iPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster.

Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2 (iPLA2) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2-VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA2-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is critical for mitochondrial integrity in the Drosophila female germline, which may provide a novel context to investigate its functions with parallels to PLAN.

Pediatrics in disasters: evaluation of a global training program.

The findings of this evaluation document partial success for the PEDS training program to achieve its 3 aims. It will take several years for the dissemination of this program to reach a critical mass of pediatricians and other physicians in many LMICs. Obtaining stronger support from MOHs and other governmental agencies is necessary to achieve this goal. Another additional approach would be to integrate the training into medical school and residency programs.

Contraceptive counseling by general internal medicine faculty and residents.

BACKGROUND: Almost half of US pregnancies are unintended, resulting in many abortions and unwanted or mistimed births. Contraceptive counseling is an effective tool to increase patients' use of contraception. METHODS: Using an online 20-item questionnaire, we evaluated the frequency of contraceptive counseling provided to reproductive-age women during a prevention-focused visit by University of Colorado internal medicine resident and faculty providers. We also evaluated factors hypothesized to affect contraceptive counseling frequency. RESULTS: Although more than 95% of the 146 medicine faculty and resident respondents agreed that contraceptive counseling is important, only one-quarter of providers reported providing contraceptive counseling "routinely" (defined as ≥80% of the time) to reproductive-age women during a prevention-focused visit. Providing contraceptive counseling routinely was strongly associated with taking an abbreviated sexual history "often"/"routinely" (odds ratio [OR]=11.6 [3.3 to 40.0]) and with high self-efficacy to provide contraceptive counseling (OR=6.5 [1.5 to 29.0]). However, fewer than two-thirds of providers reported taking an abbreviated sexual history "often"/"routinely." More than 70% of providers reported inadequate knowledge of contraceptive methods as a contraceptive counseling barrier. However, providers' perceived inadequate knowledge was not associated with traditional educational exposures, such as lectures and women's health electives. CONCLUSIONS: In prevention-focused visits with reproductive-age women, a minority of internal medicine faculty and residents reported routine contraceptive counseling. Future efforts to increase contraceptive counseling among internists should include interventions that increase provider contraceptive counseling self-efficacy and ensure that providers obtain an abbreviated sexual history.

American Society of Ophthalmic Plastic and Reconstructive Surgery fellowship survey: fellows selection criteria for training programs.

PURPOSE: To investigate the characteristics that American Society of Ophthalmic Plastic and Reconstructive Surgery fellows seek in fellowship training programs. METHODS: A 14-question anonymous SurveyMonkey survey was created for the 2011 to 2014 American Society of Ophthalmic Plastic and Reconstructive Surgery graduates. The survey evaluated fellow demographics, the interview process, and qualities fellows seek in fellowship training programs. A Likert scale was used to rate different qualities (1: not important, 9: very important), and summary statistics are reported as overall means and standard deviations. Analysis of variance comparisons were made between the different Ophthalmic Plastic and Reconstructive Surgery fellow graduate years, gender, and future practice goals. RESULTS: In total, 87 surveys were e-mailed with 67 responses, a 77% response rate. The qualities with the highest mean were variety of surgical procedures (mean ± standard deviation: 8.6 ± 0.7), volume of procedures/surgeries (8.6 ± 0.7), personality of the program director (8.2 ± 1.3), and interview (7.7 ± 1.4). The characteristics that ranked the lowest in descending order were presence of a county hospital (5.1 ± 2.2), proximity to family (4.8 ± 2.7), didactics (4.7 ± 1.9), and benefits (4.4 ± 2.0). There was no statistically significant difference when comparing the groups according to gender and year of graduation. Fellows who want to pursue a career in academic medicine ranked academic fellowships higher in importance (8.0 ± 1.0) than those who wanted a career in private practice (5.3 ± 2.2). CONCLUSIONS: American Society of Ophthalmic Plastic and Reconstructive Surgery fellows place an emphasis on surgical experience, the program director's personality, and the interview process when ranking fellowship training programs. This information is valuable for program directors to better recruit fellows.

