Amelioration of Cholesterol Rich diet-induced Impaired Cognition in AD Transgenic Mice by an LXR Agonist TO901317 Is Associated with the Activation of the LXR-ß-RXR-α-ABCA1 Transmembrane Transport System and Improving the Composition of Lipid Raft.

BACKGROUND: It has been reported that LXR agonist can inhibit Aß generation and alleviate Aß-induced various adverse reactions in vivo and in vitro experiments, but the mechanisms have not been clarified. The study aimed to observe the effect of LXR agonist TO901317 on the cognitive function of AD transgenic mice fed with cholesterol-rich diet (CRD), and to explore the possible mechanism. Methods: 32 male 6-month-old double transgenic AD mice were enrolled and randomly divided into 4 groups: control (normal diet) group, CRD treatment group, TO901317 treatment group and GSK2033 treatment group. After 3 month, Morris water maze was for the changes of spatial exploration and memory ability; ELISA was for detecting the production of Aß42 in the brain; the concentration of total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) in serum were detected by cholesterol enzyme colorimetry; Finally, the expression of LXR-ß, RXR-α, ABCA1, caveolin-1, BACE1 and APP at protein level in the brains was measured by Western blotting. RESULTS: Compared with the control group, the learning, memory ability and spatial exploration ability of the mice were more significantly serious in the CRD group (P<0.05); The contents of TC and LDL in the serum and the production of Aß42 in the brains were significantly increased (P<0.05), but HDL was remarkably decreased (P<0.05); The protein levels of LXR-ß, RXR-α and ABCA1 were also significantly decreased (P<0.05); The expression of caveolin-1, APP and BACE1 were evidently increased (P<0.05). However, after treatment with TO901317, the impaired learning and memory and spatial exploration ability of the mice were significantly improved (P<0.05); The contents of TC and LDL in serum and the production of Aß42 in the brains were significantly decreased (P<0.05), but HLD was increased (P<0.05); The protein levels of LXR-ß, RXR-α, ABCA1were all significantly increased (P<0.05), while, the expression of caveolin-1, APP and BACE1 were all significantly decreased (P<0.05). All the changes were reversed by GSK2033 (P<0.05). CONCLUSIONS: TO901317 attenuated the more serious impairment of spatial exploration, learning and memory in transgenic AD mice induced by CRD, and the mechanism may be that TO901317 could activate the LXR-ß/RXR-α/ABCA1 transmembrane transport system, promote the cholesterol efflux, and decreased caveolin-1, APP and BACE1, further reduce Aß42 in the brains.

Impact of the Location of Nasal Septal Deviation on the Nasal Airflow and Air Conditioning Characteristics.

The location of nasal septal deviation (NSD) directly impacts nasal physiology. The objective is to examine, using computational fluid dynamics (CFD), the difference in the airflow and air conditioning characteristics according to the location of NSD. Twenty patients with septal deviation were divided into two: 10 caudal septal deviation (CSD) and 10 posterior septal deviation (PSD). Physiological variables were compared and numerical models for nasal cavity were created with CT scans. Cases with CSD had distinctive features including restricted airflow partition, larger nasal resistance, and decreased surface heat flux in the more obstructed side (MOS), and lower humidity and air temperature in the lesser obstructed side (LOS). Physiological differences were observed according to the location of septal deviation, CSD cases exhibit significantly more asymmetric airflow characteristics and air conditioning capacity between LOS and MOS.

Generalized joint laxity as a predictor of recovering from low back pain during pregnancy - A prospective study.

