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Mutations in various type II transmembrane serine protease (TMPRSS) family members are associated with non-syndromic hearing loss, with some mechanisms still unclear. For instance, the mechanism underlying profound hearing loss and tectorial membrane (TM) malformations in hepsin/TMPRSS1 knockout (KO) mice remains elusive. In this study, we confirmed significantly elevated hearing thresholds and abnormal TM morphology in hepsin KO mice, characterized by enlarged TM with gaps and detachment from the spiral limbus. Transgenic mouse lines were created to express either wild-type or a serine protease-dead mutant of human hepsin in the KO background. The Tg68;KO line, expressing moderate levels of wild-type human hepsin in the cochlea, showed partial restoration of hearing function. Conversely, the Tg5;KO or TgRS;KO lines, with undetectable hepsin or protease-dead hepsin, did not show such improvement. Histological analyses revealed that Tg68;KO mice, but not Tg5;KO or TgRS;KO mice, had a more compact TM structure, partially attached to the spiral limbus. These results indicate that hepsin expression levels correlate with improvements in hearing and TM morphology, and its protease activity is critical for these effects. Hepsin's role was further examined by studying its relationship with α-tectorin (TECTA) and β-tectorin (TECTB), non-collagenous proteins crucial for TM formation. Hepsin was co-expressed with TECTA and TECTB in the developing cochlear epithelium. Immunostaining showed decreased levels of TECTA and TECTB in hepsin KO TM, partially restored in Tg68;KO mice. These findings suggest that hepsin is essential for proper TM morphogenesis and auditory function, potentially by proteolytic processing/maturation of TECTA and TECTB and their incorporation into the TM., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This systematic review and meta-analysis aimed to determine whether Olympic weightlifting (OW) exercises would improve sprint performance when compared to a control intervention, (no training, standard sport-specific training, traditional resistance training, or plyometric training). Medline, Web of Science, SportDiscus, CINAHL, and Biological Science from inception to September 2022 was searched. Two authors independently selected the included studies, extracted data, and appraised the risk of bias. Certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. The primary meta-analysis combined the results of the sprint performance over the full length of each sprint test. The secondary meta-analyses combined the results of the sprint performance at 5, 10, and 20 m distance to capture information about the acceleration phase of the sprint tests. Eight studies with 206 athletes (female n=10, age range: 18.9-24.2 years) were identified. Sprint performance did not differ significantly comparing OW to the control intervention, nor at the full length (standardized mean difference=-0.07, 95% CI=-0.47 to 0.34, p =0.75, I 2 =46%) or during the acceleration phase ( p ≥0.26) of the sprint test. OW training does not improve sprint performance to a greater extent than comparator interventions., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The vaginal microbiome's composition varies among ethnicities. However, the evolutionary landscape of the vaginal microbiome in the multi-ethnic context remains understudied. We perform a systematic evolutionary analysis of 351 vaginal microbiome samples from 35 multi-ethnic pregnant women, in addition to two validation cohorts, totaling 462 samples from 90 women. Microbiome alpha diversity and community state dynamics show strong ethnic signatures. Lactobacillaceae have a higher ratio of non-synonymous to synonymous polymorphism and lower nucleotide diversity than non-Lactobacillaceae in all ethnicities, with a large repertoire of positively selected genes, including the mucin-binding and cell wall anchor genes. These evolutionary dynamics are driven by the long-term evolutionary process unique to the human vaginal niche. Finally, we propose an evolutionary model reflecting the environmental niches of microbes. Our study reveals the extensive ethnic signatures in vaginal microbial ecology and evolution, highlighting the importance of studying the host-microbiome ecosystem from an evolutionary perspective., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

To better respond to the strategic goals of "carbon peaking" and "carbon neutrality," businesses are collaborating with suppliers and customers to jointly promote green and environmentally friendly practices to increase economic benefits, enhance social reputation, and improve environmental competitiveness while achieving environmental performance. Currently, some theoretical achievements in the field of green supply chain integration have been made. Nevertheless, systematic retrospective research needs to be improved to help us fully understand the status of research in China and elsewhere. Therefore, this article analyzed the concept of green supply chain integration using eight years of data (from 2014 to 2021) from a small and medium-sized environmental company 1 and divided the concept into four systems: the water cycle system (H 2 O), renewable energy system (CaCl 2 ), carbon peak system (CO 2 ), and carbon-neutral system (CO 2 ). These four systems were analyzed with regard to internal green integration, green supplier integration, and green customer integration, and the Scheffé method was used to analyze the impact of these four systems on corporate ecological impact and financial and social sustainability. The study also verified that the intensity of sunlight on solar panels is significantly affected by environmental temperature (ET), carbon neutrality, and the electricity generated by solar panels. The impact of carbon pricing was also explored using the probability density function (PDF) method. The contribution of this research lies in the fact that it provides evidence that solar energy can help reduce the use of fossil fuels, reducing demand for the carbon quota market. This can help lower carbon prices, thereby encouraging more businesses and countries to participate in carbon neutrality and emission reduction actions. In addition, solar power systems can replace renewable energy sources, making the carbon quota market more diverse and stable. Carbon pricing options can be used to manage the risks and uncertainties related to carbon pricing policies, and policy-makers can use them to develop appropriate risk management strategies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: The COVID-19 pandemic interrupted the organized training of softball players, similar to the abrupt cessation of sports participation that can happen after an injury. Thus, the COVID-19 pandemic offers a unique model to study how sudden detraining influences softball players., Methods: We recruited a sample of convenience of National Collegiate Athletic Association Division 1 softball players. They participated in three data collections: pre-lockdown (Jan 2020, T1), post-lockdown (Sept 2020, T2), and before the 2021 season (Jan 2021, T3). Between T1 and T2, players received an at-home conditioning and throwing program, but compliance was not strictly monitored. Between T2-T3, players resumed formal fall training (team-organized workouts, on-field practice, and within-team scrimmage games). At each time point, we collected bilaterally: 1) shoulder internal rotation (IR) and external rotation (ER) range of motion (ROM); 2) shoulder IR and ER strength; 3) hip IR and ER ROM; and 4) hip abduction and extension strength. We used four independent (2 Sides × 3 Timepoints) MANOVA with repeated measures; we followed up significant MANOVA main effect of time with Sidak posthoc tests for pairwise comparisons between time points., Results: Fifteen players participated in this study. We found a significant MANOVA main effect of time for shoulder and hip ROM (p < 0.01). Between T1-T2, dominant shoulder ER ROM decreased 6.5°, dominant shoulder IR ROM increased 4.3°, and lead hip IR ROM increased 4.4°. Between T2-T3, dominant shoulder ER ROM increased 6.3° and trail hip ER ROM increased 5.9°. We found a significant MANOVA main effect of time for shoulder strength (p = 0.03) but not for hip strength (p = 0.18). Between T2-T3, non-dominant shoulder IR and ER increased 1.8 kg and 1.5 kg, respectively., Conclusion: A sudden and prolonged cessation of organized training generated changes in shoulder and hip ROM but affected strength to a lesser extent. The loss of shoulder ER and increased lead hip IR ROM are maladaptive as they are associated with injury in overhead athletes. Resuming team-organized training and scrimmage reversed some (shoulder ER), but not all of these changes. Practitioners should monitor clinical variables regularly and be aware of potential changes due to unexpected and prolonged interruptions in training, such as when players suffer sports-related injuries., (© 2024. The Author(s).)

