Nasopharyngeal Swabs vs. Nasal Aspirates for Respiratory Virus Detection: A Systematic Review

Nasal pathogen detection sensitivities can be as low as 70% despite advances in molecular diagnostics. This may be linked to the choice of sampling method. A diagnostic test accuracy review for sensitivity was undertaken to compare sensitivity of swabbing to the nasopharynx and extracting nasal aspirates, using the PRISMA protocol, Cochrane rapid review methodology, and QUADAS-2 risk of bias tools, with meta-analysis of included studies. Sensitivities were calculated by a consensus standard of positivity by either method as the ‘gold standard.’ Insufficient sampling methodology, cross sectional study designs, and studies pooling samples across anatomical sites were excluded. Of 13 subsequently eligible studies, 8 had ‘high’ risk of bias, and 5 had ‘high’ applicability concerns. There were no statistical differences in overall sensitivities between collection methods for eight different viruses, and this did not differ with use of PCR, immunofluorescence, or culture. In one study alone, Influenza H1N1(2009) favored nasopharyngeal swabs, with aspirates having 93.3% of the sensitivity of swabs (p > 0.001). Similarly equivocal sensitivities were noted in reports detecting bacteria. The chain of sampling, from anatomical site to laboratory results, features different potential foci along which sensitivity may be lost. A fair body of evidence exists that use of a different sampling method will not yield more respiratory pathogens

Building capacity for mortality statistics programs: Perspectives from the Indonesian experience

Information on deaths by age, sex, and cause are primary inputs for health policy and epidemiological research. Currently, most developing countries lack efficient death registration systems that generate these data on a routine and timely basis. The global community is promoting initiatives to establish and strengthen national mortality statistics programs across the developing world. Building human, technical, and institutional capacity to operate these programs are essential elements for the program. In Indonesia, the government has established a national Sample Registration System (SRS) covering a population of 9 million and is looking toward further scaling up of operations of the mortality statistics program in conjunction with expansion of the national Civil Registration and Vital Statistics (CRVS) systems. This article reports the theoretical and practical perspectives gained from experiences in developing human capacity in the Indonesian context. These perspectives are described in terms of the institutional, personnel, and functional components of the program for collection, compilation, analysis, and utilisation of mortality and cause of death data. The article also describes the challenges and potential solutions for implementing capacity building activities at national and subnational level. In conclusion, the need for and availability of training resources are discussed, including the potential for involvement of public health academia and international collaborations within a research framework on program management, quality evaluation, and data utilisation. Adequate attention to capacity building is essential to ensure the success and sustainability of national mortality statistics programs.CR and MK are partially supported by a development partnership grant from the Department of Foreign Affairs and Trade, Australia, which also supports part of the capacity building activities described in this manuscript

Immunization of mice with YscF provides protection from Yersinia pestis infections

BACKGROUND: Yersinia pestis, the causative agent of plague, is a pathogen with a tremendous ability to cause harm and panic in populations. Due to the severity of plague and its potential for use as a bioweapon, better preventatives and therapeutics for plague are desirable. Subunit vaccines directed against the F1 capsular antigen and the V antigen (also known as LcrV) of Y. pestis are under development. However, these new vaccine formulations have some possible limitations. The F1 antigen is not required for full virulence of Y. pestis and LcrV has a demonstrated immunosuppressive effect. These limitations could damper the ability of F1/LcrV based vaccines to protect against F1-minus Y. pestis strains and could lead to a high rate of undesired side effects in vaccinated populations. For these reasons, the use of other antigens in a plague vaccine formulation may be advantageous. RESULTS: Desired features in vaccine candidates would be antigens that are conserved, essential for virulence and accessible to circulating antibody. Several of the proteins required for the construction or function of the type III secretion system (TTSS) complex could be ideal contenders to meet the desired features of a vaccine candidate. Accordingly, the TTSS needle complex protein, YscF, was selected to investigate its potential as a protective antigen. In this study we describe the overexpression, purification and use of YscF as a protective antigen. YscF immunization triggers a robust antibody response to YscF and that antibody response is able to afford significant protection to immunized mice following challenge with Y. pestis. Additionally, evidence is presented that suggests antibody to YscF is likely not protective by blocking the activity of the TTSS. CONCLUSION: In this study we investigated YscF, a surface-expressed protein of the Yersinia pestis type III secretion complex, as a protective antigen against experimental plague infection. Immunization of mice with YscF resulted in a high anti-YscF titer and provided protection against i.v. challenge with Y. pestis. This is the first report to our knowledge utilizing a conserved protein from the type III secretion complex of a gram-negative pathogen as a candidate for vaccine development

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema

Metabolomic Biomarkers of Prostate Cancer: Prediction, Diagnosis, Progression, Prognosis, and Recurrence