BACKGROUND: Low back pain (LBP) is a common musculoskeletal problem during pregnancy. The symptoms usually disappear gradually after delivery, but some women may have persistent problems even later in their lives. Individuals with generalized joint laxity (GJL) were expected to have more injuries on lumbar discs and require prolonged healing time. Therefore, this study aims to investigate whether the test of GJL before the pregnancy could predict the prognosis of pregnancy-related LBP. METHODS: 375 women were recruited from January 2017 to October 2017 in antenatal clinics. Those who suffered the LBP during pregnancy were analyzed and further grouped based on whether they recovered from LBP after deliver. The variables such as age, GJL level using Beighton score, and parity were recorded and examined for the risk analysis of unrecovered LBP. Also, the cut-off point for the Beighton score was determined by the receiver operating characteristic (ROC) curve, and the Pearson correlation between GJL levels and pain intensities was investigated. RESULTS: 324 pregnant women completed this study. The mean age of included participants was 29.4 ± 4.6 years. Thereinto, 210 women (64.8%) had LBP during their pregnancy. Of these, 51 women (24.3%) failed to recovery from LBP 2 years after delivery. Beighton score (≥6), LBP in a previous pregnancy, back pain, and high physical demand were risk factors for LBP without recovery (all P < 0.001). Besides, there was a significant correlation between HGS values and the intensities of LBP (r = -0.564, P = 0.002). CONCLUSIONS: Beighton score is a straightforward and reliable indicator of GJL, and the evaluation before pregnancy using it could help screen high risks for pregnancy-related LBP. The present findings may help encourage pregestational exercise targeted at trunk extensors to help alleviate and even avoid the intensities of LBP during pregnancy.

Hand grip strength as a predictor of recovery from low back pain in the pregnant women-a prospective study.

BACKGROUND: Low back pain (LBP) is a common musculoskeletal problem during pregnancy with an estimated prevalence ranging from 30% to 78%. The symptoms usually disappear gradually after delivery, but some women may have persistent problems even later in their lives. The definite mechanism behind LBP during pregnancy remains unknown. Therefore, the purpose of this study was to investigate whether hand grip strength (HGS), which is a straightforward and reliable indicator of overall muscle strength, is associated with unrecovered LBP after delivery. METHODS: 257 pregnant women who registered at obstetrics units in two tertiary hospitals from January 2016 to June 2017 and meanwhile suffered the LBP during pregnancy were included. They were grouped based on whether they recovered from LBP after delivery (recovery was defined as a pain rating of ≤3). The variables such as age, HGS, and education level were recorded and examined for the risk analysis of unrecovered LBP. Also, the Pearson correlation between HGS levels and pain intensities was investigated. RESULTS: LBP without recovery at two years after delivery was reported among 22.7% of the subjects. Women with increasing age, low HGS (<25 kg), LBP in a previous pregnancy, back pain, sick leave, and a large amount of physical demand (all p < 0.05), were more likely to report LBP without recovery. Besides, there was a significant correlation between HGS values and the intensities of LBP (r = -0.525; p = 0.003). CONCLUSIONS: Low HGS has the highest OR value (adjusted OR = 9.12, P < 0.001) among these factors. The present findings may be used to design and encourage a specific stabilization exercise regime to build well stability of the lumbar spinal column and thus alleviating the LBP.

Different types of low back pain in relation to pre- and post-natal maternal depressive symptoms.

BACKGROUND: Low back pain (LBP) is a common musculoskeletal problem during pregnancy, with an estimated prevalence ranging from 30-78% (Mota MJ et al. J Back Musculoskelet Rehabil 28(2):351-7,2015 and Abebe E et al. J Med Sc Tech 3(3). 37-44,2014). Women reporting LBP are at increased risk of developing perinatal depression. Pregnancy-related LBP is highly heterogeneous and can be divided into lumbar pain (LP), posterior pelvic pain (PPP), and combined pain (CP). Therefore, the purpose of this study was to investigate the associations between LBP and perinatal depressive symptoms. METHODS: This was a retrospective case-control study conducted from January 2016 to April 2019. A total of 484 pregnant women were enrolled in this study: a case group of 242 pregnant women who were diagnosed with LBP and an age-matched control group of 242 pregnant women without LBP. The Edinburgh Postnatal Depression Scale (EPDS), LBP characteristics, and questionnaires about pregnancy that included demographic, parity, work, comorbidity, and previous pregnancy data were completed and compared between the case group and the control group. RESULTS: A total of 68 of 242 (28.1%) women experienced PPP, 142 (58.7%) had lumbar pain(LP), and 32 (13.2%) had combined pain. Furthermore, 26.5% of women with prenatal depression in the LP subgroup remained depressed 6 months postnatally, while the percentages for women in the PPP subgroup and CP subgroup were just 10.6% and 15.6%, respectively. The percentage of women who recovered anytime between delivery and six months postnatally in the PPP subgroup was significantly higher than that in the LP subgroup (31.7% vs. 14.7%, P < 0.001). CONCLUSIONS: There is a difference in the prevalence of prenatal, postnatal, and perinatal depressive symptoms among pregnant women with different types of LBP. It is necessary to screen prenatal and postnatal depression separately and differentiate the types of LBP during pregnancy. Attention to these factors may help to outline better management strategies to improve maternal health.

