Interleukin-1 (IL-1) receptor signaling is necessary for control of
Mycobacterium tuberculosis (
Mtb) infection, yet the role of its two ligands, IL-1α and IL-1β, and their regulation in vivo are ...poorly understood. Here, we showed that both IL-1α and IL-1β are critically required for host resistance and identified two multifunctional inflammatory monocyte-macrophage and DC populations that coexpressed both IL-1 species at the single-cell level in lungs of
Mtb-infected mice. Moreover, we demonstrated that interferons (IFNs) played important roles in regulating IL-1 production by these cells in vivo. Type I interferons inhibited IL-1 production by both subsets whereas CD4
+ T cell-derived IFN-γ selectively suppressed monocyte-macrophages. These data provide a cellular basis for both the anti-inflammatory effects of IFNs and probacterial functions of type I IFNs during
Mtb infection and reveal differential regulation of IL-1 production by distinct cell populations as an additional layer of complexity in the activity of IL-1 in vivo.
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► Besides IL-1β, IL-1α is also required for IL-1R1-mediated host resistance to Mtb ► Both IL-1 species are coproduced by two subsets of inflammatory myeloid cells ► Type I IFN suppresses IL-1α and IL-1β production by inflammatory monocytes and DCs ► CD4 T cell-derived IFN-γ inhibits IL-1α and IL-1β production by inflammatory monocytes
Introduction and hypothesis
The aim was to determine the incidence and prevalence of pelvic organ prolapse surgery and describe how outcomes are reported.
Methods
Every 4 years and as part of the ...Fifth International Collaboration on Incontinence we reviewed the English-language scientific literature after searching PubMed, Medline, Cochrane library and Cochrane database of systematic reviews, published up to January 2012. Publications were classified as level 1 evidence (randomised controlled trials RCT or systematic reviews, level 2 (poor quality RCT, prospective cohort studies), level 3 (case series or retrospective studies) and level 4 (case reports). The highest level of evidence was utilised by the committee to make evidence-based recommendations based upon the Oxford grading system. A grade A recommendation usually depends on consistent level 1 evidence. A grade B recommendation usually depends on consistent level 2 and/or 3 studies, or “majority evidence” from RCTs. A grade C recommendation usually depends on level 4 studies or “majority evidence” from level 2/3 studies or Delphi processed expert opinion. A grade D “no recommendation possible” would be used where the evidence is inadequate or conflicting and when expert opinion is delivered without a formal analytical process, such as by Delphi .
Results
Pelvic organ prolapse (POP) when defined by symptoms has a prevalence of 3–6 % and up to 50 % when based upon vaginal examination. Surgery for prolapse is performed twice as commonly as continence surgery and prevalence varies widely from 6 to 18%. The incidence of POP surgery ranges from 1.5 to 1.8 per 1,000 women years and peaks in women aged 60–69. When reporting outcomes of the surgical management of prolapse, authors should include a variety of standardised anatomical and functional outcomes. Anatomical outcomes reported should include all POP-Q points and staging, utilising a traditional definition of success with the hymen as the threshold for success. Assessment should be prospective and assessors blinded as to the surgical intervention performed if possible and without any conflict of interest related to the assessment undertaken (grade C). Subjective success postoperatively should be defined as the absence of a vaginal bulge (grade C). Functional outcomes are best reported using valid, reliable and responsive symptom questionnaires and condition-specific HRQOL instruments (grade C). Sexual function is best reported utilising validated condition-specific HRQOL that assess sexual function or validated sexual function questionnaires such as the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire (PISQ) or the Female Sexual Function Index (FSFI). The sexual activity status of all study participants should be reported pre- and postoperatively under the following categories: sexually active without pain, sexually active with pain or not sexually active (grade C). Prolapse surgery should be defined as primary surgery, and repeat surgery sub-classified as primary surgery different site, repeat surgery, complications related to surgery and surgery for non-prolapse-related conditions (grade C).
Conclusion
Significant variation exists in the prevalence and incidence of pelvic organ prolapse surgery and how the outcomes are reported. Much of the variation may be improved by standardisation of definitions and outcomes of reporting on pelvic organ prolapse surgery.
Identifying risk factors for knee pain and anterior cruciate ligament (ACL) injury can be an important step in the injury prevention cycle.
We evaluated two unique prospective cohorts with similar ...populations and methodologies to compare the incidence rates and risk factors associated with patellofemoral pain (PFP) and ACL injury.
The 'PFP cohort' consisted of 240 middle and high school female athletes. They were evaluated by a physician and underwent anthropometric assessment, strength testing and three-dimensional landing biomechanical analyses prior to their basketball season. 145 of these athletes met inclusion for surveillance of incident (new) PFP by certified athletic trainers during their competitive season. The 'ACL cohort' included 205 high school female volleyball, soccer and basketball athletes who underwent the same anthropometric, strength and biomechanical assessment prior to their competitive season and were subsequently followed up for incidence of ACL injury. A one-way analysis of variance was used to evaluate potential group (incident PFP vs ACL injured) differences in anthropometrics, strength and landing biomechanics. Knee abduction moment (KAM) cut-scores that provided the maximal sensitivity and specificity for prediction of PFP or ACL injury risk were also compared between the cohorts.
KAM during landing above 15.4 Nm was associated with a 6.8% risk to develop PFP compared to a 2.9% risk if below the PFP risk threshold in our sample. Likewise, a KAM above 25.3 Nm was associated with a 6.8% risk for subsequent ACL injury compared to a 0.4% risk if below the established ACL risk threshold. The ACL-injured athletes initiated landing with a greater knee abduction angle and a reduced hamstrings-to-quadriceps strength ratio relative to the incident PFP group. Also, when comparing across cohorts, the athletes who suffered ACL injury also had lower hamstring/quadriceps ratio than the players in the PFP sample (p<0.05).
In adolescent girls aged 13.3 years, >15 Nm of knee abduction load during landing is associated with greater likelihood of developing PFP. Also, in girls aged 16.1 years who land with >25 Nm of knee abduction load during landing are at increased risk for both PFP and ACL injury.
Clinical trials have demonstrated that preventive neuromuscular training (PNMT) can be effective to reduce ACL injuries in young females. However, the magnitude of the overall effect of PNMT for ACL ...injury reduction has not reached consensus. In addition, the effects of individual exercises in PNMT that optimise ACL injury reduction are unknown.
The purpose of this project was to systematically review previously published clinical trials and evaluate types of exercises that best support ACL injury reduction in young females.
The key words 'knee', 'anterior cruciate ligament', 'ACL', 'prospective', 'neuromuscular', 'training', 'female', and 'prevention' were used for studies published from 1995 to May 2012 in PubMed and EBSCO host.
Inclusion criteria for the current analysis were: (1) documented number of ACL injuries, (2) employed a PNMT intervention that aimed to reduce ACL injuries, (3) had a comparison group, (4) used a prospective controlled study design, (5) recruited female athletes and (6) recorded exercises implemented in the PNMT.
The number of ACL injuries and female athletes in each group (control and intervention) were extracted. In addition, exercises were categorised into four types and analysed for each investigation.
A total of 14 clinical trials met the inclusion criteria. The subgroup analyses identified fewer ACL injuries in PNMT that focused on strengthening (OR 0.32, 95% CI 0.23 to 0.46, p=0.001), proximal control exercises (OR 0.33, 95% CI 0.23 to 0.47, p=0.001) and multiple exercise interventions (OR 0.32, CI 0.22 to 0.46, p=0.001).
The current subgroup analyses indicate strengthening, proximal control exercises and multi exercise genres increased efficacy in PNMT intervention designed to reduce ACL injury in young female athletes.
