Inferior Interfacial Superconductivity in 1 UC FeSe/SrVO3/SrTiO3 with Screened Interfacial Electron-Phonon Coupling.

Single-unit cell (1 UC) FeSe interfaced with TiOx or FeOx exhibits significantly enhanced superconductivity compared to that of bulk FeSe, with interfacial electron-phonon coupling (EPC) playing a crucial role. However, the reduced dimensionality in 1 UC FeSe, which may drive superconducting fluctuations, complicates our understanding of the enhancement mechanisms. We construct a new superconducting interface, 1 UC FeSe/SrVO3/SrTiO3. Here, the itinerant electrons of highly metallic SrVO3 films can screen all high-energy Fuchs-Kliewer phonons, including those of SrTiO3, making it the first FeSe/oxide system with screened interfacial EPC while maintaining the 1 UC FeSe thickness. Despite comparable doping levels, the heavily electron-doped 1 UC FeSe/SrVO3 exhibits a pairing temperature (Tg ∼ 48 K) lower than those of FeSe/SrTiO3 and FeSe/LaFeO3. Our findings disentangle the contributions of interfacial EPC from dimensionality in terms of enhancing Tg in FeSe/oxide interfaces, underscoring the critical importance of interfacial EPC. This FeSe/VOx interface also provides a platform for studying interfacial superconductivity.

Variation in Hospital Neuraxial Labor Analgesia Rates in California.

BACKGROUND: Neuraxial analgesia provides effective pain relief during labor. However, it is unclear whether neuraxial analgesia prevalence differs across U.S. hospitals. The aim of this study was to assess hospital variation in neuraxial analgesia prevalence in California. METHODS: A retrospective cross-sectional study analyzed birthing patients who underwent labor in 200 California hospitals from 2016 to 2020. The primary exposure was the delivery hospital. The outcomes were hospital neuraxial analgesia prevalence and between-hospital variability, before and after adjustment for patient and hospital factors. Median odds ratio and intraclass correlation coefficients quantified between-hospital variability. The median odds ratio estimated the odds of a patient receiving neuraxial analgesia when moving between hospitals. The intraclass correlation coefficients quantified the proportion of the total variance in neuraxial analgesia use due to variation between hospitals. RESULTS: Among 1,510,750 patients who underwent labor, 1,040,483 (68.9%) received neuraxial analgesia. Both unadjusted and adjusted hospital prevalence exhibited a skewed distribution characterized by a long left tail. The unadjusted and adjusted prevalences were 5.4% and 6.0% at the 1st percentile, 21.0% and 21.2% at the 5th percentile, 70.6% and 70.7% at the 50th percentile, 75.8% and 76.6% at the 95th percentile, and 75.9% and 78.6% at the 99th percentile, respectively. The adjusted median odds ratio (2.3; 95% CI, 2.1 to 2.5) indicated substantially increased odds of a patient receiving neuraxial analgesia if they moved from a hospital with a lower odds of neuraxial analgesia to one with higher odds. The hospital explained only a moderate portion of the overall variability in neuraxial analgesia (intraclass correlation coefficient, 19.1%; 95% CI, 18.8 to 20.5%). CONCLUSIONS: A long left tail in the distribution and wide variation exist in the neuraxial analgesia prevalence across California hospitals that is not explained by patient and hospital factors. Addressing the low prevalence among hospitals in the left tail requires exploration of the interplay between patient preferences, staffing availability, and care providers' attitudes toward neuraxial analgesia.

Assessment of extremely premature lambs supported by the Extrauterine Environment for Neonatal Development (EXTEND).