Herein, this work aims to directly visualize the morphological evolution of the controlled self-assembly of star-block polystyrene- block -polydimethylsiloxane (PS- b -PDMS) thin films via in situ transmission electron microscopy (TEM) observations. With an environmental chip, possessing a built-in metal wire-based microheater fabricated by the microelectromechanical system (MEMS) technique, in situ TEM observations can be conducted under low-dose conditions to investigate the development of film-spanning perpendicular cylinders in the block copolymer (BCP) thin films via a self-alignment process. Owing to the free-standing condition, a symmetric condition of the BCP thin films can be formed for thermal annealing under vacuum with neutral air surface, whereas an asymmetric condition can be formed by an air plasma treatment on one side of the thin film that creates an end-capped neutral layer. A systematic comparison of the time-resolved self-alignment process in the symmetric and asymmetric conditions can be carried out, giving comprehensive insights for the self-alignment process via the nucleation and growth mechanism.

Kettlebell training provides multiple health benefits, including the generation of power. The primary purpose of this study was to examine the kinematics and kinetics of lower-body joints during a repeated, maximum effort kettlebell swing protocol. Sixteen resistance and kettlebell swing experienced males performed 10 rounds of a kettlebell swing routine (where one round equates to 30s of swings followed by 30s of rest). Kinematic (i.e., swing duration and angular velocities) and kinetic (i.e., normalised sagittal plane ground reaction force, resultant joint moment [RJM] and power) variables were extracted for the early portion and late portion of the round. Average swing duration and the magnitude of normalised ground reaction forces (GRF) increased within rounds, while hip joint power decreased. Changes in swing duration were minimal, but consistent due to an increase in overall fatigue. An increase in the magnitude of GRF was observed at the end of rounds, which is a potential concern for injury. Hip joint power decreased primarily due to a slower angular velocity. This protocol may be an effective routine for those who are resistance trained with kettlebell swing experience, and who want to optimise power in their exercise program.

The mammalian central circadian clock, located in the suprachiasmatic nucleus (SCN), coordinates the timing of physiology and behavior to local time cues. In the SCN, second messengers, such as cAMP and Ca 2+ , are suggested to be involved in the input and/or output of the molecular circadian clock. However, the functional roles of second messengers and their dynamics in the SCN remain largely unclear. In the present study, we visualized the spatiotemporal patterns of circadian rhythms of second messengers and neurotransmitter release in the SCN. Here, we show that neuronal activity regulates the rhythmic release of vasoactive intestinal peptides from the SCN, which drives the circadian rhythms of intracellular cAMP in the SCN. Furthermore, optical manipulation of intracellular cAMP levels in the SCN shifts molecular and behavioral circadian rhythms. Together, our study demonstrates that intracellular cAMP is a key molecule in the organization of the SCN circadian neuronal network.

Background: Pain assessments are an important aspect of health care quality because the high prevalence of pain in inpatients may contribute to complications. Several studies revealed a gap in the pain intensity evaluated by nurses (PEN) and patients (PEP). The aim of the present study was to analyze the correlation and agreement between pain assessments conducted by nurses and patients, and to determine patients at high risk of misestimated pain., Objectives: To compare the difference of pain intensity between the questionnaires conducted by additional assessors and electronic records by nursing staff., Study Design: A retrospective study., Setting: A medical center in Taichung, Taiwan., Methods: We approached 1,034 patients admitted from January 1, 2018 to December 31, 2018 in our hospital. We compared the assessments of pain intensity using questionnaires conducted by additional assessors with those entered into electronic records by nursing staff. Continuous data were reported as the mean (± standard deviation). The analysis of agreement and correlation were performed by kappa statistics or weighted kappa statistics, and correlation (Spearman rank correlation method)., Results: Among the 1,034 patients, 307 patients were excluded. Thus, the final analysis included 686 patients. Patients' median pain intensity was 5 in PEP and 1 in PEN. The patients' pain intensity was underestimated (PEN < PEP) in 539 patients (78.6%), matched (PEN = PEP) in 126 patients (18.3%), and overestimated (PEN > PEP) in 21 patients (3.1%). The surgical interventions (chi squared = 7.996, and P = 0.018) and pain in the past 24 hours (chi squared = 17.776, and P < 0.001) led to a significant difference., Limitations: The limitation of the study was the single-center and retrospective design., Conclusions: The gap in pain assessments between inpatients and nurses is an important issue in daily practice. The underestimations of pain were more common than overestimations (78.6% vs 3.1%). Surgical interventions and persistent pain lasting over 24 hours were high risk factors for underestimation, but patients' gender, receiving anesthesia, type of anesthesia, and patient-controlled analgesia did not contribute significantly to differences in pain estimation.