[Result of Sanger sequencing for newborn carriers of single heterozygous variants of GJB2 or SLC26A4 gene by genechip analysis].

OBJECTIVE: To detect additional variants for newborn carriers of single heterozygous variants of the GJB2 or SLC26A4 gene by genechip analysis in Changsha area, and explore the variation spectrum of deafness-related genes in this region. METHODS: For 462 newborns carrying single heterozygous variants of the GJB2 or SLC26A4 gene, all exons of the genes were subjected to Sanger sequencing. The pathogenicity of the variants was analyzed by database and literature search. RESULTS: For 305 newborns carrying a heterozygous GJB2 variant, 143 (46.49%) were found to carry additional variants, including 29 (9.51%) with c.109G>A likely pathogenic variant, and 1 (6.48%) with c.551G>A pathogenic variant. Among 153 newborns carrying single heterozygous variant of the SLC26A4 gene, 2 (1.31%) were found with a c.281C>T variant, and 1 (0.65%) with a c.1547_1548ins pathogenic variant. Among 4 newborns simultaneously carrying GJB2 and SLC26A4 variants, two were found to carry c.109G>A and c.844T>C variants (clinical significance unknown), respectively. CONCLUSION: For newborns carrying single heterozygous variants of the GJB2 or SLC26A4 gene by genechip analysis, the detection rate for other variants is quite high. Sanger sequencing can significantly improve the detection rate of high-risk newborns and enrich the variant spectrum of deafness genes.

Air-conditioning characteristics in nasal cavity models exhibiting nasal cycle states.

The air-conditioning characteristics in nasal cavity models obtained from two subjects exhibiting different degrees of the nasal cycle states in terms of the airflow partition were investigated using computational fluid dynamics. A constant inspiratory flow rate of approximately 250 mL/s was considered, and the air temperature and relative humidity at the inlet were assumed to be 25 °C and 35%, respectively. The air-conditioning capacities of the congested and decongested sides were assessed by the amounts of epithelial heat and water vapor transferred to the inhaled air through the airway from the nostrils to the end of the septum. The results revealed that the air temperature and relative humidity near the end of the septum, respectively, reached approximately 31.4-32.5 °C and 81.4-88.0% in the decongested sides and 34.0-35.9 °C and 95.3-100% in the congested sides. The differences seen in the air temperatures and relative humidity between the congested and decongested sides were found to be larger in the cavity model that showed a larger degree of reciprocal change in the airflow rate. From a fluid mechanics perspective, while the congested side is in a rest period during the nasal cycle such that a lower amount of airflow is transported through it, this side, in effect, works to provide assistive air-conditioning capacity to the nasal cavity and aids when insufficiently conditioned airflow passes through the decongested side so that the inhaled air merging after the septum can approach the alveolar condition favorably through the nasopharynx.

Migraine prevention with percutaneous mastoid electrical stimulator: A randomized double-blind controlled trial.