BACKGROUND: Our team has previously reported physiologic support by the EXTra-uterine Environment for Neonatal Development (EXTEND) of 105 to 117 days gestational age (GA) lambs for up to 28 days with normal organ maturation. However, the fetal lamb brain matures more rapidly, requiring the study of 90-105 day GA fetal lambs to assess more neurodevelopmentally equivalent lambs to the 23-25 week GA extreme premature infant. METHODS: Extremely preterm lambs (90-95 days of GA) were delivered by C-section and supported by EXTEND. Estimated circuit flows were maintained at around 325 ml/kg/min. After support on EXTEND, MRI and histopathologic analysis were performed and compared to 105-112 days GA control lambs. RESULTS: The extremely preterm group includes 10 animals with a mean GA of 91.6 days, a mean weight at cannulation of 0.98 kg and a mean length of stay on EXTEND of 13.5 days (10-21 days). Hemodynamics and oxygenation showed stable parameters. Animals showed growth and physiologic cardiac function. MRI volumetric and diffusion analysis was comparable to controls. Histologic brain analysis revealed no difference between study groups. CONCLUSION: EXTEND appears to support brain and cardiac development in an earlier gestation, less mature, lamb model. IMPACT: Prolonged (up to 21 days) physiological support of extremely preterm lambs of closer neurodevelopmental equivalence to the 24-28 gestational week human was achieved using the EXTEND system. EXTEND treatment supported brain growth and development in extremely preterm fetal lambs and was not associated with intraventricular hemorrhage or white matter injury. Daily echocardiography demonstrated physiologic heart function, absence of cardiac afterload, and normal developmental increase in cardiac chamber dimensions. This study demonstrates hemodynamic and metabolic support by the EXTEND system in the extremely preterm ovine model.

Novel Phosphate Transporter-B PvPTB1;1/1;2 Contribute to Efficient Phosphate Uptake and Arsenic Accumulation in As-Hyperaccumulator Pteris vittata.

Arsenic (As) contamination in soil poses a potential threat to human health via crop uptake. As-hyperaccumulator Pteris vittata serves as a model plant to study As uptake and associated mechanisms. This study focuses on a novel P/AsV transport system mediated by low-affinity phosphate transporter-B 1 family (PTB1) in P. vittata. Here, we identified two plasma-membrane-localized PTB1 genes, PvPTB1;1/1;2, in vascular plants for the first time, which were 4.4-40-fold greater in expression in P. vittata than in other Pteris ferns. Functional complementation of a yeast P-uptake mutant and enhanced P accumulation in transgenic Arabidopsis thaliana confirmed their role in P uptake. Moreover, the expression of PvPTB1;1/1;2 facilitated the transport and accumulation of As in both yeast and A. thaliana shoots, demonstrating a comparable AsV uptake capacity. Microdissection-qPCR analysis and single-cell transcriptome analysis collectively suggest that PvPTB1;1/1;2 are specifically expressed in the epidermal cells of P. vittata roots. PTB1 may play a pivotal role in efficient P recycling during phytate secretion and hydrolysis in P. vittata roots. In summary, the dual P transport mechanisms consisting of high-affinity Pht1 and low-affinity PTB1 may have contributed to the efficient P/As uptake in P. vittata, thereby contributing to efficient phytoremediation for As-contaminated soils.

Knowledge, attitudes, and practices of primary healthcare practitioners regarding pharmacist clinics: a cross-sectional study in Shanghai.

BACKGROUND: Pharmacist clinics offer professional pharmaceutical services that can improve public health outcomes. However, primary healthcare staff in China face various barriers and challenges in implementing such clinics. To identify existing problems and provide recommendations for the implementation of pharmacist clinics, this study aims to assess the knowledge, attitudes, and practices of pharmacist clinics among primary healthcare providers. METHODS: A cross-sectional survey based on the Knowledge-Attitude-Practice (KAP) model, was conducted in community health centers (CHCs) and private hospitals in Shanghai, China in May, 2023. Descriptive analytics and the Pareto principle were used to multiple-answer questions. Chi-square test, Fisher's exact test, and binary logistic regression models were employed to identify factors associated with the knowledge, attitudes, and practices of pharmacist clinics. RESULTS: A total of 223 primary practitioners participated in the survey. Our study revealed that most of them had limited knowledge (60.1%, n = 134) but a positive attitude (82.9%, n = 185) towards pharmacist clinics, with only 17.0% (n = 38) having implemented them. The primary goal of pharmacist clinics was to provide comprehensive medication guidance (31.5%, n = 200), with medication education (26.3%, n = 202) being the primary service, and special populations (24.5%, n = 153) identified as key recipients. Logistic regression analysis revealed that education, age, occupation, position, work seniority, and institution significantly influenced their perceptions. Practitioners with bachelor's degrees, for instance, were more likely than those with less education to recognize the importance of pharmacist clinics in medication guidance (aOR: 7.130, 95%CI: 1.809-28.099, p-value = 0.005) and prescription reviews (aOR: 4.675, 95% CI: 1.548-14.112, p-value = 0.006). Additionally, practitioners expressed positive attitudes but low confidence, with only 33.3% (n = 74) feeling confident in implementation. The confidence levels of male practitioners surpassed those of female practitioners (p-value = 0.037), and practitioners from community health centers (CHCs) exhibited higher confidence compared to their counterparts in private hospitals (p-value = 0.008). Joint physician-pharmacist clinics (36.8%, n = 82) through collaboration with medical institutions (52.0%, n = 116) emerged as the favored modality. Daily sessions were preferred (38.5%, n = 86), and both registration and pharmacy service fees were considered appropriate for payment (42.2%, n = 94). The primary challenge identified was high outpatient workload (30.9%, n = 69). CONCLUSIONS: Although primary healthcare practitioners held positive attitudes towards pharmacist clinics, limited knowledge, low confidence, and high workload contributed to the scarcity of their implementation. Practitioners with diverse sociodemographic characteristics, such as education, age, and institution, showed varying perceptions and practices regarding pharmacist clinics.