Background: Coexistence of a catecholamine-secreting tumor and an adrenal cortical tumor is quite rare which makes both diagnosis and management challenging. The purpose of this article is to describe the presence of this condition, share a stepwise approach for preoperative evaluation, and review the related literature., Case Presentation: A 44-year-old male patient had a history of hypertension and aggravating hypokalemia for years. Abdominal computed tomography incidentally found concomitant bilateral adrenal and left para-aortic tumors. Comprehensive adrenal hormone tests revealed a high aldosterone renin ratio and mildly elevated 24-h urine vanillylmandelic acid and norepinephrine levels. Subsequently, a metaiodobenzylguanidine scan showed uptake over the left para-aortic tumor, and NP-59 adrenal scintigraphy showed uptake over the left adrenal tumor. Further confirmatory tests, including captopril suppression, irbesartan suppression, and saline infusion, all confirmed the diagnosis of hyperaldosteronism. Adrenal venous sampling following 2 months of preparation with an alpha blocker demonstrated a left aldosterone-producing adrenal adenoma. Combining hormonal analysis, imaging studies, and adrenal venous sampling, the patient was diagnosed with left adrenal aldosteronoma, right adrenal nonfunctional tumor, and left para-aortic paraganglioma (PGL). Accordingly, laparoscopic left adrenalectomy and left PGL excision were performed smoothly under alpha blocker maintenance. The pathology report confirmed left adrenal cortical adenoma and left para-aortic PGL. Postoperatively, the blood pressure, biochemical tests, and adrenal hormone assays returned to normal, and related symptoms disappeared and were relatively stable during the follow-up period of two years., Conclusions: This is the first case of left para-aortic PGL coexisting with an ipsilateral aldosterone-producing adenoma presenting as a left para-aortic tumor associated with bilateral adrenal tumors. Awareness of the rarity of this coexistence can avoid unexpected disasters during the process of evaluation and management., (© 2022. The Author(s).)

Oncocytic tumors comprise a group of rare benign neoplasm of salivary glands, accounting for less than 1% of all salivary gland tumors. Nodular oncocytic hyperplasia characterized by multiple unencapsulated oncocytic nodules in the salivary glands is an extremely rare condition. We report a case of bilateral nodular oncocytic hyperplasia of parotid glands with parapharyngeal space extension in an 80-year-old woman whose initial presentation was recurrent parotitis. Our case may be the first report of nodular oncocytic hyperplasia in the parapharyngeal space, arising from the parotid gland. The patient underwent total parotidectomy and excision of parapharyngeal tumors using a transparotid transcervical approach, and at the 2-year follow-up, no evidence of recurrence was found.

Background: This study aimed to determine whether drug doses per kilogram of lean body mass (LBM) were associated with dose-limiting toxicity (DLT) events in head and neck cancer (HNC) patients., Methods: This retrospective cohort study included 179 HNC patients who underwent induction chemotherapy (IC) at a medical center from May 1, 2014, to May 31, 2021. HNC patients' characteristics, tumor factors, IC regimen and dose, laboratory data, and body composition factors, including lean body mass (LBM) and skeletal muscle index (SMI), derived from CT, MRI, or PET scan images and drug dose per kilogram LBM were recorded. Dose-limiting toxicity (DLT) events were regarded as the primary outcome. Multivariate logistic regression was used to establish a novel risk score for DLT events by the abovementioned variables. The above-mentioned risk score was validated in another cohort., Results: The overall DLT events during the first cycle of IC for 179 HNC patients was 24%. After stratifying by gender, docetaxel per kilogram LBM > 2.52 mg/kg (adjusted odds ratio [aOR]: 3.18; 95% confidence interval [CI], 1.25-8.09), pre-treatment glutamic pyruvic transaminase (GPT) > 40 U/L (aOR, 2.61; 95% CI, 1.03-6.64), and history of chronic liver diseases (aOR, 3.98; 95% CI, 1.03-15.46) were significant variables in male HNC patients. The DLT events risk was categorized by summation of the above-mentioned risk factors for male HNC patients. Three risk groups were stratified by overall event of 17.6%, 25.8%, and 75%. The above-mentioned risk score had an acceptable discriminatory ability in another validation cohort., Conclusions: Among male HNC patients treated with IC, docetaxel per kilogram LBM more than 2.52 mg/kg, pre-treatment GPT > 40 U/L, and history of chronic liver disease were significant risk factors for DLT events. Identifying high-risk patients could help physicians prevent severe/fatal complications among HNC patients undergoing IC, especially for the male individuals., (© 2022. The Author(s).)

We previously showed that perceived effort during visually guided reaching was altered as task demand varied. Further, self-reported subjective fatigue correlated with perceived effort and reach performance under visually guided conditions. Memory-guided reaching often leads to performance deterioration and can provide insights about the planning and control of reach actions. It is unclear how perceived effort changes during memory-guided reaching and whether self-reported subjective fatigue is associated with perceived effort of memory-guided reaching. Twenty-three young adults performed reach actions under visually- and memory-guided conditions. Perceived effort, reaction time, and endpoint error increased significantly from the visually- to the memory-guided condition. Self-reported subjective fatigue was associated with perceived effort and reach distance error during memory-guided reaching; those with higher levels of fatigue reported greater perceived effort and tended to reach farther when visual information was not available. These findings establish a foundation to examine relationships between subjective fatigue, perceived effort, and reach control.

This work aims to demonstrate a facile method for the controlled orientation of nanostructures of block copolymer (BCP) thin films. A simple diblock copolymer system, polystyrene- block -polydimethylsiloxane (PS- b -PDMS), is chosen to demonstrate vacuum-driven orientation for solving the notorious low-surface-energy problem of silicon-based BCP nanopatterning. By taking advantage of the pressure dependence of the surface tension of polymeric materials, a neutral air surface for the PS- b -PDMS thin film can be formed under a high vacuum degree (∼10 -4 Pa), allowing the formation of the film-spanning perpendicular cylinders and lamellae upon thermal annealing. In contrast to perpendicular lamellae, a long-range lateral order for forming perpendicular cylinders can be efficiently achieved through the self-alignment mechanism for induced ordering from the top and bottom of the free-standing thin film.

