Search Results (651)

Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether the serum concentration of thyroid hormones changes over time during CVVHDF. Methods: This was a prospective observational trial that included 30 patients treated in an ICU. All patients developed acute kidney injury (AKI) and had clinical indications for implementation of CVVHDF. Blood samples were collected before initiation of CVVHDF and at 1, 2, 3, 6, 9 and 12 days after. The last sample was collected three days after CVVHDF withdrawal. Thyroid function was evaluated by determining the serum concentration of TSH, thyrotropin-releasing hormone (TRH), free triiodothyronine (fT₃), free thyroxine (fT₄), total triiodothyronine (tT₃), total thyroxine (tT₄) and reverse triiodothyronine (rT₃). We additionally calculated the total activity of peripheral deiodinases (G_D) using a mathematical model. Results: TRH and TSH levels remained mostly within normal ranges. fT4 and tT4 were in normal range or slightly below. In contrast, fT3 and tT3 were undetectably low in most patients throughout. Reverse T3 levels remained within normal limits. There were no statistically significant changes in any thyroid hormone levels over the CVVHDF treatment period. The calculated peripheral G_D activity was lower than normal, but importantly, it did not change significantly over time. Conclusions: Thyroid hormones are not lost due to hemodiafiltration. Decreased deiodinases activity is responsible for alterations in serum concentrations of thyroid hormones in patients during CVVHDF. Full article

This article examines the concept of ming 命 (mandate/command or fate/destiny) in the Analects, Mencius, and Zhuangzi, exploring its relationship to tian 天 (Heaven). Across these works, ming retains an intrinsic connection to tian—an inviolable cosmic force beyond human control. All three texts exhibit profound reverence and submission to tian, acknowledging the boundary between human control and cosmic inevitability, yet, at the same time, advocating active alignment with tian’s ordained patterns. In the Analects, a central tension emerges between tian’s teleological purpose—centered on preserving human culture and ethical cultivation—and the seemingly arbitrary fluctuations of individual fate, particularly regarding lifespan and personal fulfillment. This tension persists in the Mencius, articulated as a conflict between the political disorder of Mencius’ contemporary era and tian’s normative moral order. The Zhuangzi, by contrast, resolves this tension through advocating for withdrawal from the political life, as well as a radical reinterpretation of tian. Stripping tian off the Confucian moral–cultural imperatives, the text deconstructs dichotomies like life and death, championing inner equanimity via flowing with the cosmic transformation. Full article

This study investigates ground deformations in the southeastern Po Plain (northern Italy), focusing on the Bologna area—a densely populated region affected by natural and anthropogenic subsidence. Ground deformations in the area result from geological processes (e.g., sediment compaction and tectonic activity) and human activities (e.g., ground water production and underground gas storage—UGS). We apply a multidisciplinary approach integrating subsurface geology, ground water production, advanced differential interferometry synthetic aperture radar—DInSAR, gas storage data, and land use information to characterize and analyze the spatial and temporal variations in vertical ground deformations. Seasonal and trend decomposition using loess (STL) and cluster analysis techniques are applied to historical DInSAR vertical time series, targeting three representatives areas close to the city of Bologna. The main contribution of the study is the attempt to correlate the lateral extension of ground water bodies with seasonal ground deformations and water production data; the results are validated via knowledge of the geological characteristics of the uppermost part of the Po Plain area. Distinct seasonal patterns are identified and correlated with ground water production withdrawal and UGS operations. The results highlight the influence of superficial aquifer characteristics—particularly the geometry, lateral extent, and hydraulic properties of sedimentary bodies—on the ground movements behavior. This case study outlines an effective multidisciplinary approach for subsidence characterization providing critical insights for risk assessment and mitigation strategies, relevant for the future development of CO₂ and hydrogen storage in depleted reservoirs and saline aquifers. Full article

In medical research, random censoring often occurs due to unforeseen subject withdrawals, whereas progressive censoring is intentionally applied to minimize time and resource requirements during experimentation. This work focuses on estimating the parameters of a two-parameter exponential distribution under a progressive Type-II random censoring scheme, which integrates both censoring strategies. The use of symmetric properties in failure and censoring time models, arising from a shared location parameter, facilitates a balanced and robust inferential framework. This symmetry ensures interpretational clarity and enhances the tractability of both frequentist and Bayesian methods. Maximum likelihood estimators (MLEs) are obtained, along with asymptotic confidence intervals. A Bayesian approach is also introduced, utilizing inverse gamma priors, and Gibbs sampling is implemented to derive Bayesian estimates. The effectiveness of the proposed methodologies was assessed through extensive Monte Carlo simulations and demonstrated using an actual dataset. Full article

