Citations

ABSTRACT Catheter-associated infections are difficult to treat with available antimicrobial agents because of their biofilm etiology. We examined the effect of low-amperage direct electrical current (DC) exposure on established bacterial and fungal biofilms in a novel experimental in vitro catheter model. Staphylococcus epidermidis , Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , and Candida parapsilosis biofilms were grown on the inside surfaces of polyvinyl chloride (PVC) catheters, after which 0, 100, 200, or 500 μA of DC was delivered via intraluminally placed platinum electrodes. Catheter biofilms and intraluminal fluid were quantitatively cultured after 24 h and 4 days of DC exposure. Time- and dose-dependent biofilm killing was observed with all amperages and durations of DC administration. Twenty-four hours of 500 μA of DC sterilized the intraluminal fluid for all bacterial species studied; no viable bacteria were detected after treatment of S. epidermidis and S. aureus biofilms with 500 μA of DC for 4 days.

Key Points IV therapy with oncolytic VSV-IFNβ-NIS virus extends survival of immunocompetent mice with AML. The therapeutic outcome of VSV-IFNβ-NIS–treated mice with AML is augmented by anti-PD-L1 immunotherapy.

Endothelial dysfunction is believed to play a critical role in preeclampsia; however, it is unclear whether this dysfunction precedes the pregnancy or is caused by pathophysiological events in early pregnancy. It is also unclear for how long vascular dysfunction may persist postpartum and whether it represents a mechanism linking preeclampsia with future cardiovascular disease. Our objective was to determine whether women with preeclampsia had worse vascular function compared with women who did not have preeclampsia by performing a systematic review and meta-analysis of studies that examined endothelial dysfunction using flow-mediated dilation. We included studies published before May 29, 2015, that examined flow-mediated dilation before, during, or after preeclampsia. Differences in flow-mediated dilation between study groups were evaluated by standardized mean differences. Out of 610 abstracts identified through PubMED, EMBASE, and Web of Science, 37 studies were eligible for the meta-analysis. When compared with women who did not have preeclampsia, women who had preeclampsia had lower flow-mediated dilation before the development of preeclampsia (≈20–29 weeks gestation), at the time of preeclampsia, and for 3 years postpartum, with the estimated magnitude of the effect ranging between 0.5 and 3 standard deviations. Similar effects were observed when the analysis was limited to studies that excluded women with chronic hypertension, smokers, or both. Vascular dysfunction predates preeclampsia and may contribute to its pathogenesis. Future studies should address whether vascular changes that persist after preeclamptic pregnancies may represent a mechanistic link with increased risk for future cardiovascular disease.

Background: There is a paucity of data on the results of reverse (anteverting) periacetabular osteotomy (RPAO) for treatment of femoroacetabular impingement (FAI) secondary to acetabular retroversion. Purpose: To evaluate the midterm outcomes of RPAO for FAI secondary to acetabular retroversion in those with and without hip dysplasia. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective review identified RPAOs performed on patients with acetabular retroversion in isolation or in the setting of dysplasia (lateral center-edge angle [LCEA] ≤19°). Acetabular retroversion with FAI was diagnosed clinically and radiographically, with a positive crossover and posterior wall signs on pelvic radiographs. Twenty-three patients (30 hips) met the inclusion criteria; 20 hips with isolated retroversion and 10 hips with retroversion and hip dysplasia. The average age at the time of the procedure was 26 years (range, 13-45 years). The average length of follow-up was 5 years (range, 2-19 years). Harris Hip Score (HHS) and radiographs were evaluated preoperatively and at last follow-up. Results: The mean preoperative LCEA was 31° (range, 22°-49°) in the isolated retroversion group and 9° (range, –4° to 17°) in the dysplastic group. Postoperatively, the LCEA in the dysplastic group increased to 35° (range, 15°-46°) ( P = .0001). The crossover sign corrected in 55% (11/20) of the isolated retroversion group and 80% (8/10) of the dysplastic group. The acetabular index (mean ± SD) improved from 1.3 ± 0.3 to 1.7 ± 0.6 ( P = .0001), indicating improved anteversion. At the latest follow-up, the average HHS in the isolated retroversion group increased from 58 preoperatively (range, 23-77) to 93 (range, 68-100) ( P = .0001); the HHS in the dysplastic group improved from 49 (range, 20-74) to 92 (range, 77-100) ( P < .0001). Complication rates were similar in both groups. Excluding hardware removal, additional surgeries were performed in 13% (4/30). Conclusion: RPAO performed for FAI in the young patient with isolated acetabular retroversion or retroversion in the setting of dysplasia successfully improved clinical and radiographic results at mid- to long-term follow-up.