Objective To evaluate the effectiveness and safety of episodic migraine prevention with the percutaneous mastoid electrical stimulator (PMES). Methods This was a randomized, double-blind, and sham-controlled trial that involved four medical centers. Episodic patients with at least two migraine attacks every month were randomly 1:1 to PMES or sham stimulation treatment. The treatments were performed daily for 45 minutes over 3 months. The primary outcomes were change in migraine days per month and the 50% response rate. Results The PMES group had a significantly greater reduction of migraine days in the third month than the sham group (-71.3% vs. -14.4%, p < 0.001). The 50% response rate of migraine days in the PMES group (≥50% reduction of migraine days compared with the baseline) was significantly higher than that in the sham group (82.5% vs. 17.5%, p < 0.001). In the PMES group, 60% of the patients had a ≥75% reduction of migraine days in the third month, and 35% of the patients had no migraine attack in the third month. No patients in the sham group had a ≥75% reduction of migraine days. There were no adverse events in either group. Conclusion Treatment of migraine using non-invasive PMES was safe and effective.

Hydrophilic strips for preventing air bubble formation in a microfluidic chamber.

In a microfluidic chamber, unwanted formation of air bubbles is a critical problem. Here, we present a hydrophilic strip array that prevents air bubble formation in a microfluidic chamber. The array is located on the top surface of the chamber, which has a large variation in width, and consists of a repeated arrangement of super- and moderately hydrophilic strips. This repeated arrangement allows a flat meniscus (i.e. liquid front) to form when various solutions consisting of a single stream or two parallel streams with different hydrophilicities move through the chamber. The flat meniscus produced by the array completely prevents the formation of bubbles. Without the array in the chamber, the meniscus shape is highly convex, and bubbles frequently form in the chamber. This hydrophilic strip array will facilitate the use of a microfluidic chamber with a large variation in width for various microfluidic applications.

Impact of nasal septal perforation on the airflow and air-conditioning characteristics of the nasal cavity.

We investigated (1) how nasal septal perforations (NSPs) modify nasal airflow and air-conditioning characteristics and (2) how the modifications of nasal airflow are influenced by the size and location of the NSP. Computed tomography scans of 14 subjects with NSPs were used to generate nasal cavity models. Virtual repair of NSPs was conducted to examine the sole effect of NSPs on airflow. The computational fluid dynamics technique was used to assess geometric and airflow parameters around the NSPs and in the nasopharynx. The net crossover airflow rate, the increased wall shear stress (WSS) and the surface water-vapor flux on the posterior surface of the NSPs were not correlated with the size of the perforation. After the virtual closure of the NSPs, the levels in relative humidity (RH), air temperature (AT) and nasal resistance did not improve significantly both in the choanae and nasopharynx. A geometric parameter associated with turbinate volume, the surface area-to-volume ratio (SAVR), was shown to be an important factor in the determination of the RH and AT, even in the presence of NSPs. The levels of RH and AT in the choanae and nasopharynx were more influenced by SAVR than the size and location of the NSPs.

Utility of F-18 FDG-PET in detecting primary aldosteronism in patients with bilateral adrenal incidentalomas.

In patients with primary aldosteronism who have bilateral adrenal incidentalomas, it is important to identify which adrenal gland is secreting excess aldosterone. Traditionally, adrenal vein sampling (AVS) has been performed for lateralization despite its invasiveness. Here we report a case of bilateral adrenal incidentaloma in which 18-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) was used to identify the functional adrenal mass. A 53-yr-old man was referred to our clinic due to bilateral adrenal incidentalomas (right: 1 cm, left: 2.5 cm) on computed tomography (CT). Given his history of colon cancer, FDG-PET/CT scanning was used to rule out metastasis. Although there was focal hot uptake lesion in the right adrenal gland, the patient was suspected primary aldosteronism clinically more than metastasis because of the patient's underlying hypertension with hypokalemia. It was consistent with the results of AVS. Based on these findings, we propose that FDG-PET/CT can be used instead of AVS to identify the source of primary aldosteronism between two bilateral adrenal incidentalomas.

Dark background-surface enhanced Raman spectroscopic detection of nanoplastics: Thermofluidic strategy.

