MicroRNA-146a gene transfer ameliorates senescence and senescence-associated secretory phenotypes in tendinopathic tenocytes.

OBJECTIVE: Tendinopathy is influenced by multiple factors, including chronic inflammation and aging. Senescent cells exhibit characteristics such as the secretion of matrix-degrading enzymes and pro-inflammatory cytokines, collectively known as senescence-associated secretory phenotypes (SASPs). Many of these SASP cytokines and enzymes are implicated in the pathogenesis of tendinopathy. MicroRNA-146a (miR-146a) blocks senescence by targeting interleukin-1ß (IL-1ß) receptor-associated kinase 4 (IRAK-4) and TNF receptor-associated factor 6 (TRAF6), thus inhibiting NF-κB activity. The aims of this study were to (1) investigate miR-146a expression in tendinopathic tendons and (2) evaluate the role of miR-146a in countering senescence and SASPs in tendinopathic tenocytes. METHODS: MiR-146a expression was assessed in human long head biceps (LHB) and rat tendinopathic tendons by in situ hybridization. MiR-146a over-expression in rat primary tendinopathic tenocytes was achieved by lentiviral vector-mediated precursor miR-146a transfer (LVmiR-146a). Expression of various senescence-related markers was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunoblotting and immunofluorescence. MiR-146a expression showed a negative correlation with the severity of tendinopathy in human and rat tendinopathic tendons (p<0.001). RESULTS: Tendinopathic tenocyte transfectants overexpressing miR-146a exhibited downregulation of various senescence and SASP markers, as well as the target molecules IRAK-4 and TRAF6, and the inflammatory mediator phospho-NF-κB. Additionally, these cells showed enhanced nuclear staining of high mobility group box 1 (HMGB1) compared to LVmiR-scramble-transduced controls in response to IL-1ß stimulation. CONCLUSIONS: We demonstrate that miR-146a expression is negatively correlated with the progression of tendinopathy. Moreover, its overexpression protects tendinopathic tenocytes from SASPs and senescence through the IRAK-4/TRAF6/NF-kB pathway.

Daily supplement of sesame oil prevents postmenopausal osteoporosis via maintaining serum estrogen and aromatase levels in rats.

Estrogen deficiency is one of the main causes of postmenopausal osteoporosis in elderly women. Hormone replacement therapy has been employed to manage postmenopausal osteoporosis; however, it has raised concerns related to heart attacks and breast cancer. Sesame oil has been reported to affect sex hormone status. The aim of the present study is to evaluate the effect of sesame oil supplement on postmenopausal osteoporosis in rats. We used female Sprague Dawley rats that underwent bilaterally ovariectomy (OVX) as an experimental postmenopausal osteoporosis animal model. These rats were orally administrated sesame oil (0.25 or 0.5 mL/kg/day) for four months as the therapeutic group. We assessed bone mineral density (BMD) and the levels of osteocalcin, procollagen-I C-terminal propeptide (PICP), collagen cross-linked N-telopeptide (NTx), estradiol, and aromatase in the sera. The daily supplementation of sesame oil significantly increased BMD, serum osteocalcin levels, and trabecular areas in the OVX-treated rats. Sesame oil also elevated serum PICP levels and decreased NTx levels in these rats. Furthermore, sesame oil effectively maintained serum estradiol and aromatase levels in the OVX-induced osteoporosis rats. In conclusion, daily supplementation of sesame oil prevents postmenopausal osteoporosis by maintaining serum estrogen and aromatase levels, while also modulating the imbalance between bone formation and resorption in osteoporosis rats.

The Pulsed Nd:YAG Laser Therapy Enhanced Nerve Regeneration via Apoptosis Inhibition in a Rat Crushed Sciatic Nerve Model.

