Treatment of chronic anterior shoulder dislocation by open reduction and simultaneous Bankart lesion repair

<p>Abstract</p> <p>Background</p> <p>Untreated chronic shoulder dislocation eventually leads to functional disability and pain. Open reduction with different fixation methods have been introduced for most chronic shoulder dislocation. We hypothesized that open reduction and simultaneous Bankart lesion repair in chronic anterior shoulder dislocation obviates the need for joint fixation and leads to better results than previously reported methods.</p> <p>Methods</p> <p>Eight patients with chronic anterior dislocation of shoulder underwent open reduction and capsulolabral complex repair after an average delay of 10 weeks from injury. Early motion was allowed the day after surgery in the safe position and the clinical and radiographic results were analyzed at an average follow-up of one year.</p> <p>Results</p> <p>The average Rowe and Zarin's score was 86 points. Four out of eight shoulders were graded as excellent, three as good and one as fair (Rowe and Zarins system). All patients were able to perform their daily activities and they had either mild or no pain. Anterior active forward flexion loss averaged 18 degrees, external active rotation loss averaged 17.5 degrees and internal active rotation loss averaged 3 vertebral body levels. Mild degenerative joint changes were noted in one patient.</p> <p>Conclusion</p> <p>The results show that the overall prognosis for this method of operation is more favorable than the previously reported methods and we recommend concomitant open reduction and capsulolabral complex repair for the treatment of old anterior shoulder dislocation.</p> <p>Level of Evidence</p> <p>Therapeutic study, Level IV (case series [no, or historical, control group])</p

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

miR-27b Targets KSRP to Coordinate TLR4-Mediated Epithelial Defense against Cryptosporidium parvum Infection

Cryptosporidium is a protozoan parasite that infects the gastrointestinal epithelium and causes a diarrheal disease. Toll-like receptor (TLR)- and NF-κB-mediated immune responses from epithelial cells, such as production of antimicrobial peptides and generation of reactive nitrogen species, are important components of the host's defense against cryptosporidial infection. Here we report data demonstrating a role for miR-27b in the regulation of TLR4/NF-κB-mediated epithelial anti-Cryptosporidium parvum responses. We found that C. parvum infection induced nitric oxide (NO) production in host epithelial cells in a TLR4/NF-κB-dependent manner, with the involvement of the stabilization of inducible NO synthase (iNOS) mRNA. C. parvum infection of epithelial cells activated NF-κB signaling to increase transcription of the miR-27b gene. Meanwhile, downregulation of KH-type splicing regulatory protein (KSRP) was detected in epithelial cells following C. parvum infection. Importantly, miR-27b targeted the 3′-untranslated region of KSRP, resulting in translational suppression. C. parvum infection decreased KSRP expression through upregulating miR-27b. Functional manipulation of KSRP or miR-27b caused reciprocal alterations in iNOS mRNA stability in infected cells. Forced expression of KSRP and inhibition of miR-27b resulted in an increased burden of C. parvum infection. Downregulation of KSRP through upregulating miR-27b was also detected in epithelial cells following LPS stimulation. These data suggest that miR-27b targets KSRP and modulates iNOS mRNA stability following C. parvum infection, a process that may be relevant to the regulation of epithelial anti-microbial defense in general

Overexpression of MicroRNAs from the miR-17-92 Paralog Clusters in AIDS-Related Non-Hodgkin's Lymphomas

Individuals infected by HIV are at an increased risk for developing non-Hodgkin's lymphomas (AIDS-NHL). In the highly active antiretroviral therapy (HAART) era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma (PCNSL). However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined.We used quantitative realtime PCR to assess the expression of miRNAs from three different paralog clusters, miR-17-92, miR-106a-363, and miR-106b-25 in 24 cases of AIDS-NHLs representing four tumor types, Burkitt's lymphoma (BL, n = 6), diffuse large B-cell lymphoma (DLBCL, n = 8), primary central nervous system lymphoma (PCNSL, n = 5), and primary effusion lymphoma (PEL, n = 5). We also used microarray analysis to identify a differentiation specific miRNA signature of naïve, germinal center, and memory B cell subsets from tonsils (n = 4). miRNAs from the miR-17-92 paralog clusters were upregulated by B cells, specifically during the GC differentiation stage. We also found overexpression of these miRNA clusters in all four AIDS-NHL subtypes. Finally, we also show that select miRNAs from these clusters (miR-17, miR-106a, and miR-106b) inhibited p21 in AIDS-BL and DLBCL cases, thus providing a mechanistic role for these miRNAs in AIDS-NHL pathogenesis.Dysregulation of miR-17-92 paralog clusters is a common feature of AIDS-associated NHLs

