Search

Introduction: Recovery of lower urinary tract (LUT) and lower gastrointestinal tract (LGIT) is a high priority for people with lived experience following spinal cord injury (SCI). A universally accepted validated patient‐reported outcome (PRO) measure of the individual sensory and motor components of LGIT and LUT function, which allows tracking of recovery is lacking. To address this literature gap, the SCI Bladder and Bowel Control Questionnaire (SCI‐BBC‐Q) was developed. Methods: The SCI‐BBC‐Q was developed as a direct assessment of the micturition and defecation experiences of an individual with SCI with possible neurogenic LUT and LGIT dysfunction. The SCI‐BBC‐Q development process consisted of two phases, measure development and evaluation. Measure development was guided by a conceptual framework, review of existing instruments and literature, and an iterative process of item incorporation, review, feedback, and consensus revision. Evaluation included cognitive interviewing, and assessments of feasibility, reliability, and content validity. Results: The final 6‐item SCI‐BBC‐Q is a PRO, which assesses motor and sensory function related to micturition and defecation, requiring ~5 min to complete. Assessments of clarity of the instrument components with regard to understanding of what is being asked in the questionnaire, feasibility of administration, reliability, internal consistency, and agreement with proxy measures have demonstrated that the SCI‐BBC‐Q provides consistent, stable, and reproducible data. Significant correlations were found between SCI‐BBC‐Q scores and the anorectal motor and sensory components of the International Standards for the Neurological Classification of SCI. Conclusion: The SCI‐BBC‐Q is a practical and reliable method for baseline and ongoing evaluation of patients with neurogenic LUT and LGIT dysfunction, especially in the acute and subacute period when function is changing due to neurological plasticity. It is also appropriate for use in monitoring response to treatments related to neurological recovery. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) negatively impacts individuals' functional independence, and motor and sensory function. Intense walking training has been shown to facilitate recovery for individuals with chronic SCI. Powered robotic exoskeletons provide therapists with a tool that allows them to conduct walking training with less therapist effort as compared to conventional walking training. Exoskeletal-assisted walking (EAW) has been studied in the chronic SCI population with preliminary reports showing benefits in mobility, health, and quality-of-life outcomes. However, few reports have studied EAW's benefits in the acute (<90 days post) SCI population at a time when neural plasticity is most dynamic and modifiable. The purpose of the study was to conduct a pilot randomized controlled trial (RCT) to understand the effects of incorporated EAW in acute inpatient rehabilitation (AIR) for individuals with SCI on functional, motor, and sensory recovery. The study outcomes included the Spinal Cord Independence Measure (SCIM) III and International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor and sensory scores that were assessed by unblinded assessors. We also recorded EAW session data, including adverse events, walking and up time, step counts, Borg Rating of Perceived Exertion (RPE), and compliance with scheduled EAW training. From August 2019 to July 2022, 16 participants completed the AIR with incorporated EAW, and 12 completed the standard AIR, all with SCI and preserved leg function within 90 days post-injury. During each session, the AIR with incorporated EAW group averaged 34.3 (±9.4) min of up time, 25.4 (±7.7) min of walk time, and 536 (±157) steps. Analysis via two-by-two mixed-effects models showed significant increases in the SCIM total score and ISNCSCI total motor and sensory scores over time for the AIR with incorporated EAW group [SCIM total score: F(1, 26) = 5.59, p = 0.03; total motor score: F(1, 26) = 8.06, p < 0.01; total sensory score: F(1, 19.2) = 5.08, p = 0.04], outperforming the standard AIR group. The AIR with incorporated EAW group showed 13, 14, and 22 points higher changes in the SCIM total score, total motor score, and total sensory score (respectively) by discharge compared with the standard AIR group. Incorporating EAW into AIR may facilitate functional, motor, and sensory recovery for individuals with SCI during AIR better than standard AIR. However, the study had a limited sample size. Further studies are needed to clarify the effects of EAW in AIR. [ABSTRACT FROM AUTHOR]