This study aims to develop a cost-effective and time-efficient method for detecting nanoplastics, which have recently garnered significant attention due to their potential harmful impact on the water environment (XiaoZhi, 2021; Gigault et al., 2021; Mitrano et al., 2021; Ferreira et al., 2019). Although several techniques are available to accumulate data on microplastics, there is currently no universally accepted analytical technique for detecting nanoplastics (Gigault et al., 2021; Mitrano et al., 2021; Mitrano et al., 2019; Cai et al., 2021a; Allen et al., 2022). In this study, we have developed a substrate that exhibits Surface-enhanced Raman scattering (SERS) (Zhou et al., 2021; Lv et al., 2020; Lê et al., 2021; Hu et al., 2022; Chang et al., 2022; Yang et al., 2022; Xu et al., 2020; Jeon et al., 2021; Lee and Fang, 2022; Vélez-Escamilla and Contreras-Torres, 2022; Liu et al., 2022; Xie et al., 2023) activity over a large area and a dark background in optical (darkfield mode) vision, enabling the detection of sparkling nanoplastics on the substrate. This darkfield-based strategy allows for the point-by-point detection of single nanoplastics, offering cost and time-saving advantages over other resource-intensive analytical techniques. Our findings reveal the presence of PP nanoplastics in commonly used laboratory equipment, individual PE nanoplastics from a hot water-contained commercial paper cup, and the first detection of natural nanoplastics in coastal seawater. We believe that this technique will have a universal application in establishing a global map of nanoplastics and advancing our understanding of the environmental life cycle of plastics.

Fabrication of a PVA-Based Hydrogel Microneedle Patch.

The degree of saponification, which is a dissolution characteristic of poly(vinyl alcohol) (PVA), is used to blend PVA to prepare a hydrogel microneedle (MN) patch. The MN patch was manufactured with an adjustable disassembly time using a molding process, and it was confirmed to have morphological stability and excellent needle formation. The permeability of the gelatin sheet, which is analogous to the skin elasticity coefficient of a real human, was confirmed. The penetration ratio had a very high value of 100% and sufficient physical properties to penetrate the skin. In the disassembly experiment, the MN patch was produced with ratios of lower:higher saponification of 6:4 (PVA6), 7:3 (PVA7), 8:2 (PVA8), 9:1 (PVA9), and 10:0 (PVA10). Degradation did not occur for PVA6 and PVA7 but occurred for PVA8, PVA9, and PVA10. A cytotoxicity test to investigate its suitability for use in the human body confirmed the cell viability of 80% or more and nontoxic properties. Therefore, sufficient cell viability was confirmed when compared to the existing products.

Improvements in airflow characteristics and effect on the NOSE score after septoturbinoplasty: A computational fluid dynamics analysis.

Septoturbinoplasty is a surgical procedure that can improve nasal congestion symptoms in patients with nasal septal deviation and inferior turbinate hypertrophy. However, it is unclear which physical domains of nasal airflow after septoturbinoplasty are related to symptomatic improvement. This work employs computational fluid dynamics modeling to identify the physical variables and domains associated with symptomatic improvement. Sixteen numerical models were generated using eight patients' pre- and postoperative computed tomography scans. Changes in unilateral nasal resistance, surface heat flux, relative humidity, and air temperature and their correlations with improvement in the Nasal Obstruction Symptom Evaluation (NOSE) score were analyzed. The NOSE score significantly improved after septoturbinoplasty, from 14.4 ± 3.6 to 4.0 ± 4.2 (p < 0.001). The surgery not only increased the airflow partition on the more obstructed side (MOS) from 31.6 ± 9.6 to 41.9 ± 4.7% (p = 0.043), but also reduced the unilateral nasal resistance in the MOS from 0.200 ± 0.095 to 0.066 ± 0.055 Pa/(mL·s) (p = 0.004). Improvement in the NOSE score correlated significantly with the reduction in unilateral nasal resistance in the preoperative MOS (r = 0.81). Also, improvement in the NOSE score correlated better with the increase in surface heat flux in the preoperative MOS region from the nasal valve to the choanae (r = 0.87) than in the vestibule area (r = 0.63). Therefore, unilateral nasal resistance and mucous cooling in the preoperative MOS can explain the perceived improvement in symptoms after septoturbinoplasty. Moreover, the physical domain between the nasal valve and the choanae might be more relevant to patient-reported patency than the vestibule area.

