcomes, suggesting a threshold effect rather than a dose–response relationship. Conclusions: These findings support n3-PUFA supplementation as a complementary approach to lifestyle-based strategies for cognitive health, including diet, physical activity, sleep optimization, and cognitive training. While benefits appear modest, consistent effects across studies warrant further high-quality research and well-designed studies to strengthen clinical recommendations. Full article

Background: The insulin tolerance test (ITT) and glucagon stimulation test (GST) are commonly used for assessment of anterior pituitary function, but there are few direct comparisons of these tests, i.e., where both tests were performed on the same individuals. Methods: We designed a cross-over study, where we compared concentrations of glucose, cortisol, and GH during ITT and standard fixed-dose GST in 19 subjects (five males), with a mean age of 33.8 years (range 19–60) and a mean BMI of 27.8 kg/m² (range 16.5–47.6). Results: Optimal fall in glucose concentrations during ITT (i.e., <40 mg/dL) was obtained in all study participants. During ITT we obtained lower minimal glucose concentrations (glucose nadir), i.e., 29.7 ± 7.67 mg/dL at 30 min of ITT, than during GST, i.e., 73.6 ± 9.67 mg/dL at 180 min of GST, p < 0.01. In contrast, glucose fluctuations (ΔGlucose) were higher during GST (77.8 ± 22.6 mg/dL versus 56.7 ± 10.9 mg/dL, p = 0.002, for GST and ITT, respectively). There was, however, no difference in degree of stimulation of either cortisol or GH release during both tests: ΔCortisol 9.28 ± 3.79 µg/dL for GST versus 8.49 ± 3.46 µg/dL for ITT, p = 0.4, and ΔGH 10.23 ± 10.36 ng/mL for GST versus 10.52 ± 9.67 ng/mL for ITT, p = 1.0. Conclusions: Although hypoglycaemia is not observed during GST in contrast to ITT, it appears that both tests lead to similar increments in cortisol and growth hormone secretion. We, therefore, conclude that GST should not be automatically considered as an “inferior” option in comparison to ITT. Full article

Delta-9-Tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid and structural analog of THC, exhibits a dual pharmacological profile as a CB1 receptor agonist/antagonist and a partial CB2 agonist. This study evaluated the effects of THCV in a THC discrimination model in rats. Male Sprague-Dawley rats (n = 16, 300–340 g, PND60) were trained under a fixed ratio 20 (FR20) schedule to discriminate THC (3 mg/kg) from vehicle. Substitution tests were conducted with THC (0.325–3 mg/kg), THCV (0.75–6 mg/kg), and THC-THCV combinations. THCV produced an inverted U-shaped substitution curve, significantly differing from vehicle (p = 0.008). At 3 mg/kg, THCV partially substituted for THC (54.6% ± 17.82, p = 0.003). Response rate significantly increased during the substitution test with 3 mg/kg of THCV (p = 0.042). THCV (6 mg/kg) reversed THC (0.75 mg/kg)-induced responding (p = 0.040), with no significant change in response rate (p = 0.247). However, THCV combined with THC (1.5 mg/kg) affected response rates (p = 0.012), with 6 mg/kg significantly reducing rates vs. 3 mg/kg (p = 0.013). Blood THC and 11-OH-THC levels remained unchanged when THC was combined with THCV. The findings suggest THCV can partially mimic or block THC’s discriminative effects in a dose-dependent manner, possibly acting as a partial CB1 agonist. Full article

The sustainable intensification of forage production in Mediterranean climates requires technological solutions that optimize the use of agricultural inputs. This study aimed to evaluate the performance of proximal optical sensors in recommending and monitoring variable rate nitrogen fertilization in winter forage crops cultivated under Mediterranean conditions. A handheld multispectral active sensor (HMA), a multispectral camera on an unmanned aircraft vehicle (UAV), and one passive on-the-go sensor (OTG) were used to generate real-time nitrogen (N) application prescriptions. The sensors were assessed for their correlation with agronomic parameters such as plant fresh matter (PFM), plant dry matter (PDM), plant N content (PNC), crude protein (CP) in%, crude protein yield (CPyield) per unit of area, and N uptake (NUp). The real-time N fertilization stood out by promoting a 15.23% reduction in the total N fertilizer applied compared to a usual farmer-fixed dose of 150 kg ha⁻¹, saving 22.90 kg ha⁻¹ without compromising crop productivity. Additionally, NDVI_OTG showed moderate simple linear correlation with PFM (R² = 0.52), confirming its effectiveness in prescription based on vegetative vigor. UAV_II (NDVI after fertilization) showed even stronger correlations with CP (R² = 0.58), CPyield (R² = 0.53), and NUp (R² = 0.53), highlighting its sensitivity to physiological responses induced by N fertilization. Although the HMA sensor operates via point readings, it also proved effective, with significant correlations to NUp (R² = 0.55) and CPyield (R² = 0.53). It is concluded that integrating sensors enables both precise input prescription and efficient monitoring of plant physiological responses, fostering cost-effectiveness, sustainability, and improved agronomic efficiency. Full article