Antibiotic residues in poultry pose health and resistance risks, necessitating breed-specific WDTs. In this study, the residue elimination patterns of seven antibiotics in Taihang chicken tissues under free-range conditions were studied and the appropriate WDT was formulated. A total of 240 healthy Taihang chickens aged 100 days were randomly divided into 8 groups, each comprising 30 chickens. Chickens in groups 1 to 7 were administered oxytetracycline, chlortetracycline, erythromycin, tylosin, tylvalosin, lincomycin, and tiamulin, respectively. Regarding the administration method, we adopted the highest dose and maximum course of treatment recommended by the Veterinary Pharmacopoeia of the People’s Republic of China. Group 8 served as the control group. Muscle, sebum, liver, and kidney samples were collected at 4 h, 1 d, 2 d, 3 d, 5 d, 7 d, 10 d, 13 d, and 16 d after drug withdrawal. Our results demonstrated that the drug residues after drug withdrawal gradually decreased with the increase in drug withdrawal days, and the elimination rate in the early stage of drug withdrawal was significantly faster than that in the later stage. At 4 h after drug withdrawal, the drug residues in various tissues reached their highest values. In most cases, the drug concentrations in the kidney and liver were higher than those in the muscles and sebum; however, some drugs also exhibited concentration peaks in the sebum. On the first day of drug withdrawal, the amount of residues in various tissues decreased rapidly. In general, the elimination rate of various drugs in the muscles, liver, and kidneys is faster but slower in the sebum. Based on the WDT calculation software WT1.4, the recommended WDTs for oxytetracycline, chlortetracycline, erythromycin, tylosin, tylvalosin, lincomycin, and tiamulin chickens are 4 d, 5 d, 11 d, 8 d, 13 d, 13 d, and 7 d, respectively. These findings support food safety and industry development. Full article

Four entire male sugar gliders (Petaurus breviceps) belonging to the same colony were presented for elective orchiectomy. After clinical examination, dexmedetomidine (120 μg/kg) in combination with ketamine (5 mg/kg) were administered subcutaneously (SC). Once righting and pedal withdrawal reflexes were lost, ringer lactate solution, enrofloxacin and meloxicam were administered SC and a bilateral intratesticular block with lidocaine 0.25% was performed. Heart, respiratory rates and pulse oximetry values were recorded every minute. Onset of sedation, additional use of isoflurane, duration of anaesthesia, duration of surgery, time of recovery after atipamezole administration, quality of recovery and time of food intake were recorded. Postoperative assessment (posture, level of activity, vocalisation, response to manipulation, attention to the surgical wound) was performed hourly until discharge, five hours after surgery. Dexmedetomidine in combination with ketamine provided adequate short-lasting anaesthesia for castration in 3 out of 4 sugar gliders. One sugar glider needed additional isoflurane administration to perform orchiectomy. No perioperative additional analgesia was needed in any sugar glider. Full article

Brain-derived neurotrophic factor (BDNF) is associated with nicotine use behaviours, the intensity of nicotine cravings, and the experience of withdrawal symptoms. Given the established influence of sex, brain-derived neurotrophic factor variants, personality traits and anxiety levels on nicotine use, this study aimed to conduct a comprehensive association analysis of these factors within a cohort of women who use nicotine. The study included 239 female participants: 112 cigarette users (mean age = 29.19, SD = 13.18) and 127 never-smokers (mean age = 28.1, SD =10.65). Study participants were examined using the NEO Five-Factor Inventory and the State–Trait Anxiety Inventory. Genotyping of rs6265, rs10767664, and rs2030323 was performed by real-time PCR using an oligonucleotide assay. We did not observe significant differences in the distribution of either genotype or allele of rs6265, rs10767664 and rs2030323 between groups. However, compared to the never-smokers, cigarette users scored significantly lower on the Agreeableness (5.446 vs. 6.315; p = 0.005767; d_Cohen’s = 0.363; η² = 0.032) and the Conscientiousness (5.571 vs. 6.882; p = 0.000012; d_Cohen’s = 0.591; η²= 0.08) scales. There was significant linkage disequilibrium between all three analysed polymorphic variants—between rs6265 and rs10767664 (D′ = 0.9994962; p < 2.2204 × 10⁻¹⁶), between rs6265 and rs2030323 (D′ = 0.9994935; p < 2.2204 × 10⁻¹⁶) and between rs10767664 and rs20330323 (D′ = 0.9838157; p < 2.2204 × 10⁻¹⁶), but the haplotype association analysis revealed no significant differences. While our study did not reveal an association between the investigated brain-derived neurotrophic factor polymorphisms (rs6265, rs10767664 and rs2030323) and nicotine use, it is essential to acknowledge that nicotine dependence is a complex, multifactorial phenotype. Our study expands the current knowledge of BDNF ’s potential role in addictive behaviours by exploring the understudied variants (rs10767664 and rs2030323), offering a novel contribution to the field and paving the way for future research into their functional relevance in addiction-related phenotypes. The lower Agreeableness and Conscientiousness scores observed in women who use nicotine compared to never-smokers suggest that personality traits play a significant role in nicotine use in women. The observed relationship between personality traits and nicotine use lends support to the self-medication hypothesis, suggesting that some women may initiate or maintain nicotine use as a coping mechanism for stress and negative affect. Public health initiatives targeting women should consider personality and psychological risk factors in addition to biological risks. Full article

