Genetic modification of scAAV‐equine‐BMP‐2 transduced bone‐marrow‐derived mesenchymal stem cells before and after cryopreservation: An “off‐the‐shelf” option for fracture repair

Optimizing the environment of complex bone healing and improving treatment of catastrophic bone fractures and segmental bone defects remains an unmet clinical need both human and equine veterinary medical orthopaedics. The objective of this study was to determine whether scAAV‐equine‐BMP‐2 transduced cells would induce osteogenesis in equine bone marrow derived mesenchymal stem cells (BMDMSCs) in vitro, and if these cells could be cryopreserved in an effort to osteogenically prime them as an “off‐the‐shelf” gene therapeutic approach for fracture repair. Our study found that transgene expression is altered by cell expansion, as would be expected by a transduction resulting in episomal transgene expression, and that osteoinductive levels could still be achieved 5 days after recovery, and protein expression would continue up to 14 days after transduction. This is the first evidence that cryopreservation of genetically modified BMDMSCs would not alter the osteoinductive potential or clinical use of allogeneic donor cells in cases of equine fracture repair. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1310–1317, 2019.     

Hearing assessment data in HIV-infected and uninfected children of Cape Town,South Africa

Researchers are showing that the rate of hearing loss in children with perinatal HIV infection (PHIV) is higher than in HIV-unexposed, uninfected children. These data, however, have been collected mostly in the USA; extensive hearing data from low- and middle-income countries are lacking. The purpose of this study was to collect audiometric data in PHIV and HIV-uninfected children living in Cape Town, South Africa. Questionnaire data along with distortion product otoacoustic emissions (DPOAEs) and pure-tone testing were completed. Hearing loss was determined using the pure-tone thresholds defined as a pure-tone average (PTA) of 500, 1000, 2000, and 4000 Hz of >15 dB HL in the poorer ear. All data were compared between PHIV and HIV-uninfected children. Sixty-one (37 PHIV and 24 HIV-uninfected) children had hearing data. HIV status was not significantly associated with DPOAEs. The rate of conductive hearing loss was 11.5%; five PHIV and two HIV-uninfected children. The rate of any hearing loss was higher in PHIV children, but this difference was not statistically significant. PHIV children had a significantly higher mean PTA in the poorer ear than HIV-uninfected children. Conductive type of hearing loss was more common than sensorineural hearing loss. The underlying cause of hearing loss in the present study therefore remains unclear. Future research should include an examination of auditory neural function in an effort to determine the possible reason for differences in hearing.     

Limited correlation between systemic biomarkers and neurocognitive performance before and during HIV treatment

The AIDS Clinical Trials Group (ACTG) study A5303 investigated the associations between neuropsychological performance (NP) and inflammatory biomarkers in HIV-infected participants. Fifteen NP tests were administered at baseline and week 48 to 233 ART naïve participants randomized to maraviroc- or tenofovir-containing ART. Neurocognition correlated modestly with markers of lymphocyte activation and inflammation pre-ART (percent CD38+/HLA-DR+(CD4+) (r = − 0.22, p = 0.02) and percent CD38+/HLA-DR+(CD8+) (r = − 0.25, p = 0.02)), and with some monocyte subsets during ART (r = 0.25, p = 0.02). Higher interleukin-6 and percent CD38+/HLA-DR+(CD8+) were independently associated with worse severity of HIV-associated neurocognitive disorders (HAND) (p = 0.04 and 0.01, respectively). More studies to identify HAND biomarkers are needed.     

Identification of Distinct Latent Classes Related to Sleep,PTSD, Depression,and Anxiety in Individuals Diagnosed With Severe Alcohol Use Disorder

Objective/Background: Alcohol use disorders (AUDs) are often accompanied by comorbid physiologic and psychosocial conditions, including sleep disturbances. Sleep disturbances in these individuals may be associated with increased risk of relapse to drinking following detoxification and rehabilitation. Participants: The sample of inpatient treatment-seeking individuals with AUDs (N = 164) was 70.1% male and 47.6% African American with a mean age of 45.6 years (±9.5 years). Methods: Latent class analysis (LCA) was used to identify unmeasured class membership based on seven indicators: maximum Clinical Institute Withdrawal Assessment (CIWA) scores; sleep efficiency (actigraphy); sleep disturbances (Pittsburgh Sleep Quality Index-PSQI); anxiety or depression (Comprehensive Psychopathological Rating Scale [CPRS]); and current and lifetime posttraumatic stress disorder (PTSD). Results: The average number of drinking days in the 90 days preceding admission was 72.0 (±22.0 days), with an average of 13.16 drinks per day (±5.70 drinks). Nearly one quarter (24.4%) of respondents reported lifetime PTSD. Three latent classes were identified: Sleep Disturbance (SD); Sleep Disturbance, Anxiety and Depression (SD/AD); and Sleep Disturbance, Anxiety and Depression, and PTSD (SD/AD/PTSD). Members of the SD/AD/PTSD group were more likely to be female and had the highest withdrawal and sleep disturbance scores of all three groups. Conclusion: Findings support the use of LCA to identify subgroups of individuals with AUDs and accompanying sleep disturbances. Class identification may provide clinicians with insight into the integrative tailoring of interventions that meet the varied needs of individuals with AUDs, accompanying comorbidities, and sleep disturbances.