The study was aimed to validate the efficacy of the pulsed Nd:YAG laser on nerve regeneration in a rat sciatic nerve crushed model. 54 Wistar rats were randomly assigned into three groups: shame control, crush control, and laser treated group. For the laser treated group, the pulsed Nd:YAG laser (10 Hz) with 350 mJ per pulse in energy density and 50 J/cm2 in fluence was applied extracorporeally at the lesion site for 12 min to daily deliver 500 J immediately and consecutive 9 days following the crush injury. At week 1, the apoptosis-related activities in the injured nerve were examined (n = 8/each group). The sciatic functional index (SFI) was measured preoperatively and weekly until 4 weeks after the index procedure. The injured nerve and the innervated gastrocnemius muscle histology were assessed at week 4 (n = 10/each group). At week 1, the laser group showed the significant less TUNEL-positive ratio (P < 0.05), and the lower expression of cleaved caspase3/procaspase-3 and beclin-2/beclin-2-associated protein X ratios compared with the crush control. Furthermore, the laser group revealed significantly better SFI since week 1 and throughout the study (P < 0.05, all) compared with the crush control. At week 4, the laser group showed significantly higher axon density, lower myelin g-ratio, and the corresponding higher glycogen expression (P < 0.05, all) in the gastrocnemius muscle compared with those in the crush control. The pulsed Nd:YAG might enhance the injured nerve regeneration via apoptosis inhibition.

Is delayed fixation worthwhile in patients with long bone fracture concomitant with mild traumatic brain injury? A propensity score-matched study.

INTRODUCTION: Early definite treatment for orthopedic patients is strongly advocated. However, a consensus has not been reached on the optimal timing of long bone fracture fixation for patients with associated mild traumatic brain injury (TBI). Surgeons lack evidence on the basis on which they should decide on the operation timing. METHODS: We retrospectively reviewed the data of patients with mild TBI and lower extremity long bone fractures from 2010 to 2020. The patients receiving internal fixation within and after 24 h were defined as the early- and delayed-fixation groups. We compared the discharge Glasgow Coma Scale (GCS) scores, lengths of stay, and in-hospital complications. Propensity score matching (PSM) with multiple adjusted variables and a 1:1 matching ratio was applied to reduce selection bias. RESULTS: In total, 181 patients were enrolled; 78 (43.1%) and 103 (56.9%) patients received early and delayed fracture fixation, respectively. After matching, each group had 61 participants and were statistically identical. The delayed group did not have better discharge GCS scores (early vs. delayed: 15.0 ± 0 vs. 15.0 ± 0.1; p = 0.158). The groups did not differ in their lengths of hospital stay (15.3 ± 10.6 vs. 14.8 ± 7.9; p = 0.789), intensive care unit stay (2.7 ± 4.3 vs. 2.7 ± 3.8; p = 0.947), or incidence of complications (23.0% vs. 16.4%; p = 0.494). CONCLUSIONS: Delayed fixation for patients with lower extremity long bone fractures concurrent with mild TBI does not result in fewer complications or improved neurologic outcomes compared with early fixation. Delaying fixation may not be necessary to prevent the second hit phenomenon and has not demonstrated any clear benefits.

Jigless Knotless Internal Brace Versus Other Minimal Invasive Achilles Tendon Repair Techniques in Biomechanical Testing Simulating the Progressive Rehabilitation Protocol.

The jigless knotless internal brace surgery (JKIB), an alternative method for minimal invasive surgery (MIS) repair of acute Achilles tendon rupture, has advantages of preventing sural-nerve injury in MIS and superficial wound infection in open surgery, as previous clinical research demonstrates. However, no comparative study on the biomechanical performance between JKIB and other MIS techniques has been reported until now. In this study, 50 fresh porcine Achilles tendons were used to compare the JKIB with open surgery (two-stranded Krachow suture) with other MIS techniques, including Percutaneus Achilles Repair System (PARS), Speedbridge (SB), and Achillon Achilles Tendon Suture System (ACH), using a biomechanical testing with cyclic loading at 1 Hz. This test was used to simulate a progressive rehabilitation protocol where 20 to 100 N was applied in the first 250 cycles, followed by 20 to 190 N in the second 250 cycles, and then 20 to 369 N in the third 250 cycles. The cyclic displacement after 10, 100 and 250 cycles were recorded. The survived cycles were defined as a sudden drop in measured load. In survived cycles, the JKIB group (552.3 ± 72.8) had significantly higher cycles than the open, PARS, and ACH groups (204.3 ± 33.3, 395.9 ± 96.0, and 397.1 ± 80.9, respectively, p < .01) as analyzed by post hoc analysis, but no significant difference as compared with the SB group (641.6 ± 48.7). In cyclic displacement after 250 cyclic loadings, the JKIB group (11.29 ± 1.29) showed no significant difference as compared with PARS, SB, and ACH groups (12.21 ± 1.18, 9.80 ± 0.80, and 11.57 ± 1.10 mm, respectively) and significant less displacement than the open group (14.50 ± 1.85, p < .01). These findings suggest that JKIB could be an option for acute Achilles tendon repair in the MIS fashion due to no larger cyclic elongation compared with other MIS techniques.

