Interpretable modeling of time-resolved single-cell gene-protein expression with CrossmodalNet.

Cell-surface proteins play a critical role in cell function and are primary targets for therapeutics. CITE-seq is a single-cell technique that enables simultaneous measurement of gene and surface protein expression. It is powerful but costly and technically challenging. Computational methods have been developed to predict surface protein expression using gene expression information such as from single-cell RNA sequencing (scRNA-seq) data. Existing methods however are computationally demanding and lack the interpretability to reveal underlying biological processes. We propose CrossmodalNet, an interpretable machine learning model, to predict surface protein expression from scRNA-seq data. Our model with a customized adaptive loss accurately predicts surface protein abundances. When samples from multiple time points are given, our model encodes temporal information into an easy-to-interpret time embedding to make prediction in a time-point-specific manner, and is able to uncover noise-free causal gene-protein relationships. Using three publicly available time-resolved CITE-seq data sets, we validate the performance of our model by comparing it with benchmarking methods and evaluate its interpretability. Together, we show that our method accurately and interpretably profiles surface protein expression using scRNA-seq data, thereby expanding the capacity of CITE-seq experiments for investigating molecular mechanisms involving surface proteins.

Gene knockout inference with variational graph autoencoder learning single-cell gene regulatory networks.

In this paper, we introduce Gene Knockout Inference (GenKI), a virtual knockout (KO) tool for gene function prediction using single-cell RNA sequencing (scRNA-seq) data in the absence of KO samples when only wild-type (WT) samples are available. Without using any information from real KO samples, GenKI is designed to capture shifting patterns in gene regulation caused by the KO perturbation in an unsupervised manner and provide a robust and scalable framework for gene function studies. To achieve this goal, GenKI adapts a variational graph autoencoder (VGAE) model to learn latent representations of genes and interactions between genes from the input WT scRNA-seq data and a derived single-cell gene regulatory network (scGRN). The virtual KO data is then generated by computationally removing all edges of the KO gene-the gene to be knocked out for functional study-from the scGRN. The differences between WT and virtual KO data are discerned by using their corresponding latent parameters derived from the trained VGAE model. Our simulations show that GenKI accurately approximates the perturbation profiles upon gene KO and outperforms the state-of-the-art under a series of evaluation conditions. Using publicly available scRNA-seq data sets, we demonstrate that GenKI recapitulates discoveries of real-animal KO experiments and accurately predicts cell type-specific functions of KO genes. Thus, GenKI provides an in-silico alternative to KO experiments that may partially replace the need for genetically modified animals or other genetically perturbed systems.

Phonological processing in Chinese word repetition: Dementia effect and age effect.

This paper examined phonological processing as reflected in Mandarin word and non-word repetition. Issues related to dementia effects, age effects, and linguistic variables are discussed. Forty-five speakers of Mandarin Chinese in Taiwan took part in this study. Fourteen seniors with Alzheimer's disease (AD), 14 healthy adults, and 17 healthy seniors individually completed a task of word repetition. Scores of accurate repetition were calculated, and error types as well as error frequency were analysed. Linguistic variables, including lexicality, frequency, non-word, and syllable length, were discussed. Major findings were indicative of a significant dementia effect, in which participants with AD were significantly impaired in repeating words with more syllables, specifically 5-syllable non-words of low frequency. Numerous significant age effects were noted. Theoretical implications and directions for future study are discussed.

The association of potentially inappropriate medications, polypharmacy and anticholinergic burden with readmission and emergency room revisit after discharge: A hospital-based retrospective cohort study.

