Outcome of revision anterior cruciate ligament reconstruction: a systematic review

BACKGROUND: Revision anterior cruciate ligament (ACL) reconstruction is believed to have an inferior outcome compared with primary ACL reconstruction. The available literature on the outcome of revision ACL reconstruction is sparse compared with that for primary reconstruction. The purpose of this systematic review was to test the hypothesis that the outcome of revision ACL reconstruction compares unfavorably with the historical outcome of primary ACL reconstruction. METHODS: A systematic review of studies evaluating the outcome of revision ACL reconstructions with a minimum of two years of follow-up was performed. Pooled data were collected when appropriate and a mixed-effect-model meta-analysis was performed for important outcome measures that were reported in several studies (objective graft failure, Lysholm score, International Knee Documentation Committee [IKDC] subjective score, and IKDC objective score). Objective failure was defined as repeat revision, a side-to-side difference of >5 mm measured with use of a KT1000 arthrometer, or a pivot-shift grade of 2+ or 3+. RESULTS: Twenty-one studies were included, and 863 of the 1004 patients in these studies had a minimum of two years of follow-up and were analyzed. The pooled mean age of the patients at the time of the revision procedure was 30.6 years, and 66% were male. Objective failure occurred in 13.7% ± 2.7% of the patients (95% confidence interval, 8.0% to 19.4%). The mean Lysholm score in 491 patients was 82.1 ± 3.3 (95% confidence interval, 74.6 to 89.5) according to a mixed-model meta-analysis. The mean IKDC subjective score in 202 patients was 74.8 ± 4.4 (95% confidence interval, 62.5 to 87.0). CONCLUSIONS: Revision ACL reconstruction resulted in a worse outcome compared with primary ACL reconstruction. Patient-reported outcome scores were inferior to previously published results of primary ACL reconstruction, but these differences may not be clinically important. A dramatically elevated failure rate was noted after revision ACL reconstruction; this rate was nearly three to four times the failure rate in prospective series of primary ACL reconstructions

Facilitators and Barriers to Participation in a Peer Support Intervention for Veterans With Chronic Pain

OBJECTIVE: To understand facilitators and barriers to participation in a peer support intervention for self-management of chronic pain. METHODS: After completing a pilot intervention study, peer coaches and their veteran patients took part in a qualitative, semistructured interview to explore their experiences with the intervention. Data were analyzed using an immersion/crystallization approach. RESULTS: Three facilitators and 2 barriers to patient participation in a peer support intervention for veterans with chronic pain emerged. Facilitators were (1) having a shared identity as veterans, (2) being partnered with a person who also has chronic pain, and (3) support from the study staff. Barriers were (1) logistical challenges, and (2) challenges to motivation and engagement in the intervention. DISCUSSION: Awareness of facilitators and barriers to participation in a peer-supported self-management program for chronic pain, as well as strategies to capitalize on facilitators and mitigate barriers, are essential for further study and ultimate clinical implementation of such a program

Elevated tau and interleukin-6 concentrations in adults with obstructive sleep apnea

The article of record as published may be found at http://dx.doi.org/10.1016/j.sleep.2017.11.1121Obstructive sleep apnea (OSA) is characterized by apneas and hypopneas that result in hypoxia, cerebral hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress. These pathophysiologic processes likely contribute to neuronal damage. Tau is a protein that stabilizes microtubules and, along with amyloid beta (Ab), is associated with neurodegenerative processes. We sought to determine if tau and other biomarkers of inflammation were related to OSA severity. Concentrations of tau, Ab40, Ab42, c-reactive protein (CRP), TNF-a, interleukin (IL)-6, and IL-10 were measured in blood and compared between participants with moderate-severe OSA (n 1⁄4 28), those with mild OSA (n 1⁄4 22), and healthy controls (n 1⁄4 24). The cohort included relatively young, primarily male active duty military personnel without a history of traumatic brain injury or neurodegenerative disease. Total biomarker concentrations were determined from plasma samples using an ultra-sensitive detection method, SimoaTM, and CRP was assayed by ELISA. Total tau and IL-6 concentrations were elevated in participants with moderate-severe OSA, with a mean apnea-hypopnea index (AHI) of 26.1/h, compared to those with mild OSA (mean AHI 8.6/h) and healthy controls (mean AHI 2.1/h). Tau concentrations were also significantly correlated with the AHI (r 1⁄4 0.342, p 1⁄4 0.004). Our findings show that tau is elevated in the blood of young patients with moderate-severe OSA, suggesting that this degree of sleep-disordered breathing is a contributing factor in the development of neurodegenerative disorders. The finding of increased IL-6 further suggests that inflammatory biomarkers are present early in the course of this chronic disease