Triptolide Attenuates Muscular Inflammation and Oxidative Stress in a Delayed-Onset Muscle Soreness Animal Model.

Delayed-onset muscle soreness (DOMS) is associated with exercise-induced muscle damage and inflammation, which is mainly caused by prolonged eccentric exercise in humans. Triptolide, an extract from the Chinese herb Tripterygium wilfordii Hook F, has been used for treating autoimmune and inflammatory diseases in clinical practice. However, whether triptolide attenuates acute muscle damage is still unclear. Here, we examined the effect of triptolide on carrageenan-induced DOMS in rats. Rats were injected with 3% of carrageenan into their muscles to induce acute left gastrocnemius muscular damage, and triptolide treatment attenuated carrageenan-induced acute muscular damage without affecting hepatic function. Triptolide can significantly decrease lipid hydroperoxide and nitric oxide (NO) levels, proinflammatory cytokine production, and the activation of nuclear factor (NF)-ĸB, as well as increase a reduced form of glutathione levels in carrageenan-treated rat muscles. At the enzyme levels, triptolide reduced the inducible nitric oxide synthase (iNOS) expression and muscular myeloperoxidase (MPO) activity in carrageenan-treated DOMS rats. In conclusion, we show that triptolide can attenuate muscular damage by inhibiting muscular oxidative stress and inflammation in a carrageenan-induced rat DOMS model.

Single Injection of Cross-Linked Hyaluronate in Knee Osteoarthritis: A 52-Week Double-Blind Randomized Controlled Trial.

Background: to compare the 52-week effectiveness and safety between HYAJOINT Plus (HJP) and Durolane in knee osteoarthritis (OA) treatment. Methods: consecutive patients received a single injection of 3 mL HJP or Durolane. The primary outcome was a visual analog scale (VAS) pain measurement at 26 weeks post-injection. Secondary outcomes included other clinical, satisfaction, and safety assessments for 52 weeks. Results: 142 patients were equally randomized. At week 26, the HJP group had less VAS pain than the Durolane group (18.1 ± 9.5 versus 24.4 ± 14.0, p = 0.001). Both groups showed improvement in their VAS pain and stiffness scores, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and total scores for 52 weeks after injection (p < 0.001). However, the HJP group showed lower VAS pain and stiffness scores, reduced WOMAC pain and stiffness scores, a shorter Timed "Up & Go" (TUG) time, and a higher satisfaction score than the Durolane group for 39 weeks (p < 0.05). Only mild and self-limited adverse events occurred (40.8%). Conclusion: While a single injection of either HJP or Durolane is safe and effective for at least 52 weeks, HJP provided superior improvement in terms of VAS pain and stiffness scores, WOMAC pain and stiffness scores, and satisfaction score within 39 weeks of treatment.

Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects.

The combination of cross-linked hyaluronate (cHA) and corticosteroid showed more rapid pain or functional improvement in knee osteoarthritis and adhesive capsulitis. However, rare evidence of this combination in treating tendinopathy has been reported. We hypothesized that the specific formulations of cHA and dexamethasone (DEX) conferred amelioration of tendinopathy via anti-apoptosis and anti-senescence. In this controlled laboratory study, primary tenocytes from the human tendinopathic long head of biceps were treated with three cHA formulations (cHA:linealized HA = 80:20, 50:50, and 20:80) + DEX with or without IL-1ß stimulation. Cell viability, inflammatory cytokines, tendon-related proliferation markers, matrix metalloproteinases (MMPs), senescent markers, and apoptosis were examined. The in vivo therapeutic effects of the selected cHA + DEX combinations were evaluated in a collagenase-induced rat patellar tendinopathy model. The expression levels of inflammatory mediators, including IL-1ß, IL-6, COX-2, MMP-1, and MMP-3 were significantly reduced in all cHA + DEX-treated tenocytes (p < 0.05, all). The cHA (50:50) + DEX and cHA (20:80) + DEX combinations protected tenocytes from cytotoxicity, senescence, and apoptosis induced by DEX in either IL-1ß stimulation or none. Furthermore, the two combinations significantly improved the rat experimental tendinopathy by reducing ultrasound feature scores and histological scores as well as the levels of apoptosis, senescence, and senescence-associated secretory phenotypes (p < 0.05, all). We identified two specific cHA formulations (cHA (50:50) and cHA (20:80)) + DEX that could ameliorate tendinopathy through anti-senescence and -apoptosis without cytotoxicity. This study provides a possible approach to treating tendinopathy using the combination of two well-known agents.

