Fatal Cases of Influenza A in Childhood

In the northern hemisphere winter of 2003–04 antigenic variant strains (A/Fujian/411/02 –like) of influenza A H3N2 emerged. Circulation of these strains in the UK was accompanied by an unusually high number of laboratory confirmed influenza associated fatalities in children. This study was carried out to better understand risk factors associated with fatal cases of influenza in children.Case histories, autopsy reports and death registration certificates for seventeen fatal cases of laboratory confirmed influenza in children were analyzed. None had a recognized pre-existing risk factor for severe influenza and none had been vaccinated. Three cases had evidence of significant bacterial co-infection. Influenza strains recovered from fatal cases were antigenically similar to those circulating in the community. A comparison of protective antibody titres in age stratified cohort sera taken before and after winter 2003–04 showed that young children had the highest attack rate during this season (21% difference, 95% confidence interval from 0.09 to 0.33, p = 0.0009). Clinical incidences of influenza-like illness (ILI) in young age groups were shown to be highest only in the years when novel antigenic drift variants emerged.This work presents a rare insight into fatal influenza H3N2 in healthy children. It confirms that circulating seasonal influenza A H3N2 strains can cause severe disease and death in children in the apparent absence of associated bacterial infection or predisposing risk factors. This adds to the body of evidence demonstrating the burden of severe illness due to seasonal influenza A in childhood

The infuence of skin colour on the experience of ownership in the rubber hand illusion

Racial prejudice is associated with a fundamental distinction between "us" and "them"-a distinction linked to the perceived overlap between representations of the self and others. Implicit prejudice has been shown to reduce the intensity of White individuals' hand ownership sensation as induced by the Rubber Hand Illusion (RHI) with dark rubber hands. However, evidence for this link to implicit prejudice comes from self-report questionnaire data regarding the RHI. As an alternative, we assessed the onset time of the RHI. We hypothesized that onset time of the RHI would be higher for the black compared to the white RH, acting as the mediator between implicit prejudice and magnitude of the RH illusion and proprioceptive drift. As expected, participants took longer to incorporate the black RH and presented lower RH illusion magnitude and a smaller proprioceptive drift for the black RH. Mediation analysis revealed a significant indirect effect of implicit racial bias on proprioceptive drift and magnitude of illusion through onset time to illusion only for the black RH. These findings further illuminate the connection between implicit prejudice and embodied perception, suggesting new perspectives on how implicit biases operate.This work was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; grant numbers: 466922/2014-0 and 401143/2014-7).info:eu-repo/semantics/publishedVersio

Assessment of cardiovascular risk factors prior to NHS Health Checks in an urban setting: cross-sectional study

OBJECTIVES: To assess the completeness of cardiovascular disease (CVD) risk factor recording and levels of risk factors in patients eligible for the NHS Health Check. DESIGN: Cross-sectional study. SETTING: Twenty-eight general practices located in Hammersmith and Fulham, London, UK. PARTICIPANTS: 42,306 patients aged 40 to 74 years without existing cardiovascular disease or diabetes. MAIN OUTCOME MEASURES: MEASUREMENT AND LEVEL OF CVD RISK FACTORS: blood pressure, cholesterol, body mass index (BMI), blood glucose and smoking status. RESULTS: There was a high recording of smoking status (86.1%) and blood pressure (82.5%); whilst BMI, cholesterol and glucose recording was lower. There was large variation in BMI, cholesterol, glucose recording between practices (29.7-91.5% for BMI). Women had significantly better risk factor recording than men (AOR = 1.70 [1.61-1.80] for blood pressure). All risk factors were better recorded in the least deprived patient group (AOR = 0.79 [0.73-0.85] for blood pressure) and patients with diagnosed hypertension (AOR = 7.24 [6.67-7.86] for cholesterol). Risk factor recording varied considerably between practices but was more strongly associated with patient than practice level characteristics. Age-adjusted levels of cholesterol and BMI were not significantly different between men and women. More men had raised blood glucose, blood pressure and BMI than women (29.7% [29.1-30.4] compared to 19.8% [19.3-20.3] for blood pressure). CONCLUSIONS: Before the NHS Health Check, CVD risk factor recording varied considerably by practice and patient characteristics. We identified significant elevated levels of raised CVD risk factors in the population eligible for a Health Check, which will require considerable work to manage