AIMS: While certain drug-use indicators are known to be associated with clinical outcomes, the relationship is unclear for some highly prevalent conditions in in patients aged ≥65 years. We examine correlations between 3 drug-use indicators and postdischarge healthcare services use by older patients according to the presence of dementia, advanced age and frailty. METHODS: This retrospective cohort study analysed data collected from hospital electronic health records between April and December 2017. Potentially inappropriate medications (PIMs) and anticholinergic burden were assessed using the 2015 Beers Criteria and anticholinergic cognitive burden scale (ACBS) score. Minor and major polypharmacy were defined as the use of 5-9 and ≥10 drugs, respectively. Outcomes were set as emergency room revisits and readmissions at 1, 3 and 6 months postdischarge. The correlation between drug-use indicators and outcomes was analysed by multivariable logistic regression. RESULTS: The final cohort included 3061 patients for the analysis, and 2930, 2671 and 2560 patients were followed up to 1, 3 and 6 months after discharge. After controlling for confounders, all 3 drug-use indicators were significantly associated with readmission and emergency room revisits except for the relationship between PIMs and readmission within 6 months. These associations were significantly observed among patients without dementia, aged >80 years and with frailty. CONCLUSION: PIMs, polypharmacy and anticholinergic burden are common at discharge and correlate with future use of healthcare services. In older patients, the absence of dementia, advanced age and frailty should be given extra consideration with regard to medication safety.

Physical activity plays a crucial role in multidomain intervention for frailty prevention.

BACKGROUND AND AIMS: Taiwan is one of the most rapidly aging countries worldwide. Both physical activity and frailty affect older adults, and multidomain interventions prevent frailty. This study investigated the associations between physical activity, frailty, and the effects of multidomain intervention. METHODS: This study enrolled individuals aged 65 years or older. The physical activity level was assessed using the Physical Activity Scale for the Elderly (PASE). Enrollees participated in a multidomain intervention program that consisted of twelve 120-min sessions administered over a 12-week period that included health education, cognitive training, and exercise programs. The effects of the intervention were evaluated using the instrumental activities of daily living scale (IADL), Mini Nutritional Assessment short form (MNA-SF), five-item Geriatric Depression Scale (GDS-5), Mini-Mental State Examination (MMSE), timed up and go test (TUGT), and Fried's frailty phenotype. RESULTS: In total, 106 older adults (aged 65-96 years) were enrolled in this study. The mean age was 77.47 ± 7.19 years, and 70.8% of participants were women. PASE scores were significantly lower among participants who were of older age, frail, and had a history of falls in the last 12 months. Frailty could be improved by multidomain interventions and was significantly positively correlated with depression, and negatively correlated with physical activity, mobility, cognition and daily living skills. Moreover, daily living skills were significantly positively correlated with cognition, mobility and physical activity, and negatively correlated with age, sex, and frailty. However, multidomain interventions did not affect daily living skills suggesting daily living skills may need to be maintained from a young age. Finally, results from multiple regressions suggest that physical activity, mobility and depression may be predictors of frailty. CONCLUSIONS: Physical activity has an important role in frailty, may be a predictor of frailty, and strongly contributes to reducing frailty through multidomain intervention. Policies that encourage healthy aging should focus on increasing physical activity, maintaining basic daily living skills and reducing frailty.

Preliminary Prospective Preoperative and Postoperative Evaluation of Median Nerve Stiffness by Using Sonoelastography.

ABSTRACT: Carpal tunnel syndrome is the most common peripheral nerve entrapment syndrome. No previous studies have compared preoperative and follow-up sonoelastography results or investigated the correlation of median nerve stiffness with the subjective/objective outcomes. Therefore, the aim of this study was to compare the preoperative and postoperative elastography after carpal tunnel release and find the correlation with associated subjective/objective outcomes.From May 2017 to March 2020, 32 patients (6 males, 26 females; 34 hands) with carpal tunnel syndrome were enrolled in this prospective study. Demographic data, QuickDASH score (Chinese version), Boston Carpal Tunnel Questionnaire (Chinese version), nerve conduction velocity/electromyography, and median nerve stiffness by sonoelastography were recorded.Comparisons of preoperative and average sonoelastography findings 1.5 years postoperatively showed a significant decrease in stiffness presented by velocity (Vs) (preoperative Vs, 4.63 ± 1.27 m/s, vs postoperative Vs, 3.39 ± 0.59 m/s; P < 0.001). Changes in subjective functional outcomes also showed the same significant trend. Based on the neurophysiologic study, the improvement of nerve conduction study and elastography have the significant correlation.The same trend of preoperative and postoperative changes in median nerve stiffness and subjective questionnaires/objective neurophysiologic studies may imply that sonoelastography can be used to assess the response to surgery in patients with carpal tunnel syndrome.

Heterotopic Digital Replantation in Mutilating Hand Injuries: An Algorithmic Approach Based on 53 Cases and Literature Review.

BACKGROUND: Reconstruction of the mutilated hand is one of the most difficult challenges for hand microsurgeons. When multiple digits are amputated, orthotopic digital replantation of the available remnants may not adequately restore the hand function. In such cases, heterotopic digital replantation may provide a more functional reconstruction. METHODS: Between 1997 and 2018, 53 patients with mutilating hand injuries were treated with heterotopic digital replantation at our institution. A retrospective chart review was conducted to determine the details of the injury, indications for heterotopic digital replantation, and functional outcomes. RESULTS: In total, 173 digits were amputated from 53 patients (one patient suffered from bilateral hand injuries, so totally 54 hands). Sixty-eight digits underwent heterotopic digital replantation, 30 digits had orthotopic digital replantation, and 75 stumps were terminalized. The survival rate of digits treated by heterotopic digital replantation and orthotopic digital replantation was 83.8% (57/68) and 86.7% (26/30), respectively (p = 1). Tripod grip was achieved in 83.3% (45/54) of patients following replantation and optional secondary reconstructive surgeries. CONCLUSION: Heterotopic digital replantation is a practical and reliable method for achieving optimal hand function following mutilating hand injuries. The basic principles are to restore a functional thumb in the first instance, followed by at least two adjacent fingers against which the thumb can oppose. This method is particularly indicated when orthotopic digital replantation of the available amputated parts would yield a suboptimal result.

Comparison of the clinical outcomes between vascularized bone graft and the Masquelet technique for the reconstruction of Gustilo type III open tibial fractures.

BACKGROUND: Gustilo type III tibial fractures commonly involve extensive soft tissue and bony defects, requiring complex reconstructive operations. Although several methods have been proposed, no research has elucidated the efficacies and differences between vascular bone graft (VBG) and the Masquelet technique (MT) to date. We aimed to evaluate and compare the clinical effectiveness of VBG and the MT for the reconstruction of Gustilo type III tibial fractures. METHODS: This retrospective cohort study enrolled patients who underwent reconstruction for Gustilo type III tibial fractures using VBG or the MT in a single center from January 2000 to December 2020. The patients' demographics, injury characteristics, and surgical interventions were documented for analysis. The clinical outcomes including union status, time to union, postoperative infections, and the causes of union failure were compared between the two groups. RESULTS: We enrolled 44 patients: 27 patients underwent VBG, and 17 underwent MT. The average union time was 20.5 ± 15.4 and 15.1 ± 9.0 months in the VBG and MT groups, respectively (p = 0.232). The postoperative deep infection rates were 70.4% and 47.1% in the VBG and MT groups (p = 0.122), respectively. Though not statistically significant, the VBG group had a shorter union time than did the MT group when the bone defect length was > 60 mm (21.0 ± 17.0 versus 23.8 ± 9.4 months, p = 0.729), while the MT group had a shorter union time than did the VBG group when the bone defect was length < 60 mm (17.2 ± 5.6 versus 10.7 ± 4.7 months, p = 0.067). CONCLUSIONS: VBG and MT are both promising reconstruction methods for Gustilo type III tibial fractures. VBG appears to have more potential in reconstructing larger bone defects, while MT may play an important role in smaller bone defects, severe surgical site infections, and osteomyelitis. Therefore, flexible treatment strategies are required for good outcomes in Gustilo type III open tibial fractures.

Treatment Strategies for Acute Seymour Fractures in Children and Adolescents: Including Crushed Open Fractures.

PURPOSE: We aimed to suggest treatment strategies for Seymour fractures (SFs) with varying clinical manifestations, based on the retrospective outcomes of patients seen at our institute. METHODS: Between March 2000 and December 2019, a total of 26 SF patients were categorized into 3 groups: acute typical SF (category 1; open fracture/exposed germinal matrix and physis), acute injuries but delayed presentation (category 2; presented to our institute more than 24 hours after the injury with misdiagnosis as simple nail injuries), and direct crush injuries (category 3; the most severe injury type, characterized by nail loss, nail bed lacerations, or maceration of the germinal matrix). In category 1, reduction was maintained using K-wire fixation without nail plate sutures. In 2, massive irrigation/debridement was followed by reduction and nail plate suturing without K-wire fixation. Finally, in 3, nail bed repair, reinsertion of the extracted nail plate after creating a penetration hole for drainage, K-wire fixation, and nail plate suturing were sequentially performed. RESULTS: The mean age of the patients was 8.92 years. At the final follow-up, the mean dorsal angulation was 1.73 degrees, and the length ratio was 97.88%; no significant differences were observed compared with the contralateral normal side ( P = 0.498 and P = 0.341, respectively). The final visual analog scale pain score; the Disabilities of the Arm, Shoulder, and Hand score; and the active range of motion ratio were 0.50, 1.52, and 96.92%, respectively. There were no significant complications requiring revision surgery. Although the overall outcomes were satisfactory, category 3 patients had slightly worse visual analog scale pain scores; Disabilities of the Arm, Shoulder, and Hand scores; and range of motion compared with those in the other categories ( P = 0.003, P = 0.002, and P < 0.001, respectively). CONCLUSIONS: Satisfactory clinical outcomes were obtained by applying different surgical treatments to the different SF categories. We have suggested appropriate treatment strategies for acute SF varying in severity.

Popliteal Artery Injury After Fracture and/or Dislocation of the Knee: Risk Stratification for Revascularization Outcome.

BACKGROUND: Managing complex knee trauma involving both vascular and osseous injuries is challenging, yet the available guidelines for efficient popliteal artery injury management after high-velocity blunt knee trauma remain conflicting and inconsistent. In this study, the authors aim to identify the risk factors associated with delayed limb amputation and ischemic muscular sequela postrevascularization. Furthermore, we propose a treatment algorithm to improve the limb salvage rate. METHODS: Patients who presented with traumatic popliteal artery injury resulting in vessel occlusion or rupture, followed by fracture and/or dislocation of the knee from January 2008 to December 2013, were included for retrospective review. RESULTS: Overall delayed amputation rate was 24% (7/29) and 16% (4/25) after successful revascularization. Mangled Extremity Severity Score is higher in the delayed amputation group than the limb-salvaged group (P = 0.02). Higher-impact force (P = 0.03), ischemic limb on presentation (P = 0.03), prolonged ischemia time (P = 0.04), unstable hemodynamics (P = 0.01), longer operation time (P = 0.04), and prolonged intensive care unit stay (P = 0.03) are risk factors of delayed amputation. Longer ischemia time (P = 0.04) and length of popliteal artery injury (P = 0.02) are associated with ischemic muscular sequela. CONCLUSIONS: Mangled Extremity Severity Score is a reliable predictor of limb salvage. An algorithmic approach may improve the outcome of popliteal artery injury after high-velocity blunt knee trauma.

Risk Factors of Carpal Tunnel Syndrome in Taiwan: A Population-Based Cohort Study.