Amelioration of experimental tendinopathy by lentiviral CD44 gene therapy targeting senescence-associated secretory phenotypes.

CD44 exerts anti-senescence effects in many disease models. We examined senescence in tendinopathy and the effect of CD44 on senescence-associated secretory phenotypes (SASPs). Senescent markers were determined in human tendinopathic long head of bicep (LHB) and normal hamstring tendons. CD44 gene transfer in rat tendinopathic tenocytes stimulated with interleukin (IL)-1ß and a rat Achilles tendinopathy model were performed using lentiviral vectors. Expression levels of p53, p21, and p16 and senescence-associated ß-galactosidase (SA-ß-gal) activity were positively correlated with the severity of human tendinopathy and were higher in rat and human tendinopathic tenocytes than in normal controls. CD44 overexpressed tenocyte transfectants exhibited reduced levels of IL-6, matrix metalloproteinases (MMPs), cyclooxygenase (COX)-2, p53, p21, p16, SA-ß-gal, and phospho-nuclear factor (NF)-κB, whereas their collagen type I alpha 1 (COL1A1) and tenomodulin (tnmd) levels were increased when compared with control transfectants under IL-1ß-stimulated conditions. In the animal model, CD44 overexpression lowered the ultrasound and histology scores and expression levels of the senescent and SASP markers COX-2 and phospho-NF-κB. Bromodeoxyuridine (BrdU)- and tnmd-positive cell numbers were increased in the LVCD44-transduced tendinopathic tendons. Senescence is positively correlated with tendinopathic severity, and CD44 overexpression may protect the tendinopathic tendons from SASPs via anti-inflammation and maintenance of extracellular matrix homeostasis.

The Correlation of Carpal Tunnel Pressure with Clinical Outcomes following Ultrasonographically-Guided Percutaneous Carpal Tunnel Release.

Background: To evaluate the correlation between carpal tunnel pressure (CTP) and the clinical presentations, and to explore the possible predictors for the postoperative recovery pattern in patients with carpal tunnel syndrome (CTS). Materials and Methods: Consecutive patients with idiopathic CTS following percutaneous ultrasound-guided carpal tunnel release (UCTR) were enrolled. CTP was measured preoperatively and immediately after operation. The Boston Carpal Tunnel Questionnaire (BCTQ) and the cross-sectional area (CSA) of median nerve were recorded preoperatively and at 1, 3, and 12 months postoperatively. Results: 37 patients (37 hands; 8 men and 29 females; median age, 59.0 years) were enrolled. CTP significantly decreased immediately from 40.0 (28.0−58.0) to 13.0 (8.0−20.0) mmHg after UCTR. BCTQ scores significantly improved at 1 month postoperatively, and the improvement trend persisted until 12 months postoperatively (p < 0.001). Preoperative CTP was positively correlated with preoperative CSA and preoperative BCTQ scores (p < 0.05, all). Using group-based trajectory modeling, all patients were categorized into the "gradual recovery" or "fast recovery" group. Higher preoperative CTP was significantly associated with a faster recovery pattern (odds ratio: 1.32). Conclusions: Preoperative CTP was well correlated with the clinical presentations and might be a useful predictor for the postoperative clinical recovery pattern.

Diagnosis of Carpal Tunnel Syndrome in Patients Without Diabetes With Hemodialysis Using Ultrasonography: Is It a Useful Adjunctive Tool?