The objective of this research was to evaluate the effect of two doses of hCG (100 and 300 IU) administered at two different times after fixed-time artificial insemination (FTAI) on some response variables related to early fetal loss and total litter weight in goats during the reproductive transition period. Crossbred multiparous goats (n = 40) were subjected to an estrus induction protocol, subsequently inseminated, and randomly distributed into five experimental groups (n = 8): (1). G100-7, 100 IU hCG, 7 d post FTAI; (2). G100-14, 100 IU hCG, 14 days post FTAI; (3). G300-7, 300 IU hCG, 7 d post FTAI; (4). G300-14, 300 IU hCG, 14 days post FTAI; and (5). CONT, 0.5 mL of saline solution, 7 and 14 days post FTAI. The variables of corpus luteum area, embryonic implantation rate, embryonic efficiency index 1 and 2, conception rate, fertility rate, fecundity rate, fetal losses at days 30 and 45, total fetal losses, and the total weight of the litter favored G300-14. The use of hCG (300 IU) in the reproductive transition period is an effective reproductive strategy, reducing early fetal losses, improving embryonic efficiency, and increasing total litter weight, all of which are fundamental to the reproductive success of marginal goat production systems. Full article

Sludge dewatering remains a resource-intensive process, often constrained by high residual moisture content and inefficient chemical conditioning. Conventional systems typically rely on fixed polymer dosages and predetermined filtration pressures, which are unable to respond to variations in sludge characteristics, resulting in inconsistent and suboptimal performance. In this study, a real-time control system for municipal wastewater sludge dewatering was developed to dynamically regulate coagulant dosing and filtration pressure based on continuous monitoring of critical sludge parameters, including total solids (TS), viscosity, sludge temperature, and pH change following coagulant addition. The control logic, derived from empirical correlations between sludge dewaterability metrics such as time-to-filter (TTF) and capillary suction time (CST) and operational variables, enables adaptive adjustment of polyoxyethylene alkyl ether (POAE) injection and pressing conditions. Implementation of this system achieved a final cake moisture content of approximately 63% after 60 min of filtration, substantially lower than the ~84% moisture observed under static conditions. Real-time flux feedback facilitated timely pressure escalation (from 15 to 20 bar to 25–30 bar), improving water removal efficiency while avoiding premature cake blinding. The pH drop (~0.7 units) post-polymer addition served as a practical indicator of adequate flocculation, supporting dose optimization and minimizing chemical waste. The proposed system demonstrated enhanced dewatering performance, reduced polymer consumption, and greater operational robustness compared to conventional approaches. These findings highlight the potential of integrated sensor-based control to advance sludge treatment technologies by promoting smarter, adaptive, and resource-efficient dewatering operations. Full article

Introduction: Anemia, characterized by a reduction in hemoglobin concentration, is a widespread health concern globally, impacting individuals across various demographics. Iron deficiency, often compounded by inadequate folic acid levels, is a primary driver. This review aims to consolidate current evidence and offer a practical recommendation regarding the role of folic acid 1 mg + iron (ferrous sulfate) 90 mg supplementation in both preventing and treating anemia. Objective: We aimed to provide a comprehensive review and recommendation regarding the use of folic acid 1 mg + iron (ferrous sulfate) 90 mg supplementation in the prevention and treatment of anemia in adults, based on current evidence and clinical experience. Methods: A thorough literature review was conducted, encompassing studies, guidelines, and meta-analyses related to iron deficiency, anemia, and folic acid supplementation. This review incorporated data from sources such as the World Health Organization (WHO), the European Hematology Association (EHA), and Cochrane Database. Clinical experience of the authors was also taken into account. Results: Anemia, a prevalent hematological condition, affects a significant portion of the global population. The risk factors for iron deficiency and iron deficiency anemia include age, menstruation, pregnancy, dietary restrictions, chronic diseases, and inflammatory conditions. Accurate diagnosis of anemia involves reticulocyte count, morphological classification, and identification of the underlying etiology. Oral iron salts, particularly ferrous sulfate, are the first-line treatment for uncomplicated iron deficiency anemia, with lower doses or alternate-day dosing improving tolerability. Adequate folic acid availability is crucial for erythropoiesis, and supplementation is safe and enhances treatment response, especially in mixed deficiency anemia. A fixed-dose combination of folic acid 1 mg + iron (ferrous sulfate) 90 mg is effective and well-tolerated for the treatment of iron deficiency anemia, mixed nutritional anemia, and iron deficiency without anemia in adults. Conclusions: Based on extensive scientific evidence and clinical experience, the combination of folic acid 1 mg + iron (ferrous sulfate) 90 mg is a valuable therapeutic option for the prevention and treatment of anemia. This combination should be indicated for iron and folic acid deficiency during pregnancy, lactation, and the postpartum period and for the prophylaxis and treatment of anemia during pregnancy and in adults in general. This approach enables correction of folate deficiencies, optimizing treatment response and ensuring sufficient folic acid levels, particularly in cases of incomplete adherence or missed doses, and is critical during pregnancy to minimize the risk of neural tube defects. Full article

