Viral competition assay to assess the role of HIV-1 proteins in immune evasion.

CD8+ T lymphocytes can recognize and eliminate cells infected by viruses. However, the human immunodeficiency virus (HIV-1) has developed mechanisms to evade CD8+ T-cell-mediated clearance. Here, we describe a protocol to assess the role of the HIV-1 protein Nef in immune evasion. The viral competition assay reveals the preferential killing of HIV-1-infected cells unable to express Nef. This methodology can be extended to study HIV-1 proteins involved in immune evasion and viral variants encoding cytotoxic T lymphocyte escape mutations. For complete details on the use and execution of this protocol, please refer to Duette et al. (2022).1.

Retrospective Comparison of Midterm Survivorship, Radiographic, and Clinical Outcomes of the INBONE II and Salto Talaris Total Ankle Arthroplasty Systems.

BACKGROUND: Prior studies on the INBONE II and Salto Talaris total ankle arthroplasty (TAA) systems have reported promising outcomes for both implants. This retrospective study aimed to compare the midterm differences between INBONE II and Salto Talaris TAA. METHODS: Between 2007 and 2015, a total of 44 INBONE II consecutive cases and 85 Salto Talaris consecutive cases had minimum 5-year clinical and radiographic follow-up. Preoperative and midterm survivorship, postoperative Foot and Ankle Outcome Score (FAOS), and radiographic measures including tibiotalar alignment (TTA), medial distal tibial angle (MDTA), and sagittal tibial angle (STA) were compared. RESULTS: Survivorship to revision was 97.6% (95% CI, 93.1%-100%) for the INBONE II group and 97% (95% CI, 93%-100%) for the Salto Talaris group (P = .93). Survivorship to reoperation was significantly different: 95.5% for the INBONE II and 76.4% for Salto Talaris (P = .021). Postoperative FAOS pain (P = .01), symptoms (P = .004), and sports activity (P = .02) scores were significantly higher in the INBONE II group. The INBONE group had greater preoperative deformity (varus TTA P < .001, valgus TTA P = .02, valgus MDTA P = .005). CONCLUSION: Although both implants had similar longevity and postoperative alignment, the INBONE II resulted in greater clinical improvement and fewer reoperations than the Salto Talaris at midterm follow-up. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Relationship Between Demographic and Radiographic Characteristics and Second Ray Pathology in Hallux Valgus Patients.

BACKGROUND: Hallux valgus can alter load bearing in the foot leading to abnormal forces on the second toe. The purpose of this study was to determine demographic and radiographic factors associated with second ray hammertoes in hallux valgus using 3-dimensional weightbearing CT scans. METHODS: Seventy-one patients who underwent a modified Lapidus procedure for hallux valgus with preoperative weightbearing CT scans were separated into 2 groups: (1) hallux valgus only (47 feet) and (2) hallux valgus with second ray hammertoe (29 feet). Preoperative age, body mass index (BMI), sex, hallux valgus angle (HVA), intermetatarsal angle (IMA), absolute and effective metatarsal (MT) lengths, ratios between metatarsal lengths, Meary angle, metatarsus adductus angle (MAA), and pronation were measured. Mean values of continuous variables were compared and both simple and multivariable logistic regression models were used to evaluate associations between variables and hammertoe occurrence. RESULTS: Patients in the hammertoe group were found to be significantly older and have higher BMIs, HVAs, effective second MT lengths, IMAs, and more apex plantar Meary angles (all P < .05). The multivariable analysis demonstrated that a higher IMA and a more apex plantar Meary angle were the only significant predictors of second ray hammertoe risk (P = .03 and P = .01, respectively) once corrected for age and BMI. CONCLUSION: Significant associations were found between older age, higher BMI, and more severe deformity and the occurrence of hammertoe in hallux valgus patients. These results may help clinicians counsel hallux valgus patients about the risk of developing an advanced hammertoe deformity. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

Gene Therapy Correction of Aldehyde Dehydrogenase 2 Deficiency.

Aldehyde dehydrogenase 2 (ALDH2) deficiency causes "Asian flush syndrome," presenting as alcohol-induced facial flushing, tachycardia, nausea, and headaches. One of the most common hereditary enzyme deficiencies, it affects 35%-40% of East Asians and 8% of the world population. ALDH2 is the key enzyme in ethanol metabolism; with ethanol challenge, the common ALDH2*2 (E487K) mutation results in accumulation of toxic acetaldehyde. ALDH2*2 heterozygotes have increased risk for upper digestive tract cancers, compounded by smoking and drinking alcohol. We hypothesized that a one-time administration of an adeno-associated virus (AAV) gene transfer vector expressing the human ALDH2 coding sequence (AAVrh.10hALDH2) would correct the deficiency state. AAVrh.10hALDH2 was administered intravenously to Aldh2 knockout (Aldh2 -/-) and Aldh2 E487K knockin homozygous (Aldh2 E487K+/+) mice. Following acute ethanol ingestion, untreated ALDH2-deficient mice had elevated acetaldehyde levels and performed poorly in behavioral tests. In contrast, treated Aldh2 -/- and Aldh2 E487K+/+ mice had lower serum acetaldehyde levels and improved behavior. Thus, in vivo AAV-mediated ALDH2 therapy may reverse the deficiency state in ALDH2*2 individuals, eliminating the Asian flush syndrome and reducing the risk for associated disorders.