OBJECTIVE: (1) To examine the ultrasonography (US) characteristics in patients with hemodialysis-related carpal tunnel syndrome (H-CTS) and (2) to evaluate the accuracy of a proposed US parameter-dynamic ratio of median nerve-to-hamate hook distance (RMHD) in diagnosis of H-CTS. DESIGN: A case-control study. SETTING: A tertiary medical center and a secondary hospital from November 2017 to March 2021. PARTICIPANTS: Consecutive patients (N=207) without diabetes under hemodialysis were recruited and divided into a hemodialysis without carpel tunnel syndrome (CTS) (H-Control) group and an H-CTS group. Age-matched volunteers (N=89) without diabetes or upper extremity disorders were enrolled as the control group. INTERVENTION: US examinations by 2 operators blinded to the patient's clinical information. MAIN OUTCOME MEASURES: US parameters including cross-sectional area of the median nerve at the carpal tunnel inlet (CSA-I) and outlet (CSA-O), the flattening ratio of the median nerve at the inlet (FR-I) and outlet (FR-O), and RMHD. RESULTS: Handedness and arteriovenous fistula showed no associations with CSA-I/O and FR-I/O. Compared with the control group (n=69), the CSA-I was significantly larger in the H-Control group (n=63) and H-CTS group (n=76) (P<.001, both). There were no significant differences in the FR-I/-O among the 3 groups. For the second aim, in the H-CTS group (n=38), there was a significantly lower RMHD compared with both the control (n=20) and H-Control groups (n=30) (0.1%±2.2% vs 3.5±2.3% and 3.8±1.7%, P<.001, both). An RMHD cutoff value of <2.7% yielded a specificity of 80.0%, a sensitivity of 94.7%, and an overall accuracy of 88.2% in the diagnosis of H-CTS. CONCLUSIONS: Neither CSA-I/-O or FR-I/-O have a role in the diagnosis of H-CTS. RMHD might be a useful US parameter in the diagnosis of CTS in patients without diabetes undergoing hemodialysis.

Jigless knotless internal brace versus other open Achilles tendon repairs using a progressive rehabilitation protocol: a biomechanical study.

BACKGROUND: The jigless knotless internal brace surgery (JKIB), a modified minimal invasive surgery (MIS) for acute Achilles tendon injury, has advantages of preventing sural-nerve injury in MIS and superficial wound infection in open surgery, as demonstrated in previous clinical research. However, to date, biomechanical testing has not yet been validated. MATERIALS AND METHODS: Sixty fresh porcine Achilles tendons were used to compare the JKIB with other open surgery techniques, the four-stranded Krackow suture (4sK) and the triple-bundle suture (TBS) in biomechanical testing with cyclic loading set at 1 Hz. This approach simulated a progressive rehabilitation protocol where 20-100 N was applied in the first 1000 cycles, followed by 20-190 N in the second 1000 cycles, and then 20-369 N in the third 1000 cycles. The cycles leading to repair gaps of 2 mm, 5 mm, and 10 mm were recorded. The survival cycles were defined as repair gap of 10 mm. RESULTS: With respect to survival cycles, a significant difference was found among the three groups, in which the TBS was the most robust, followed by the JKIB and the 4sK, where the mean survived cycles were 2639.3 +/- 263.55, 2073.6 +/- 319.92, and 1425.25 +/- 268.96, respectively. Significant differences were verified via a post hoc analysis with the Mann-Whitney U test after the Bonferroni correction (p < 0.017). CONCLUSIONS: The TBS was the strongest suture structure in acute Achilles tendon repair. However, the JKIB could be an option in acute Achilles tendon repair with the MIS technique due to it being more robust than the 4sK, which has been typically favored for use in open repair.

Jigless knotless internal brace technique for acute Achilles tendon rupture: a case series study.

PURPOSE: To mitigate the risk of poor wound healing and of infection associated with the open repair of Achilles tendon midsubstance ruptures, minimally invasive techniques have been developed. We report our preliminary results after reviewing our "jigless knotless internal brace technique." METHODS: Patients were placed in prone position and a transverse 3-cm incision was made proximal to the palpable ruptured end. The proximal ruptured end was pulled out, gently debrided, and sutured using Krackow locking loops. Percutaneous sutures were crisscrossed through the distal tendon stump and looped around the Krackow sutures over the proximal stump. The ipsilateral Krackow sutures and the contralateral crisscrossed sutures were subcutaneously passed through two mini-incisions over the posterior calcaneus tuberosity and seated at the tuberosity with two 4.5-mm knotless suture anchors. All patients underwent the same post-operative rehabilitation protocol and regular follow-ups for at least 1 year. RESULTS: We recruited 10 patients (mean age, 37.3 years) who scored 100 points on the American Orthopaedic Foot and Ankle Society (AOFAS) scale, and who returned to their preoperative exercise levels 1-year post-operatively with no complications. CONCLUSION: Our method is simple, effective, and requires no special tools. It might be a reliable option for Achilles tendon repair. LEVEL OF EVIDENCE: III.