Recently, high-performance self-healing electromagnetic interference (EMI) shielding materials with superior electrical conductivity, excellent shielding efficiency, and effective self-repairing ability have gained great attention. However, the practical development of such systems still encounters considerable challenges. In this study, a highly efficient EMI shielding self-healing nanocomposite system composed of multiple components of multiwalled carbon nanotubes (MWCNTs), graphene nanosheets (GNSs), and Fe3O4 nanoparticles was developed by integrating a novel amphiphilic poly-(ethylene glycol)-block-poly-(caprolactone-co-furfuryl glycidyl ether) block copolymer (PEG-b-PCLF) with 1,1′-(methylenedi-4,1-phenylene)-bismaleimide and nanofillers via Diels–Alder (DA) chemistry and molecular affinity. Within this composite system, MWCNTs were distributed within the GNSs and served as connecting bridges across adjacent GNSs. Simultaneously, Fe3O4 nanoparticles were uniformly interspersed in the space around the MWCNT/GNS staggered framework due to good affinity with the hydrophilic PEG block, thereby forming MWCNT/GNS/Fe3O4 tricontinuous networks. Upon heating, the retro-DA mechanisms endowed the material system with excellent reprocessability and self-repairability. More importantly, the MWCNT/GNS/Fe3O4 tricontinuous networks not only provided efficient channels for charge transport but also served as an electromagnetic framework that synergistically endowed the material system with excellent EMI shielding properties. Accordingly, a favorable electrical conductivity of 18.5 S m–1 and an extremely high shielding effectiveness of 92.7 dB in the X-band were achieved. Additionally, the material system also possessed sufficient performances in the recovery of mechanical properties and shielding efficiency after repair, thereby leading to a prolonged service life. This study offers a promising strategy for the effective integration of multiple electromagnetic nanofillers into a self-healing polymeric system, which leads to highly efficient electrical and EMI shielding properties as well as remarkable self-repairability. We believe that these results can guide the development of advanced, durable EMI shielding applications. [ABSTRACT FROM AUTHOR]

Abstract Background The rear-wheel camber, defined as the inclination of the rear wheels, is usually used in wheelchair sports, but it is becoming increasingly employed in daily propulsion. Although the rear-wheel camber can increase stability, it alters physiological performance during propulsion. The purpose of the study is to investigate the effects of rear-wheel cambers on temporal-spatial parameters, joint angles, and propulsion patterns. Methods Twelve inexperienced subjects (22.3±1.6 yr) participated in the study. None had musculoskeletal disorders in their upper extremities. An eight-camera motion capture system was used to collect the three-dimensional trajectory data of markers attached to the wheelchair-user system during propulsion. All participants propelled the same wheelchair, which had an instrumented wheel with cambers of 0°, 9°, and 15°, respectively, at an average velocity of 1 m/s. Results The results show that the rear-wheel camber significantly affects the average acceleration, maximum end angle, trunk movement, elbow joint movement, wrist joint movement, and propulsion pattern. The effects are especially significant between 0° and 15°. For a 15° camber, the average acceleration and joint peak angles significantly increased (p < 0.01). A single loop pattern (SLOP) was adopted by most of the subjects. Conclusions The rear-wheel camber affects propulsion patterns and joint range of motion. When choosing a wheelchair with camber adjustment, the increase of joint movements and the base of support should be taken into consideration.

