Estimation of the national disease burden of influenza-associated severe acute respiratory illness in Kenya and Guatemala : a novel methodology

Background: Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden. Methods and Findings: This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases. Conclusions: Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries

Acute transcutaneous auricular vagus nerve stimulation modulates presynaptic SV2A density in healthy rat brain: An in vivo microPET study

\ua9 2024 The Author(s). Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.Vagus nerve stimulation (VNS) is the subject of exploration as an adjunct treatment for neurological disorders such as epilepsy, chronic migraine, pain, and depression. A non-invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS. We evaluated the acute effect of electrical stimulation of the left vagus nerve via the ear on brain synaptic vesicle glycoprotein 2A (SV2A) as a measure of presynaptic density and glucose metabolism in na\uefve rats. Female Sprague–Dawley rats were imaged with [11C]UCB-J (n = 11) or [18F]fluorodeoxyglucose ([18F]FDG) PET (n = 13) on two separate days, (1) at baseline, and (2) after acute unilateral left taVNS or sham stimulation (30 min). We calculated the regional volume of distribution (VT) for [11C]UCB-J and standard uptake values (SUV) for [18F]FDG. We observed regional reductions of [11C]UCB-J binding in response to taVNS ranging from 36% to 59%. The changes in taVNS compared to baseline were significantly larger than those induced by sham stimulation. The differences were observed bilaterally in the frontal cortex, striatum, and midbrain. The [18F]FDG PET uptake remained unchanged following acute taVNS or sham stimulation compared to baseline values. This proof-of-concept study shows for the first time that acute taVNS for 30 min can modulate in vivo synaptic SV2A density in cortical and subcortical regions of healthy rats. Preclinical disease models and PET ligands of different targets can be a powerful combination to assess the therapeutic potential of taVNS

Heavy Ion Carcinogenesis and Human Space Exploration

Prior to the human exploration of Mars or long duration stays on the Earth s moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated. Space radiation, comprised of energetic protons and heavy nuclei, has been show to produce distinct biological damage compared to radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, while obscuring evaluation of the effectiveness of possible countermeasures. Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets

Body mass index and height over three generations: evidence from the Lifeways cross-generational cohort study

Background: Obesity and its measure of body mass index are strongly determined by parental body size. Debate continues as to whether both parents contribute equally to offspring body mass which is key to understanding the aetiology of the disease. The aim of this study was to use cohort data from three generations of one family to examine the relative maternal and paternal associations with offspring body mass index and how these associations compare with family height to demonstrate evidence of genetic or environmental cross-generational transmission. Methods: 669 of 1082 families were followed up in 2007/8 as part of the Lifeways study, a prospective observational cross-generation linkage cohort. Height and weight were measured in 529 Irish children aged 5 to 7 years and were self-reported by parents and grandparents. All adults provided information on self-rated health, education status, and indicators of income, diet and physical activity. Associations between the weight, height, and body mass index of family members were examined with mixed models and heritability estimates computed using linear regression analysis. Results: Self-rated health was associated with lower BMI for all family members, as was age for children. When these effects were accounted for evidence of familial associations of BMI from one generation to the next was more apparent in the maternal line. Heritability estimates were higher (h2 = 0.40) for mother-offspring pairs compared to father-offspring pairs (h2 = 0.22). In the previous generation, estimates were higher between mothersparents (h2 = 0.54-0.60) but not between fathers-parents (h2 = -0.04-0.17). Correlations between mother and offspring across two generations remained significant when modelled with fixed variables of socioeconomic status, health, and lifestyle. A similar analysis of height showed strong familial associations from maternal and paternal lines across each generation. Conclusions: This is the first family cohort study to report an enduring association between mother and offspring BMI over three generations. The evidence of BMI transmission over three generations through the maternal line in an observational study corroborates the findings of animal studies. A more detailed analysis of geno and phenotypic data over three generations is warranted to understand the nature of this maternal-offspring relationship.TS 24.4.1