Cervical exenteration with anterior mediastinal tracheostomy is rarely performed for extensive cervicothoracic malignancies. Although it provides effective palliation and occasional cure, reconstruction remains a formidable challenge owing to its complexity and high mortality. The resultant defects usually require an intestinal flap or tubed skin flap to restore the alimentary tract, soft-tissue interposition to separate the relocated trachea from the innominate artery, and another tubed or fenestrated skin flap to create a tension-free tracheocutaneous anastomosis and provide coverage for the exposed vessels, hopefully in one stage. We report a case involving a 60-year-old woman with recurrent medullary thyroid cancer who developed dyspnea and dysphagia. Salvage cervical exenteration and anterior mediastinal tracheostomy were complicated by tissue fibrosis caused by previous surgical and radiation therapies, resulting in complex defects with segmental loss of the esophagus, a short stump of trachea incapable of tracheocutaneous anastomosis, and great-vessel exposure. We used a chimeric anterolateral thigh flap consisting of a tubed skin flap for pharyngoesophageal reconstruction, a fenestrated skin flap for tracheostomy and neck coverage, and a vastus lateralis muscle bulk to separate the innominate artery from the relocated trachea. To our knowledge, this is the first report describing the reconstruction of such a complex defect with a single skin flap in a single stage., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: In-laboratory, polysomnography (PSG) is the gold standard for diagnosing obstructive sleep apnea syndrome (OSAS). However, the long waiting list and sleeping at a hospital make patients hesitate to undergo the examination, thereby delaying diagnosis. During coronavirus disease 2019 (COVID-19) pandemic, sleep labs are almost closed, and the delay is worsening. The home sleep test (HST) enables subjects to be tested at home, a familiar and comfortable environment, without a long waiting list. This study assessed the accuracy of a type III HST in diagnosing OSAS in the Taiwanese population and identified factors affecting the diagnostic accuracy., Methods: This retrospective study included 67 patients with clinically suspected OSAS. All patients were allocated to receive both PSG and the HST. The apnea-hypopnea index (AHI) measured through PSG was used as the standard. The sensitivity, specificity, and accuracy of the HST in diagnosing and evaluating the severity of OSAS were analyzed., Results: Among the 67 patients, no significant difference was noted in the average AHI values obtained using PSG and the HST ( p = 0.103). The AHI obtained from HST was significantly correlated with that obtained from PSG, with the correlation coefficient being 0.779 ( p < 0.001). The sensitivity, specificity, and accuracy of the HST in diagnosing OSAS were 94.9%, 62.5%, and 91.0%, respectively, and 80.0%, 74.1%, and 77.6% in diagnosing moderate to severe OSAS. Furthermore, the difference in AHIs measured using the two tests were positively correlated with the severity of sleep apnea., Conclusion: The HST used in preliminary screening of patients with suspected OSAS achieved an accuracy of >90%. For patients with moderate to severe OSAS, the accuracy was below 80%. Therefore, for patients who receive an OSAS diagnosis through the HST, arrangement of PSG is recommended for determining the severity of the OSAS and giving proper treatment., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Spinal microglia are crucial to neuronal hyper-excitability and pain hypersensitivity. The local anesthetic bupivacaine is commonly used for both peripheral and spinal anesthesia. The pain-relief effects resulting from the peripheral and systemic administration of bupivacaine have been previously reported. In this study, the preventive effects of intrathecal bupivacaine administration against neuropathic pain were revealed in a rat model of sciatic nerve chronic constriction injury (CCI). Using a CCI rat model, pain hypersensitivity, characterized by mechanical allodynia and thermal hyperalgesia, correlated well with microglia M1 polarization, activation and pro-inflammatory cytokine expression in both spinal cord dorsal horns and sciatic nerves. Bupivacaine attenuated pain behaviors and inflammatory alternations. We further identified that the Interferon Regulatory Factor 5 (IRF5)/P2X Purinoceptor 4 (P2X4R) and High Mobility Group Box 1 (HMGB1)/Toll-Like Receptor 4 (TLR4)/NF-κB inflammatory axes may each play pivotal roles in the acquisition of microglia M1 polarization and pro-inflammatory cytokine expression under CCI insult. The relief of pain paralleled with the suppression of microglia M1 polarization, elevation of microglia M2 polarization, and inhibition of IRF5/P2X4R and HMGB1/TLR4/NF-κB in both the spinal cord dorsal horns and sciatic nerve. Our findings provide molecular and biochemical evidence for the anti-neuropathic effect of preventive bupivacaine.

Dietary fibers act through the microbiome to improve cardiovascular health and prevent metabolic disorders and cancer. To understand the health benefits of dietary fiber supplementation, we investigated two popular purified fibers, arabinoxylan (AX) and long-chain inulin (LCI), and a mixture of five fibers. We present multiomic signatures of metabolomics, lipidomics, proteomics, metagenomics, a cytokine panel, and clinical measurements on healthy and insulin-resistant participants. Each fiber is associated with fiber-dependent biochemical and microbial responses. AX consumption associates with a significant reduction in LDL and an increase in bile acids, contributing to its observed cholesterol reduction. LCI is associated with an increase in Bifidobacterium. However, at the highest LCI dose, there is increased inflammation and elevation in the liver enzyme alanine aminotransferase. This study yields insights into the effects of fiber supplementation and the mechanisms behind fiber-induced cholesterol reduction, and it shows effects of individual, purified fibers on the microbiome., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Warthin tumor with ulceration of the surrounding skin is extremely rare, making it difficult to differentiate from parotid cancer in the clinical setting. We report a 65-year-old man with a Warthin tumor in the right parotid gland that had ulceration of the overlying skin. The patient presented with right upper neck mass 2 years ago. Ultrasound and fine needle aspiration were done, and Warthin tumor was suspected. One year later, the mass was enlarged with ulceration of the skin. Superficial parotidectomy with fusiform excision of the skin was performed, and histopathological diagnosis revealed a Warthin tumor with inflammatory change. We proposed that this unique manifestation may have been induced by fine needle aspiration, enlargement of the tumor, and ischemic changes secondary to pulmonary arteriovenous malformations.

Sleep and wakefulness are regulated by both the homeostatic mechanism and circadian clock. In mammals, the central circadian clock, the suprachiasmatic nucleus, in the hypothalamus plays a crucial role in the timing of physiology and behavior. Recently, we found that the circadian regulation of wakefulness was transmitted via corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus to orexin neurons in the lateral hypothalamus. However, it is still unclear how the molecular clock in the CRF neurons contributes to the regulation of sleep and wakefulness. In the present study, we established CRF neuron-specific Bmal1 -deficient mice and measured locomotor activity or electroencephalography and electromyography. We found that these mice showed normal circadian locomotor activity rhythms in both light-dark cycle and constant darkness. Furthermore, they showed normal daily patterns of sleep and wakefulness. These results suggest that Bmal1 in CRF neurons has no effect on either circadian locomotor activity or sleep and wakefulness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hung, Yamanaka and Ono.)