A simple method for synthesis of titanium carbide (TiC) nanofibers by a modified carbothermal reduction of electrospun titanium‐based fibers is reported. The effect of synthesis steps on the final product is discussed. Continuous TiC fibers synthesized have a smooth surface morphology, with average diameter of 148 nm and length in the centimeter range. X‐ray diffraction and high‐resolution transmission electron microscopy analysis results indicate that the fibers consist of TiC of high purity. Impact of heat treatment on the morphology and chemical and crystalline composition of the product is also investigated. Based on the experimental evidence, it is hypothesized that the carbothermal reduction of calcined electrospun fibers with precoated carbon proceeds through diffusion‐limited shrinking core pathway while that of the as‐spun fibers follows the reaction‐limited solution precipitation mechanism. The TiC nanofibers also show superior sintering properties by increasing theoretical density of hot pressed TiB2 from 94.5% of theoretical density to 97.9% of theoretical density. When sintered with ceria, it improves the conductivity of the ceria by 18.29 times as compared to 2.94 times by TiC nanoparticles at 800 °C. The TiC nanofibers show metallic behavior as well as potential for application as electrochemical double layer capacitor supercapacitors. [ABSTRACT FROM AUTHOR]

Hyperuricemia has been associated with chronic kidney disease (CKD) progression. The antihyperuricemic febuxostat's potential renoprotective effect has been demonstrated in stage 1–3 CKD. Large‐scale studies comparing the renoprotective potential of febuxostat and allopurinol in advanced CKD are lacking. We exclusively selected 6,057 eligible patients with predialysis stage 5 CKD prescribed either febuxostat or allopurinol using the National Health Insurance Research Database in Taiwan during 2012–2015. There were 69.57% of allopurinol users and 42.01% febuxostat users who required long‐term dialysis (P < 0.0001). The adjusted hazard ratio (HR) of 0.65 (95% confidence interval (CI) 0.60–0.70) indicated near 35% lower hazards of long‐term dialysis with febuxostat use. The renal benefit of febuxostat was consistent across most patient subgroups and/or using the propensity score‐matched cohort. The adjusted HR was 0.66 (95% CI, 0.61–0.70) for long‐term dialysis or death. In conclusion, lower risk of progression to dialysis was observed in predialysis stage 5 CKD febuxostat users without compromising survival. [ABSTRACT FROM AUTHOR]

Argininosuccinate synthetase 1 (ASS1) is a rate‐limited enzyme in arginine biosynthesis. The oncogenic potential of ASS1 in terms of prognosis and cancer metastasis in arginine prototrophic gastric cancer (GC) remains unclear at present. We identify differentially expressed proteins in microdissected GC tumor cells relative to adjacent nontumor epithelia by isobaric mass tag for relative and absolute quantitation proteomics analysis. GC cells with stable expression or depletion of ASS1 were further analyzed to identify downstream molecules. We investigated their effects on chemoresistance and cell invasion in the presence or absence of arginine. ASS1 was highly expressed in GC and positively correlated with GC aggressiveness and poor outcome. Depletion of ASS1 led to inhibition of tumor growth and decreased cell invasion via induction of autophagy‐lysosome machinery, resulting in degradation of active β‐catenin, Snail, and Twist. Ectopic expression of ASS1 in GC cells reversed these effects and protected cancer cells from chemotherapy drug‐induced apoptosis via activation of the AKT–mammalian target of rapamycin signaling pathway. ASS1 contributes to GC progression by enhancing aggressive potential resulting from active β‐catenin, Snail, and Twist accumulation. Our results propose that ASS1 might contribute to GC metastasis and support its utility as a prognostic predictor of GC—Tsai, C.‐Y., Chi, H.‐C, Chi, L.‐M., Yang, H.‐Y., Tsai, M.‐M., Lee, K.‐F., Huang, H.‐W., Chou, L.‐F., Cheng, A.‐J., Yang, C.‐W., Wang, C.‐S., Lin, K.‐H. Argininosuccinate synthetase 1 contributes to gastric cancer invasion and progression by modulating autophagy. FASEB J. 32, 2601–2614 (2018). www.fasebj.org [ABSTRACT FROM AUTHOR]