Usefulness of Therapeutic Hypothermia to Improve Survival in Out-of-Hospital Cardiac Arrest.

BACKGROUND: In recent years, therapeutic hypothermia (TH) has been used to improve outcomes in patients with out-of-hospital cardiac arrest (OHCA). Despite these recommendations, many centers are still hesitant to implement such hypothermia protocols. In this study, we assessed the effects of TH for OHCA patients. METHODS: A total of 58 OHCA patients who had return of spontaneous circulation after OHCA presumed to be due to cardiac causes were enrolled. Twenty-three patients underwent TH, which was performed using a large volume of ice crystalloid fluid infusions in the emergency room and conventional cooling blankets in the ICU to maintain a body temperature of 32-34 °C for 24 hours using a tympanic thermometer. Patients in the control group received standard supportive care without TH. Hospital survival and neurologic outcomes were compared. RESULTS: There were no significant differences between the groups in patient characteristics, underlying etiologies and disease severity. In the 23 patients who received TH, 17 were alive at hospital discharge. In the 35 patients who received supportive care, only 11 were alive at hospital discharge (73.91% vs. 31.43%, p = 0.0015). Approximately 52% of the patients in the TH group had good neurologic outcomes (12 of 23) compared with the 20% (7 of 35) of the patients in the supportive group (p = 0.01). CONCLUSIONS: TH can improve the outcomes of OHCA patients. Further large-scale studies are needed to verify our results.

Immediate effects of real-time postural biofeedback on spinal posture, muscle activity, and perceived pain severity in adults with neck pain.

BACKGROUND: Previous studies have investigated various types of postural biofeedback devices on different body regions to improve posture; however, they focused only on healthy adults without a history of chronic musculoskeletal disorders. In addition, those postural biofeedback devices used in previous studies are often designed for experimental research. The designs are usually bulky with many wires, which is not practical for everyday use. RESEARCH QUESTION: The aim of this study was to determine the immediate effect of a commercially available real-time postural biofeedback device on spinal posture, muscle activity, and perceived pain severity in adults with neck pain. METHODS: 21 adults who had chronic or recurrent nonspecific neck pain for more than 3 months and whose pain was induced or aggravated by prolonged computer work were enrolled in this study. Spinal posture (head tilt, neck flexion, cervical and thoracic angles), muscle activity (cervical erector spinae, upper trapezius, and thoracic erector spinae), and self-reported neck and shoulder pain were measured during computer typing tasks, with and without biofeedback. RESULTS: Compared with the non-biofeedback condition, the biofeedback condition significantly decreased neck flexion, upper cervical, and lower thoracic angles and lowered the activity of the cervical erector spinae. Self-reported neck pain was not influenced by the application of biofeedback, but significantly increased over the 1-hour typing task. SIGNIFICANCE: The application of a commercially available wearable real-time biofeedback device improves sitting posture and reduces muscular activity in adults with nonspecific neck pain during computer work. Future studies should examine the long-term effects of wearable real-time postural biofeedback devices for prevention and management of neck pain.

Schwann-Cell Autophagy, Functional Recovery, and Scar Reduction After Peripheral Nerve Repair.

The functional outcome after peripheral nerve repair is often unpredictable for many reasons, e.g., the severity of neuronal death and scarring. Axonal degeneration significantly affects outcomes. Post-injury axonal degeneration in peripheral nerves is accompanied by myelin degradation initiated by Schwann cells (SCs), which activate autophagy, a ubiquitous cytoprotective process essential for degrading and recycling cellular constituents. Scar formation occurs concomitantly with nerve insult and axonal degeneration. The association between SC autophagy and the mechanisms of nerve scar formation is still unknown. A rat model of peripheral nerve lesions induced by sciatic nerve transection injuries was used to examine the function of autophagy in fibrosis reduction during the early phase of nerve repair. Rats were treated with rapamycin (autophagy inducer) or 3-methyladenine (autophagy inhibitor). One week after the nerve damage, fibrosis was potently inhibited in rapamycin-treated rats and, based on gait analysis, yielded a better functional outcome. Immunohistochemistry showed that the autophagic activity of SCs and the accumulation of neurofilaments were upregulated in rapamycin-treated rats. A deficiency of SC autophagic activity might be an early event in nerve scar formation, and modulating autophagy might be a powerful pharmacological approach for improving functional outcomes.