Introduction: Foreign body ingestion is the most common reason for otolaryngology specialist consultations in emergency departments. Among the different types of foreign bodies, fish bones are the most common, particularly in Asian populations. In Taiwan, upper aerodigestive tract foreign bodies (UADT-FBs) are mostly managed by residents in the otorhinolaryngology (ORL) department. Considering the learning curve required for all procedures, different management types between residents, and possible resulting safety issues, this study explored the outcomes of UADT-FB management by residents in different years of ORL training., Materials and Methods: The medical records of 2,283 patients who visited Kaohsiung Veterans General Hospital's Emergency Department for UADT-FB during June 2013-August 2019 were retrospectively reviewed. The reviewed data included the demographic data of enrolled patients, outcomes of foreign body management, and follow-up chart records of the patients., Results: Among the 2,283 patients, 1,324 (58%) were found to be negative for foreign bodies, and foreign bodies in 951 (41.7%) were removed immediately. In the negative finding (NF) group, 2 (4.9%) patients were later found to be positive for foreign bodies during follow-up in the outpatient department. One (2.4%) patient developed a deep neck infection and esophageal perforation. The percentage of NFs decreased from 62.58% in residents in the first half of their first year (R1a) to 54% for third-year residents (R3). Comparing R1a with R3, the number needed to harm for retained UADT-FBs after patients visited the emergency department was 12.2., Discussion/conclusion: This study provides data from 1 referral center regarding the management of UADT-FBs. With increasing resident training, the percentage of NFs declined from 62.58 to 54%. Young residents, especially those in the first 6 months of their training, should have senior residents perform a second examination if UADT-FBs are not found in suspected cases., (© 2021 S. Karger AG, Basel.)

Perceived effort for goal-directed reaching may be impacted by the level of self-reported fatigue, however, the relationship between self-reported fatigue and perceived effort has not been examined. We examined how perceived effort changed under varied reach conditions and the relationship between fatigue, perceived effort and reach performance. Twenty-three young adults performed reach actions toward 9 different targets on a digitizing tablet. Perceived effort was measured using the Borg Rate of Perceived Exertion and Paas Mental Effort Rating Scale. Self-reported fatigue was quantified using the Fatigue Scales for Motor and Cognitive Functions. As reach conditions became more difficult, perceived effort increased significantly. Further, individuals who reported greater fatigue also reported greater perceived effort and showed greater endpoint error during reaching.

In this paper, the impact of both gender and age on the claim rates of dread disease and cancer insurance policies were examined using unique data taken from Taiwan's private health insurance policies issued by non-life insurers during the 2012 to 2015 policy years. Those aged 30-39 served as the reference group. For the total number of dread disease policies, male insureds had a higher non-cancer claim probability than female insureds, while an age under 20 was associated with much lower claim rates for dread disease policies than for ages over 50. The claim rate for dread disease policies increased rapidly beginning at age 40 for both cancerous and non-cancerous diseases amongst male insureds. Amongst female insureds, those under 20 had much lower claim rates for dread disease policies. Only those aged 50-59 had a higher claim rate for non-cancerous diseases. For the total number of cancer insurance policies, male insureds had lower claim rates than female insureds, with an upward trend being associated with age. For male (female) insureds aged over 40 (20), the claim rates of cancer increased with age.

The purpose of this study was to investigate the linear relationships among the hand/clubhead motion characteristics in golf driving in skilled male golfers (n = 66; handicap ≤ 3). The hand motion plane (HMP) and functional swing plane (FSP) angles, the HMP-FSP angle gaps, the planarity characteristics of the off-plane motion of the clubhead, and the attack angles were computed from the drives captured by an optical motion capture system. The HMP angles were identified as the key variables, as the HMP and FSP angles were intercorrelated, but the plane angle gaps, the planarity bias, and the attack angles showed correlations to the HMP angles primarily. Three main swing pattern clusters were identified. The parallel HMP-FSP alignment pattern with a small direction gap was associated with neutral planarity and planar swing pattern. The inward alignment pattern with a large inward direction gap was characterized by flat planes, follow-through-centric planarity, spiral swing pattern, and inward/downward impact. The outward alignment pattern with a large outward direction gap was associated with steep planes, downswing-centric planarity, reverse spiral swing, and outward/upward impact. The findings suggest that practical drills targeting the hand motion pattern can be effective in holistically reprogramming the swing pattern.

From the popularity of flipped teaching in United States primary and high schools, it is thought that students have more learning control to adjust to the learning progress and are assisted in problem solving and learning guidance during class period. It is believed that flipped teaching could prompt underachieving learners' active learning and thereby enhance learning effectiveness. A total of 386 high school students in Chungli, Taiwan, were part of an experimental study and the research results are summarized below: (1) Students who participated in the flipped teaching models demonstrated better comprehension levels with the teaching content due to this change in learning style and attitude, which in turn, enhanced learning effectiveness. (2) To eliminate poor language performance of underachieving students, it is necessary to lay solid foundations to gradually enhance language learning effectiveness regarding this particular group of students. Films suitable for students' individual ability could be combined with new language learned in the unit to genuinely assist underachieving learners' language learning effectiveness. (3) For students who care about their performance, a "system of play" style grouping should be determined in order to enable the tracking of group performance and term performance. According to the results, further developments regarding active learning ability, boosts in learning interests, enhanced learning effectiveness, and the prompting of creativity resulting in a shift from passive learner to active learner have been proposed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chou, Chen and Hung.)

Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article.

Gold nanoparticles (AuNPs) are biocompatible nanomaterials with potential application in the food industry. The safety of AuNPs oral consumption remains inconclusive, and information on possible long-term toxicity is limited. The current study aimed to evaluate the subchronic oral toxicity of AuNPs in male and female Institute of Cancer Research (ICR) mice. Citrate-coated spherical AuNPs with 53 nm diameters were prepared and orally administered to the mice. No mortality or clinical abnormalities were observed following daily administration of AuNPs at the dosages of 0.2, 2, and 20 mg/kg for 90 days. There was no significant difference in body weight or the relative organs' weights between the control and AuNPs-treated mice. No gross abnormalities or histopathological changes were observed except that the male mice treated with high dose (20 mg/kg AuNPs) showed minor infiltration in the kidneys, and female mice showed a reduced A/G ratio and elevated platelet indices. Overall, the 90-day long-term oral consumption of AuNPs did not cause significant toxicity in mice., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Published by Elsevier Ltd.)