Radiotherapy is a well-established regimen for nearly half the cancer patients worldwide. However, not all cancer patients respond to irradiation treatment, and radioresistance is highly associated with poor prognosis and risk of recurrence. Elucidation of the biological characteristics of radioresistance and development of effective prognostic markers to guide clinical decision making clearly remain an urgent medical requirement. In tumorigenic and radioresistant cancer cell populations, phenotypic switch is observed during the course of irradiation treatment, which is associated with both stable genetic and epigenetic changes. While the importance of epigenetic changes is widely accepted, the irradiation-triggered specific epigenetic alterations at the molecular level are incompletely defined. The present review provides a summary of current studies on the molecular functions of DNA and RNA m6A methylation, the key epigenetic mechanisms involved in regulating the expression of genetic information, in resistance to irradiation and cancer progression. We additionally discuss the effects of DNA methylation and RNA N6-methyladenosine (m6A) of specific genes in cancer progression, recurrence, and radioresistance. As epigenetic alterations could be reversed by drug treatment or inhibition of specific genes, they are also considered potential targets for anticancer therapy and/or radiotherapy sensitizers. The mechanisms of irradiation-induced alterations in DNA and RNA m6A methylation, and ways in which this understanding can be applied clinically, including utilization of methylation patterns as prognostic markers for cancer radiotherapy and their manipulation for anticancer therapy or use as radiotherapy sensitizers, have been further discussed. [ABSTRACT FROM AUTHOR]

NEK2 (NIMA-related expressed kinase 2) is a serine/threonine centrosomal kinase that acts as a critical regulator of centrosome structure and function. Aberrant NEK2 activities lead to failure in regulating centrosome duplication. NEK2 overexpression promotes tumorigenesis and is associated with poor prognosis in several cancers. Increased NEK2 expression during the late pathological stage has been detected in the Oncomine liver dataset and hepatocellular carcinoma (HCC) specimens. Elevated NEK2 protein is associated with poor overall survival in patients with HCC. However, the precise roles and mechanisms of NEK2 in liver cancer progression remain largely unknown. An earlier functional study revealed that NEK2 mediates drug resistance (cisplatin or lipo-doxorubicin) via expression of an ABCC10 transporter. Active angiogenesis and metastasis underlie the rapid recurrence and poor survival of HCC. Results from the current study showed that NEK2 mediates tumor growth, metastasis and angiogenesis in vivo. NEK2-mediated drug resistance was blocked by a specific PI3K or AKT inhibitor. Moreover, NEK2 mediated liver cancer cell migration via pAKT/NF-κB signaling and matrix metalloproteinase (MMP) activation. Angiogenesis was induced via the same signaling pathway and IL-8 stimulation. Our findings collectively indicate that NEK2 modulates hepatoma cell functions, including growth, drug resistance, metastasis and angiogenesis via downstream genes activation. [ABSTRACT FROM AUTHOR]

Electrospun manganese oxide nanofibers were synthesized to improve the observed capacitance of MnOx based capacitor electrodes by exploiting the high surface to volume ratios and the nano voids present in the non-woven mats that would result in providing larger available electrode surface and reduced charge transfer resistance. In addition, MnO x hybrid nanofibers containing heterogeneously mixed CNTs and co-spun MnO x / SnO 2 nanofibers were also prepared by the electrospinning method to further improve the specific capacitance by reducing the overall electrode conductivity. The specific capacitance measured at 10 mV/s are 161.22 and 182.20 F/g for MnO x and MnO x /CNT hybrid nanofibers, while the specific capacitance of MnO x /SnO 2 fibers was found to be 472.31 F/g. An additional MnO x nanofiber matrix was prepared by electrospinning followed by calcination at 700 °C which resulted in hollow nanofibers. The specific capacitance of this nanostructure was 361.23 F/g. The primary crystalline phase in these fibers was Mn 2 O 3 . EIS revealed that the ESR of the fibers were low and that the electrochemical process was primarily diffusion controlled. [ABSTRACT FROM AUTHOR]