Three-Dimensional Evaluation of Changes in Condylar Position After Orthognathic Surgery With Different Types of Jaw Deformities.

BACKGROUND: Assessing condyle position postorthognathic surgery is pivotal for optimizing surgical accuracy, sustaining postoperative stability, and ensuring predictable treatment outcomes. PURPOSE: The aim of this study was to analyze the changes of condyle position after orthognathic surgery with different types of jaw deformity and to analyze whether the changes of condyle position are different. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study was designed and conducted, involving adults who underwent orthognathic surgery for jaw deformities at the affiliated Stomatological Hospital of Nanchang University between 2019 and 2022. Patients with incomplete CT data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was time (preoperative and postoperative) and types of jaw deformities (skeletal Class III, skeletal Class II, and mandibular deviation). MAIN OUTCOME VARIABLE(S): The main outcome variables were the three-dimensional linear and rotational positional changes of the condyle. COVARIATES: Evaluated covariates included sex and age. ANALYSES: MIMICS 20.0 software measured all data, and SPSS 22.0 software facilitated statistical analyses. Intragroup and intergroup correlation analyses employed paired t-tests and independent t-tests, with statistical significance set at P < .05. RESULTS: The study sample was composed of 32 subjects with a mean age of 22.43 ± 1.6 and 9 were male. The analysis of changes of condylar position from virtual surgical planning to the immediate postoperative period showed that the maximum condylar displacement was 1.74 mm and the maximum angular change was 3.92°. The analysis of changes in condylar position from the immediate postoperative period to 1 year postoperatively showed no statistically significant changes for the same type of jaw deformity. But patients with Class II malocclusion exhibited distinct condylar displacement and rotation patterns compared to those with Class III malocclusion and mandibular deformity. CONCLUSION AND RELEVANCE: The application of virtual surgical planning in orthognathic surgery ensures a high degree of consistency in achieving the desired condylar position. Moreover, no significant change in condylar position was observed after orthognathic surgery for the same type of jaw deformity. However, patients with Class II deformities exhibited a higher susceptibility to rotational displacement of the condyles compared to those with other types of jaw deformities.

Three-dimensional measurement and analysis of Mandibular Molar Distalization assisted by micro-implant anchorage combined with clear aligner.

Objective: To investigate the effect of micro-implant anchorage combined with a clear aligner on the efficiency of mandibular molar distalization and the protection of anterior teeth anchorage, provide reference for clinical scheme design. Methods: This is a prospective study. Seventeen patients who were treated in the Orthodontics Department of the Hospital of Stomatology affiliated to Fujian Medical University from 2019 to 2021 and used Invisalign clear aligners to move mandibular molars distally were included and divided into two groups according to anchorage types: Group-A and Group-B. Group-A (ten cases) were treated without micro-implant anchorage, while Group-B (seven cases) were treated with micro-implant anchorage nails for enhanced anchorage. The effect of micro-implant anchorage on crown and root distal movement of mandibular molars and the difference in three-dimensional movement between mandibular molars and mandibular central incisors were analyzed. Results: The crown distalization efficiency of mandibular first and second molars in Group-B was 68.66% and 71.02%, respectively, which were higher than those in Group-A(p<0.05). The mandibular central incisors in Group-A showed labial displacement and a small amount of elongation, while those in Group-B showed less anchorage loss(p<0.05). In Group-A, the crown was tilted in the distal direction and moved in the buccal direction during mandibular molar distalization(p<0.05). While in Group-B, the crown was tilted in the distal directio (p<0.05) and the mandibular second molar was depressed(p<0.05). Conclusion: In the process of mandibular molar distalization assisted by micro-implant anchorage combined with a clear aligner, better protects the anchorage of the mandibular central incisor and improves the efficiency of the molar crown distalization.