Over the past decades the notion of ＇inflammation＇ has been extended beyond the original hallmarks of rubor （redness）, calor （heat）, tumor （swelling） and dolor （pain） described by Celsus. We have ...gained a more detailed understanding of the cellular players and molecular mediators of inflammation which is now being applied and extended to areas of biomedical research such as cancer, obesity, heart disease, metabolism, auto-inflammatory disorders, autoimmunity and infectious diseases. Innate cytokines are often central components of inflammatory responses. Here, we discuss how the type I interferon and interleukin-1 cytokine pathways represent distinct and specialized categories of inflammatory responses and how these key mediators of inflammation counter-regulate each other.
Jpred (http://www.compbio.dundee.ac.uk/jpred) is a secondary structure prediction server powered by the Jnet algorithm. Jpred performs over 1000 predictions per week for users in more than 50 ...countries. The recently updated Jnet algorithm provides a three-state (α-helix, β-strand and coil) prediction of secondary structure at an accuracy of 81.5%. Given either a single protein sequence or a multiple sequence alignment, Jpred derives alignment profiles from which predictions of secondary structure and solvent accessibility are made. The predictions are presented as coloured HTML, plain text, PostScript, PDF and via the Jalview alignment editor to allow flexibility in viewing and applying the data. The new Jpred 3 server includes significant usability improvements that include clearer feedback of the progress or failure of submitted requests. Functional improvements include batch submission of sequences, summary results via email and updates to the search databases. A new software pipeline will enable Jnet/Jpred to continue to be updated in sync with major updates to SCOP and UniProt and so ensures that Jpred 3 will maintain high-accuracy predictions.
Summary
A major approach for immunologic intervention in tuberculosis involves redirecting the outcome of the host immune response from the induction of disease to pathogen control. Cytokines and ...lipid mediators known as eicosanoids play key roles in regulating this balance and as such represent important targets for immunologic intervention. While the evidence for cytokine/eicosanoid function derives largely from the investigation of murine and zebrafish experimental infection models, clinical studies have confirmed the existence of many of the same pathways in tuberculosis patients. Here, we summarize new data that reveal important intersections between the cytokine and eicosanoid networks in the host response to mycobacteria and discuss how targeting this crosstalk can promote resistance to lethal Mycobacterium tuberculosis infection. This approach could lead to new host‐directed therapies to be used either as an adjunct for improving the efficacy of standard antibiotic treatment or for the management of drug‐resistant infections.
Context: An estimated 40 million school-aged children (age range = 5-18 years) participate annually in sports in the United States, generating approximately 4 million sport-related injuries and ...requiring 2.6 million emergency department visits at a cost of nearly $2 billion. Objective: To determine the effects of a school-based neuromuscular training (NMT) program on sport-related injury incidence across 3 sports at the high school and middle school levels, focusing particularly on knee and ankle injuries. Design: Randomized controlled clinical trial. Setting: A total of 5 middle schools and 4 high schools in a single-county public school district. Patients or Other Participants: A total of 474 girls (222 middle school, 252 high school; age = 14.0 ± 1.7 years, height = 161.0 ± 8.1 cm, mass = 55.4 ± 12.2 kg) were cluster randomized to an NMT (CORE; n = 259 athletes) or sham (SHAM; n = 215 athletes) intervention group by team within each sport (basketball, soccer, and volleyball). Intervention(s): The CORE intervention consisted of exercises focused on the trunk and lower extremity, whereas the SHAM protocol consisted of resisted running using elastic bands. Each intervention was implemented at the start of the season and continued until the last competition. An athletic trainer evaluated athletes weekly for sport-related injuries. The coach recorded each athlete-exposure (AE), which was defined as 1 athlete participating in 1 coach-directed session (game or practice). Main Outcome Measure(s): Injury rates were calculated overall, by sport, and by competition level. We also calculated rates of specific knee and ankle injuries. A mixed-model approach was used to account for multiple injuries per athlete. Results: Overall, the CORE group reported 107 injuries (rate = 5.34 injuries/1000 AEs), and the SHAM group reported 134 injuries (rate = 8.54 injuries/1000 AEs; F1,578 = 18.65, P ( .001). Basketball (rate = 4.99 injuries/1000 AEs) and volleyball (rate = 5.74 injuries/1000 AEs) athletes in the CORE group demonstrated lower injury incidences than basketball (rate = 7.72 injuries/1000 AEs) and volleyball (rate = 11.63 injuries/1000 AEs; F1,275 = 9.46, P = .002 and F1,149 = 11.36, P = .001, respectively) athletes in the SHAM group. The CORE intervention appeared to have a greater protective effect on knee injuries at the middle school level (knee-injury incidence rate = 4.16 injuries/1000 AEs) than the SHAM intervention (knee-injury incidence rate = 7.04 injuries/1000 AEs; F1,261 = 5.36, P = .02). We did not observe differences between groups for ankle injuries (F1,578 = 1.02, P = .31). Conclusions: Participation in an NMT intervention program resulted in a reduced injury incidence relative to participation in a SHAM intervention. This protective benefit of NMT was demonstrated at both the high school and middle school levels.