Rationale: The Pisa syndrome (PS) is defined as a kind of reversible postural deformity which causes a lateral trunk flexion of 10 degrees or more. A prevalence of approximately 7.4% to 10.3% of patients with Parkinson disease (PD) also have PS. Though unbalanced function of the basal ganglia network and impaired visual-spatial functions including parietal cortices in PS is known, the pathophysiology of PS remains to be unclear., Patient Concerns: A 67-year-old male patient with PD visited our Rehabilitation outpatient department because of his trunk which involuntarily deviated to the left side when he stood up., Diagnoses: Based on the history, physical examination, X-ray images, Tc-99m brain TRODAT-1 single-photon emission computed tomography (SPECT), and regional cerebral perfusion Tc-99m ethyl cysteinate dimer SPECT, the patient was diagnosed with PD with PS., Interventions: The patient refused our recommendation of admission for pharmaceutical treatment due to personal reasons and was only willing to accept physical training programs at our outpatient department., Outcomes: We arranged functional neuroimaging of the brain to survey possible neurologic deficits. The patient's images of ethyl cysteinate dimer SPECT and TRODAT SPECT showed abnormalities, including hypoperfusion and diminished dopamine transporter uptake, in the areas of the basal ganglia network and other brain regions., Lessons: Based on previous literature and the imaging of our patient, we hypothesize that PS results from unbalanced function of the basal ganglia network and impaired visual-spatial functions of bilateral parietal cortices., Competing Interests: The authors have no funding and conflicts of interest to disclose, (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Comprehensive pre-reoperative localization is essential in complicated persistent or recurrent renal hyperparathyroidism. The widely used imaging studies sometimes lead to ambiguous results. Our study aimed to clarify the role of tissue aspirate parathyroid hormone (PTH) assay with a new positive assay definition for imaging suspicious neck lesions in these challenging scenarios., Methods: All patients with complicated recurrent or persistent renal hyperparathyroidism underwent parathyroid sonography and scintigraphy. Echo-guided tissue aspirate PTH assay was performed in suspicious lesions revealed by localization imaging studies. The tissue aspirate PTH level was determined by an immunoradiometric assay. We proposed a newly-developed definition for positive assay as a washout level higher than one-thirtieth of the serum PTH level obtained at the same time. The final diagnosis after re-operation was confirmed by the pathologists., Results: In total, 50 tissue aspirate PTH assays were performed in 32 patients with imaging suspicious neck lesions, including discrepant results between scintigraphy and sonography in 47 lesions (94%), unusual locations in 19 lesions (38%), multiple foci in 28 lesions (56%), and locations over previously explored areas in 31 lesions (62%). Among 39 assay-positive lesions, 13 lesions (33.3%) were not identified by parathyroid scintigraphy, and 28 lesions (71.8%) had uncertain parathyroid sonography findings. The final pathology in patients who underwent re-operative surgery proved the tissue aspirate PTH assays had a 100% positive predictive value., Conclusions: Our findings suggest tissue aspirate PTH assay with this new positive assay definition is beneficial to clarify the nature of imaging suspicious lesions in patients with complicated persistent or recurrent renal hyperparathyroidism.

Background: Sorafenib has been shown to prolong the progression free survival (PFS) of advanced radioiodine (RAI) refractory differentiated thyroid cancer (DTC) and has been approved by the FDA as the result of the phase III DECISION trial. Sorafenib has been reimbursed for the treatment of RAI refractory DTC in Taiwan since Jan 2017. High percentage of adverse events (AE) was noted in DECISION trial. We conducted a study to show the real-world experience of sorafenib in Taiwan., Methods: We retrospectively collected the clinical data, including dose, AE, and PFS of sorafenib, of the DTC patients who received sorafenib treatment in National Cheng Kung University Hospital and China Medical University Hospital by chart review from 2012 to 2018., Results: Thirty-six advanced DTC patients with progression were included in this study. The starting dose of sorafenib in most patients was 200 mg twice daily and the mean daily maintenance dose was 433 mg. Five patients had partial response (13.9%) and 28 patients had stable disease (77.8%). The median PFS was 17.3 months (95% confidence interval: 11.9-33.6 months). Daily maintenance dose ≥ 600 mg was associated with better PFS (median PFS, not reached). The most common toxicity of sorafenib was hand foot skin reaction (69%), followed by diarrhea (42%), and skin rash (33%). Most of the toxicities were grade I/II., Conclusion: Higher maintenance dose of sorafenib is associated with longer PFS while starting from half dose is feasible to minimize the incidence of high grade toxicities in the real-world use of sorafenib., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Objective: The pain prevalence of inpatients is not a well-studied medical issue in Asia. We have aimed to evaluate pain prevalence and characterize those patients who have suffered from severe, persistent pain., Methods: We investigated pain prevalence using a quota sampling from 19 general wards during the year 2018. Using a structured questionnaire, eight interviewers visited patients at an age ≥ 20 years, and who had been staying in general wards for ≥ 3 days. Those patients were excluded if they were unable to respond to the interview questions. If they reported pain during hospitalization, the maximum pain level and the duration of pain suffered in the past 24 hours were assessed. Care-related pain was also surveyed., Results: A total of 1,034 patients (M/F, 537/497) completed the survey. Amongst them, 719 patients (69.5%) experienced pain, with moderate and severe pain levels being 27.3% and 43%, respectively. Surgery was considered as it related to pain, including significantly severe pain. The top 3 care-related pain causes were needle pain, wound dressing, and change in position/chest percussion. Change in position/chest percussion and rehabilitation were associated with severe, persistent pain., Conclusions: Pain is common in approximately 70% of inpatients, with surgery being associated with severe pain. Mobilization and rehabilitation may lead to severe, persistent pain. The periodic study of pain prevalence is essential in order to provide precise pain management., Competing Interests: The authors have declared that no competing interests exist.

In mammals, the daily rhythms of physiological functions are timed by the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the importance of the SCN for the regulation of sleep/wakefulness has been suggested, little is known about the neuronal projections from the SCN, which regulate sleep/wakefulness. Here, we show that corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus mediate circadian rhythms in the SCN and regulate wakefulness. Optogenetic activation of CRF neurons promoted wakefulness through orexin/hypocretin neurons in the lateral hypothalamus. In vivo Ca 2+ recording showed that CRF neurons were active at the initiation of wakefulness. Furthermore, chemogenetic suppression and ablation of CRF neurons decreased locomotor activity and time in wakefulness. Last, a combination of optical manipulation and Ca 2+ imaging revealed that neuronal activity of CRF neurons was negatively regulated by GABAergic neurons in the SCN. Our findings provide notable insights into circadian regulation of sleep/wakefulness in mammals., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Design and exploration of new intermediates for chemo-, regio-, and stereoselective cycloadditions remain a formidable challenge in modern organic synthesis. Compared to the well-developed 1,3-dipolar cycloadditions, Pd-catalyzed1,4-dipolar cycloadditions are generally limited to specialized substrates due to the inherent nature of the thermodynamically driven intramolecular transformations and undesired isomerizations. Herein, we demonstrate the use of ligated palladium catalysts to control and modulate the intermolecular reactivity of aliphatic 1,4-dipoles, enabling two distinctive cycloaddition pathways with a broad scope of acceptors. This atom-economic process also features an eco-friendly in situ deprotonation strategy to generate the corresponding active palladium-mediated dipoles. Overall, a diverse array of chiral 6-membered rings and spiro [2.4] heptanes were prepared in high yield and selectivity. In addition, an unexpected property of cyano-stabilized carbanions was discovered and investigated, which can be useful in designing and predicting future transformations.