Dynamic characteristics of heat capacity of the human nasal cavity during a respiratory cycle.

The dynamic characteristics of air-conditioning in the human nasal cavity during a respiratory cycle were investigated using unsteady numerical simulations to assess whether inhaled air is sufficiently conditioned by the nasal cavity. Variations in the epithelial surface temperature, surface heat, and water vapor fluxes were found to vary significantly during inspiration while providing substantial air conditioning to the inhaled air, but variations and magnitudes were significantly reduced during the expiration period. Air temperature (31.3-35.3 °C) and relative humidity (85.1-100 %) in the nasopharynx exhibited significant variations during inspiration. Flow rate-weighted average values of the air temperature and relative humidity during inspiration were estimated to be 32.0 °C and 89.1 %, respectively. Inhaled air did not attain alveolar conditions before reaching the nasopharynx, and was therefore thought to be insufficiently conditioned by the nasal cavity alone. A steady flow of approximately 250 mL/s appears to be useful for evaluating the accumulated thermal state of air in the nasopharynx during inspiration.

Polyurethane Sponge with a Modified Specific Surface for Repeatable Oil-Water Separation.

Oil spill accidents contaminate the oceanic environment and cause economic distress, and they continue to occur. Many methods have been developed to restore waters contaminated with spilled oil. However, still most commercially available methods are not environmentally or economically sustainable solutions. Therefore, there is a need for the development of sustainable materials with running water treatment capabilities. In recent years, a polyurethane (PU) sponge-based adsorbent has been reported as an oil-water separation and reusable adsorbent. This is because the porous 3D structure of the PU sponge provides a large surface area. However, as the PU sponge has a carboxyl group and an amino group, it exhibits hydrophilicity, so surface modification is essential for oil-water separation. Therefore, to modify the surface of PU to have hydrophobic/oleophilic properties, a hydrophobic/oleophilic adsorbent (HOA) was prepared using graphite and polydimethylsiloxane. On the basis of this, a PU sponge, a porous material, was used to manufacture an adsorbent that can be used in a sustainable and environmentally friendly way. The prepared HOA can selectively adsorb water or oil and can be reused. Furthermore, continuous oil-water separation is possible through a simple flow of fluid. Therefore, it is confirmed that the studied HOA can have great potential for ocean restoration in the future as an adsorbent that mitigates the disadvantages of the currently commercialized method.

Development of a Tough, Self-Healing Polyampholyte Terpolymer Hydrogel Patch with Enhanced Skin Adhesion via Tuning the Density and Strength of Ion-Pair Associations.

Polyampholyte (PA) hydrogels have great potential for biomedical applications, owing to their high toughness and good self-recovery and self-healing (SELF) behavior in addition to their physical properties similar to human tissue. However, their implementation as practical biomedical skin patches or wearable devices has so far been limited by their insufficient transdermal adhesion strength. In this work, a new polyampholytic terpolymer (PAT) hydrogel with enhanced skin adhesion was developed using a novel and simple strategy that tunes the structure of ion-pair associations (IPAs), acting as cross-links, in the hydrogel via adding an extra neutral monomer component into the network without changing the total charge balance. The PAT hydrogels were synthesized by the terpolymerization of the neutral monomer N,N-dimethylacrylamide (DMAAm) (or 2-hydroxyethyl methacrylate (HEMA)) as well as the cationic monomer 3-(methacryloylamino) propyl-trimethylammonium chloride (MPTC) and the anionic monomer sodium p-styrenesulfonate (NaSS). Their IPA, which determines their network structure, was modulated by varying the feed concentration of the neutral monomer, Cnm. An increase of Cnm within an optimized Cnm window (0.3-0.4 M) decreased the cross-linking density (strength and density of the IPAs) of the PAT hydrogels, reducing the softening temperature and Young's modulus, which increased compliance but maintained sufficient mechanical strength and thereby maximized the contact surface and enhanced skin adhesion. The DMAAm monomers, compared to the HEMA monomers, produced the higher skin adhesion of the PAT hydrogel, which was explained by the difference in their reactivity to the MPTC and NaSS. This study demonstrated this new method to develop the PAT hydrogels with excellent skin adhesion and biocompatibility while maintaining good toughness, compliance, and SELF behavior and the potential of the PAT hydrogels for biomedical skin patches and wearable devices.

