Edwardskelley8358

Gene augmentation therapy based on subretinal delivery of Adeno-Associated Viral (AAV) vectors is proving to be highly efficient in treating several inherited retinal degenerations. However, due to potential complications and drawbacks posed by subretinal injections, there is a great impetus to find alternative methods of delivering the desired genetic inserts to the retina. One such method is an intravitreal delivery of the vector. Our aim was to evaluate the efficacy of two capsid modified vectors that are less susceptible to cellular degradation, AAV8 (doubleY-F) and AAV2 (quadY-F+T-V), as well as a third, chimeric vector AAV[max], to transduce photoreceptor cells following intravitreal injection in sheep. We further tested whether saturation of inner limiting membrane (ILM) viral binding sites using a non-modified vector, prior to the intravitreal injection, would enhance the efficacy of photoreceptor transduction. Only AAV[max] resulted in moderate photoreceptor transduction following intravitreal injection. Intravitreal injection of the two other vectors did not result in photoreceptor transduction, nor did the saturation of the ILM prior to the intravitreal injection. On the other hand, two of the vectors efficiently transduced photoreceptor cells following subretinal injection in positive control eyes. Previous trials with the same vectors in both murine and canine models resulted in robust and moderate transduction efficacy, respectively, of photoreceptors following intravitreal delivery, demonstrating the importance of utilizing as many animal models as possible when evaluating new strategies for retinal gene therapy. The successful photoreceptor transduction of AAV[max] injected intravitreally makes it a potential candidate for intravitreal delivery, but further trials are warranted to determine whether the transduction efficacy is sufficient for a clinical outcome.Significance Fungal endogenous endophthalmitis is an uncommon and potentially blinding infection. Aspergillus is a causative organism in immunocompromized although is virulent enough to afflict immunocompetents. Their propensity to affect macula usually results in a dismal prognosis; thus, improving visual outcome has always been challenging to clinicians. A. nidulans has only rarely been implicated in exogenous endophthalmitis. Purpose To report the first case of A. nidulans endogenous endophthalmitis. Case report An asthmatic 42-year-old female presented with sudden unilateral vision loss due to a submacular abscess that progressively worsened in a matter of days. Vitreous PCR analysis after an urgent vitrectomy was positive for A. nidulans with no active systemic foci found. Oral and intravitreal Voriconazole was prescribed but multiple reactivations led to three vitrectomies in total alongside with subretinal Voriconazole, abscess aspiration, and endolaser. There was complete resolution of the infection and, although visual acuity was poor due to macular scar, enucleation was avoided. Conclusion Although uncommon, we must consider Aspergillus as the causative organism in apparently immunocompetent patients with history of recent systemic corticosteroids treatment, especially if they suffer a broncopulmonary disorder. Aspergillus is an aggressive organism so a high index of suspicion along with early diagnosis and prompt treatment is the key for better outcomes. We highlight A. nidulans as the causative agent as there are no other reported cases.Background Surface replacement arthroplasty (SRA) can be used in the treatment of rheumatoid arthritis (RA) affecting the metacarpophalangeal (MCP) joint. The authors of this study sought to investigate the outcomes of MCP SRA in patients with RA. Methods Retrospective review of medical records and an institutional joint registry were used to gather data on 80 MCP SRAs performed in 27 patients with RA. Data collected included demographics, SRA revisions, reoperations, complications, pain, and MCP arc of motion. Results The mean postoperative follow-up was 9.5 years (range, 2.1-20.5 years), with all SRAs achieving at least 2 years of follow-up. Thirteen digits (16%) underwent revision arthroplasty, and 29 (36%) required reoperation. The 5-, 10-, 15-, and 20-year rates of survival from implant revision were 95%, 85%, 80%, and 69%, respectively. The 5-, 10-, 15-, and 20-year rates of survival from overall reoperation were 80%, 65%, 55%, and 46%, respectively. Metacarpophalangeal joint arc of motion, grip strength, and pain levels significantly improved following surgery. Conclusions Metacarpophalangeal SRA can offer benefit to patients with RA for improvement in function and pain. High overall reoperation rates remain concerning; however, most do not involve arthroplasty revision.Xia, Du, Olivier Girard, Fan Rong yun, and Ma Fuhai. Effects of active and passive hypoxic conditioning for 6 weeks at different altitudes on blood lipids, leptin, and weight in rats. High Alt Med Biol. 00000-000, 2020. Objective To compare the effects of 6 weeks of passive and active hypoxia exposure at different altitudes on lipid metabolism, leptin, and weight in rats. Materials and Methods Eighty 9-week-old male Wistar rats were assigned to either non-exercise or exercise groups. Each group was subdivided into four categories (n = 10) based on hypoxic conditions 0, 2200, 2200 + 3500, and 3500 m. Rats in the exercise group trained on a treadmill at a speed of 20-22 m/min (0° incline) for 90 minutes, 5 days per week for 6 weeks. selleck products Serum lipid and leptin levels and weight were measured following the intervention. Results Total cholesterol (-8.2% ± 3.5%), low-density lipoproteins (-29.8% ± 8.1%), and triglyceride (TG) levels (-17.2% ± 3.8%) were lower, and high-density lipoproteins (+7.4% ± 4.0%) higher, in exercise versus non-exercise groups (all p less then 0.001), independent of condition. TG levels were lower at altitude (-13.0% ± 27.3%, -10.9% ± 24.3%, and -9.2% ± 20.9% at 2200, 2200 + 3500, and 3500 m, respectively) compared to 0 m (p less then 0.001). Hypoxic exposure decreased leptin with lower values at 2200 + 3500 m and 3500 m compared to 0 m (p less then 0.05). Weight was lower in exercise than non-exercise groups (-8.2% ± 21.0%; p less then 0.001), and at altitude (-2.7% ± 2.6%, -5.5% ± 3.7%, and -5.7% ± 2.7% at 2200, 2200 + 3500, and 3500 m, respectively) compared to 0 m. Conclusion Regular aerobic exercise led to more favorable responses for lipid metabolism and weight control than the oxygenation conditions the animals are in.