Lovastatin Protects against Experimental Plague in Mice

Background: Plague is an ectoparasite-borne deadly infection caused by Yersinia pestis, a bacterium classified among the group A bioterrorism agents. Thousands of deaths are reported every year in some African countries. Tetracyclines and cotrimoxazole are used in the secondary prophylaxis of plague in the case of potential exposure to Y. pestis, but cotrimoxazole-resistant isolates have been reported. There is a need for additional prophylactic measures. We aimed to study the effectiveness of lovastatin, a cholesterol-lowering drug known to alleviate the symptoms of sepsis, for plague prophylaxis in an experimental model. Methodology: Lovastatin dissolved in Endolipide was intraperitoneally administered to mice (20 mg/kg) every day for 6 days prior to a Y. pestis Orientalis biotype challenge. Non-challenged, lovastatin-treated and challenged, untreated mice were also used as control groups in the study. Body weight, physical behavior and death were recorded both prior to infection and for 10 days post-infection. Samples of the blood, lungs and spleen were collected from dead mice for direct microbiological examination, histopathology and culture. The potential antibiotic effect of lovastatin was tested on blood agar plates. Conclusions/Significance: Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5%) and lovastatin-treated mice (3/15; 20%) was significant (P,0.004; Mantel-Haensze

Using coherence to enhance function in chemical and biophysical systems

Coherence phenomena arise from interference, or the addition, of wave-like amplitudes with fixed phase differences. Although coherence has been shown to yield transformative ways for improving function, advances have been confined to pristine matter and coherence was considered fragile. However, recent evidence of coherence in chemical and biological systems suggests that the phenomena are robust and can survive in the face of disorder and noise. Here we survey the state of recent discoveries, present viewpoints that suggest that coherence can be used in complex chemical systems, and discuss the role of coherence as a design element in realizing function

Anthrax Toxins Induce Shock in Rats by Depressed Cardiac Ventricular Function

Anthrax infections are frequently associated with severe and often irreversible hypotensive shock. The isolated toxic proteins of Bacillus anthracis produce a non-cytokine-mediated hypotension in rats by unknown mechanisms. These observations suggest the anthrax toxins have direct cardiovascular effects. Here, we characterize these effects. As a first step, we administered systemically anthrax lethal toxin (LeTx) and edema toxin (EdTx) to cohorts of three to twelve rats at different doses and determined the time of onset, degree of hypotension and mortality. We measured serum concentrations of the protective antigen (PA) toxin component at various time points after infusion. Peak serum levels of PA were in the µg/mL range with half-lives of 10–20 minutes. With doses that produced hypotension with delayed lethality, we then gave bolus intravenous infusions of toxins to groups of four to six instrumented rats and continuously monitored blood pressure by telemetry. Finally, the same doses used in the telemetry experiments were given to additional groups of four rats, and echocardiography was performed pretreatment and one, two, three and twenty-four hours post-treatment. LeTx and EdTx each produced hypotension. We observed a doubling of the velocity of propagation and 20% increases in left ventricular diastolic and systolic areas in LeTx-treated rats, but not in EdTx-treated rats. EdTx-but not LeTx-treated rats showed a significant increase in heart rate. These results indicate that LeTx reduced left ventricular systolic function and EdTx reduced preload. Uptake of toxins occurs readily into tissues with biological effects occurring within minutes to hours of serum toxin concentrations in the µg/mL range. LeTx and EdTx yield an irreversible shock with subsequent death. These findings should provide a basis for the rational design of drug interventions to reduce the dismal prognosis of systemic anthrax infections

Cytokine Gene Polymorphisms across Tuberculosis Clinical Spectrum in Pakistani Patients