The Mechanism for RNA Recognition by ANTAR Regulators of Gene Expression

ANTAR proteins are widespread bacterial regulatory proteins that have RNA–binding output domains and utilize antitermination to control gene expression at the post-initiation level. An ANTAR protein, EutV, regulates the ethanolamine-utilization genes (eut) in Enterococcus faecalis. Using this system, we present genetic and biochemical evidence of a general mechanism of antitermination used by ANTARs, including details of the antiterminator structure. The novel antiterminator structure consists of two small hairpins with highly conserved terminal loop residues, both features being essential for successful antitermination. The ANTAR protein dimerizes and associates with its substrate RNA in response to signal-induced phosphorylation. Furthermore, bioinformatic searches using this conserved antiterminator motif identified many new ANTAR target RNAs in phylogenetically diverse bacterial species, some comprising complex regulons. Despite the unrelatedness of the species in which they are found, the majority of the ANTAR–associated genes are thematically related to nitrogen management. These data suggest that the central tenets for gene regulation by ANTAR antitermination occur widely in nature to specifically control nitrogen metabolism

Successful Determination of Larval Dispersal Distances and Subsequent Settlement for Long-Lived Pelagic Larvae

Despite its importance, we still have a poor understanding of the level of connectivity between marine populations in most geographical locations. Taking advantage of the natural features of the southeast coast of New Zealand's North Island, we deployed a series of settlement stations and conducted plankton tows to capture recent settlers and planktonic larvae of the common intertidal gastropod Austrolittorina cincta (6–8 week larval period). Satellite image analysis and ground truthing surveys revealed the absence of suitable intertidal rocky shore habitat for A. cincta over a 100 km stretch of coastline between Kapiti Island to the south and Wanganui to the north. Fifteen settlement stations (3 replicates×5 sites), which were used to mimic intertidal habitat suitable for A. cincta, were deployed for two months around and north of Kapiti Island (at 0.5, 1, 5, 15, 50 km). In addition, we also conducted plankton tows at each settlement station when the stations were first deployed to collect A. cincta larvae in the water column. On collection, all newly settled gastropods and larvae in the plankton samples were individually isolated, and a species-specific microsatellite marker was used to positively identify A. cincta individuals. Most of the positively identified A. cincta settlers and larvae were collected at the first three sampling stations (<5 km). However, low numbers of A. cincta settlers and larvae were also recorded at the two more distant locations (15 and 50 km). Dispersal curves modeled from our data suggested that <1% of gastropod larvae would travel more than 100 km. While our data show that most larvae are retained close to their natal populations (<5 km), a small proportion of larvae are able to travel much larger geographic distances. Our estimates of larval dispersal and subsequent settlement are one of only a few for marine species with a long-lived larva

High-Throughput Functional MicroRNAs Profiling by Recombinant AAV-Based MicroRNA Sensor Arrays

BACKGROUND: microRNAs (miRNAs) are small and non-coding RNAs which play critical roles in physiological and pathological processes. A number of methods have been established to detect and quantify miRNA expression. However, method for high-throughput miRNA function detection is still lacking. PRINCIPAL FINDINGS: We describe an adeno-associated virus (AAV) vector-based microRNA (miRNA) sensor (Asensor) array for high-throughput functional miRNA profiling. Each Asensor contains a Gaussia luciferase (Gluc) and a firefly luciferase (Fluc) expression cassette to sense functional miRNA and to serve as an internal control respectively. Using this array, we acquired functional profiles of 115 miRNAs for 12 cell lines and found "functional miRNA signatures" for several specific cell lines. The activities of specific miRNAs including the let-7 family, miR-17-92 cluster, miR-221, and miR-222 in HEK 293 cells were compared with their expression levels determined by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). We also demonstrate two other practical applications of the array, including a comparison of the miRNA activity between HEK293 and HEK293T cells and the ability to monitor miRNA activity changes in K562 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). CONCLUSIONS/SIGNIFICANCE: Our approach has potential applications in the identification of cell types, the characterization of biological and pathological processes, and the evaluation of responses to interventions

A systematic review of the effectiveness of self-management interventions in people with multiple sclerosis at improving depression, anxiety and quality of life.

BACKGROUND: Self-management interventions have become increasingly popular in the management of long-term health conditions; however, little is known about their impact on psychological well-being in people with Multiple Sclerosis (MS). PURPOSE: To examine the effectiveness of self-management interventions on improving depression, anxiety and health related quality of life in people with MS. METHOD: A structured literature search was conducted for the years 2000 to 2016. The review process followed the PRISMA guidelines, and is registered with PROSPERO (no. CRD42016033925). RESULTS: The review identified 10 RCT trials that fulfilled selection criteria and quality appraisal. Self-management interventions improved health-related quality of life in 6 out of 7 studies, with some evidence of improvement in depression and anxiety symptoms. CONCLUSION: Although the results are promising more robust evaluation is required in order to determine the effectiveness of self-management interventions on depression, anxiety and quality of life in people with MS. Evaluation of the data was impeded by a number of methodological issues including incomplete content and delivery information for the intervention and the exclusion of participants representing the disease spectrum. Recommendations are made for service development and research quality improvement