Efficient Inverted Solar Cells Using Benzotriazole-Based Small Molecule and Polymers.

We synthesized medium-band-gap donor-acceptor (D-A) -type conjugated polymers (PBTZCZ-L and PBTZCZ-H) consisting of a benzotriazole building block as an acceptor and a carbazole unit as a donor. In comparison with the polymers, a small conjugated molecule (BTZCZ-2) was developed, and its structural, thermal, optical, and photovoltaic properties were investigated. The power conversion efficiency (PCE) of the BTZCZ-2-based solar cell devices was less than 0.5%, considerably lower than those of polymer-based devices with conventional device structures. However, inverted solar cell devices configured with glass/ITO/ZnO:PEIE/BTZCZ-2:PC71BM/MoO3/Ag showed a tremendously improved efficiency (PCE: 5.05%, Jsc: 9.95 mA/cm2, Voc: 0.89 V, and FF: 57.0%). We believe that this is attributed to high energy transfer and excellent film morphologies.

Efficacy and safety of a switch from twice-daily tacrolimus to once-daily generic tacrolimus in stable liver transplant patients.

Background: Once-daily tacrolimus reduces non-compliance relative to twice-daily tacrolimus. However, little is known about the safety and efficacy of conversion from twice-daily tacrolimus to generic once-daily tacrolimus in liver transplantation (LT). Herein, we investigated the efficacy and safety of a switch from twice-daily tacrolimus to generic once-daily tacrolimus in patients with stable liver graft function. Methods: This prospective, multicenter, open-label, single-arm study was conducted in 17 medical centers for 1 year from July 2019 to July 2020 (NCT04069065). Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR) for 24 weeks after conversion. Secondary endpoints were graft failure, patient death, and adverse events (AEs). Results: Of 151 screened LT patients, 144 patients were enrolled. BPAR, graft failure, and patient death did not occur in this patient population. There were no statistical differences in blood tests, liver function tests, or biochemical tests between visits in any of the patients. Median tacrolimus trough level decreased abruptly from 4.7 ng/mL to 3.2 ng/mL after generic once-daily tacrolimus conversion, but median tacrolimus dose increased due to low tacrolimus trough level. Ninety-two adverse events occurred in 54 patients. Liver enzyme levels increased in seven patients (4.9%) after the switch to generic once-daily tacrolimus, but the liver function tests of these patients normalized thereafter. There were three cases of severe AEs not related to investigational drug. Conclusions: Present study suggests that conversion from twice-daily tacrolimus to generic once-daily tacrolimus is effective and safe in stable LT patients.

Numerical study on the heat-recovery capacity of the human nasal cavity during expiration.

The characteristics of the thermal field in the human nasal cavity during the expiration period were investigated using computational fluid dynamics. Heat and water-vapor recovery features were quantitatively investigated under realistic distributions of the epithelial surface and air temperature. A constant expiratory flow rate of 250 mL/s was assumed. The epithelial surface temperature was approximately 34.3-34.4 °C in the nasopharynx and 33.5-33.6 °C in the vestibule region, and these values are in good agreement with the measurement data in the literature. We observed that heat-recovery from the exhaled air mostly occurred in the posterior turbinate region, and the amount of heat recovered is estimated to be approximately 1/3 of the heat supply during inspiration. Because of this heat transfer from the exhaled air to the epithelial surface, the temperature of the epithelial surface increased in this region, and the exhaled air temperature dropped through the turbinate airway. Water-vapor recovery primarily occurs in the posterior segments of the turbinates; however, the amount of water-vapor transfer was approximately 1/5 of that in inspiration. Accordingly, the relative humidity of the exhaled air remained constant throughout the airway.