Evolutionary Dynamics of Intratumor Heterogeneity

Intraneoplastic diversity in human tumors is a widespread phenomenon of critical importance for tumor progression and the response to therapeutic intervention. Insights into the evolutionary events that control tumor heterogeneity would be a major breakthrough in our comprehension of cancer development and could lead to more effective prevention methods and therapies. In this paper, we design an evolutionary mathematical framework to study the dynamics of heterogeneity over time. We consider specific situations arising during tumorigenesis, such as the emergence of positively selected mutations (“drivers”) and the accumulation of neutral variation (“passengers”). We perform exact computer simulations of the emergence of diverse tumor cell clones over time, and derive analytical estimates for the extent of heterogeneity within a population of cancer cells. Our methods contribute to a quantitative understanding of tumor heterogeneity and the impact of heritable alterations on this tumor trait

Movement Behavior of High-Heeled Walking: How Does the Nervous System Control the Ankle Joint during an Unstable Walking Condition?

The human locomotor system is flexible and enables humans to move without falling even under less than optimal conditions. Walking with high-heeled shoes constitutes an unstable condition and here we ask how the nervous system controls the ankle joint in this situation? We investigated the movement behavior of high-heeled and barefooted walking in eleven female subjects. The movement variability was quantified by calculation of approximate entropy (ApEn) in the ankle joint angle and the standard deviation (SD) of the stride time intervals. Electromyography (EMG) of the soleus (SO) and tibialis anterior (TA) muscles and the soleus Hoffmann (H-) reflex were measured at 4.0 km/h on a motor driven treadmill to reveal the underlying motor strategies in each walking condition. The ApEn of the ankle joint angle was significantly higher (p<0.01) during high-heeled (0.38±0.08) than during barefooted walking (0.28±0.07). During high-heeled walking, coactivation between the SO and TA muscles increased towards heel strike and the H-reflex was significantly increased in terminal swing by 40% (p<0.01). These observations show that high-heeled walking is characterized by a more complex and less predictable pattern than barefooted walking. Increased coactivation about the ankle joint together with increased excitability of the SO H-reflex in terminal swing phase indicates that the motor strategy was changed during high-heeled walking. Although, the participants were young, healthy and accustomed to high-heeled walking the results demonstrate that that walking on high-heels needs to be controlled differently from barefooted walking. We suggest that the higher variability reflects an adjusted neural strategy of the nervous system to control the ankle joint during high-heeled walking

Comparing Pandemic to Seasonal Influenza Mortality: Moderate Impact Overall but High Mortality in Young Children

Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality. Methods and Findings: We used data on all-cause mortality (1999-2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266-958) influenza-attributed deaths; for seasonal influen

Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season

<p>Abstract</p> <p>Background</p> <p>In contrast to seasonal influenza epidemics, where the majority of deaths occur amongst elderly, a considerable part of the 2009 pandemic influenza related deaths concerned relatively young people. In the Netherlands, all deaths associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection had to be notified, both during the 2009-2010 pandemic season and the 2010-2011 influenza season. To assess whether and to what extent pandemic mortality patterns were reverting back to seasonal patterns, a retrospective analyses of all notified fatal cases associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection was performed.</p> <p>Methods</p> <p>The notification database, including detailed information about the clinical characteristics of all notified deaths, was used to perform a comprehensive analysis of all deceased patients with a laboratory-confirmed influenza A(H1N1) 2009 virus infection. Characteristics of the fatalities with respect to age and underlying medical conditions were analysed, comparing the 2009-2010 pandemic and the 2010-2011 influenza season.</p> <p>Results</p> <p>A total of 65 fatalities with a laboratory-confirmed influenza A(H1N1) 2009 virus infection were notified in 2009-2010 and 38 in 2010-2011. During the pandemic season, the population mortality rates peaked in persons aged 0-15 and 55-64 years. In the 2010-2011 influenza season, peaks in mortality were seen in persons aged 0-15 and 75-84 years. During the 2010-2011 influenza season, the height of first peak was lower compared to that during the pandemic season. Underlying immunological disorders were more common in the pandemic season compared to the 2010-2011 season (p = 0.02), and cardiovascular disorders were more common in the 2010-2011 season (p = 0.005).</p> <p>Conclusions</p> <p>The mortality pattern in the 2010-2011 influenza season still resembled the 2009-2010 pandemic season with a peak in relatively young age groups, but concurrently a clear shift toward seasonal patterns was seen, with a peak in mortality in the elderly, i.e. ≥ 75 years of age.</p