BACKGROUND: Carpal tunnel syndrome (CTS), 1 of the most common peripheral neuropathies of the upper extremity, has been studied for decades regarding its epidemiology and associated medical conditions. We conducted a large-scale, age- and gender-matched study from an Asian population database to investigate the relationship between the incidence and the demographic characteristics. METHODS: A retrospective cohort study using data of National Health Insurance Research Database was conducted. One million enrollees in Taiwan was used to identify 9442 patients with CTS and 37,768 randomly selected controls, in a control-case ratio of 4:1. Diagnoses of CTS were ascertained from January 1, 2003, to December 31, 2012. Sociodemographic and medical characteristics were evaluated to assess the correlation with CTS. RESULTS: Annual incidence of CTS was approximately 0.4% during the 10-year-period in Taiwan, with higher incidence rate in female sex and middle age of group (50-59 years). Among the medical conditions, previous wrist injuries, obesity, gout, and rheumatoid arthritis were associated with CTS most significantly. CONCLUSIONS: Carpal tunnel syndrome has presented a relatively constant incidence in Taiwan. Female gender with middle age seemed to have the highest incident rate during a 10-year period from 2003 to 2012. Among the risk factors of CTS, previous wrist injuries, obesity, gout, and rheumatoid arthritis were demonstrated to be the most significantly correlated comorbidities.

The Effect on Venous Congestion of Diverting Arterial Flow in the Arterialized Venous Flap.

An arterialized venous flap is a cutaneous flap based solely on subcutaneous veins. The flap is perfused by nonphysiologic flow of blood from the vein into the peripheral tissue. This nonphysiologic perfusion limits the indications for an arterialized venous flap, and its postoperative complications make it an unpopular choice for reconstruction. When venous flaps are designed following the direction of venous valves (antegrade) in a flow-through fashion, the blood may bypass the peripheral tissue without perfusing the flap. A higher pressure within the efferent end of the vein impedes venous return from the peripheral tissue into this draining vein. Thus, venous congestion of the arterialized venous flap becomes inevitable. We describe our approach to designing an arterialized venous flap in which direct arteriovenous shunting is largely eliminated, thereby transmitting a higher pressure in the periphery of the flap while maintaining a physiologic venous pressure in the efferent vein. This restriction of shunting can be accomplished in a number of ways, depending on the venous pattern within the flap.

MitoTox: a comprehensive mitochondrial toxicity database.

BACKGROUND: Mitochondria play essential roles in regulating cellular functions. Some drug treatments and molecular interventions have been reported to have off-target effects damaging mitochondria and causing severe side effects. The development of a database for the management of mitochondrial toxicity-related molecules and their targets is important for further analyses. RESULTS: To correlate chemical, biological and mechanistic information on clinically relevant mitochondria-related toxicity, a comprehensive mitochondrial toxicity database (MitoTox) was developed. MitoTox is an electronic repository that integrates comprehensive information about mitochondria-related toxins and their targets. Information and data related to mitochondrial toxicity originate from various sources, including scientific journals and other electronic databases. These resources were manually verified and extracted into MitoTox. The database currently contains over 1400 small-molecule compounds, 870 mitochondrial targets, and more than 4100  mitochondrial toxin-target associations. Each MitoTox data record contains over 30 fields, including biochemical properties, therapeutic classification, target proteins, toxicological data, mechanistic information, clinical side effects, and references. CONCLUSIONS: MitoTox provides a fully searchable database with links to references and other databases. Potential applications of MitoTox include toxicity classification, prediction, reference and education. MitoTox is available online at http://www.mitotox.org .

All-cause mortality, cardiovascular mortality, major cardiovascular events and hypoglycaemia of patients with diabetes onset at an older age: results from the 10-year nationwide cohort study.