Judith Teixeira: emancipação e construção de uma nova identidade feminina no início do século XX

Esta dissertação apresenta a obra de Judith Teixeira, bem como o seu percurso de vida, esquecidos durante décadas pelas Letras Portuguesas. Num primeiro momento desta investigação, tentamos compreender o papel da mulher na sociedade portuguesa, assim como a sua evolução durante o início do século XX. Num segundo momento, direcionamos a nossa atenção para a escritora Judith Teixeira, dando a conhecer um pouco da sua obra em poesia e prosa. Terminamos com uma análise de alguns dos elementos mais recorrentes do imaginário de Judith Teixeira, é possível depreender-se a relevância da temática da saudade e das cores para a construção e leitura da sua escrita.The goal of this dissertation is to present the work and life path of the Portuguese writer Judith Teixeira (1880–1959). Labelled by many as improper in her lifetime due to the sexual nature of her poetry and prose, Judith remained forgotten for decades by the Portuguese Faculties of Letters. The first part of this investigation is based on the Portuguese society, which revolves around the portrayal of roles usually associated with women at the dawn of the twentieth century. On a second part, we focus on the Portuguese writer and on her work (both poetry and prose). Upon further analysis, it becomes apparent that some of the most reoccurring elements in Judith Teixeira’s works are nostalgia (saudade) and the use of colours as the building blocks of her work become visible, which may be found on the last part of this research

Chemical activation of a food deprivation signal extends lifespan

Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug-like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology

Effects of Aerobic Exercise Training in Community-Based Subjects Aged 80 and Older: A Pilot Study

To assess the ability of sedentary, frail subjects aged 80 and older to train in a community-based exercise program and to evaluate clinical factors that predict improvements in peak oxygen consumption (VO 2 peak). DESIGN: Pretest, posttest. SETTING: Charlestown Retirement Community, Catonsville, Maryland PARTICIPANTS: Twenty-two (11 male, 11 female; mean age ± standard deviation = 84 ± 4.0, range 80–92) self-referred. INTERVENTION: Six months of moderate-intensity aerobic exercise training, two to three sessions/week, 20 to 30 minutes per session. Training modes included treadmill walking and/or stationary cycling. MEASUREMENTS: Baseline and follow-up maximal exercise treadmill tests (ETTs) with electrocardiogram monitoring and respiratory gas analysis. RESULTS: Six months of aerobic exercise training resulted in significant increases (mean ± standard deviation) in ETT duration (11.9 ± 3.3 vs 15.9 ± 4.3 minutes; P = .01), VO 2 peak (1.23 ± 0.37 vs 1.31 ± 0.36 L/min; P = .04), and oxygen pulse (9.3 ± 2.8 vs 10.1 ± 3.2; P = .03). Mean heart rate was significantly lower during submaximal ETT stages 1 through 4 ( P < .05), and resting systolic blood pressure decreased (146 ± 18 vs 133 ± 14 mmHg; P = .01) after training. Multiple regression analysis indicated that baseline VO 2 peak ( r = 0.75, P = .002) and the total amount of time spent in exercise training ( r = 0.55, P = .008) were independent predictors of the training-related improvements in VO 2 peak. CONCLUSION: Subjects aged 80 and older can increase aerobic capacity and reduce systolic blood pressure in a community-based exercise program of moderate intensity. The most important predictors of change in VO 2 peak were baseline VO 2 peak and the time spent in exercise training. Subjects with a lower baseline VO 2 peak had the greatest improvements in VO 2 peak after training.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65501/1/j.1532-5415.2002.50613.x.pd

Magazine and reader constructions of 'metrosexuality' and masculinity: a membership categorisation analysis

Since the launch of men's lifestyle magazines in the 1980s, academic literature has predominantly focused on them as a cultural phenomenon arising from entrepreneurial and commercial initiatives and/or as cultural texts that proffer representations of masculinity such as 'new lad' and 'new dad'. This paper steps aside from the focus on culture and, instead, treats magazine content as a discursive space in which gender and sexuality are oriented to, negotiated, and accomplished within and beyond the magazine itself (i.e. through readers' responses). Specifically, membership categorisation analysis is deployed to explore how the relatively new (and perhaps alternative) category for men - 'metrosexual' - is presented and received. Our analysis suggests that masculinity concerns are central in debates about 'metrosexuality', with self-identified 'metrosexuals' invoking heterosexual prowess and self-respect on the one hand, and critics (e.g. selfidentified 'real men') lamenting 'metrosexuality' for its perceived effeminacy and lack of authenticity on the other. Implications for understanding contemporary masculinities are discussed

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments

Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone