The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

The timing of umbilical cord clamping at birth: physiological considerations

While it is now recognized that umbilical cord clamping (UCC) at birth is not necessarily an innocuous act, there is still much confusion concerning the potential benefits and harms of this common procedure. It is most commonly assumed that delaying UCC will automatically result in a time-dependent net placental-to-infant blood transfusion, irrespective of the infant’s physiological state. Whether or not this occurs, will likely depend on the infant’s physiological state and not on the amount of time that has elapsed between birth and umbilical cord clamping (UCC). However, we believe that this is an overly simplistic view of what can occur during delayed UCC and ignores the benefits associated with maintaining the infant’s venous return and cardiac output during transition. Recent experimental evidence and observations in humans have provided compelling evidence to demonstrate that time is not a major factor influencing placental-to-infant blood transfusion after birth. Indeed, there are many factors that influence blood flow in the umbilical vessels after birth, which depending on the dominating factors could potentially result in infant-to-placental blood transfusion. The most dominant factors that influence umbilical artery and venous blood flows after birth are lung aeration, spontaneous inspirations, crying and uterine contractions. It is still not entirely clear whether gravity differentially alters umbilical artery and venous flows, although the available data suggests that its influence, if present, is minimal. While there is much support for delaying UCC at birth, much of the debate has focused on a time-based approach, which we believe is misguided. While a time-based approach is much easier and convenient for the caregiver, ignoring the infant’s physiology during delayed UCC can potentially be counter-productive for the infant

A Rapid Subtractive Immunization Method to Prepare Discriminatory Monoclonal Antibodies for Food E. coli O157:H7 Contamination

To detect food E. coli O157:H7 contamination rapidly and accurately, it is essential to prepare high specific monoclonal antibodies (mAbs) against the pathogen. Cyclophosphamide (Cy)-mediated subtractive immunization strategy was performed in mice to generate mAbs that react with E. coli O157:H7, but not with other affiliated bacteria. Specificity of 19 mAbs was evaluated by ELISA and/or dot-immunogold filtration assay (DIGFA). Immunogloubin typing, affinity and binding antigens of 5 selected mAbs were also analysed. MAbs 1D8, 4A7, 5A2 were found to have high reactivity with E. coli O157:H7 and no cross-reactivity with 80 other strains of bacteria including Salmonella sp., Shigella sp., Proteus sp., Yersinia enterocolitica, Staphylococcus aureus, Klebsiella pneumoniae, Citrobacter freundii and other non-E. coli O157:H7 enteric bacteria. Their ascetic titers reached 1∶106 with E. coli O157:H7 and affinity constants ranged from 1.57×1010 to 2.79×1010 L/mol. The antigens recognized by them were different localized proteins. Furthermore, immune-colloidal gold probe coated with mAb 5A2 could specifically distinguish minced beef contaminated by E. coli O157:H7 from 84 other bacterial contaminations. The Cy-mediated subtractive immunization procedure coupled with hybridoma technology is a rapid and efficient approach to prepare discriminatory mAbs for detection of E. coli O157:H7 contamination in food

Challenges of self-reported medical conditions and electronic medical records among members of a large military cohort

<p>Abstract</p> <p>Background</p> <p>Self-reported medical history data are frequently used in epidemiological studies. Self-reported diagnoses may differ from medical record diagnoses due to poor patient-clinician communication, self-diagnosis in the absence of a satisfactory explanation for symptoms, or the "health literacy" of the patient.</p> <p>Methods</p> <p>The US Department of Defense military health system offers a unique opportunity to evaluate electronic medical records with near complete ascertainment while on active duty. This study compared 38 self-reported medical conditions to electronic medical record data in a large population-based US military cohort. The objective of this study was to better understand challenges and strengths in self-reporting of medical conditions.</p> <p>Results</p> <p>Using positive and negative agreement statistics for less-prevalent conditions, near-perfect negative agreement and moderate positive agreement were found for the 38 diagnoses.</p> <p>Conclusion</p> <p>This report highlights the challenges of using self-reported medical data and electronic medical records data, but illustrates that agreement between the two data sources increases with increased surveillance period of medical records. Self-reported medical data may be sufficient for ruling out history of a particular condition whereas prevalence studies may be best served by using an objective measure of medical conditions found in electronic healthcare records. Defining medical conditions from multiple sources in large, long-term prospective cohorts will reinforce the value of the study, particularly during the initial years when prevalence for many conditions may still be low.</p

Large-Scale Screening of a Targeted Enterococcus faecalis Mutant Library Identifies Envelope Fitness Factors

Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% Gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky