Hammondcopeland5702

023; risk difference [RD], 22.3%; 95% CI, 3.0% to 41.6%) and their subanalysis minor chipping or chipping that can be solved with polishing (P = .044; RD, 19.5%; 95% CI, 0.5% to 38.4%), and major chipping or chipping that needs repair in the laboratory (P = .023; RD, 6.0%; 95% CI, 0.8% to 11.3%). CONCLUSIONS AND PRACTICAL IMPLICATIONS Posterior multiunit ZC restorations are considered a predictable treatment in the medium term, although they are slightly more susceptible to chipping of the veneering ceramic than MC restorations. Muscle atrophy is the loss of skeletal muscle mass and strength in response to diverse catabolic stimuli. At present, no effective treatments except exercise have been shown to reduce muscle atrophy clinically. Here, we report that CRISPR/Cas9-mediated genome editing through local injection into gastrocnemius muscles or tibialis anterior muscle efficiently targets the biogenesis processing sites in pre-miR-29b. In vivo, this CRISPR-based treatment prevented the muscle atrophy induced by angiotensin II (AngII), immobilization, and denervation via activation of the AKT-FOXO3A-mTOR signaling pathway and protected against AngII-induced myocyte apoptosis in mice, leading to significantly increased exercise capacity. Our work establishes CRISPR/Cas9-based gene targeting on miRNA as a potential durable therapy for the treatment of muscle atrophy and expands the strategies available interrogating miRNA function in vivo. Generalized severe junctional epidermolysis bullosa (GS-JEB) is an incurable and fatal autosomal recessively inherited blistering skin disease caused by mutations in the LAMA3, LAMB3, or LAMC2 genes. Most of these mutations are nonsense mutations that create premature termination codons that lead to impaired production of functional laminin 332, a protein needed for epidermal-dermal adherence. Gentamicin induces readthrough of nonsense mutations and restores the full-length protein in various genetic diseases. Using primary keratinocytes from three GS-JEB patients, we showed that gentamicin induced functional laminin 332 that reversed a JEB-associated, abnormal cell phenotype. In a subsequent open-label trial involving the same patients, we examined whether 0.5% gentamicin ointment applied topically to open skin wounds could promote nonsense mutation readthrough and create new laminin 332 in the patients' skin. Gentamicin-treated wounds exhibited increased expression of laminin 332 at the dermal-epidermal junction for at least 3 months and were associated with improved wound closure. There were no untoward side effects from topical gentamicin. The newly induced laminin 332 did not generate anti-laminin 332 autoantibodies in either the patients' blood or skin. Gentamicin readthrough therapy may be a treatment for GS-JEB patients with nonsense mutations. BACKGROUND Clinical and basic investigations have indicated a significant association between circulating growth differentiation factor 15 (GDF15) and cardiovascular disease; however, the relationship between GDF15 and lower extremity atherosclerotic disease (LEAD) has been less studied. The present study aimed to explore the association between GDF15 and LEAD in Chinese patients with type 2 diabetes mellitus (T2DM). Considering that obesity is an important factor associated with circulating GDF15 levels, whether the relationship between serum GDF15 levels and LEAD is affected by body mass index (BMI) was also analysed. METHODS A total of 376 hospitalized T2DM patients were enrolled (161 with LEAD and 215 without LEAD). A sandwich enzyme-linked immunosorbent assay was used to detect the serum GDF15 levels. The femoral intima-media thickness (F-IMT) and LEAD were assessed by ultrasonography. RESULTS Patients with LEAD had significantly higher serum GDF15 levels than those without LEAD, regardless of whether their BMI was less then  25 kg/m2 or ≥ 25 kg/m2 (both P  less then  0.05). Serum GDF15 levels were independently positively related to the F-IMT (standardized β = 0.162, P = 0.002). SGC707 cell line After adjusting for confounding factors, per 1-standard deviation (SD) increase in the serum GDF15 levels was significantly related to an approximately 1.4-fold increased risk of LEAD in the total population (P  less then  0.05). Regardless of whether the BMI was less then  25 kg/m2 or ≥ 25 kg/m2, this association remained significant, with approximately 1.6- and 1.4-fold increased risks of LEAD, respectively (both P  less then  0.05). CONCLUSIONS High serum GDF15 levels were significantly correlated with an increased risk of LEAD in T2DM patients, and this relationship was independent of BMI.BACKGROUND Contralateral cervical 7 nerve (cC7) was used to repair two recipient nerves simultaneously for patients with total brachial plexus avulsion (TBPA). OBJECTIVE To evaluate the effect of cC7 transfer to axillary and median nerves in rats with TBPA. METHODS Eighty S-D rats were divided into 4 groups randomly on average. Group A cC7-median nerve, Group B cC7-axillary nerve, Group C cC7-median and axillary nerves, Group D TBPA without repair. The evaluation tools included behavioral tests, electromyogram (EMG), measurement of cross-sectional area of muscle fiber, nerve fiber count and gene expression assay. RESULTS The effective rates of EMG were 90 and 70% in Flexor Carpi Radialis (FCR) in Group A and C, while 70 and 60% in deltoid (DEL) in Group B and C, respectively. In behavioral test, the differences of effective rates between groups were not significant. The mean cross-sectional area of FCR in Group A or C was significantly larger than that in Group D. Either the number of median or axillary nerve fibers in Group A, B or C was statistically more than that in Group D. No matter for FCR or DEL, there were no significant differences in the ratios of relative expression of Muscle Atrophy F-box(MAFBOX)and Muscle RING Finger 1(MURF1)among these groups. CONCLUSION Compared with cC7 transfer to median nerve, cC7 transfer to both median and axillary nerves did not affect median nerve recovery. The deltoid muscle also could be restored. The recovery proportion of axillary nerve was less than that of median nerve.