BACKGROUND: Longitudinal adverse outcomes are unclear among adults with diabetes according to the age of onset. OBJECTIVE: To investigate the longitudinal diabetes-related outcomes in adults with new-onset diabetes stratified by age. DESIGN: Retrospective cohort study. SETTING: Taiwan National Health Insurance Research Database claims data from 2000 to 2015. SUBJECTS: In total, 115,751 participants aged ≥40 years with new-onset diabetes in 2003 were recruited and stratified by the ages 40-64 (64.3%), 65-74 (21.2%), 75-84 (11.8%) and ≥85 years (2.7%) at the time of diagnosis. METHODS: Time-varying multivariate Cox proportional hazards model adjusted for covariates was used to examine the associations between the ages of the patients at diabetes onset and the outcomes of interest [all-cause mortality, cardiovascular (CV) mortality, major cardiovascular events (MACE) and hypoglycaemia] during a 10-year follow-up period. RESULTS: The results showed that compared with those patients aged 40-64 at diagnosis, patients with older-onset diabetes had significantly higher comorbidities (P < 0.01) and a higher diabetes severity (P < 0.01). Patients with older-onset diabetes had a higher risk of all-cause mortality [adjusted hazard ratio (aHR) 2.28, 4.48 and 10.07 in 65-74, 75-84 and ≥85 years old, respectively], CV mortality (aHR = 2.82, 6.06 and 15.91), MACE (aHR = 2.19, 3.01 and 4.15) and hypoglycaemia (aHR = 2.41, 3.59 and 4.62) than patients aged 40-64 during a 10-year follow-up period. CONCLUSIONS: Patients with diabetes onset at an older age was associated with increased risks of all-cause mortality, CV mortality, MACE and hypoglycaemia after adjusting for the severity of diabetes and anti-diabetic treatment.

Caregiving, care burden and awareness of caregivers and patients with dementia in Asian locations: a secondary analysis.

BACKGROUND: This study investigated the differences in caregiver activity, caregiver burden, and awareness of both caregivers and patients with Alzheimer's disease (AD) across different Asian locations. METHODS: This was a secondary analysis of a multi-national cohort study that aimed to assess caregiver activity and caregiver burden using the Caregiver Activity Scale (CAS) and Zarit Burden Interview (ZBI), respectively. Patients' awareness of their dementia diagnosis was assessed by asking the following yes/no question: "Do you have dementia?" Caregivers' awareness of the patient's dementia diagnosis was assessed by asking the following yes/no question: "Does your patient have dementia?" RESULTS: In total, 524 caregivers of patients with AD from China, Hong Kong, South Korea, the Philippines, Singapore, Thailand, and Taiwan participated. The CAS and ZBI score were significantly different across most locations (p < 0.001 and p = 0.033, respectively). Overall, 56.6% of caregivers and 37.5% of patients had awareness of the dementia diagnosis, and the proportion of patients and caregivers with awareness were also different between each location (all, p < 0.001). CONCLUSIONS: Caregiving, caregiver burden, and the awareness of caregivers and patients were different across many Asian locations. With understanding of cultural differences, further public education on dementia could help increase the awareness of patients and caregivers and reduce caregiver burden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02262975 . Registered 13 October 2014.

Factors associated with insomnia in older adult outpatients vary by gender: a cross-sectional study.

