Search Results (80)

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

Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds synthesized showed affinities in radioligand competition binding assays in the nM and µM range at the opioid and NPFF receptors, respectively, and displayed substitution-dependent functional profiles in the [³⁵S]GTPγS functional assay. From six compounds screened in vivo for antinociception and ability to prevent NPFF-induced hyperalgesia in mouse warm water tail withdrawal tests, compound 22b produced dose-dependent MOR-mediated antinociception with an ED₅₀ value (and 95% confidence interval) of 6.88 (4.71–9.47) nmol, i.c.v., and also prevented NPFF-induced hyperalgesia. Meanwhile, 22b did not demonstrate the respiratory depression, hyperlocomotion, or impaired intestinal transit of morphine. Moreover, repeated treatment with 22b produced a 1.6-fold rightward shift in antinociceptive dose response, significantly less acute antinociceptive tolerance than morphine. Evaluated for microsomal stability in vitro and in vivo pharmacokinetic profile, 22b showed suitable microsomal stability paired in vivo with a large apparent volume of distribution and a clearance smaller than the hepatic flow in rats, suggesting no extra-hepatic metabolism. In conclusion, the present study confirms that dual-action opioid–NPFF ligands may offer therapeutic promise as analgesics with fewer liabilities of use. Full article

Background/Objectives: The vestibulo-respiratory reflex regulates the tension of the respiratory muscles, which prevents apneas and awakenings during sleep. This study aimed to determine whether functional deficits in the inner ear disturb sleep quality. Methods: We compared sleep parameters in patients with their first episode of acute inner ear deficit (Group A: sudden idiopathic vertigo attack, sudden sensorineural hearing loss), chronic functional inner ear impairment (Group B: chronic peripheral vertigo, permanent hearing loss), and in healthy individuals (Group C). Polygraphy recordings were performed twice, in Group A at the onset of acute otoneurological symptoms and the second time after their withdrawal with an interval of 1 to 13 days, in Group B after 1 to 6 days, and in Group C after 1 to 8 days. Results: In Group A during the symptomatic night, overall and central apnea-hypopnea indices were significantly higher and snoring time was longer. Group A also had higher central apnea-hypopnea index on the first night compared to healthy individuals. In chronic disorders, sleep recordings showed lower autonomic arousal index than in controls or symptomatic nights in Group A. Conclusions: These findings highlight the severity of sleep apnea indicators in Group A. Our results suggest that acute dysfunction of the inner ear substantially impacts central neuronal signaling responsible for regulating normal sleep-related breathing and leads to a deterioration in sleep quality in contrast to individuals with chronic inner ear impairments. It can also be assumed that people with chronic vertigo or hearing loss experience less interrupted sleep than healthy individuals. Full article

Sulfamethoxazole (SMZ), a widely used broad-spectrum antibiotic in aquaculture, lacks comprehensive research on its residual elimination kinetics in tilapia. This study investigated SMZ residue depletion, withdrawal periods, and dietary risks in 1-year-old GIFT tilapia (Genetically Improved Farmed Tilapia Oreochromis niloticus) weighing 500 ± 50 g, following oral gavage administration of a loading dose (200 mg/kg BW on day 1) and then 100 mg/kg BW daily for 6 more days, at 22 ± 2 °C. Tissue samples (plasma, muscle, skin, liver, kidney, gill, and remaining tissues) were collected from five fish per time point at intervals from 0.33 to 30 days post-administration, with SMZ residues quantified via HPLC-MS/MS. Results revealed peak SMZ concentrations at 0.33 days (8 h), ordered as liver > skin > plasma > kidney > remaining tissues > gill > muscle. Muscle residues fell below the maximum residue limit (MRL, 100 μg/kg) by day 3, while skin required 10 days. Kidney residues dropped below the limit of detection (LOD) earliest (16 days), followed by muscle, gill, and remaining tissues (25 days), whereas plasma, liver, and skin retained detectable levels until day 30. Elimination equations for SMZ across tissues exhibited first-order kinetics. Based on the specific conditions of this study, a minimum 11-day withdrawal period is recommended for edible tissues (muscle + skin) after SMZ administration. Hazard quotient (HQ) values for all tissues remained below the safety threshold (HQ = 1), indicating low dietary risk. These findings support SMZ use standardization in tilapia aquaculture to ensure food safety compliance. Full article