Downstaging disease in patients with hepatocellular carcinoma outside of Milan criteria: strategies using drug-eluting bead chemoembolization.

PURPOSE: To assess downstaging rates in patients with United Network for Organ Sharing stage T3N0M0 hepatocellular carcinoma (HCC) treated with doxorubicin-eluting bead transarterial chemoembolization to meet Milan criteria for transplantation. MATERIALS AND METHODS: A single-center retrospective review of 239 patients treated with doxorubicin-eluting bead (DEB) chemoembolization between September 2008 and December 2011 was undertaken. Baseline and follow-up computed tomography or magnetic resonance imaging was assessed for response based on the longest enhancing axial dimension of each tumor (ie, modified Response Evaluation Criteria In Solid Tumors measurements), and medical records were reviewed. Fisher exact tests and exact logistic regression were used to test the association of patient and disease characteristics with downstaging. RESULTS: After exclusions, 22 patients remained in the analysis, 17 of whom (77%) had their HCC downstaged to meet Milan criteria. Among those whose disease was downstaged, seven underwent transplantation, one remained listed for transplantation, six had disease progression beyond Milan criteria, two underwent conventional transarterial chemoembolization, and one underwent radiofrequency ablation. The seven patients who received transplants were still living, but recurrent HCC developed in two. Baseline age (P = .25), Model for End-stage Liver Disease score (P = .77), and α-fetoprotein (AFP) level (P = 1.00) were similar between patients with and without downstaged HCC. No associations were observed between the odds of downstaging and sex (P = .21), Child-Pugh class (P = .14), Child-Pugh class controlling for baseline tumor multiplicity (P = .15), Eastern Cooperative Oncology Group performance status (P = 1.00), tumor burden (P = .31), multiple tumors (P = .31), or hepatitis C virus infection (P = 1.00). Fifteen patients who did not receive transplants were alive at 1 year, with two progression-free. Baseline AFP levels differed between those who survived 1 year and those who did not (P = .02), but did not differ by progression-free survival status (P = .62). CONCLUSIONS: T3N0M0 HCC treatment with DEB chemoembolization has a high likelihood (77%) of downstaging the disease to meet Milan criteria.

Parathyroid imaging: the importance of pinhole collimation with both single- and dual-tracer acquisition.

UNLABELLED: Our objective was to rigorously compare pinhole and parallel-hole collimation in an intrapatient, intrastudy design in 2 parathyroid imaging protocols: the first was dual-phase (99m)Tc-sestamibi imaging, and the second was dual-phase (99m)Tc-sestamibi plus dual-tracer ((99m)Tc-sestamibi and (123)I) simultaneous-acquisition subtraction imaging. METHODS: Thirty-three patients with 37 surgically proven nonectopic parathyroid adenomas were evaluated. Anterior pinhole and parallel-hole images of the neck were available for (99m)Tc-sestamibi at 15 min and 3 h, and for simultaneously acquired (99m)Tc-sestamibi and (123)I subtraction at 15 min, all from a single study. The images were modified so that all had a square border and so that the thyroid filled approximately three quarters of the image. The images were evaluated by 2 experienced nuclear medicine physicians who did not know the surgical results or whether the images were acquired with pinhole or parallel-hole collimation. The observers indicated the location of any identified adenoma and graded the certainty of diagnosis on a 3-point scale. RESULTS: The localization success rate for the 2 observers combined for the single-tracer dual-phase images was 66.2% with pinhole collimation and 43.2% with parallel-hole collimation (P < 0.0001). The localization success rate with the addition of the dual-tracer simultaneous-acquisition subtraction image was 83.8% with pinhole collimation and 62.2% with parallel-hole collimation (P = 0.0018). In addition, the degree of certainty of localization was greater with pinhole collimation with both imaging protocols (P < 0.001 in both cases). CONCLUSION: In the anterior projection, pinhole collimation is superior to parallel-hole collimation for parathyroid imaging with either dual-phase (99m)Tc-sestamibi or dual-phase (99m)Tc-sestamibi plus dual-tracer ((99m)Tc-sestamibi and (123)I) simultaneous-acquisition subtraction.