Epigenetic signature associated with thyroid cancer progression and metastasis.

Thyroid cancer is not among the top cancers in terms of diagnosis or mortality but it still ranks fifth among the cancers diagnosed in women. Infact, women are more likely to be diagnosed with thyroid cancer than the males. The burden of thyroid cancer has dramatically increased in last two decades in China and, in the United States, it is the most diagnosed cancer in young adults under the age of twenty-nine. All these factors make it worthwhile to fully understand the pathogenesis of thyroid cancer. Towards this end, microRNAs (miRNAs) have constantly emerged as the non-coding RNAs of interest in various thyroid cancer subtypes on which there have been numerous investigations over the last decade and half. This comprehensive review takes a look at the current knowledge on the topic with cataloging of miRNAs known so far, particularly related to their utility as epigenetic signatures of thyroid cancer progression and metastasis. Such information could be of immense use for the eventual development of miRNAs as therapeutic targets or even therapeutic agents for thyroid cancer therapy.

High-performance distributed dynamic strain sensing by synthesizing φ-OTDR and BOTDR.

We propose and demonstrate a high-performance distributed dynamic absolute strain sensing technique by synthesizing φ-OTDR and BOTDR. The technique synthesizes the relative strain obtained by the φ-OTDR part and the initial strain offset estimated by fitting the relative strain with the absolute strain signal from the BOTDR part. As a result, it provides not only the characteristics of high sensing accuracy and high sampling rate like φ-OTDR, but also the absolute strain measurement and the large sensing dynamic range like BOTDR. The experiment results indicate the proposed technique can realize the distributed dynamic absolute strain sensing with a sensing dynamic range of over 2500 µÉ›, a peak-to-peak amplitude of 1165 µÉ›, and a wide frequency response range from 0.1 to over 30 Hz over a sensing range of about 1 km.

Long-period D-fiber grating based robust and efficient bidirectional coupler for whispering gallery mode excitation.

A robust and efficient bidirectional coupler for whispering gallery mode (WGM) excitation based on a long-period grating (LPG) inscribed in D-fiber is theoretically and experimentally demonstrated. The LPG coupling the fundamental core mode to the forward propagating cladding modes according to the phase-matching condition not only enhances the evanescent field of the fiber but also selectively excites the WGM in a wavelength band of interest. Experimental results show that a maximum resonance contrast as high as 10.5 dB and a quality factor (Q-factor) on the order of 104 can be achieved in an LPG coupled spherical silica WGM resonator with a diameter of 242 µm, where the LPG with a pitch of 680 µm is fabricated by arc-discharging in a side-polished D-fiber with a maximum polishing depth of 56 µm. In addition to high robustness and efficiency, such an LPG-based WGM coupler also demonstrates bidirectionality, i.e., it is independent of the injection direction of the input light, which provides a reliable and flexible fiber coupler for the WGM resonator based practical applications.

Knock out of amino acid transporter gene OsLHT1 accelerates leaf senescence and enhances resistance to rice blast fungus.