Background/Objectives: Individuals diagnosed with substance use disorders (SUD) exhibit notable deficits in executive function (EFs). Notably, the pro-inflammatory cytokine interleukin-6 (IL-6) has been associated with cognitive impairments in individuals with substance use disorders. The specific neuropsychological parameters most affected by executive dysfunction remain poorly understood. Methods: In this study, sixteen patients diagnosed with SUD in the withdrawal phase were compared to twenty age-matched control subjects to ascertain which aspects of EFs were most adversely impacted. Plasma levels of IL-6 were quantified using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using the Confidence Interval-Based Estimation of Relevance (CIBER) model to determine the most sensitive executive performance indicators. Results: Findings from the CIBER analysis revealed that the Wisconsin Card Sorting Test yielded the most pronounced cognitive discrepancies between males with and without SUD diagnoses. Elevated levels of IL-6 and associated executive dysfunction were observed to persist in males with SUD throughout the withdrawal phase. Conclusions: Notably, cognitive flexibility emerged as the most sensitive parameter indicative of executive dysfunction, suggesting its potential utility in tailoring clinical interventions for SUD patients during this critical recovery period. Full article

Background: Gastrointestinal endoscopy is crucial for diagnosing colorectal cancer and inflammatory bowel diseases, but its effectiveness can be impacted by peristalsis, poor bowel preparation, and inadequate withdrawal time. Conventional antispasmodics, though effective, may not be suitable for elderly patients or those with comorbidities. L-menthol, derived from peppermint oil, has emerged as a safer alternative. Through calcium channel blockade, L-menthol promotes GI smooth muscle relaxation. This study evaluated L-menthol’s efficacy and safety as a potential alternative to antispasmodic agents in endoscopy. Methods: Following PRISMA2020 guidelines and the Cochrane Handbook, we conducted a systematic review and meta-analysis of randomized controlled trials involving adults undergoing endoscopy, comparing L-menthol to placebo. The primary outcome was the adenoma detection rate, with secondary outcomes, including severity of peristalsis, safety, withdrawal time, and ease of examination. We searched five databases on 31 May 2023, with updates on 20 October 2024. Results: Fourteen studies were included. L-menthol reduced peristalsis during colonoscopy and upper endoscopy, achieving a suppression rate of 55.9% (560/1002 patients; odds ratio (OR) = 3.88, 95% confidence interval (95% CI): 2.13–7.07), which improved mucosal visualization. It improved ease of examination (OR = 2.53, 95% CI: 1.35–4.73), allowing endoscopists to perform procedures with less technical difficulty. However, L-menthol had no significant impact on the adenoma detection rate (OR = 1.06, 95% CI: 0.69–1.64), indicating no added benefit for lesion detection, and did not prolong withdrawal time (MD = 3.24 s, 95% CI: −101.05–107.53). Adverse event rates remained low and comparable to placebo (OR = 0.97, 95% CI: 0.74–1.27). Conclusions: L-menthol reduces peristalsis and enhances ease of examination without adverse events. Although its effect on the adenoma detection rate remains inconclusive, its antispasmodic properties make it a promising alternative for patients who cannot tolerate conventional agents. Full article

Traditional reliability methods using fixed removal plans often overlook withdrawal randomness, leading to biased estimates for asymmetric data. This study advances classical and Bayesian frameworks for the inverse Chen distribution, which is suited for modeling asymmetric data under adaptive progressively Type-II censoring with binomial removals. Here, removals post-failure follow a dynamic binomial process, enhancing a more realistic approach for reliability studies. Maximum likelihood estimates are computed numerically, with confidence intervals derived asymptotically. Bayesian approaches employ gamma priors, symmetric squared error loss, and posterior sampling for estimates and credible intervals. A simulation study validates the methods, while two asymmetric real-world applications demonstrate practicality: (1) analyzing diamond sizes from South-West Africa, capturing skewed geological distributions, and (2) modeling failure times of airborne communication transceivers, vital for aviation safety. The flexibility of the inverse Chen in handling asymmetric data addresses the limitations of symmetric assumptions, offering precise reliability tools for complex scenarios. This integration of adaptive censoring and asymmetric distributions advances reliability analysis, providing robust solutions where traditional approaches falter. Full article