It has been suggested that minimisation of energy cost is one of the primary determinants of wheelchair designs. Wheel camber is one important parameter related to wheelchair design and its angle may affect usability during manual propulsion. However, there is little available literature addressing the effect of wheel camber on the mechanical energy or power flow involved in manual wheelchair propulsion. Twelve normal subjects (mean age, 22.3 years; SD, 1.6 years) participated in this study. A video-tracking system and an instrumented wheel were used to collect 3D kinematic and kinetic data. Wheel camber of 0° and 15° was chosen to examine the difference between mechanical power and power flow of the upper extremity during manual wheelchair propulsion. The work calculated from power flow and the discrepancy between the mechanical work and power flow work of upper extremity had significantly greater values with increased camber. The upper arm had a larger active muscle power compared with that in the forearm and hand segments. While propelling the increased camber, the magnitude of both the proximal and distal joint power and proximal muscle power was increased in all three segments. While the propelling wheel with camber not only needs a greater energy cost but also there is greater energy loss. [ABSTRACT FROM PUBLISHER]

In contrast to Western counties, the incidence of urothelial carcinoma (UC) remains mar-edly elevated in Taiwan. Regulatory T cells (Tregs) play a crucial role in limiting immune responses within the tumor microenvironment. To elucidate the relationship between immune checkpoints in the tumor immune microenvironment and UC progression, we utilize the Gene Expression Omnibus (GEO) to analyze a microarray obtained from 308 patients with UC. We observed that the expression level of CD276 or TIM-3 was positively correlated with late-stage UC and poor prognosis. Patients with simultaneously high CD276 and TIM-3 expression in tumors have significantly reduced both univariate and multivariate survival, indicating that mRNA levels of these immune checkpoints could be independent prognostic biomarkers for UC overall survival and recurrence. Our cohort study showed rare CD8+ cytotoxic T-cells and Tregs infiltration during early-stage UC-known as cold tumors. Approximately 30% of late-stage tumors exhibited highly infiltrated cytotoxic T cells with high PD-1 and FOXP3 expression, which implied that cytotoxic T cells were inhibited in the advanced UC microenvironment. Collectively, our findings provide a better prognosis prediction by combined immune checkpoint biomarkers and a basis for early-stage UC standard treatment to convert cold tumors into hot tumors, followed by immune checkpoint therapy. [ABSTRACT FROM AUTHOR]

Approximately 1 million cases of leptospirosis, an emerging infectious zoonotic disease, are reported each year. Pathogenic Leptospira species express leucine-rich repeat (LRR) proteins that are rarely expressed in non-pathogenic Leptospira species. The LRR domain-containing protein family is vital for the virulence of pathogenic Leptospira species. In this study, the biological mechanisms of an essential LRR domain protein from pathogenic Leptospira were examined. The effects of Leptospira and recombinant LRR20 (rLRR20) on the expression levels of factors involved in signal transduction were examined using microarray, quantitative real-time polymerase chain reaction, and western blotting. The secreted biomarkers were measured using an enzyme-linked immunosorbent assay. rLRR20 colocalized with E-cadherin on the cell surface and activated the downstream transcription factor β-catenin, which subsequently promoted the expression of MMP7, a kidney injury biomarker. Additionally, MMP7 inhibitors were used to demonstrate that the secreted MMP7 degrades surface E-cadherin. This feedback inhibition mechanism downregulated surface E-cadherin expression and inhibited the colonization of Leptospira. The degradation of surface E-cadherin activated the NF-κB signal transduction pathway. Leptospirosis-associated acute kidney injury is associated with the secretion of NGAL, a downstream upregulated biomarker of the NF-κB signal transduction pathway. A working model was proposed to illustrate the crosstalk between E-cadherin/β-catenin and NF-κB signal transduction pathways during Leptospira infection. Thus, rLRR20 of Leptospira induces kidney injury in host cells and inhibits the adhesion and invasion of Leptospira through the upregulation of MMP7 and NGAL. [ABSTRACT FROM AUTHOR]

