Novel translational model of resolving inflammation triggered by UV-killed E. coli

Whilst numerous studies investigating the aetiology of inflammatory diseases have been performed in rodents, the applicability of these data to human pathophysiology is frequently debated. Regardless of the strengths and weaknesses of rodent models in biomedical research, there is a need to develop models of experimental inflammation in humans. Here, we describe a self-resolving acute inflammatory response triggered by the intradermal injection of UV-killed Escherichia coli into the forearm of healthy volunteers. Cells and exudates were harvested from onset to resolution by applying negative pressure over the inflamed site. Onset was characterized by high blood flow, neutrophilia and peak levels of pro-inflammatory cytokines, whilst resolution showed a decline in blood blow, reduction in neutrophils, increase in monocytes/macrophages and waning of classic pro-inflammatory cytokine levels. An anti-inflammatory effect, defined as suppression of onset phase events, was demonstrated by administering naproxen, a conventional non-steroidal anti-inflammatory drug. In summary, this model of resolving acute inflammation is minimally invasive, highly tractable and allows simultaneous investigation of the vascular response, cellular trafficking and chemical mediator profile of onset and resolution phases of acute inflammation in humans. It can serve as a translational platform to provide mechanistic insights and to test the clinical efficacy of novel anti-inflammatory and pro-resolving drugs, and also as a tool in patients to explore inherent defects in resolution pathways

Measuring governance at health facility level: developing and validation of simple governance tool in Zambia.

BACKGROUND: Governance has been cited as a key determinant of economic growth, social advancement and overall development. Achievement of millennium development goals is partly dependant on governance practices. In 2007, Health Systems 20/20 conducted an Internet-based survey on the practice of good governance. The survey posed a set of good practices related to health governance and asked respondents to indicate whether their experience confirmed or disconfirmed those practices. We applied the 17 governance statements in rural health facilities of Zambia. The aim was to establish whether the statements were reliable and valid for assessing governance practices at primary care level. METHODS: Both quantitative and qualitative methods were used. We first applied the governance statements developed by the health system 20/20 and then conducted focus group discussion and In-depth interviews to explore some elements of governance including accountability and community participation. The target respondents were the health facility management team and community members. The sample size include 42 health facilities. Data was analyzed using SPSS version 17 and Nvivo version 9. RESULTS: The 95% one-sided confidence interval for Cronbach's alpha was between 0.69 and 0.74 for the 16 items.The mean score for most of the items was above 3. Factor analysis yielded five principle components: Transparency, community participation, Intelligence & vision, Accountability and Regulation & oversight. Most of the items (6) clustered around the transparency latent factor. Chongwe district performed poorly in overall mean governance score and across the five domains of governance. The overall scores in Chongwe ranged between 51 and 94% with the mean of 80%. Kafue and Luangwa districts had similar overall mean governance scores (88%). Community participation was generally low. Generally, it was noted that community members lacked capacity to hold health workers accountable for drugs and medical supplies. CONCLUSIONS: The study successfully validated and applied the new tool for evaluating health system governance at health facility level. The results have shown that it is feasible to measure governance practices at health facility level and that the adapted tool is fairly reliable with the 95% one-sided confidence interval for Cronbach's alpha laying between 0.69 and 0.74 for the 16 items. Caution should be taken when interpreting overall scores as they tended to mask domain specific variations

The interaction of caseload and usage in determining outcomes of unicompartmental knee arthroplasty: A meta-analysis

Background: Outcomes following UKA are variable and influenced by surgical caseload (UKA/year) and usage (percentage of primary knee arthroplasty that are UKA), which relates to indications. This meta-analysis assesses the relative importance of these factors. Methods: MEDLINE (Ovid), Embase (Ovid) and the Web of Science (ISI) were searched for consecutive series of minimally invasive cemented Phase 3 Oxford medial UKA. The primary outcome measure was revision-rate/100 observed component years (%pa). Series were divided into groups according to caseload and usage. Results 46studies, including 12,520 knees, were identified. The annual revision-rate varied from 0%pa to 4.35%pa, mean 1.21%pa (95%CI 0.97-1.47). In series with mean follow-up of ten-years or more the revision-rate was 0.63%pa (95%CI 0.46-0.83), which equates to a ten-year survival of 94% (95%CI 92%-95%). Aseptic loosening, lateral arthritis, bearing dislocation, and unexplained pain were the predominant failure mechanisms with revision for patello-femoral problems and polyethylene wear exceedingly rare (<0.1%). Both increasing caseload (p=0.02) and usage (p<0.001) were associated with decreasing revision-rate. The lowest revision-rates were achieved with a caseload >24 UKA/year (0.88%pa, 95%CI 0.63-1.61) and usage >30% (0.69%pa, 95%CI 0.50-0.90). Usage was more important than caseload: with high-usage (≥20%) the revision-rate was low, whether the caseload was high (>12UKA/year) or low (≤12UKA/year), (0.94%pa (95%CI 0.69-1.23) and 0.85%pa (95%CI 0.65-1.08) respectively); whereas with low-usage (<20%) the revision-rate was high, whether the caseload was high or low (1.58%pa, 95%CI 0.57- 3.05 and 1.76%pa, 95%CI 1.21-2.41). Conclusion: To achieve optimum results with mobile-bearing UKA surgeons, whether high or low-caseload, should adhere to the recommended indications such that ≥20%, or ideally >30% of their knee replacements are UKA. If they do this then they can expect to achieve results similar to those of the long-term series, which all had high-usage (>20%) and an average ten-year survival of 94%