Plant amino acid transporters regulate not only long-distance transport and reallocation of nitrogen (N) from source to sink organs, but also the amount of amino acids in leaves hijacked by invading pathogens. However, the function of amino acid transporters in plant defense responses to pathogen infection remains unknown. In this study, we found that the rice amino acid transporter gene OsLHT1 was expressed in leaves and up-regulated by maturation, N starvation, and inoculation of the blast fungus Magnaporthe oryzae. Knock out of OsLHT1 resulted in development stage- and N supply-dependent premature senescence of leaves at the vegetative growth stage. In comparison with the wild type, Oslht1 mutant lines showed sustained rusty red spots on fully mature leaf blades irrespective of N supply levels. Notably, no relationship between the severity of leaf rusty red spots and concentration of total N or amino acids was found in Oslht1 mutants at different developmental stages. Disruption of OsLHT1 altered transport and metabolism of amino acids and biosynthesis of flavones and flavonoids, enhanced expression of jasmonic acid- and salicylic acid-related defense genes, production of jasmonic acid and salicylic acid, and accumulation of reactive oxygen species. OsLHT1 inactivation dramatically prevented the leaf invasion by M. oryzae, a hemi-biotrophic ascomycete fungus. Overall, these results establish a link connecting the activity of an amino acid transporter with leaf metabolism and defense against rice blast fungus.

Narrow linewidth semiconductor multi-wavelength DFB laser array simultaneously self-injection locked to a single microring resonator.

We experimentally demonstrate a narrow linewidth semiconductor multi-wavelength distributed feedback (DFB) laser array by simultaneously injection locking each laser to the corresponding resonance of a single on-chip microring resonator. The white frequency noises of all the DFB lasers is reduced by more than 40 dB once they are simultaneously injection locked to a single microring resonator with a quality factor (Q-factor) of 2.38 million. Correspondingly, the instantaneous linewidths of all the DFB lasers are narrowed by a factor of 104. In addition, frequency combs originating from non-degenerate four-wave mixing (FWM) between the locked DFB lasers are also observed. Simultaneously injection locking multi-wavelength lasers to a single on-chip resonator may enable the possibilities of integrating a narrow-linewidth semiconductor laser array on a single chip and having multiple microcombs in a single resonator, which are in high demand in wavelength division multiplexing coherent optical communication systems and metrological applications.

Prevalence and genotype distribution of human papillomavirus infections in Beijing, China between 2016 and 2020.

BACKGROUND: Certain types of human papillomavirus (HPV) induce long-lasting infections that cause cervical cancer. This study evaluated the prevalence of HPV infections and the distribution of their genotypes among clinic patients and healthy women in Beijing, China. METHODS: Cervical specimens were collected from 12,100 patients and 1176 subjects who underwent physical examinations at Dongzhimen Hospital, Beijing University of Chinese Medicine, between March 2016 and September 2020. HPV genotyping was performed using commercial kits designed to detect 15 high-risk and 2 low-risk HPV genotypes. RESULTS: There was a higher overall prevalence of HPV among the clinic patients (21.0%) than among the healthy women (11.9%). The most common HPV genotypes among the patients were: HPV-52 (5.4%), HPV-16 (3.4%), HPV-58 (3.2%), HPV-51 (2.6%), HPV-39 (2.0%), HPV-56 (2.0%), and HPV-66 (2.0%). Among the healthy women: HPV-52 (3.0%), HPV-51 (1.8%), HPV-58 (1.6%), HPV-66 (1.5%), HPV-16 (1.2%), HPV-56 (1.2%), and HPV-18 (1.1%). Multiple HPVs were detected in 29.1% of the gynecological outpatients and in 23.6% of the women receiving physical examinations. The most common pairs of HPV types detected were HPV-52 and HPV-16 in the clinic patients, and HPV-52 and HPV-56 in the healthy women. Age-specific HPV positivity and peak prevalence were observed among the individuals in both groups for women aged less than 25 years and those between 61 and 65 years of age. CONCLUSIONS: Our results provide current estimates of HPV prevalence and genotypes in the Beijing region. The epidemiological characteristics observed also provide a reference for the development of cervical cancer screening strategies and selection of HPV vaccine antigen targets for this region. A comparison of these HPV prevalence data with those from other regions suggests that regional vaccines may be an important direction for future research.

Real-world applications of PARPi maintenance therapy for recurrent ovarian cancer: A single-center study in China.

OBJECTIVE: To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS). METHODS: We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors. RESULTS: Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2-32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081-9.757, P = 0.036). CONCLUSIONS: PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode.

Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Population Pharmacokinetics and Pharmacogenetics Analyses of Dasatinib in Chinese Patients with Chronic Myeloid Leukemia.