Among hemodialysis patients aged more than 40 years old, previous large-scale studies showed statin treatment had no effect on reducing cardiovascular adverse events. However, young-adult-onset end-stage renal disease (ESRD) patients have different physicosocial factors compared to older ESRD patients. The benefit of statins in such a specific group has not been well evaluated. Through the use of Taiwan's National Health Insurance Research Database (NHIRD), young adult patients aged 20–40 with incident ESRD requiring permanent dialysis between 1 January 2003 and 31 December 2015 were identified. The enrollees were further divided into two groups depending on whether they received statin therapy for more than 90 days (statin group) or never received any statin (nonstatin group) in the first year after initiation of dialysis. Propensity score weighting (PSW) was used to balance the baseline characteristics between the two groups. After PSW, the statin group (n = 771) exhibited a higher rate of major adverse cardiac and cerebrovascular events (MACCEs) (2.65% vs. 1.44%, hazard ratio (HR): 1.87, 95% confidence interval (CI): 1.43–2.45), and acute myocardial infarction (1.51% vs. 0.30%, HR: 5.34, 95% CI: 3.40–8.39) compared to the nonstatin group (n = 1709). The risk of all-cause mortality, cardiovascular (CV) death. and stroke did not significantly differ between the two groups. Similar to older patients, this study demonstrated that statin therapy cannot offer any protective effects in reducing CV outcomes among young adult ESRD patients undergoing dialysis. [ABSTRACT FROM AUTHOR]

The presence of fever has long been a warning sign of severe urinary tract infection (UTI). However, we previously identified that inpatients with afebrile UTI had an increased risk of developing acute kidney injury (AKI). After expanding this cohort, 1132 inpatients with UTI diagnosed between January 2006 and April 2019 were analyzed. Overall, 159 (14%) of these patients developed AKI; bacteremia, urolithiasis, septic shock, hypertension, lower baseline renal function, marked leukocytosis, and the absence of fever were independently linked to AKI. When we further studied the cohort of inpatients with fever during hospitalization, we identified a group of "delayed fever" UTI inpatients who did not have fever as their initial presentation. Compared to patients presenting with fever at the emergency department, patients with delayed fever tended to be younger and have less frequent infection with Escherichia coli, more frequent AKI, upper tract infection, and a longer hospital stay. Despite the initial absence of fever, these patients demonstrated larger extents of elevations in both serum white blood cell counts and C-reactive protein levels. In short, besides UTI patients with lower baseline renal function that remain afebrile during their hospital stay, clinical awareness of the increased incidence of AKI in younger patients with "delayed fever" should also be noted. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the second most widespread cause of cancer-related mortality worldwide. The discovery of novel biomarkers of oncoproteins can facilitate the development of therapeutic strategies for GC treatment. In this study, we identified novel biomarkers by integrating isobaric tags for relative and absolute quantitation (iTRAQ), a human plasma proteome database, and public Oncomine datasets to search for aberrantly expressed oncogene-associated proteins in GC tissues and plasma. One of the most significantly upregulated biomarkers, DEK, was selected and its expression validated. Our immunohistochemistry (IHC) (n = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 72) analyses disclosed a marked increase in DEK expression in tumor tissue, compared with paired nontumor mucosa. Importantly, significantly higher preoperative plasma DEK levels were detected in GC patients than in healthy controls via enzyme-linked immunosorbent assay (ELISA). In clinicopathological analysis, higher expression of DEK in both tissue and plasma was significantly associated with advanced stage and poorer survival outcomes of GC patients. Data from receiver operating characteristic (ROC) curve analysis disclosed a better diagnostic accuracy of plasma DEK than carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), and C-reactive protein (CRP), highlighting its potential as an effective plasma biomarker for GC. Plasma DEK is also more sensitive in tumor detection than the other three biomarkers. Knockdown of DEK resulted in inhibition of GC cell migration via a mechanism involving modulation of matrix metalloproteinase MMP-2/MMP-9 level and vice versa. Our results collectively support plasma DEK as a useful biomarker for making diagnosis and prognosis of GC patients. [ABSTRACT FROM AUTHOR]