Pharmacokinetics and tissue depletion of doxycycline administered at high dosage to broiler chickens via the drinking water

The recommended use of doxycycline (DC) to broiler chicken is 100 mg/L via the drinking water and a 7-day withdrawal time (WDT). However, study of a higher dosage is desirable because of the possible increase of antimicrobial resistance and disease spectrum. Tissue DC residues exceeding the current maximum residue levels (MRL) was our major concern. Therefore, serum concentration and tissue depletion of DC hyclate after administration of 200 mg/L of DC in the drinking water for five consecutive days were studied. The steady-state DC concentration (8.3 ± 0.9 μg/mL) was reached on the third day of medication. The elimination constant (0.05 ± 0.01 1/h), half-life (14.9 ± 1.4 h), area under concentration versus time curve (81.0 ± 9.9 h·μg/mL) and mean residence time (22.7 ± 2.5 h) were obtained using a non-compartmental pharmacokinetic model. It was determined that the current 7-day WDT regulation was still legitimate for the kidney and liver as well as for the breast and leg muscles, which were estimated by linear regression analysis of the 99% upper distribution limit. The unregulated heart and gizzard were considered safe even when the lowest MRL of muscle (100 ng/g) was applied. While at the present time the extra-label use of drugs is only allowed under specific conditions, in the future it may become necessary to increase the general dosage of DC, and the current results suggest a safe range of DC hyclate in chicken; however, skin/fat tissue residues warrant further studies

Memory Impairment and Plasma BDNF Correlates of the BDNF Val66Met Polymorphism in Patients With Bipolar II Disorder

Studies suggest that a functional polymorphism of brain-derived neurotrophic factor (BDNF), polymorphism BDNF Val66Met affects cognitive functions, however, the effect is unclear in bipolar II (BD-II) disorder. We used the Wechsler Memory Scale-third edition (WMS-III), the presence of the BDNF Val66Met polymorphism, and plasma concentrations of BDNF to investigate the association between memory impairment and BDNF in BD-II disorder. We assessed the memory functions of 228 BD-II patients and 135 healthy controls (HCs). BD-II patients had significantly lower scores on five of the eight WMS-III subscales. In addition to education, the BDNF polymorphism were associated with the following subscales of WMS-III, auditory delayed memory, auditory delayed recognition memory and general memory scores in BD-II patients, but not in HC. Moreover, BD-II patients with the Val-homozygote scored significantly higher on the visual immediate memory subscale than did those with the Met/Met and Val/Met polymorphisms. The significantly positive effect of the Val-homozygote did not have a significantly positive effect on memory in the HC group, however. We found no significant association between BDNF polymorphisms and plasma concentrations of BDNF. The plasma BDNF was more likely to be associated with clinical characteristics than it was with memory indices in the BD-II group. The impaired memory function in BD-II patients might be dependent upon the association between the BDNF Val66Met polymorphism and peripheral BDNF levels

Neuromagnetic Index of Hemispheric Asymmetry Prognosticating the Outcome of Sudden Hearing Loss

The longitudinal relationship between central plastic changes and clinical presentations of peripheral hearing impairment remains unknown. Previously, we reported a unique plastic pattern of “healthy-side dominance” in acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). This study aimed to explore whether such hemispheric asymmetry bears any prognostic relevance to ISSNHL along the disease course. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole amplitude and latency of N100m to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at two stages: initial and fixed stage (1 month later). Dynamics/Prognostication of hemispheric asymmetry were assessed by the interplay between hearing level/hearing gain and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m amplitude was observed in ISSNHL initially. The pattern changed with disease process. There is a strong correlation between the hearing level at the fixed stage and initial I/Camplitude on affected-ear stimulation in ISSNHL. The optimal cut-off value with the best prognostication effect for the hearing improvement at the fixed stage was an initial I/Clatency on affected-ear stimulation of 1.34 (between subgroups of complete and partial recovery) and an initial I/Clatency on healthy-ear stimulation of 0.76 (between subgroups of partial and no recovery), respectively. This study suggested that a dynamic process of central auditory plasticity can be induced by peripheral lesions. The hemispheric asymmetry at the initial stage bears an excellent prognostic potential for the treatment outcomes and hearing level at the fixed stage in ISSNHL. Our study demonstrated that such brain signature of central auditory plasticity in terms of both N100m latency and amplitude at defined time can serve as a prognostication predictor for ISSNHL. Further studies are needed to explore the long-term temporal scenario of auditory hemispheric asymmetry and to get better psychoacoustic correlates of pathological hemispheric asymmetry in ISSNHL