AIMS: Dasatinib, a second-generation tyrosine kinase inhibitor of BCR-ABL 1, used for first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML), exhibits high pharmacokinetic (PK) variability. However, its PK data in Chinese patients with CML remains rarely reported to date. Thus, we developed a population pharmacokinetic (PPK) model of dasatinib in Chinese patients and identified the covariate that could explain the individual variability of PK for optimal individual administration. METHODS: PPK modeling for dasatinib was performed based on 754 plasma concentrations obtained from 140 CML patients and analysis of various genetic and physicochemical parameters. Modeling was performed with nonlinear mixed-effects (NLME) using Phoenix NLME. The finally developed model was evaluated using internal and external validation. Monte Carlo simulations were used to predict drug exposures at a steady state for various dosages. RESULTS: The PK of dasatinib were well described by a two-compartment with a log-additive residual error model. Patients in the current study had a relatively low estimate of CL/F (126 L/h). A significant association was found between the covariate of age and CL/F of dasatinib, which was incorporated into the final model. None of the genetic factors was confirmed as a significant covariate for dasatinib. The results of external validation with 140 samples from 36 patients were acceptable. Simulation results showed significantly higher exposures in elderly patients. CONCLUSIONS: This study's findings suggested that low-dose dasatinib would be better suited for Chinese patients, and the dosage can be appropriately reduced according to the increase of age, especially for the elderly.

Outpatient Treatment With Gabapentin in Women With Severe Acute Pain After Cesarean Delivery Is Ineffective: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Most of the 1.1 million women who deliver by cesarean in the United States each year have an uncomplicated recovery. However, severe pain resistant to standard multimodal therapy within the first days after surgery is associated with an increased risk for prolonged pain and opioid use. The best outpatient management for parturients with severe resistant early onset pain is not known. METHODS: We performed a prospective, double-blind, placebo-controlled, randomized trial of up to 12 weeks of outpatient treatment with gabapentin to evaluate its effectiveness to facilitate opioid cessation in women with at least 2 reports of severe pain during the immediate postpartum period resistant to standard multimodal pain management. Time to opioid cessation was the primary outcome. Time to pain resolution; time to discontinuation of gabapentin, acetaminophen, and ibuprofen; time to self-reported recovery; and National Institute of Health Patient-Reported Outcomes System (PROMIS) surveys for anxiety, depression, fatigue, and physical function were assessed as secondary outcomes. RESULTS: There was no difference in time to opioid cessation between patients who were randomly assigned to be treated with gabapentin (Kaplan-Meier estimated median of 2 [25th-75th percentiles of 1-3] weeks, n = 35) versus those who were treated with placebo (2 [1-3] weeks, n = 35). The hazard ratio was 1.1 (95% confidence interval [CI], 0.67-1.8), P = .65. There were no differences in any secondary end points between the study groups. CONCLUSIONS: Outpatient supplementation with gabapentin did not reduce time to opioid cessation, pain, anxiety, depression, fatigue, or improve physical function in women with severe pain after cesarean delivery. Gabapentin should not be routinely added to the standard outpatient multimodal regimen of ibuprofen, acetaminophen, and opioids.

Feasibility of Focused Cardiac Ultrasound Performed by Trainees During Cesarean Delivery.