An external focus of attention has consistently been associated with improved balance (Wulf, 2013). Recent work has considered whether changes in postural control entropy, a measure of repeated movement patterns, could be a factor influencing this benefit. Rheaet al. (2019) reported that during quiet standing sample entropy when using an external focus was increased relative to baseline, whereas an internal focus did not differ from baseline. External and internal focus conditions did not differ from each other, but the authors speculated this difference may emerge with more complex balance tasks. The purpose of the present study was to determine if sample entropy and standard deviation of angular displacement differed when balancing on a stability platform while using an external, internal, or holistic focus. Young healthy adults (N = 36) completed three familiarization trials on the stability platform, followed by three trials each using an external focus (focus on keeping markers level), an internal focus (focus on keeping feet level), and a holistic focus (focus on feeling calm and stable). All trials lasted 20 s, and focus condition order was counterbalanced. Angular displacement of the platform was recorded at a frequency of 25 Hz, and sample entropy and standard deviation of angular displacement were calculated using a custom MATLAB code. Separate mixed ANOVAs for each dependent variable were used to assess differences due to focus and condition order, and Sidak post-hoc tests were used for pairwise comparisons. Results indicated an external focus led to higher sample entropy than a holistic focus (p = .001) and internal focus (p = .031). Standard deviation trended toward lower values with an external focus, but was influenced by a Focus x Order interaction. These results suggest that an external focus may promote more adaptive movement adjustments relative to a holistic focus and an internal focus., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Anesthetics, particularly volatile anesthetics, have been shown to impair glucose metabolism and cause hyperglycemia, closely linking them with mortality and morbidity as related to surgery. Beyond being an anesthetic used for general anesthesia and sedation, intravenous hypnotic propofol displays an effect on glucose metabolism. To extend the scope of propofol studies, its effects on glucose metabolism were evaluated in male Sprague-Dawley rats of various ages. Unlike chloral hydrate and isoflurane, propofol had little effect on basal glucose levels in rats at 2 months of age, although it did reduce chloral hydrate- and isoflurane-induced hyperglycemia. Propofol reduced postload glucose levels after either intraperitoneal or oral administration of glucose in both 7- and 12-month-old rats, but not those at 2 months of age. These improved effects regarding propofol on glucose metabolism were accompanied by an increase in insulin, fibroblast growth factor-21 (FGF-21), and glucagon-like peptide-1 (GLP-1) secretion. Additionally, an increase in hepatic FGF-21 expression, GLP-1 signaling, and FGF-21 signaling, along with a decrease in endoplasmic reticulum (ER) stress, were noted in propofol-treated rats at 7 months of age. Current findings imply that propofol may turn into insulin-sensitizing molecules during situations of existing insulin resistance, which involve FGF-21, GLP-1, and ER stress.

Background: Inflammation plays a crucial role in both type 2 diabetes mellitus (T2DM) and psoriasis pathogenesis; thus, a bidirectional association between them is likely suspected., Aims: We investigated the possible bidirectional association between T2DM and psoriasis., Methods: Using the Taiwan National Health Insurance Research Database, we conducted two retrospective cohort studies. The analysis of psoriasis onset in relation to T2DM status included 31,697 patients with diabetes and 126,788 nondiabetic control subjects (Analysis 1). The analysis of T2DM onset in relation to psoriasis status included 1,947 psoriatic patients and 7,788 nonpsoriatic control subjects (Analysis 2). The follow-up period was from 2000 to the date of the outcome of interest, date of death, or December 31, 2013. Cox proportional models were used to estimate the relative hazards., Results: In Analysis 1, Kaplan-Meier (KM)-based cumulative incidence of psoriasis was higher in the T2DM cohort than that in the non-T2DM cohort (1.2% vs. 0.7%). The covariate-adjusted hazard ratio (HR) was 1.40 [95% confidence interval (CI), 1.20-1.63] for patients with T2DM. Analysis 2 revealed KM-based cumulative T2DM incidences of 18.7% and 13.1% in psoriatic and nonpsoriatic subjects, respectively. The adjusted HR for incident T2DM was higher in patients with psoriasis (1.38; 95% CI, 1.20-1.58)., Limitation: This article may not represent the population worldwide and patient selection bias may exist., Conclusion: Our results provide evidence for a bidirectional T2DM-psoriasis association. T2DM and psoriasis are common worldwide; thus, our findings have public health implications for the early identification and management of these comorbid diseases., Competing Interests: None

Chronic treatment involving opioids exacerbates both the risk and severity of ischemic stroke. We have provided experimental evidence showing the anti-inflammatory and neuroprotective effects of the μ opioid receptor antagonist β-funaltrexamine for neurodegenerative diseases in rat neuron/glia cultures and a rat model of cerebral Ischemia/Reperfusion (I/R) injury. Independent of in vitro Lipopolysaccharide (LPS)/interferon (IFN-γ)-stimulated neuron/glia cultures and in vivo cerebral I/R injury in Sprague-Dawley rats, β-funaltrexamine downregulated neuroinflammation and ameliorated neuronal degeneration. Alterations in microglia polarization favoring the classical activation state occurred in LPS/IFN-γ-stimulated neuron/glia cultures and cerebral I/R-injured cortical brains. β-funaltrexamine shifted the polarization of microglia towards the anti-inflammatory phenotype, as evidenced by decreased nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2, along with increased CD163 and arginase 1. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by β-funaltrexamine was accompanied by the reduction of NF-κB, AP-1, cyclic AMP response element-binding protein, along with signal transducers and activators of transcription transcriptional activities and associated upstream activators. The effects of β-funaltrexamine are closely linked with its action on neuroinflammation by switching microglia polarization from pro-inflammatory towards anti-inflammatory phenotypes. These findings provide new insights into the anti-inflammatory and neuroprotective mechanisms of β-funaltrexamine in combating neurodegenerative diseases, such as stroke.