Background and Clinical Significance: Cocaine use disorder (CUD) is characterized by recurrent, cue-triggered and intrusive urges to use cocaine (craving), compulsive drug-seeking despite adverse consequences, and impaired control over intake, often co-occurring with excess weight and hedonic overeating. A dual-target rationale supports the fixed-dose naltrexone–bupropion (NB) combination: μ-opioid receptor (MOR) antagonism may mitigate opioid-facilitated mesolimbic reinforcement, while bupropion’s catecholaminergic effects and POMC activation support satiety and weight loss. Case Presentation: We describe a case study from an Italian outpatient setting of a 35-year-old man with a 10-year history of CUD, multiple failed detoxifications, and class I obesity (body mass index [BMI] 31 kg/m²) who initiated fixed-dose NB and was followed for 12 weeks under routine care. NB was associated with progressive attenuation of cue-reactive cocaine craving and improved appetite control, alongside clinically meaningful weight reduction, without psychiatric destabilization or emergent safety concerns; medication adherence remained stable. The patient maintained abstinence throughout follow-up and reported improved psychosocial functioning. Quantitatively, CCQ-B scores decreased from 7.2 at baseline to 2.1 at Week 12 (≈70% reduction), while BMI decreased from 31.0 to 25.5 kg/m² (≈−17.7%), with clinically meaningful weight loss and stable adherence. Conclusions: This case study supports the mechanistic rationale that dual NB therapy can simultaneously attenuate cocaine craving and facilitate weight control, addressing two clinically relevant targets in CUD. Although evidence for NB in CUD remains limited and mixed across stimulant populations, this observation highlights a plausible, testable therapeutic hypothesis that integrates mesolimbic and hypothalamic pathways and may inform the design of controlled trials in patients with co-occurring CUD and obesity. Full article

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article

Background: While disparities in vaccine uptake have been well documented, few studies have evaluated the impact of local vaccine programs on COVID-19 outcomes, namely cases, hospitalizations, and deaths. Objectives: Evaluate the impact of COVID-19 vaccine doses coordinated by the Louisville Metro Department of Public Health and Wellness (LMPHW) on COVID-19 outcomes by race across ZIP codes from December 2020 to May 2022 in Jefferson County, Kentucky. Methods: Fixed-effects longitudinal models with ZIP codes as ecological time-series units were estimated to measure the association between COVID-19 vaccine doses and outcomes with time lags of one week, two weeks, three weeks, four weeks, and one month. Models were adjusted for time (week or month of the year) and its interaction with ZIP code. Results: In the one-week lag model, significant negative associations were observed between LMPHW-coordinated vaccine doses and COVID-19 outcomes, indicating reductions of 11.6 cases, 0.4 hospitalizations, and 0.3 deaths per 100 doses administered. Vaccine doses were consistently associated with fewer deaths among White residents across all lags, with an average reduction of 0.2 deaths per 100 doses. No significant associations were found for Black residents. Temporal trends also indicated declines in COVID-19 outcomes when LMPHW’s vaccine administration program peaked, between March and May 2021. Conclusions: Timely uptake of COVID-19 vaccines remains critical in avoiding severe outcomes, especially with emerging variants. Racial disparities in vaccine–outcome associations emphasize the potential need for equitable, community-driven vaccine campaigns to improve population health outcomes. Full article