BACKGROUND: Insomnia is a common sleep disturbance in older adults and is associated with many poor health outcomes. This study aimed to explore factors associated with insomnia in older adult outpatient clinics, and to further analyze the influence of gender on factors associated with insomnia. METHODS: This cross-sectional study was conducted in the outpatient clinics of a tertiary hospital in Southern Taiwan from July to September 2018. A total of 400 consecutive subjects aged 60 years or older were recruited. Insomnia was defined as a score of ≥6 points on the Athens Insomnia Scale (AIS). Socio-demographics, health behaviors and clinical data were collected by face-to-face interview. Multivariable logistic regression was adopted for statistical analysis of the entire sample and stratified by gender. RESULTS: Participants' mean age was 74.74 ± 8.54 years, and the majority (93%) had more than one chronic disease. The prevalence of insomnia accounted for 30% (120/400) of all subjects, with males 22.9% (46/201) and females 37.2% (74/199). Gender, appetite, exercise, depressive symptoms, and sleep-related conditions such as short sleep duration, sleeping pills usage, medium-high risk of obstructive sleep apnea (OSA) and restless leg syndrome (RLS) were factors associated with insomnia in older adults. Exercise, sleeping pills usage, and RLS were independently associated with insomnia only in men, while appetite and medium-high risk of OSA were associated with insomnia in women only. In addition, after further adjusting for covariates, prevalence of the insomnia-related symptoms such as sleep induction, total sleep duration, sleep quality and sleepiness during the day was significantly higher in females than in males. CONCLUSIONS: Insomnia symptoms are highly prevalent among older adults, predominantly females. Significant differences are found between genders in factors associated with insomnia and insomnia-related symptoms. Understanding gender differences may help clinicians to modify associated factors when managing older adults with insomnia.

Sonoelastography in the Diagnosis of Carpal Tunnel Syndrome: A Systematic Review of Diagnostic Values Compared With the Normative Population.

BACKGROUND: Sonoelastography (SEL) is widely used for assessing tissue stiffness and pathophysiology. It has also been used to diagnose carpal tunnel syndrome (CTS). However, the current criteria to diagnose CTS in SEL are diverse. The aim of this study was to systematically review the literature and assess the diagnostic value of SEL for CTS. METHODS: A literature review was performed using MEDLINE (PubMed), EMBASE, and the Cochrane Collaboration Library for primary research articles using the keywords sonoelastography and carpal tunnel syndrome. Data related to diagnostic and cutoff value were extracted. Bias assessment was performed. RESULTS: A total of 121 publications were reviewed. Nineteen primary case series met the inclusion criteria and were selected for full analysis. Different diagnostic approaches were identified, with units/expressions including kilopascals, conduct velocity, and strain ratio. The kilopascals and conduct velocity were measured using shear wave elastography, whereas strain ratio was calculated by relative compression quantification. A mean shear modulus cutoff value from 38.25 to 86 kPa and an acoustic radiation force impulse cutoff value of 3.0 to 3.23 m/s were used to diagnose CTS. Eight articles reported strain ratio between the median nerve and nearby tissues with diverse results due to different reference points. The other 3 additional diagnostic values were reported. CONCLUSIONS: Sonoelastography is a useful noninvasive and promising modality to diagnose CTS. It may reflect both the condition of soft tissue scarring and quantitative values for CTS and median nerve stiffness. A diversity of examination values was found in different modalities. A high level of evidence was absent.

End-to-Side Anterior Interosseous Nerve Transfer: A Valuable Alternative for Traumatic High Ulnar Nerve Palsy.

BACKGROUND: The prognosis of high ulnar nerve injury is poor despite nerve repair or grafting. Anterior interosseous nerve (AIN) transfers provide a satisfactory recovery. However, the efficacy of end-to-side (ETS) AIN transfer and optimal timing in Sunderland grade IV/V of high ulnar nerve injury is lacking. OBJECTIVE: The goals were to compare the outcomes of high ulnar nerve injury managed with ETS AIN transfers with those managed with conventional procedures (nerve repair or graft only) and identify differences between early and delayed transfers. METHODS: Patients with isolated high ulnar nerve injury (Sunderland grade IV/V) from 2010 to 2017 were recruited. Patients with conventional treatments and AIN transfers were designated as the control and AIN groups, respectively. Early transfer was defined as the AIN transfer performed within 8 weeks postinjury. Outcomes were measured and analyzed by the British Medical Research Council (BMRC) score, grip strength, and pinch strength. RESULTS: A total of 24 patients with high ulnar nerve injury (Sunderland grade IV/V) were included. There were 11 and 13 patients in the control and AIN groups, respectively. In univariate analysis, both early and delayed AIN transfers demonstrated significantly better motor recovery among BMRC score and strength of grip and pinch at 12 months (P < 0.05). No statistical significance was found between early and delayed transfer. In multivariate analysis, both early and delayed transfers were regarded as strong and independent factors for motor recovery of ulnar nerve. Compared with the control, early [odds ratio (OR), 1.83; P < 0.001] and delayed (OR, 1.59; P < 0.001) transfers showed significant improvement with regard to BMRC scores. The pinch strength in early (OR, 31.68; P < 0.001) and delayed (OR, 26.45; P < 0.001) transfers was also significantly better. CONCLUSION: The ETS AIN transfer, in either early or delayed fashion, significantly improved intrinsic motor recovery in high ulnar nerve injuries classified as Sunderland grade IV/V. The early transfer group demonstrated a trend toward better functional recovery with less downtime.

Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice.

Spinocerebellar ataxia type 3 (SCA3) is a genetic neurodegenerative disease for which a cure is still needed. Growth hormone (GH) therapy has shown positive effects on the exercise behavior of mice with cerebellar atrophy, retains more Purkinje cells, and exhibits less DNA damage after GH intervention. Insulin-like growth factor 1 (IGF-1) is the downstream mediator of GH that participates in signaling and metabolic regulation for cell growth and modulation pathways, including SCA3-affected pathways. However, the underlying therapeutic mechanisms of GH or IGF-1 in SCA3 are not fully understood. In the present study, tissue-specific genome-scale metabolic network models for SCA3 transgenic mice were proposed based on RNA-seq. An integrative transcriptomic and metabolic network analysis of a SCA3 transgenic mouse model revealed that metabolic signaling pathways were activated to compensate for the metabolic remodeling caused by SCA3 genetic modifications. The effect of IGF-1 intervention on the pathology and balance of SCA3 disease was also explored. IGF-1 has been shown to invoke signaling pathways and improve mitochondrial function and glycolysis pathways to restore cellular functions. As one of the downregulated factors in SCA3 transgenic mice, IGF-1 could be a potential biomarker and therapeutic target.

Developing an Integrated Electronic Medication Reconciliation Platform and Evaluating its Effects on Preventing Potential Duplicated Medications and Reducing 30-Day Medication-Related Hospital Revisits for Inpatients.

The aims were to develop an integrated electronic medication reconciliation (ieMR) platform, evaluate its effects on preventing potential duplicated medications, analyze the distribution of the potential duplicated medications by the Anatomical Therapeutic and Chemical (ATC) code for all inpatients, and determine the rate of 30-day medication-related hospital revisits for a geriatric unit. The study was conducted in a tertiary medical center in Taiwan and involved a retrospective quasi pre-intervention (July 1-November 30, 2015) and post-intervention (October 1-December 31, 2016) study design. A multidisciplinary team developed the ieMR platform covering the process from admission to discharge. The ieMR platform included six modules of an enhanced computer physician order entry system (eCPOE), Pharmaceutical-care, Holistic Care, Bedside Display, Personalized Best Possible Medication Discharge Plan, and Pharmaceutical Care Registration System. The ieMR platform prevented the number of potential duplicated medications from pre (25,196 medications, 2.3%) to post (23,413 medications, 3.8%) phases (OR 1.71, 95% CI, 1.68-1.74; p < .001). The most common potential duplicated medications classified by the ATC codes were cardiovascular system (28.4%), alimentary tract and metabolism (26.4%), and nervous system (14.9%), and by chemical substances were sennoside (12.5%), amlodipine (7.5%), and alprazolam (7.4%). The rate of medication-related 30-day hospital revisits for the geriatric unit was significantly decreased in post-intervention compared with that in pre-intervention (OR = 0.12; 95% CI, 0.03-0.53; p < .01). This study indicated that the ieMR platform significantly prevented the number of potential duplicated medications for inpatients and reduced the rate of 30-day medication-related hospital revisits for the patients on the geriatric unit.