Objectives: To assess the impact of bowel cleansing quality on polyp detection rate (PDR) and adenoma detection rate (ADR) and explore predictors of lesion detection rate in patients undergoing colonoscopy. Methods: This is a post-hoc analysis of a multicenter randomized controlled trial (RCT) comparing 1L polyethylene glycol plus ascorbate (1L PEG+ASC) vs. 4L PEG as bowel preparation for colonoscopy. Results: PDR was significantly higher (35.6% vs. 18.5%, p = 0.013), and ADR was higher even if not significantly (25.6% vs. 16.7%, p = 0.153) in patients with Boston Bowel Preparation Scale (BBPS) ≥6 over BBPS <6. Comparing patients with BBPS = 9 over BBPS = 7–8, no significant differences were found in PDR (34.5% vs. 38.4%, p = 0.483) nor ADR (24.1% vs. 27.2%, p = 0.553). At multivariable regression analysis, older age (OR = 1.042, 95%CI = 1.021–1.063; p < 0.001), shorter intubation time (OR = 0.891, 95%CI = 0.816–0.972; p = 0.010), higher withdrawal time (OR = 1.171, 95%CI = 1.094–1.253; p < 0.001) and full consumption of the first dose (OR = 8.368, 95%CI = 1.025–68.331; p = 0.047) were independently associated with ADR. Conclusions: This post-hoc analysis of a RCT showed that excellent cleansing (BBPS = 9) over high-quality cleansing (BBPS = 7–8) does not significantly improve PDR or ADR. Neither cleansing success nor preparation types were independently associated with ADR. Compliance with bowel preparation, timing of colonoscopy and withdrawal time are key elements for adequate ADR with potential implications for reducing interval colorectal cancer. Full article

Black-bone fowls are rich in melanin and regarded as being rich in nutritional value. However, the metabolism of antibiotics in black-bone fowls remains poorly understood. This study aimed to determine the tissue residue depletion kinetics of Sulfamonomethoxine (SMM) or Doxycycline in Taihe black-bone silky fowls. The tissue residue experiments involved a total of two hundred and forty Taihe black-boned silky fowls. The birds were raised to 100 days old in the same laboratory conditions and divided into a control group, SMM group, and Doxycycline group (80 birds for each group). The control group was provided normal drinking water. The SMM group was oral-administered SMM at concentrations of 50 mg/kg bw per day, and the Doxycycline group was oral-administered Doxycycline at concentrations of 40 mg/kg bw for 5 days, respectively. After the last dose, liver, kidney, muscle, and skin/fat were collected at various time points (0.16, 1, 3, 5, 7, 9, 12, 20, 30, and 40 days, eight birds for each time point). Concentrations of SMM or Doxycycline were analyzed using the UPLC–MS/MS method. The terminal elimination half-lives of SMM in muscle, skin/fat, liver, and kidney were 1.82 ± 1.24, 15.3 ± 4.97, 4.36 ± 1.49, and 5.42 ± 3.46 days, respectively, and 8.62 ± 2.82, 6.88 ± 2.06, 4.12 ± 1.28, and 1.53 ± 0.28 days for Doxycycline. The estimated withdrawal times (WDIs) of SMM were 4, 27, 10, and 12 days, while the estimated WDIs of Doxycycline were 18, 15, 4, and 6 days for muscle, skin/fat, liver, and kidney, respectively. The SMM or Doxycycline bioaccumulate in the skin/fat and may cause antimicrobial residues to be absorbed by human when the skin/fat is used in the diet. Doxycycline persists in muscle for a longer duration compared to SMM. This highlights the significance of muscle and skin/fat as a target organ for future food safety research. Full article

To improve the efficiency of prostaglandin F_2α (PG)-based estrus synchronization in sheep, this study assessed the effect of the gonadotropin-releasing hormone (GnRH) included in the long-interval PG treatment regimen for sheep estrus synchronization during the breeding season. In experiment 1, 30 multiparous Mongolian sheep (3–4.5 years old) were randomly divided into three groups. In the progesterone (P4)–equine chorionic gonadotropin (eCG) group (P4-eCG, n = 10), the ewes were synchronized with intravaginal P4 sponges for 14 days, and received an injection of 330 IU of eCG at sponge withdrawal. In the PG group (n = 10), the ewes received two doses of 0.1 mg PG with a 14 day interval. In the PG-GnRH-PG group (n = 10), the ewes were synchronized by two doses of 0.1 mg PG with a 14 day interval like that in the PG group, but received 50 μg of GnRH 7 days after the first injection of PG. It was found that, at the end of treatment, the number of corpus luteum on the ovaries and the concentration of the serum P4 in the PG-GnRH-PG group were significantly higher than that of the PG and P4-eCG groups. In experiment 2, 59 multiparous Mongolian sheep (3–4.5 years old) were assigned to three groups, like in experiment 1 (n = 20, 20 and 19 for the P4-eCG, PG and PG-GnRH-PG groups, respectively). The estrus of ewes in the PG-GnRH-PG group was more synchronous compared to the PG group. After insemination of the estrus ewes, the pregnancy rate was numerically but not significantly higher in the PG-GnRH-PG group than that in the P4-eCG and the PG groups. In a field test, 285 multiparous Hu sheep (3–4.5 years old) were randomly assigned to a P4-eCG group (n = 142) and PG-GnRH-PG group (n = 143). Timed artificial insemination showed no significant differences in the rates of pregnancy and lambing between the PG-GnRH-PG and P4-eCG groups. We conclude that the addition of GnRH in the long-interval PG protocol may improve the efficiency of PG-based estrus synchronization, and would represent a potential alternative to the conventional P4-eCG based protocol during the breeding season in sheep. Full article