Orexin/hypocretin-producing and melanin-concentrating hormone-producing (MCH) neurons are co-extensive in the hypothalamus and project throughout the brain to regulate sleep/wakefulness. Ablation of orexin neurons decreases wakefulness and results in a narcolepsy-like phenotype, whereas ablation of MCH neurons increases wakefulness. Since it is unclear how orexin and MCH neurons interact to regulate sleep/wakefulness, we generated transgenic mice in which both orexin and MCH neurons could be ablated. Double-ablated mice exhibited increased wakefulness and decreased both rapid eye movement (REM) and non-REM (NREM) sleep. Double-ablated mice showed severe cataplexy compared with orexin neuron-ablated mice, suggesting that MCH neurons normally suppress cataplexy. Double-ablated mice also showed frequent sleep attacks with elevated spectral power in the delta and theta range, a unique state that we call 'delta-theta sleep'. Together, these results indicate a functional interaction between orexin and MCH neurons in vivo that suggests the synergistic involvement of these neuronal populations in the sleep/wakefulness cycle., Competing Interests: CH, DO, TK, AY No competing interests declared, (© 2020, Hung et al.)

Enantioselective incorporation of trifluoromethyl (-CF 3 ) and trifuoromethylthio (-SCF 3 ) groups in small molecules is of high interest to modulate the potency and pharmacological properties of drug candidates. Herein, we report a Zn-ProPhenol catalyzed diastereo- and enantioselective Mannich addition of α-trifluoromethyl- and α-trifuoromethylthio-substituted ketones. This transformation uses cyclic and acyclic ketones and generates quaternary trifluoromethyl and tetrasubstituted trifuoromethylthio stereogenic centers in excellent yields and selectivities.

The ProPhenol ligand is a member of the chiral aza-crown family that spontaneously forms a bimetallic complex upon treatment with alkyl metal reagents, such as Et 2 Zn and Bu 2 Mg. The resulting complex features Lewis acidic and Brønsted basic sites, enabling simultaneous activation of both nucleophile and electrophile in the same chiral environment. Since the initial report in 2000, metal-ProPhenol catalysts have been used to facilitate a broad range of asymmetric transformations, including aldol, Mannich, and Henry reactions, as well as alkynylations and conjugation additions. By promoting such a diverse array of reactions, these complexes provide rapid and atom-economical access to valuable complex building blocks. In this Review, we describe in detail the development and synthetic applications of these versatile catalysts with a special focus on recent efforts to improve reactivity and selectivity through ligand design and structural modification., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of new methodologies that enable chemo- and stereoselective construction of fluorinated substituents, such as the trifluoromethyl (CF 3 ) group, plays an essential role in the synthesis of new pharmaceutical agents. The exceptional ability of the CF 3 moiety to prevent in vivo metabolism as well as improve other pharmacological properties has led to numerous innovative strategies for installing this unique functional group. One potential yet underdeveloped approach to access these trifluoromethylated products is direct substitution of α-trifluoromethyl carbanions. Although the electron-withdrawing nature of the CF 3 group should facilitate deprotonation of adjacent hydrogens, the propensity of the resulting carbanions to undergo α-elimination of fluoride renders this process highly challenging. Herein, we describe a new strategy for stabilizing and utilizing transient α-trifluoromethyl carbanions that relies on a neighbouring cationic π-allyl palladium complex. These palladium-stabilized zwitterions participate in asymmetric [3 + 2] cycloadditions with a broad range of acceptors, generating valuable di- and trifluoromethylated cyclopentanes, pyrrolidines and tetrahydrofurans.

The preparation of acyclic β-fluoro amines bearing tetrasubstituted fluorine stereocenters is described via a direct Zn/ProPhenol-catalyzed Mannich reaction. The reaction utilizes branched vinyl or alkynyl α-fluoro ketones that can be coupled with a range of aryl, heteroaryl, vinyl, or cyclopropyl aldimines in high yield and with excellent diastereo- (up to >20:1) and enantioselectivity (up to 99 %). The use of readily cleaved tert-butoxycarbonyl (Boc) or carboxybenzyl (Cbz) imine protecting groups adds utility to the reaction by allowing for easy access to the free amine products under mild and chemoselective reaction conditions., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Loss of the neuromonitoring signal (LOS) during thyroidectomy signifies recurrent laryngeal nerve (RLN) injury, which is one of the common complications, especially by traction injury. Transient intraoperative LOS means spontaneous recovery of nerve function during surgery or within 6-month post-surgery. Few articles discuss intraoperative recovery time and transient LOS, and there is no consensus on the risk factors for RLN traction injury and its recovery course; thus, we wanted to determine the maximum intraoperative recovery time., Materials and Methods: This retrospective study included patients who had undergone thyroidectomies at Tainan National Cheng Kung University Hospital between January 2015 and August 2018. A total of 775 patients (with 1000 nerves at risk) who underwent intermittent intraoperative neuromonitoring during thyroidectomy were included in this study. The LOS nerves were divided into 4 groups based on the LOS subtype and the intraoperative status of the recovery. The postoperative vocal cord function was determined by thyroid ultrasound and/or laryngoscope. All the patients would be followed up postoperatively in 2-3 days, 1 week, 2 weeks, and 4-6 weeks., Results: LOS occurred in 67 of 775 (8.6%) patients and in 70 of 1000 nerves at risk (7.0%). There were 2 in 70 nerves (2.9%) with LOS type 1 (segmental nerve traction injury) with intraoperative recovery (Group 1), 5 (7.1%) with LOS type 1 without intraoperative recovery (Group 2), 47 (67.1%) with LOS type 2 (global injury) with intraoperative recovery (Group 3), and 16 (22.8%) with LOS type 2 without intraoperative recovery (Group 4). All LOS type 1 (segmental nerve injury) nerves had pathologic lesions near the RLN or vagus nerve, but none had invaded the nerves (p < 0.05). The resolving time intraoperatively in the 2 patients in Group 1 was 5 min and 10 min, respectively. The resolving time intraoperatively in Group 3 was 1-20 min, and the average time was 4.8 min. In Group 2, 3 injured nerves recovered within 6 weeks postoperatively, and 2 nerves in 12 weeks. In Group 4, all the 16 injured nerves recovered within 6 weeks postoperatively., Conclusion: Applying intermittent intraoperative neuromonitoring during thyroidectomy, traction recurrent laryngeal nerve injury still happened in 7.0%. 70% of the injured nerves recovered the function intraoperatively after releasing the traction, and the longest duration of recovery is 20 min.