Background/Objectives: Immune-mediated necrotizing myopathy (IMNM) is a severe inflammatory myopathy marked by proximal muscle weakness, elevated creatine kinase (CK), and the presence of anti-HMGCR antibodies. Statin exposure is a recognized trigger for anti-HMGCR-positive IMNM, which may persist despite statin withdrawal. This pilot case series explores, for the first time, the use of bempedoic acid—a liver-specific lipid-lowering agent with minimal muscle toxicity—as an alternative to statins in these patients. Methods: We report 10 anti-HMGCR-antibody-positive IMNM patients (6 females, 4 males) previously on statins for primary prevention (8 on atorvastatin, 2 on simvastatin) without prior cardiovascular events. Statins were discontinued at myositis onset. All patients received prednisone and immunosuppressants (methotrexate in 7, mycophenolate in 3), plus bempedoic acid. Anti-HMGCR antibodies were measured using a chemiluminescence method. Results: Their mean anti-HMGCR antibody levels decreased significantly from 390.93 ± 275.22 to 220.89 ± 113.37 CU/L (p = 0.027) after 6 months of treatment. Their CK levels dropped from 1278.9 ± 769.39 to 315.1 ± 157.72 IU/L (p = 0.001), and aldolase dropped from 11.63 ± 2.18 to 6.61 ± 1.22 U/L (p = 0.0001). The mean LDL-C value was 96.1 ± 8.16 mg/dL. No disease recurrence was observed. Autoimmune panels were negative for other myositis-associated and/or -specific antibodies. Conclusions: Bempedoic acid appears to be a safe, effective, and cost-efficient lipid-lowering alternative in statin-intolerant IMNM patients. Larger studies are warranted to confirm its efficacy across different subgroups and to optimize dyslipidemia management in this setting. Full article

The objective of this study is to define groundwater management zones for a complex deformed and fissured Precambrian karst aquifer, which underlies one of the most important agricultural areas in the semi-arid region of Irecê, Bahia, Brazil. It is an unconfined aquifer, hundreds of meters thick, resulting from a large sequence of carbonates piled up by thrust faults during tectonic plate collisions. Groundwater recharge and flow in this aquifer are greatly influenced by karst features, through the high density of sinkholes and vertical wells. Over the past four decades, population and agricultural activities have increased in the region, resulting in unsustainable groundwater withdrawal and, at the same time, water quality degradation. Therefore, it is important to develop legal and environmental management strategies. This work proposes the division of the karst area into three well-defined management zones by mapping karst structures, land use, and urban occupation, as well as the concentrations of chloride and nitrate in the region’s groundwater. Zone 1 in the north possesses the lowest levels of karstification, anthropization, and contamination, while zone 2 in the central region has the highest levels and zone 3 in the south ranging in-between (except for stronger karstification). The delimitation of management zones will contribute to the development and implementation of optimized zone-specific groundwater preservation and restoration strategies. Full article

Droughts are predicted to intensify with climate change, posing a serious threat to global crop production. Increasing drought tolerance in plants requires an understanding of the underlying mechanisms. This study measured the physiological, phytohormonal and transcriptomic responses to drought in two apple rootstocks to identify drought ‘biomarkers’ and investigated whether the application of acibenzolar-S-methyl (ASM) to the roots could enhance drought tolerance. Two potted-plant trials were conducted on dwarfing (M9) and semi-dwarfing (CG202) apple rootstocks. In both trials, the response patterns in the roots and leaves were compared between irrigated and non-irrigated plants over a 14-day period. In trial 2, ASM was applied 14 days before and immediately before withdrawing irrigation. Drought induced significant decreases in transpiration, photosynthesis and stomatal conductance in both trials. This was accompanied by the accumulation of abscisic acid (ABA) metabolites and the upregulation of ABA pathway transcripts (CYP707A1/A2 and NCED3), a decrease in 12-oxophytodienoic acid (cis-OPDA) and the downregulation of ABA receptor genes (PYL4). The responses to drought were greater in the roots than the leaves, broadly similar across both rootstocks, but differed in strength and timing between the rootstocks. The application of ASM to the roots did not significantly affect the responsiveness to drought in either rootstock. The identified phytohormonal and transcriptomic biomarkers require further validation across a broader range of genotypes. Full article