Metabolite profiling is being increasing employed in the study of prostate cancer as a means of identifying predictive, diagnostic, and prognostic biomarkers. This review provides a summary and critique of the current literature. Thirty-three human case-control studies of prostate cancer exploring disease prediction, diagnosis, progression, or treatment response were identified. All but one demonstrated the ability of metabolite profiling to distinguish cancer from benign, tumor aggressiveness, cases who recurred, and those who responded well to therapy. In the subset of studies where biomarker discriminatory ability was quantified, high AUCs were reported that would potentially outperform the current gold standards in diagnosis, prognosis, and disease recurrence, including PSA testing. There were substantial similarities between the metabolites and the associated pathways reported as significant by independent studies, and important roles for abnormal cell growth, intensive cell proliferation, and dysregulation of lipid metabolism were highlighted. The weight of the evidence therefore suggests metabolic alterations specific to prostate carcinogenesis and progression that may represent potential metabolic biomarkers. However, replication and validation of the most promising biomarkers is currently lacking and a number of outstanding methodologic issues remain to be addressed to maximize the utility of metabolomics in the study of prostate cancer.National Institutes of Health (U.S.) (Grant P01 CA055075)National Institutes of Health (U.S.) (Grant CA133891)National Institutes of Health (U.S.) (Grant CA141298)National Institutes of Health (U.S.) (Grant CA136578)National Institutes of Health (U.S.) (Grant UM1 CA167552

The receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis

PTPRB is a transmembrane protein tyrosine phosphatase known to regulate blood vessel remodelling and angiogenesis. Here we demonstrate that PTPRB negatively regulates branching morphogenesis in the mammary epithelium. We show that Ptprb is highly expressed in adult mammary stem cells and also, although at lower levels, in estrogen receptor positive luminal cells. During mammary development Ptprb expression is down-regulated during puberty, a period of extensive of ductal outgrowth and branching. In vivo shRNA knockdown of Ptprb in the cleared mammary fat pad transplant assay resulted in smaller epithelial outgrowths with an increased branching density and also increased branching in an in vitro organoid assay. Organoid branching was dependent on stimulation by FGF2, and Ptprb knockdown in mammary epithelial cells resulted in a higher level of FGFR activation and ERK1/2 phosphorylation, both at baseline and following FGF2 stimulation. Therefore, PTPRB regulates branching morphogenesis in the mammary epithelium by modulating the response of the FGFR signalling pathway to FGF stimulation. Considering the importance of branching morphogenesis in multiple taxa, our findings have general importance outside mammary developmental biology

Results of surgical management of acute thromboembolic lower extremity ischemia

ObjectiveAcute lower extremity ischemia secondary to arterial thromboembolism is a common problem. Contemporary data regarding this problem are sparse. This report examines a 10-year single-center experience and describes the surgical management and outcomes observed.MethodsProcedural codes were used to identify consecutive patients treated surgically for acute lower extremity embolization from January 2002 to September 2012. Patients presenting >7 days after onset of symptoms, occlusion of grafts/stents, and cases secondary to trauma or iatrogenic injury were excluded. Data collected included demographics, medical comorbidities, presenting clinical characteristics, procedural specifics, and postoperative outcomes. Results were evaluated using descriptive statistics, product-limit survival analysis, and logistic regression multivariable modeling.ResultsThe study sample included 170 patients (47% female). Mean age was 69.1 ± 16.0 years. Of these, 82 patients (49%) had a previous history of atrial fibrillation, and four (2%) were therapeutically anticoagulated (international normalized ratio ≥2.0) at presentation. Presentation for 83% was >6 hours after symptom onset, and 9% presented with a concurrent acute stroke. Femoral artery exploration with embolectomy was the most common procedural management and was used for aortic, iliac, and infrainguinal occlusion. Ten patients (6%) required bypass for limb salvage during the initial operation. Local instillation of thrombolytic agents as an adjunct to embolectomy was used in 16%, fasciotomies were performed in 39%, and unexpected return to the operating room occurred in 24%. Ninety-day amputation above or below the knee was required during the index hospitalization in 26 patients (15%). In-hospital or 30-day mortality was 18%. Median (interquartile range) length of stay was 8 days (4, 16 days), and 36% of patients were discharged to a nursing facility. Recurrent extremity embolization occurred in 23 patients (14%) at a median interval of 1.6 months. The 5-year amputation freedom and survival estimates were 80% and 41%, respectively. Predictors of 90-day amputation included prior vascular surgery, gangrene, and fasciotomy. Predictors of 30-day mortality included age, history of coronary artery disease, prior vascular surgery, and concurrent stroke.ConclusionsDespite advances in contemporary medical care, lower extremity arterial embolization remains a condition that is associated with significant morbidity and mortality. Furthermore, the condition is resource-intensive to treat and is likely preventable (initially or in recurrence) in a substantial subset of patients