AbstractBackground and Aim:Patients with celiac disease (CD) might be at an increased risk of developing venous thromboembolism (VTE) due to chronic inflammation and vitamin deficiency. However, epidemiologic studies attempting to investigate this risk have yielded inconsistent results. We conducted this meta‐analysis with the aims to better characterize this possible association.Methods:We conducted a systematic review and meta‐analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing the risk of VTE in patients with CD versus participants without CD. Generic inverse variance method of DerSimonian and Laird was used to calculate the pooled risk ratio.Results:Out of 279 potentially relevant articles, four studies met the inclusion criteria and were included in the meta‐analysis. We found a statistically significant increased risk of VTE among patients with CD with the pooled risk ratio of 1.25 (95% confidence interval, 1.02–1.53). The statistical heterogeneity was moderate with an I2 of 69%.Conclusions:A significantly increased risk of VTE among patients with CD was demonstrated in this meta‐analysis. Further studies are required to clarify how this risk should be addressed in clinical practice.

Context:Numerous factors are purported to influence insulin sensitivity including age, adiposity, mitochondrial function, and physical fitness. Univariate associations cannot address the complexity of insulin resistance or the interrelationship among potential determinants.Objective:The objective of the study was to identify significant independent predictors of insulin sensitivity across a range of age and adiposity in humans.Design, Setting, and Participants:Peripheral and hepatic insulin sensitivity were measured by two stage hyperinsulinemic-euglycemic clamps in 116 men and women (aged 19–78 y). Insulin-stimulated glucose disposal, the suppression of endogenous glucose production during hyperinsulinemia, and homeostatic model assessment of insulin resistance were tested for associations with 11 potential predictors. Abdominal subcutaneous fat, visceral fat (AFVISC), intrahepatic lipid, and intramyocellular lipid (IMCL) were quantified by magnetic resonance imaging and spectroscopy. Skeletal muscle mitochondrial respiratory capacity (state 3), coupling efficiency, and reactive oxygen species production were evaluated from muscle biopsies. Aerobic fitness was measured from whole-body maximum oxygen uptake (VO2 peak), and metabolic flexibility was determined using indirect calorimetry.Results:Multiple regression analysis revealed that AFVISC (P &lt; .0001) and intrahepatic lipid (P = .002) were independent negative predictors of peripheral insulin sensitivity, whereas VO2 peak (P = .0007) and IMCL (P = .023) were positive predictors. Mitochondrial capacity and efficiency were not independent determinants of peripheral insulin sensitivity. The suppression of endogenous glucose production during hyperinsulinemia model of hepatic insulin sensitivity revealed percentage fat (P &lt; .0001) and AFVISC (P = .001) as significant negative predictors. Modeling homeostatic model assessment of insulin resistance identified AFVISC (P &lt; .0001), VO2 peak (P = .001), and IMCL (P = .01) as independent predictors.Conclusion:The reduction in insulin sensitivity observed with aging is driven primarily by age-related changes in the content and distribution of adipose tissue and is independent of muscle mitochondrial function or chronological age.

AbstractAccumulation of amyloid β (Aβ) in the brain is a key pathological hallmark of Alzheimer's disease (AD). Because aging is the most prominent risk factor for AD, understanding the molecular changes during aging is likely to provide critical insights into AD pathogenesis. However, studies on the role of miRNAs in aging and AD pathogenesis have only recently been initiated. Identifying miRNAs dysregulated by the aging process in the brain may lead to novel understanding of molecular mechanisms of AD pathogenesis. Here, we identified that miR‐186 levels are gradually decreased in cortices of mouse brains during aging. In addition, we demonstrated that miR‐186 suppresses β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1) expression by directly targeting the 3′UTR of Bace1 mRNA in neuronal cells. In contrast, inhibition of endogenous miR‐186 significantly increased BACE1 levels in neuronal cells. Importantly, miR‐186 over‐expression significantly decreased Aβ level by suppressing BACE1 expression in cells expressing human pathogenic mutant amyloid precursor protein. Taken together, our data demonstrate that miR‐186 is a potent negative regulator of BACE1 in neuronal cells and it may be one of the molecular links between brain aging and the increased risk for AD during aging. image We identified that miR‐186 levels are gradually decreased in mouse cortices during aging. Furthermore, we demonstrated that miR‐186 is a novel negative regulator of beta‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1) expression in neuronal cells. Therefore, we proposed that reduction in miR‐186 levels during aging may lead to the up‐regulation of BACE1 in the brain, thereby increasing a risk for Alzheimer's disease in aged individuals. Read the Editorial Highlight for this article on page 308.

Abstract Injuries to the medial collateral ligament (MCL) and posteromedial corner can occur in isolation or in the setting of multiligamentous knee injuries. Reconstruction of the MCL and posteromedial corner is indicated in the setting of a multiligamentous knee injury. Isolated cases failing nonoperative treatment may also undergo surgical treatment. Our preferred technique for anatomic medial‐sided knee reconstruction is an open anatomic MCL reconstruction using an Achilles tendon allograft along with direct repair of all associated medial and posteromedial structures. Technique Video video See video under supplementary data.