Minimally invasive total knee arthroplasty: surgical implications for recovery.

BACKGROUND: Despite growing interest in minimally invasive surgery (MIS) techniques for total knee arthroplasty (TKA), few randomized controlled trials have compared MIS and conventional TKA using a combination of functional performance, knee pain, knee range of motion (ROM), and surgical and radiographic outcomes. METHODS: A prospective, randomized investigation comparing early outcomes of TKA using conventional or MIS approaches (n = 44). Patients were assessed preoperatively, 48 hours, 4 and 12 weeks postoperatively by blinded evaluators. Outcome measures included timed-up-and-go, 100-ft walk, knee pain, passive knee ROM, Knee Society Score, blood loss, tourniquet time, hospital length of stay, surgical complications, and radiographic outcomes. RESULTS: No significant differences in functional performance, knee pain, knee ROM, surgical, or radiographic outcomes were observed between groups at 48 hours, 4 or 12 weeks postoperatively. CONCLUSION: While surgical and radiographic outcomes were not compromised with MIS surgery, there were also no improvements in pain, ROM, or functional performance with MIS TKA.

N-acetyl-4-aminophenol and musculoskeletal adaptations to resistance exercise training.

N-acetyl-4-aminophenol (ACET) may impair musculoskeletal adaptations to progressive resistance exercise training (PRT) by inhibiting exercise-induced muscle protein synthesis and bone formation. To test the hypothesis that ACET would diminish training-induced increases in fat-free mass (FFM) and osteogenesis, untrained men (n = 26) aged ≥50 years participated in 16 weeks of high-intensity PRT and bone-loading exercises and were randomly assigned to take ACET (1,000 mg/day) or placebo (PLAC) 2 h before each exercise session. Total body FFM was measured by DXA at baseline and week 16. Serum bone-specific alkaline phosphatase (BAP) and C-terminal crosslinks of type-I collagen (CTX) were measured at baseline and week 16. Vastus lateralis muscle biopsies were performed at baseline and weeks 3 and 16 for prostanoid, anabolic, and catabolic gene expression by RT-PCR. In exercise-compliant men (ACET, n = 10; PLAC, n = 7), the increase in FFM was not different between groups (p = 0.91). The changes in serum BAP and CTX were not different between groups (p > 0.7). There were no significant changes in any of the target genes at week 3. After 16 weeks of PRT, the mRNA expressions of the anabolic marker p70S6K (p = 0.003) and catabolic marker muscle-atrophy F-box (MAFbx) (p = 0.03) were significantly reduced as compared to baseline in ACET. The mRNA expression of the prostanoids were unchanged (all p ≥ 0.40) in both groups. The administration of ACET (1,000 mg) prior to each exercise session did not impair PRT-induced increases in FFM or significantly alter bone formation markers in middle aged and older men.

Minimally invasive total knee arthroplasty improves early knee strength but not functional performance: a randomized controlled trial.

A prospective, randomized investigation compared early clinical outcomes of total knee arthroplasty (TKA) using conventional or minimally invasive surgical (MIS) approaches (n = 44). Outcome measures included isometric quadriceps and hamstrings strength, quadriceps activation, functional performance, knee pain, active knee range of motion, muscle mass, the Short Form-36, and Western Ontario and McMaster University Osteoarthritis Index, assessed preoperatively and 4 and 12 weeks after TKA. Four weeks after TKA, the MIS group had greater hamstring strength (P = .02) and quadriceps strength (P = .07), which did not translate to differences in other outcomes. At 12 weeks, there were no clinically meaningful differences between groups on any measure. Although MIS may lead to faster recovery of strength in patients undergoing TKA, there was no benefit on longer-term recovery of strength or functional performance.