The objective of this study was to examine the residue elimination patterns of seven antibiotics in the eggs of Taihang chickens under free-range conditions and develop suitable withdrawal times (WDTs). A total of 240 healthy Taihang chickens, aged 180 days, were randomly divided into eight groups of 30 birds each. The first seven groups were administered oxytetracycline, chlortetracycline, erythromycin, tylosin, tylvalosin, lincomycin, and tiamulin, respectively, in accordance with the maximum dosages and longest durations of treatment recommended by the Veterinary Pharmacopoeia of the People’s Republic of China. Group 8 served as the control group, and the test period continued until no drug residue could be detected. The results demonstrate that the residues of oxytetracycline, chlortetracycline, tylosin, tylvalosin, and tiamulin throughout the test period were below the maximum residue limits (MRLs) outlined in GB 31650-2019, “National food safety standard-Maximum residue limits for veterinary drugs in foods”. The egg yolk was identified as the target tissue for estimating the withdrawal time periods (WDTs) of these seven drugs. It was thus concluded that the recommended withdrawal time for tiamulin should be 0 days. However, the WDTs of oxytetracycline, chlortetracycline, tylosin, tylvalosin, were 2.8, 0.3, 2.4, and 7.4, respectively, when the upper limit of the 95% confidence interval was found to be lower than the MRLs. It was thus determined that the recommended WDTs for oxytetracycline, chlortetracycline, tylosin, and tylvalosin should be 3, 1, 3, and 8 days, respectively. In contrast, erythromycin and lincomycin exhibited concentrations below the permitted MRLs on days 7 and 8, respectively. However, the upper limits of the 95% confidence intervals for erythromycin and lincomycin were found to be below the MRLs when the WDTs were 11 and 8.9, respectively. This suggests that the recommended WDTs for these two antibiotics should be 11 days and 9 days. Full article

There is limited information regarding factors related to education workers’ responses to traumatic stress during the COVID-19 pandemic. The study goal was to determine whether personal factors, behaviours that mitigate viral spread, and work-related factors were associated with post-traumatic symptoms. This observational study, embedded within a cohort study, recruited Ontario education workers from February 2021 to June 2023. Exposure data were collected at enrollment and updated annually. Participants completed the Impact of Event Scale (IES) at withdrawal/study completion. Modified Poisson regression was used to build hierarchical models of dichotomized IES scores (≥26: moderate/severe post-traumatic symptoms). Of the 1518 education workers who submitted an IES between September 2022 and December 2023, the incidence rate ratio of IES scores ≥26 was significantly higher among participants who usually/always wore a mask at work (1.48; 95% confidence interval 1.23, 1.79), usually/always practiced physical distancing (1.31; 1.06, 1.62), lived in larger households (1.06; 1.01, 1.12), and reported poor/fair/good health (1.27; 1.11, 1.46). However, models accounted for little of the variance in IES scores, suggesting the need for future studies to collect data on other factors associated with the development of PTSD, such as pre-existing mental health challenges. Early identification of those experiencing traumatic stress and the implementation of stress reduction strategies are needed to ensure the ongoing health of education workers. Full article