Attachment styles and personal growth following romantic breakups: The mediating roles of distress, rumination, and tendency to rebound

© 2013 Marshall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.The purpose of this research was to examine the associations of attachment anxiety and avoidance with personal growth following relationship dissolution, and to test breakup distress, rumination, and tendency to rebound with new partners as mediators of these associations. Study 1 (N = 411) and Study 2 (N = 465) measured attachment style, breakup distress, and personal growth; Study 2 additionally measured ruminative reflection, brooding, and proclivity to rebound with new partners. Structural equation modelling revealed in both studies that anxiety was indirectly associated with greater personal growth through heightened breakup distress, whereas avoidance was indirectly associated with lower personal growth through inhibited breakup distress. Study 2 further showed that the positive association of breakup distress with personal growth was accounted for by enhanced reflection and brooding, and that anxious individuals’ greater personal growth was also explained by their proclivity to rebound. These findings suggest that anxious individuals’ hyperactivated breakup distress may act as a catalyst for personal growth by promoting the cognitive processing of breakup-related thoughts and emotions, whereas avoidant individuals’ deactivated distress may inhibit personal growth by suppressing this cognitive work

Epidemiology of HIV Infection in Large Urban Areas in the United States

Background: While the U.S. HIV epidemic continues to be primarily concentrated in urban area, local epidemiologic profiles may differ and require different approaches in prevention and treatment efforts. We describe the epidemiology of HIV in large urban areas with the highest HIV burden. Methods/Principal Findings: We used data from national HIV surveillance for 12 metropolitan statistical areas (MSAs) to determine disparities in HIV diagnoses and prevalence and changes over time. Overall, 0.3 % to 1 % of the MSA populations were living with HIV at the end of 2007. In each MSA, prevalence was.1 % among blacks; prevalence was.2 % in Miami, New York, and Baltimore. Among Hispanics, prevalence was.1 % in New York and Philadelphia. The relative percentage differences in 2007 HIV diagnosis rates, compared to whites, ranged from 239 (San Francisco) to 1239 (Baltimore) for blacks and from 15 (Miami) to 413 (Philadelphia) for Hispanics. The epidemic remains concentrated, with more than 50 % of HIV diagnoses in 2007 attributed to male-to-male sexual contact in 7 of the 12 MSAs; heterosexual transmission surpassed or equaled male-to-male sexual transmission in Baltimore, Philadelphia, and Washington, DC. Yet in several MSAs, including Baltimore and Washington, DC, AIDS diagnoses increased among men-who-have sex with men in recent years. Conclusions/Significance: These data are useful to identify local drivers of the epidemic and to tailor public health effort

Jejunum free flap in hypopharynx reconstruction: Case series

BACKGROUND: Surgical treatment of hypopharyngeal cancers with extension to the retrocricoid region generally requires a circumferential pharyngolaryngectomy followed by a reconstruction of the removed segment of the upper digestive tract. Historically, many techniques have been used in order to achieve a safe and functional reconstruction. Jejunum interposition is generally considered the best reconstructive technique. METHODS: This study examines the details of the surgical technique, the complications, the oncological and the functional results in a series of 29 consecutive patients submitted to circumferential pharyngoesophageal resection for advanced hypopharyngeal cancer followed by reconstruction with a free flap of jejunum. RESULTS: Three of the transplants failed because of venous thrombosis. The overall success rate was 90%. There were no general complications. A good swallowing has been preserved in all our patients. All our patients where a phonatory prosthesis was positioned (20/29) were able to achieve speech following speech therapy and all were satisfied with their own capacity to communicate. CONCLUSIONS: The prognosis of hypopharyngeal tumours (18–40% at 5 years) remains poor, but jejunum autografts are being shown to be an excellent choice for the reconstruction of the cervical hypopharyngo-oesophagus offering the patient fast rehabilitation and a reasonable quality of survival. Our experience confirm that this kind of reconstruction is safe with a good results in improving oncologic controls and restoring a good quality of life