Background/Objectives: Substance use disorders, particularly opioid addiction, continue to pose a major global health and toxicological challenge. Morphine dependence represents a significant problem in both clinical practice and preclinical research, particularly in modeling the pharmacodynamics of withdrawal. Rodent models remain indispensable for investigating the neurotoxicological effects of chronic opioid exposure and withdrawal. However, conventional behavioral assessments rely on manual observation, limiting objectivity, reproducibility, and scalability—critical constraints in modern drug toxicity evaluation. This study introduces MWB_Analyzer, an automated and high-throughput system designed to quantitatively and objectively assess morphine withdrawal behaviors in rats. The goal is to enhance toxicological assessments of CNS-active substances through robust, scalable behavioral phenotyping. Methods: MWB_Analyzer integrates optimized multi-angle video capture, real-time signal processing, and machine learning-driven behavioral classification. An improved YOLO-based architecture was developed for the accurate detection and categorization of withdrawal-associated behaviors in video frames, while a parallel pipeline processed audio signals. The system incorporates behavior-specific duration thresholds to isolate pharmacologically and toxicologically relevant behavioral events. Experimental animals were assigned to high-dose, low-dose, and control groups. Withdrawal was induced and monitored under standardized toxicological protocols. Results: MWB_Analyzer achieved over 95% reduction in redundant frame processing, markedly improving computational efficiency. It demonstrated high classification accuracy: >94% for video-based behaviors (93% on edge devices) and >92% for audio-based events. The use of behavioral thresholds enabled sensitive differentiation between dosage groups, revealing clear dose–response relationships and supporting its application in neuropharmacological and neurotoxicological profiling. Conclusions: MWB_Analyzer offers a robust, reproducible, and objective platform for the automated evaluation of opioid withdrawal syndromes in rodent models. It enhances throughput, precision, and standardization in addiction research. Importantly, this tool supports toxicological investigations of CNS drug effects, preclinical pharmacokinetic and pharmacodynamic evaluations, drug safety profiling, and regulatory assessment of novel opioid and CNS-active therapeutics. Full article

Background: Thymus numidicus Poiret. (Lamiaceae) is an endemic plant with well-known antibacterial properties. It has been largely used in traditional Algerian medicine. This study aimed to compare the chemical composition of essential oils (EOs) extracted from leaves and flowers using the gas chromatography–mass spectrometry method, as well as to investigate its analgesic and anti-inflammatory activities. Results: The EOs were rich in monoterpenes and classified as a thymol chemotype. In vivo experiments revealed that acute treatment with T. numidicus EO (20 and 80 mg/kg) significantly increased the thermal threshold on the hot-plate at all tested hours compared to the control animals (p < 0.001, respectively), while only the higher dose had a similar effect to the metamizole group at 2 and 3 h. In the mechanical stimulus test, both doses of the EO led to a late analgesic effect presented with increased paw withdrawal threshold only during the third hour compared to the control group (p < 0.05, respectively). In the plethysmometer test both doses of the EO dose-dependently reduced paw volume with nearly 10% and 15% compared to the control animals at all tested hours (p < 0.001, respectively), with a more pronounced volume reduction in the higher dose. In a neuropathic pain model, the EO (20 mg/kg and 80 mg/kg) dose-dependently increased the withdrawal latency time towards thermal stimuli and enhanced the paw withdrawal threshold in response to mechanical pressure at all tested hours compared to the CCI-group (p < 0.001, respectively). These findings demonstrate the potent analgesic and anti-inflammatory effects of T. numidicus EO in models of acute and neuropathic pain. Full article