BACKGROUND: Pakistan ranks 7(th) globally in terms of tuberculosis (TB) disease burden (incidence 181/100000 pop./yr; prevalence of 329/pop./yr). Reports from different populations show variable associations of TB susceptibility and severity with cytokine gene polymorphisms. Tuberculosis clinical severity is multi-factorial and cytokines play a pivotal role in the modulation of disease severity. We have recently reported that the ratio of two key cytokines (IFNgamma and IL10) show significant correlation with the severity spectrum of tuberculosis. The objective of the current study was to analyze the frequency of cytokine gene polymorphisms linked to high and low responder phenotypes (IFNgamma +874 T(hi)-->A(lo) and IL10 -1082 G(lo)-->A(hi)) in tuberculosis patients. METHODS AND FINDINGS: STUDY GROUPS WERE STRATIFIED ACCORDING TO DISEASE SITE AS WELL AS DISEASE SEVERITY: Pulmonary N = 111 (Minimal, PMN = 19; Moderate, PMD = 63; Advance, PAD = 29); Extra-pulmonary N = 67 (Disseminated DTB = 20, Localized LTB = 47) and compared with healthy controls (TBNA = 188). Genotype analyses were carried out using amplification refractory mutation system-PCR (ARMS-PCR) and stimulated whole blood (WB) culture assay was used for assessing cytokine profiles. Our results suggest that the IFNgamma +874 TT genotype and T allele was overrepresented in PMN (p = 0.01) and PMD (p = 0.02). IFNgamma +874 TT in combination with IL10 GG(lo) genotypes showed the highest association (chi(2) = 6.66, OR = 6.06, 95% CI = 1.31-28.07, p = 0.01). IFNgamma AA(lo) on the other hand in combination with IL10 GG(lo) increased the risk of PAD (OR = 5.26; p = 0.005) and DTB (OR = 3.59; p = 0.045). CONCLUSION: These findings are consistent with the role of IL10 in reducing collateral tissue damage and the protective role of IFNgamma in limiting disease in the lung

Experimental Meningococcal Sepsis in Congenic Transgenic Mice Expressing Human Transferrin

Severe meningococcal sepsis is still of high morbidity and mortality. Its management may be improved by an experimental model allowing better understanding of its pathophysiology. We developed an animal model of meningococcal sepsis in transgenic BALB/c mice expressing human transferrin. We studied experimental meningococcal sepsis in congenic transgenic BALB/c mice expressing human transferrin by transcriptional profiling using microarray analysis of blood and brain samples. Genes encoding acute phase proteins, chemokines and cytokines constituted the largest strongly regulated groups. Dynamic bioluminescence imaging further showed high blood bacterial loads that were further enhanced after a primary viral infection by influenza A virus. Moreover, IL-1 receptor–associated kinase–3 (IRAK-3) was induced in infected mice. IRAK-3 is a negative regulator of Toll-dependant signaling and its induction may impair innate immunity and hence result in an immunocompromised state allowing bacterial survival and systemic spread during sepsis. This new approach should enable detailed analysis of the pathophysiology of meningococcal sepsis and its relationships with flu infection

Merkel cell carcinoma of skin-current controversies and recommendations

The review covers the current recommendations for Merkel cell carcinoma (MCC), with detailed discussion of many controversies. The 2010 AJCC staging system is more in-line with other skin malignancies although more complicated to use. The changes in staging system over time make comparison of studies difficult. A wide excision with margins of 2.5–3 cm is generally recommended. Even for primary </= 1 cm, there is a significant risk of nodal and distant metastases and hence sentinel node biopsy should be done if possible; otherwise adjuvant radiotherapy to the primary and nodal region should be given. Difficulties of setting up trials owing to the rarity of the disease and the mean age of the patient population result in infrequent reports of adjuvant or concurrent chemotherapy in the literature. The benefit, if any, is not great from published studies so far. However, there may be a subgroup of patients with high-risk features, e.g. node-positive and excellent performance status, for whom adjuvant or concurrent chemotherapy may be considered. Since local recurrence and metastases generally occur within 2 years of the initial diagnosis, patients should be followed more frequently in the first 2 years. However delayed recurrence can still occur in a small proportion of patients and long-term follow-up by a specialist is recommended provided that the general condition of the patient allows it. In summary, physician judgment in individual cases of MCC is advisable, to balance the risk of recurrence versus the complications of treatment