Expression signatures of TP53 mutations in serous ovarian cancers

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>TP53 </it>gene are extremely common and occur very early in the progression of serous ovarian cancers. Gene expression patterns that relate to mutational status may provide insight into the etiology and biology of the disease.</p> <p>Methods</p> <p>The <it>TP53 </it>coding region was sequenced in 89 frozen serous ovarian cancers, 40 early stage (I/II) and 49 advanced stage (III/IV). Affymetrix U133A expression data was used to define gene expression patterns by mutation, type of mutation, and cancer stage.</p> <p>Results</p> <p>Missense or chain terminating (null) mutations in <it>TP53 </it>were found in 59/89 (66%) ovarian cancers. Early stage cancers had a significantly higher rate of null mutations than late stage disease (38% vs. 8%, p < 0.03). In advanced stage cases, mutations were more prevalent in short term survivors than long term survivors (81% vs. 30%, p = 0.0004). Gene expression patterns had a robust ability to predict <it>TP53 </it>status within training data. By using early versus late stage disease for out of sample predictions, the signature derived from early stage cancers could accurately (86%) predict mutation status of late stage cancers.</p> <p>Conclusions</p> <p>This represents the first attempt to define a genomic signature of <it>TP53 </it>mutation in ovarian cancer. Patterns of gene expression characteristic of <it>TP53 </it>mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of <it>TP53 </it>mutation in breast cancer.</p

A novel emergency department based prevention intervention program for people living with HIV: evaluation of early experiences

<p>Abstract</p> <p>Background</p> <p>HIV prevention is increasingly focused on people living with HIV (PLWH) and the role of healthcare settings in prevention. Emergency Departments (EDs) frequently care for PLWH, but do not typically endorse a prevention mission. We conducted a pilot exploratory evaluation of the first reported ED program to address the prevention needs of PLWH.</p> <p>Methods</p> <p>This retrospective observational cohort evaluation reviewed program records to describe the first six months of participants and programmatic operation. Trained counselors provided a risk assessment and counseling intervention combined with three linkage interventions: i) linkage to health care, ii) linkage to case management, and iii) linkage to partner counseling and referral.</p> <p>Results</p> <p>Of 81 self-identified PLWH who were approached, 55 initially agreed to participate. Of those completing risk assessment, 17/53 (32%, 95 CI 20% to 46%) reported unprotected anal/vaginal intercourse or needle sharing in the past six months with a partner presumed to be HIV negative. Counseling was provided to 52/53 (98%). For those requesting services, 11/15 (73%) were linked to healthcare, 4/23 (17%) were coordinated with case management, and 1/4 (25%) completed partner counseling and referral.</p> <p>Conclusion</p> <p>Given base resources of trained counselors, it was feasible to implement a program to address the prevention needs for persons living with HIV in an urban ED. ED patients with HIV often have unmet needs which might be addressed by improved linkage with existing community resources. Healthcare and prevention barriers for PLWH may be attenuated if EDs were to incorporate CDC recommended prevention measures for healthcare providers.</p

Estimated HIV Incidence in the United States, 2006–2009

Background The estimated number of new HIV infections in the United States reflects the leading edge of the epidemic. Previously, CDC estimated HIV incidence in the United States in 2006 as 56,300 (95% CI: 48,200–64,500). We updated the 2006 estimate and calculated incidence for 2007–2009 using improved methodology. Methodology We estimated incidence using incidence surveillance data from 16 states and 2 cities and a modification of our previously described stratified extrapolation method based on a sample survey approach with multiple imputation, stratification, and extrapolation to account for missing data and heterogeneity of HIV testing behavior among population groups. Principal Findings Estimated HIV incidence among persons aged 13 years and older was 48,600 (95% CI: 42,400–54,700) in 2006, 56,000 (95% CI: 49,100–62,900) in 2007, 47,800 (95% CI: 41,800–53,800) in 2008 and 48,100 (95% CI: 42,200–54,000) in 2009. From 2006 to 2009 incidence did not change significantly overall or among specific race/ethnicity or risk groups. However, there was a 21% (95% CI:1.9%–39.8%; p = 0.017) increase in incidence for people aged 13–29 years, driven by a 34% (95% CI: 8.4%–60.4%) increase in young men who have sex with men (MSM). There was a 48% increase among young black/African American MSM (12.3%–83.0%; p<0.001). Among people aged 13–29, only MSM experienced significant increases in incidence, and among 13–29 year-old MSM, incidence increased significantly among young, black/African American MSM. In 2009, MSM accounted for 61% of new infections, heterosexual contact 27%, injection drug use (IDU) 9%, and MSM/IDU 3%. Conclusions/Significance Overall, HIV incidence in the United States was relatively stable 2006–2009; however, among young MSM, particularly black/African American MSM, incidence increased. HIV continues to be a major public health burden, disproportionately affecting several populations in the United States, especially MSM and racial and ethnic minorities. Expanded, improved, and targeted prevention is necessary to reduce HIV incidence