Background: Polysubstance use, particularly combining opioids with stimulants such as cocaine, is rising among individuals with substance use disorders. This practice aims to balance cocaine’s stimulant effects with opioids’ sedative effect, potentially decreasing adverse outcomes. We hypothesized that concurrent exposure to cocaine and opioids would reduce the risk of neonatal opioid withdrawal syndrome (NOWS) compared to opioid use alone. Methods: This analysis draws from an ongoing prospective study of maternal substance use (SUD) at Regional One Health’s perinatal center in Memphis, TN, and included mothers and their infants born between 2018 and 2022. Maternal SUD was identified via screening questionnaires, urine toxicology, or umbilical cord tissue analysis. Participants were grouped into using (a) opioids with cocaine (OwC) and (b) opioids without cocaine (OwoC). Univariate and regression analyses were conducted to assess the risk of NOWS. Results: A total of 353 infants were born to 342 mothers, with 31% (110/353) of the infants born to women who used cocaine along with opioids. While maternal demographics were similar, the OwC group had significantly lower rates of prenatal care, chronic pain history, and MOUD enrollment (p = 0.03). Infants in the OwC group had significantly higher rates of NOWS (p < 0.01), longer hospital stays (p < 0.01), and 6.5 times greater odds of developing NOWS (p < 0.001). NOWS was associated with an average 15-day increase in the length of stay for term infants (95% CI: 11.2, 18.8; p < 0.001). Conclusions: Contrary to our hypothesis, our study highlights the significant impact of maternal cocaine use on the increased likelihood of NOWS and extended hospital stays for affected infants. Full article

The change in the socio-political formation of Russia from a socialist planned system to a capitalist market system significantly influenced agriculture and one of its components—arable land. The loss of the sustainability of land management for arable land led to a reduction in sown areas by 38% (from 119.7 to 74.7 million ha) and a synchronous drop in gross harvests of grain and leguminous crops by 48% (from 117 to 61 million tons). The situation stabilized in 2020, with a sowing area of 80.2 million ha and gross harvests of grain and leguminous crops of 120–150 million tons. This process was not formalized legally, and the official (legal) area of arable land decreased by only 8% from 132.8 to 122.3 million ha. Legal conflict arose for 35 million ha for unused arable land, for which there was no classification of its condition categories and no monitoring of the withdrawal time of the arable land from actual agricultural use. The aim of this study was to resolve the challenges in the method of retrospective monitoring of soil–land cover, which allowed for the achievement of the aims of the investigation—to elucidate the history of land use on arable lands from 1985 to 2025 with a time step of 5 years and to obtain a detailed classification of the arable lands’ abandonment degrees. It was also established that on most of the abandoned arable land, carbon sequestration occurs in the form of secondary forests. In the course of this work, it was shown that the reasons for the formation of an array of abandoned arable land and the stabilization of agricultural production turned out to be interrelated. The abandonment of arable land occurred proportionally to changes in the soil’s natural fertility and the degree of land degradation. Economically unprofitable lands spontaneously (without centralized planning) left the sowing zone. The efficiency of land use on the remaining lands has increased and has allowed for the mass application of modern farming systems (smart, precise, landscape-adaptive, differentiated, no-till, strip-till, etc.), which has further increased the profitability of crop production. The prospect of using abandoned lands as a carbon sequestration zone in areas of forest overgrowth has arisen. Full article

Florfenicol (FF) is one of the common antimicrobials used to control bacterial disease in shrimp aquaculture. This study aimed to determine the pharmacokinetics (PK) parameters of FF in white leg shrimp plasma, hepatopancreas and muscle as well as its residue depletion in shrimp muscle and the impact on shrimp hepatopancreas histology during and after FF medication. In the PK experiment, shrimp were fed once at 10 mg FF/kg body weight (bw) via oral in-feed administration to determine PK parameters in plasma, hepatopancreas and muscle. The maximum concentration (C_max) of 60.56 μg/L in plasma was observed after 1.77 h (T_max). In muscle, a C_max of 11.76 μg/kg was attained after 0.20 h, while in hepatopancreas, the C_max was higher (386.92 μg/kg) and was rapidly obtained (T_max = 0.19 h). The C_max values in shrimp plasma were below the minimum inhibitory concentration (MIC) against Vibrio parahaemolyticus, known to cause acute hepatopancreatic necrosis disease (AHPND) in shrimp. Therefore, it can be concluded that to ensure the effectiveness of this treatment, the dose should be higher than 10 mg FF/kg bw. FF depletion in white leg shrimp muscle and its histological impact on hepatopancreas were determined after feeding FF-medicated feed once-a-day or twice-a-day for 3 consecutive days with a dose of 10 mg FF/kg bw. The residues in shrimp muscle were rapidly eliminated and fell below the limit of quantification at 24 h after stopping medication. The withdrawal time of FF in shrimp muscle was 27.9 degree-days (2 days at 26.5 °C) according to the maximum residue limit (MRL) of 100 µg/kg set by the European Commission and Korean Ministry and when feeding FF twice-a-day for 3 days. The results from histological analysis showed that there was no negative effect on shrimp hepatopancreas after stopping medication in both once- and twice-a-day treatments. Full article