Diabetes mellitus increased all-cause mortality rate among newly-diagnosed tuberculosis patients in an Asian population: A nationwide population-based study.

AIMS: To investigate the effect of diabetes mellitus (DM) on all-cause mortality among patients with newly-diagnosed tuberculosis (TB) in an Asian population. We also identified risk factors for mortality in these patients. METHODS: The data were obtained from the National Health Insurance Research Database and included 9831 newly-diagnosed TB individuals and 1627 TB mortality cases in the period of 2000-2010. The mortality data were divided into a DM group and a non-DM group. We measured the incidence density of mortality and identified the risk factors of mortality. RESULTS: The all-cause mortality of newly-diagnosed TB patients progressively increased with an average rate of 16.5% during 2000-2010. DM is an independent risk factor for all-cause mortality with HRs 1.17-1.27 by various models. TB patients with ages above 75years had the highest risk of mortality (HR=11.93) compared with those under 45 years. TB patients with heart failure, peripheral vascular disease, ischemic heart disease, cerebral vascular disease, hypertension, chronic kidney disease, pulmonary disease, liver disease, cancer, peptic ulcer disease, gout, and autoimmune disease had higher mortality compared to those without the aforementioned factors. CONCLUSIONS: The one-year all-cause mortality after TB diagnosis was high among TB patients in Taiwan and it tended to increase in the past decade. While treating these newly-diagnosed TB patients, it is crucial to detect the factors predisposing to death, such as old age, male gender, certain kinds of aforementioned factors and diabetes.

The relationships of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease.

Hypertension, blood pressure variation, and resistant hypertension have close relations to sleep apnea, which lead to target organ damage, including the kidney. The complex relationships between sleep apnea and blood pressure cause their interactions with chronic kidney disease ambiguous. The aim of the study was to elucidate the separate and joint effects of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease. A cross-sectional study was done to see the associations of sleep apnea, hypertension, and resistant hypertension with chronic kidney disease in 998 subjects underwent overnight polysomnography without device-therapy or surgery for their sleep-disordered breathing. Multivariate logistic regression was used to analyze the severity of SA, hypertension stage, resistant hypertension, and their joint effects on CKD. The multivariable relative odds (95% CI) of chronic kidney disease for the aged (age ≥65 years), severe sleep apnea, stage III hypertension, and resistant hypertension were 3.96 (2.57-6.09) (P < 0.001), 2.28 (1.13-4.58) (P < 0.05), 3.55 (1.70-7.42) (P < 0.001), and 9.42 (4.22-21.02) (P < 0.001), respectively. In subgroups analysis, the multivariable relative odds ratio of chronic kidney disease was highest in patients with both resistant hypertension and severe sleep apnea [13.42 (4.74-38.03)] (P < 0.001). Severe sleep apnea, stage III hypertension, and resistant hypertension are independent risk factors for chronic kidney disease. Patients with both severe sleep apnea and resistant hypertension have the highest risks.

High diabetes mellitus prevalence with increasing trend among newly-diagnosed tuberculosis patients in an Asian population: A nationwide population-based study.

AIMS: Our aims were to investigate the prevalence of diabetes mellitus (DM) among patients with newly-diagnosed tuberculosis (TB) and to determine its associated factors in an Asian population. METHODS: The data were obtained from the National Health Insurance Research Database and included 9831 newly-diagnosed TB individuals in the period of 2000-2010. The data were divided into a DM group and a non-DM group. We measured the prevalence and the associated comorbidities of DM. RESULTS: During 2000-2010, the prevalence of DM progressively increased, with an average prevalence rate of 27.9%. The patients with ages of 55-64 years had the highest association of DM (OR=3.53) compared with those under 45 years. TB patients with heart failure, ischemic heart disease, cerebral vascular disease, hypertension, dyslipidemia, chronic kidney disease, and liver disease were more likely to associate with DM (ORs=1.27, 1.23, 1.30, 2.32, 3.26, 1.6, and 1.68, respectively) compared to those without the variables. CONCLUSIONS: The prevalence of DM among TB patients in Taiwan was high and tended to increase in the past decade. Clinically, inquiring about DM history and screening routinely for those without DM history among TB patients should be carried out in Taiwan.