Tuberculosis remains second only to HIV/AIDS as the leading cause of mortality worldwide due to a single infectious agent. Despite chemotherapy, the global tuberculosis epidemic has intensified ...because of HIV co-infection, the lack of an effective vaccine and the emergence of multi-drug-resistant bacteria. Alternative host-directed strategies could be exploited to improve treatment efficacy and outcome, contain drug-resistant strains and reduce disease severity and mortality. The innate inflammatory response elicited by Mycobacterium tuberculosis (Mtb) represents a logical host target. Here we demonstrate that interleukin-1 (IL-1) confers host resistance through the induction of eicosanoids that limit excessive type I interferon (IFN) production and foster bacterial containment. We further show that, in infected mice and patients, reduced IL-1 responses and/or excessive type I IFN induction are linked to an eicosanoid imbalance associated with disease exacerbation. Host-directed immunotherapy with clinically approved drugs that augment prostaglandin E2 levels in these settings prevented acute mortality of Mtb-infected mice. Thus, IL-1 and type I IFNs represent two major counter-regulatory classes of inflammatory cytokines that control the outcome of Mtb infection and are functionally linked via eicosanoids. Our findings establish proof of concept for host-directed treatment strategies that manipulate the host eicosanoid network and represent feasible alternatives to conventional chemotherapy.
Purpose Anterior cruciate ligament (ACL) reconstruction is commonly performed in athletes, with the goal of return to sports activities. Unfortunately, this operation may fail, and the rates of ...either reinjuring an ACL-reconstructed knee or sustaining an ACL rupture to the contralateral knee range from 3% to 49%. One problem that exists is a lack of information and consensus regarding the appropriate criteria for releasing patients to unrestricted sports activities postoperatively. The purpose of this study was to determine the published criteria used to allow athletes to return to unrestricted sports activities after ACL reconstruction. Methods A systematic search was performed to identify the factors investigators used to determine when return to athletics was allowed after primary ACL reconstruction. Inclusion criteria were English language, publication within the last 10 years, clinical trial, all adult patients, primary ACL reconstruction, original research investigation, and minimum 12 months' follow-up. Results Of 716 studies identified, 264 met the inclusion criteria. Of these, 105 (40%) failed to provide any criteria for return to sports after ACL reconstruction. In 84 studies (32%) the amount of time postoperatively was the only criterion provided. In 40 studies (15%) the amount of time along with subjective criteria were given. Only 35 studies (13%) noted objective criteria required for return to athletics. These criteria included muscle strength or thigh circumference (28 studies), general knee examination (15 studies), single-leg hop tests (10 studies), Lachman rating (1 study), and validated questionnaires (1 study). Conclusions The results of this systematic review show noteworthy problems and a lack of objective assessment before release to unrestricted sports activities. General recommendations are made for quantification of muscle strength, stability, neuromuscular control, and function in patients who desire to return to athletics after ACL reconstruction, with acknowledgment of the need for continued research in this area. Level of Evidence Level IV, systematic review of Level I to IV studies.
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