Integration, Launch, and First Results from IDEASSat/INSPIRESat-2 - A 3U CubeSat for Ionospheric Physics and Multi-National Capacity Building

The Ionospheric Dynamics and Attitude Subsystem Satellite (IDEASSat) is a 3U CubeSat carrying a Compact Ionospheric Probe (CIP) to detect ionospheric irregularities that can impact the usability and accuracy of global satellite navigation systems (GNSS), as well as satellite and terrestrial over the horizon communications. The spacecraft was developed by National Central University (NCU) in Taiwan, with additional development and operational support from partners in the International Satellite Program in Science and Education (INSPIRE) consortium. The spacecraft system needed to accommodate these mission objectives required three axis attitude control, dual band communications capable of supporting both tracking, telemetry and command (TT&C) and science data downlink, as well as flight software and ground systems capable of supporting the autonomous operation and short contact times inherent to a low Earth orbit mission developed on a limited university budget with funding agency-imposed constraints. As the first spacecraft developed at NCU, lessons learned during the development, integration, and operation of IDEASSat have proven to be crucial to the objective of developing a sustainable small satellite program. IDEASSat was launched successfully on January 24, 2021 aboard the SpaceX Falcon 9 Transporter 1 flight. and successfully began operations, demonstrating power, thermal, and structural margins, as well as validation of uplink and downlink communications functionality, and autonomous operation. A serious anomaly occurred after 22 days on orbit when communication with the spacecraft were abruptly lost. Communication was re-established after 1.5 months for sufficient time to downlink stored flight data, which allowed the cause of the blackout to be identified to a high level of confidence and precision. In this paper, we will report on experiences and anomalies encountered during the final flight model integration and delivery, commissioning, and operations. The agile support from the international amateur radio community and INSPIRE partners were extremely helpful in this process, especially during the initial commissioning phase following launch. It is hoped that the lessons learned reported here will be helpful for other university teams working to develop spaceflight capacity

3D Effects of permeability and strength anisotropy on the stability of weakly cemented rock slopes subjected to rainfall infiltration

Weakly cemented sedimentary rocks with pronounced stratification exhibit permeability and strength anisotropy. The influence of permeability and strength anisotropy on the groundwater flow and slope stability depends on the orientation of the bedding planes. The stability of slopes with different orientations of bedding planes under rainfall infiltration was evaluated in this study using three-dimensional finite element modeling. The groundwater table and pore water pressure in slopes before and after rainfall were simulated, and the calculated pore pressure corresponding to the initial and highest groundwater tables was used for slope stability analyses. The results showed that in comparison with gently dipping bedding planes, a slope with steeply dipping bedding planes exhibits a greater rise of the groundwater table and a greater increase of pore pressure, leading to a larger reduction in the factor of safety. Also, a shorter time is required to reach the highest groundwater table and the maximum pore pressure at a certain position. In consideration of the anisotropic behavior and the groundwater table rise during rainfall, unfavorable conditions were identified for the slope stability. The four unfavorable conditions, where the bedding planes and the slope face approximately strike in the same direction are: (1) the daylight condition of the bedding planes, (2) the coincidence of the bedding planes and the slope face, and (3) steep bedding planes dipping out or (4) into the slope. Slopes with the unfavorable orientations of bedding planes need additional attention in order to ensure a safe land development in the mountainous areas

Pharmacokinetics and tissue depletion of doxycycline administered at high dosage to broiler chickens via the drinking water

The recommended use of doxycycline (DC) to broiler chicken is 100 mg/L via the drinking water and a 7-day withdrawal time (WDT). However, study of a higher dosage is desirable because of the possible increase of antimicrobial resistance and disease spectrum. Tissue DC residues exceeding the current maximum residue levels (MRL) was our major concern. Therefore, serum concentration and tissue depletion of DC hyclate after administration of 200 mg/L of DC in the drinking water for five consecutive days were studied. The steady-state DC concentration (8.3 ± 0.9 μg/mL) was reached on the third day of medication. The elimination constant (0.05 ± 0.01 1/h), half-life (14.9 ± 1.4 h), area under concentration versus time curve (81.0 ± 9.9 h·μg/mL) and mean residence time (22.7 ± 2.5 h) were obtained using a non-compartmental pharmacokinetic model. It was determined that the current 7-day WDT regulation was still legitimate for the kidney and liver as well as for the breast and leg muscles, which were estimated by linear regression analysis of the 99% upper distribution limit. The unregulated heart and gizzard were considered safe even when the lowest MRL of muscle (100 ng/g) was applied. While at the present time the extra-label use of drugs is only allowed under specific conditions, in the future it may become necessary to increase the general dosage of DC, and the current results suggest a safe range of DC hyclate in chicken; however, skin/fat tissue residues warrant further studies

Comparative Effectiveness of Smoking Cessation Medications: A National Prospective Cohort From Taiwan

<div><p>Background and objective</p><p>Relative effectiveness of smoking cessation medications—varenicline, bupropion and nicotine replacement therapy (NRT)—remains unclear among smokers in real-world settings. Evidence in females and smokers with light/moderate nicotine dependence is particularly insufficient. This study compared the effectiveness of varenicline, bupropion or NRT gum relative to NRT patch, in achieving abstinence among recent quitters.</p><p>Methods</p><p>In a national smoking cessation program in Taiwan (2012–2015), a cohort of 11,968 participants received varenicline (n = 5,052), bupropion (n = 823), NRT gum (n = 1944) or NRT patch (n = 4,149). The 7-day, 1-month or 6-month point-prevalence was calculated based on self-reported last smoking event via telephone interview after 6 months. Logistic regression modellings estimated odds ratios (OR) and 95% confidence intervals (CI) for achieving abstinence using different modalities (NRT patch as referent). Models included age, sex, education, marital status, geographic region, smoke-years, nicotine-dependence level, medical institution, number of clinic visits and medication use duration. Analyses were further stratified by sex and dependence severity.</p><p>Results</p><p>Participants were predominantly male (83%) with a mean age of 43.7±12.6 years. Varenicline users were more likely than NRT patch users to achieve abstinence, based on 7-day point-prevalence (OR = 1.30, CI: 1.19–1.44), 1-month point-prevalence (OR = 1.36, CI: 1.24–1.50) or 6-month point-prevalence (OR = 1.30, CI: 1.14–1.47). Compared with NRT patch, varenicline was associated with greater odds of being abstinent in women (OR = 1.29, CI: 1.01–1.65), men (OR = 1.31, CI: 1.18–1.46), those with light/moderate dependence (OR = 1.42, CI: 1.24–1.63) or smokers with severe dependence (OR = 1.19, CI: 1.04–1.37), based on 7-day point-prevalence. Differences in effectiveness were not observed between users of bupropion, NRT gum and NRT patch.</p><p>Conclusions</p><p>In smoking cessation clinics in Taiwan, varenicline users reported higher abstinence rates than NRT patch users after 6 months. Women and smokers with light/moderate nicotine dependence may also benefit from varenicline in actual clinical practice.</p></div