BACKGROUND: Anesthesiology experts advocate for formal education in maternal critical care, including the use of focused cardiac ultrasound (FCU) in high-acuity obstetric units. While benefits and feasibility of FCU performed by experts have been well documented, little evidence exists on the feasibility of FCU acquired by examiners with limited experience. The primary aim of this study was to assess how often echocardiographic images of sufficient quality to guide clinical decision-making were attained by trainees with limited experience performing FCU in term parturients undergoing cesarean delivery (CD). METHODS: In this prospective cohort study, healthy term parturients (American Society of Anesthesiologists [ASA] ≤ 3, ≥37 weeks of gestation) with singleton pregnancy, body mass index (BMI) <40 kg/m2, and no history of congenital and acquired cardiac disease undergoing scheduled, elective CD were recruited by a trainee. After undergoing standardized training, including an 8-hour online E-learning module, a 1-day hands-on FCU course, and 20 to 30 supervised scans until the trainee was assessed competent in image acquisition, 8 trainees with limited FCU experience performed apical 4-chamber (A4CH), parasternal long-axis (PLAX), and short-axis (PSAX) view preoperatively after spinal anesthesia (SPA) and intraoperatively after neonatal delivery (ND). Obtained FCU images were graded 1 to 5 by 2 blinded instructors (1 = no image to 5 = perfect image obtainable; ≥3 defined as image quality sufficient for clinical decision-making). RESULTS: Following the screening of 95 women, 8 trainees with limited FCU experience each performed a median of 5 [3-8] FCUs in a total of 64 women. Images of sufficient quality were obtainable in 61 (95.3 %) and 57 (89.1 %) of women after SPA and ND, respectively. FCU images of perfect image quality were obtainable in 9 (14.1 %) and 7 (10.9 %) women preoperatively after SPA and intraoperatively after ND, respectively. A PLAX, PSAX, and A4CH view with grade ≥3 was obtained in 53 (82.8 %), 58 (90.6 %) and 40 (62.5 %) of women preoperatively after SPA and in 50 (78.1 %), 49 (76.6 %), and 29 (45.3 %) of women intraoperatively after ND. Left ventricular function could be assessed in 39 of 40 women (97.5 %) preoperatively after SPA and 39 of 40 (97.5%) intraoperatively after ND. Right ventricular function could be assessed in 31 of 40 (77.5 %) after SPA and in 23 of 40 (59%) after ND. We observed a difference in image grading between different trainees in the AP4CH-view (P = .0001). No difference in image grading was found between preoperative and intraoperative FCUs. CONCLUSIONS: FCU is feasible in the parturient undergoing CD and images of sufficient quality for clinical decision-making were obtained by trainees with limited experience in almost all parturients. Image acquisition and quality in the A4CH view may be impacted by the individual trainee performing the FCU.

A novel NOTCH1 missense variant in two fetuses with a non-syndromic conotruncal heart defect from a single family.

AIMS: We describe two fetuses with conotruncal heart defects (CTDs) (persistent truncus arteriosus and pulmonary atresia/ventricular septal defect, respectively) in a Chinese family whose parents were both healthy. Testing was performed to identify any underlying genetic cause. MATERIALS AND METHODS: Genomic DNA was extracted from the peripheral blood of the proband's parents and the skeletal muscle tissue of the two aborted fetuses for genetic testing. RESULTS: A heterozygous likely pathogenic missense variant, c.1724G〉C (:p.Cys575Ser), in the NOTCH1 gene (NM_017617.5) was detected in the two affected fetuses but not in the parents, and the next generation sequencing test of the proband's father showed a normal result. It is therefore presumed to result from germline mosaicism in the proband's mother or, less likely, is a recurrent de novo variant in the fetuses. CONCLUSION: This is the first description of fetal non-syndromic CTD caused by a variant in NOTCH1. This report not only expands the gene variant spectrum of CTDs, but also emphasizes the importance of NOTCH1 testing when a fetal of CTD is detected.

Gender-specific co-developmental trajectories of internalizing and externalizing problems from middle childhood to early adolescence: Environmental and individual predictors.

This study aimed to identify gender-specific co-developmental trajectories of internalizing and externalizing problems from middle childhood to early adolescence, along with key environmental and individual predictors among Chinese youth. A total of 1653 Chinese elementary school students (M age = 9.40; SD = 0.51; 54.57% boys) participated in assessments at six time points, using 6-month assessment intervals. Parallel process latent class growth modeling identified four trajectories for boys: Congruent-low (65.74%), moderate-decreasing internalizing and moderate-stable externalizing problems (18.40%), high increasing-internalizing and low-stable externalizing problems (8.20%), and high decreasing-internalizing and low-stable externalizing problems (7.65%). Three trajectories were identified for girls: Congruent-low (81.09%), moderate co-occurring (7.19%), and high increasing-internalizing and low-stable externalizing problems (11.72%). Multivariate logistic regression analyses revealed that peer victimization served as an environmental risk predictor for the adverse co-developmental trajectories of internalizing and externalizing problems for boys and girls. High sensation-seeking and low self-control served as individual risk variables predicting the trajectories of high increasing-internalizing and low-stable externalizing problems, and low self-control also predicted the trajectories of high decreasing-internalizing and low-stable externalizing problems for boys. The findings highlight the importance of gender differences in understanding the progression of internalizing and externalizing problems and inform effective strategies for prevention and intervention.