Dimensions of the Lateral Malleolar Fossa and Its Potential Violation With Lateral Distal Fibular Plate Fixation.

A previously undescribed pitfall of lateral distal fibular locking plates is the risk of violating the lateral malleolar fossa (MF). No previous study has described the dimensions of this fossa. All cases using a lateral distal fibular plate for a fibula fracture from December 2012 to December 2015 (n=365) at a single institution were reviewed. Screws that violated the medial fibular cortical density corresponding to the MF were identified as "at-risk" screws. Available preoperative computed tomography (CT) scans were reviewed (n=69) to measure MF dimensions. Of 365 patients, 115 (31.5%) patients had distal fibular screws at risk of MF violation. There were no significant differences between MF violation and non-violation groups in terms of age, sex, open fracture, syndesmotic fixation, and Weber classification. The MF dimensions were measured on CT scans. Mean height was 12.96 mm (SD, 2.09 mm; range, 9.0-17.3 mm). Mean width was 7.52 mm (SD, 1.37 mm; range, 4.2-10.4 mm). Mean depth was 8.32 mm (SD, 1.59 mm; range, 5.3-11.8 mm). Mean ratio of MF to total fibular width was 0.46 mm (SD, 0.07 mm; range, 0.3-0.65 mm). Mean MF to total fibular depth was 0.42 mm (SD, 0.07 mm; range, 0.28-0.58 mm). There was a difference in dimensions of patients with screws at risk of MF violation compared with those without (MF height: 13.77 vs 12.56, P=.02; MF width: 7.98 vs 7.30, P=.05; MF to fibula width ratio: 0.49 vs 0.44, P=.01; MF to fibula depth ratio: 0.43 vs 0.42, P=.05). The MF violation is a previously unreported but potentially prevalent pitfall of lateral distal fibular plate fixation. Surgeons should be aware of the MF size and exhibit caution when placing screws in the distal locking holes during fibula fixation. [Orthopedics. 2020;43(3):e141-e146.].

Aerobic Exercise Improves Microvascular Function in Older Adults.

Microvascular function is reduced with age, disease, and inactivity. Exercise is well known to improve vascular health and has the potential to improve microvascular function in aging and disease. PURPOSE: The study aimed to assess changes in peripheral microvascular function in sedentary older adults after aerobic exercise training. METHODS: Twenty-three sedentary older adults (67 ± 5 yr, body mass index = 29 ± 5, mean ± SD) successfully completed a randomized 12-wk graded treadmill walking intervention. The exercise group (EX) performed 40 min of uphill walking 4 d·wk at 70% heart rate reserve. The control group (CON) maintained a sedentary lifestyle for 12 wk. Blood oxygen level-dependent (BOLD) responses of the soleus measured by magnetic resonance imaging were used to evaluate microvascular function; brief (1 s) maximal plantarflexion contractions were performed. Separately, blood flow in the popliteal artery was measured by ultrasound after brief contraction. Phosphorus magnetic resonance spectroscopy of the calf was used to examine muscle oxidative capacity, and whole-body peak oxygen consumption (V˙O2peak) was used to confirm training-induced cardiorespiratory adaptations. RESULTS: Peak postcontraction BOLD response increased by 33% in EX (PRE, 3.3% ± 1.0%; POST, 4.4% ± 1.4%) compared with CON (PRE, 3.0% ± 1.3%; POST, 3.2% ± 1.5%), P < 0.05. EX with hypertension tended to show a blunted peak BOLD increase (n = 6, 15%) compared with EX normotensive (n = 7, 50%), P = 0.056. Peak postcontraction blood flow increased by 39% in EX (PRE, 217 ± 88 mL·min; POST, 302 ± 167 mL·min) compared with CON (PRE, 188 ± 54 mL·min; POST, 184 ± 44 mL·min), P < 0.05. EX muscle oxidative capacity (kPCr) improved by 40% (PRE, 1.60 ± 0.57 min; POST, 2.25 ± 0.80 min) compared with CON (PRE, 1.69 ± 0.28 min; POST, 1.76 ± 0.52 min), P < 0.05. V˙O2peak increased by 9% for EX (PRE, 19.0 ± 3.1 mL·kg·min; POST, 20.8 ± 2.9 mL·kg·min) compared with a 7% loss in CON (PRE, 21.9 ± 3.6 mL·kg·min; POST, 20.4 ± 3.5 mL·kg·min), P < 0.05. CONCLUSION: Moderate aerobic exercise significantly improved microvascular function of the leg in older adults.

Synthesis of 4'-methyl and 4'-cyano carbocyclic 2',3'-didehydro nucleoside analogues via 1,4-addition to substituted cyclopentenones.

Carbocyclic 4'-methyl and 4'-cyano nucleoside analogues were synthesized using the Michael reaction to introduce the 4'-substituent and Pd-catalyzed allylic substitution to introduce the nucleoside base. Use of both the desired beta- and undesired alpha-1'-carbonate diastereomers in the Pd-catalyzed substitution was demonstrated in principle by epimerization of the alpha-diastereomer and kinetic diastereodifferentiation of a 1:1 alpha/beta mixture of 1'-carbonates.

Transduction of human and mouse pancreatic islet cells using a bicistronic recombinant adeno-associated viral vector.

Recent reports indicate successful transduction of pancreatic islets using recombinant adeno-associated viral (rAAV) vectors. This advance offers new possibilities in rendering islets resistant to rejection and recurrence of autoimmune destruction in the setting of islet transplantation as treatment of type 1 diabetes. Most gene delivery approaches using islets have thus far involved transduction with a single gene. However, the concomitant delivery of more than one gene encoding cytoprotective and/or immunoregulatory molecules may offer superior clinical utility. Here, we have generated a bicistronic rAAV (serotype 2) vector incorporating a viral internal ribosome entry site (IRES), derived from polio virus type 1, to allow for translation of two coupled cDNAs from a single mRNA transcript. Our study demonstrates the ability of this vector to produce significant expression of two reporter proteins in human and mouse islets in vitro. This expression did not interfere with beta-cell function. Transduction was maintained in vivo following transplantation of mouse islets. These data are the first report of efficient islet cell transduction with two genes using a single bicistronic rAAV vector and have direct implications for strategies aimed at enhancing islet transplant survival.