The section span of the withdrawal space of fully mechanized top coal caving in an extra-thick coal seam is large, and with the gradual withdrawal of the hydraulic support, a series of strong dynamic pressure disasters occur in the withdrawal space, and the difficulty of surrounding rock support control increases sharply. In order to study the control mechanism of surrounding rock in the final mining withdrawal space in detail and put forward a reasonable support technology scheme, taking the large-section withdrawal space of an 8309 fully mechanized caving face in an extra-thick coal seam of a mine as the research object—through the theoretical investigation of whether the key blocks of the main roof are stably hinged under varied stopping coal caving distances and fracture locations of the main roof—the reasonable and optimal stopping coal caving distances and roadway formation time are determined. Using numerical simulation and similar simulation methods, the vertical stress and the maximum shear stress research indicators were introduced to verify the accuracy of the theoretical analysis results. The results show the following: (1) The reasonable stopping coal caving span is 1~2 times the cycle weighting interval, the best stopping coal caving distance in this geological condition is 30 m, and the best fracture position of the main roof is located above the goaf. (2) The migration of overlying strata in the withdrawal space has obvious zoning characteristics, and the zoning is as follows: a stopping coal caving area, support area of the hydraulic support, withdrawal channel area, and stopping coal pillar area. (3) According to the zoning characteristics of overlying strata movement, the asymmetric zoning support control scheme of the withdrawal space is proposed. The field monitoring results show that the maximum roof subsidence in the withdrawal space is 151 mm, the maximum internal squeezing amount of the stopping coal pillar is 82 mm, and the supporting and anchoring effect of each partition in the withdrawal space is good. The set of partition asymmetric support control schemes has been successfully applied to field practice. Full article

Background: Frailty and polymedication are closely interrelated. Addressing these concurrent conditions in primary care settings relies on the utilization of potentially inappropriate medication (PIM) lists and medication reviews (MRs), particularly in rural areas, where healthcare professionals serve as the sole point of access to the medical system. The aim of this study was to examine the relationship between medication appropriateness and variables related to frailty in a rural municipality in order to propose potential strategies for therapy optimization. Methods: This cross-sectional study included all adult community dwellers aged 50 and above officially registered in the municipality of Tiriez (Albacete, Spain) in 2023 (n = 241). The primary outcome variable was frailty (assessed using the fatigue, resistance, ambulation, illness, and loss of weight (FRAIL) scale). The independent variables were age, gender, medication regimen, history of falls, comorbidities, PIMs (evaluated using the screening tool of older persons’ prescriptions (STOPP) 2023 criteria), fall-risk-increasing drugs (FRID), and anticholinergic burden (ACB). Results: The prevalence of frailty was approximately 20%. FRID and ACB scores were statistically associated (p-value < 0.001) with frailty, 1.1 ± 1.3 vs. 2.5 ± 1.7, and 1.0 ± 1.3 vs. 2.8 ± 2.5, respectively. Regardless of age, frailty was observed to be more prevalent among females (odds ratio (OR) [95% confidence interval (CI)]: 3.5 [1.5, 9.0]). On average, 2.1 ± 1.6 STOPP criteria were fulfilled, with the prolonged use of anxiolytics and anti-peptic-ulcer agents being the most frequent. Priority interventions (PIs) included opioid dose reduction, benzodiazepine withdrawal, and the assessment of antidepressant and antiplatelet treatment plans. Conclusions: The optimization of medication in primary care is of paramount importance for frail patients. Interventional measures should focus on ensuring the correct dosage and combination of drugs for each therapeutic regimen. Full article

The acoustic communication system (ACS) in bark beetles has been studied mainly in species of the genera Dendroctonus, Ips and Polygraphus. Specifically, ACS of the roundheaded pine beetle, Dendroctonus adjunctus, has been little studied. In this study, we described the stridulatory apparatus of this beetle using optical and scanning electron microscopy and recorded the call types produced by males in three behavioral contexts: stress, female–male–, and male–male interactions. From the spectrograms and waveforms, call types, as well as temporal (tooth strike, tooth strike rate, and intertooth strike interval) and spectral features (minimum, maximum and dominant frequency), were determined. Males have a functional elytro–tergal stridulatory apparatus—females do not—consisting of a file for the pars stridens and two lobes for the plectrum. Most of spectro–temporal features were statistically different between single– and multi–noted calls and across the three behavioral contexts. In the male–male interaction, a new type of call named “withdrawal” was produced by the male withdrawing or fleeing. Our results suggest that the spectro–temporal features of single– and multiple–noted calls in the three behavioral conditions are specific and different from each other. Yet, the combination of single and multiple calls determines an overall calling pattern characteristic of the tested behaviors and, therefore, is species–specific. Full article