Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father

Tightening slip knots in raw and degummed silk to increase toughness without losing strength

NMP is supported by the European Research Council (ERC StG Ideas 2011 BIHSNAM n. 279985 on “Bio-Inspired hierarchical super-nanomaterials”, ERC PoC 2013-1 REPLICA2 n. 619448 on “Large-area replication of biological anti-adhesive nanosurfaces”, ERC PoC 2013-2 KNOTOUGH n. 632277 on “Super-tough knotted fibres”), by the European Commission under the Graphene Flagship (WP10 “Nanocomposites”, n. 604391) and by the Provincia Autonoma di Trento (“Graphene Nanocomposites”, n. S116/2012-242637 and reg.delib. n. 2266)

Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis

<p>Abstract</p> <p>Background</p> <p>Previous observations demonstrate that <it>Cftr</it>-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation, increased <it>de novo </it>synthesis, and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by <it>de novo </it>cholesterol synthesis.</p> <p>Methods</p> <p>Electrochemical detection of cholesterol at the plasma membrane is achieved with capillary microelectrodes with a modified platinum coil that accepts covalent attachment of cholesterol oxidase. Modified electrodes absent cholesterol oxidase serves as a baseline control. Cholesterol synthesis is determined by deuterium incorporation into lipids over time. Incorporation into cholesterol specifically is determined by mass spectrometry analysis. All mice used in the study are on a C57Bl/6 background and are between 6 and 8 weeks of age.</p> <p>Results</p> <p>Membrane cholesterol measurements are elevated in both R117H and ΔF508 mouse nasal epithelium compared to age-matched sibling wt controls demonstrating a genotype correlation to membrane cholesterol detection. Expression of wt CFTR in CF epithelial cells reverts membrane cholesterol to WT levels further demonstrating the impact of CFTR on these processes. In wt epithelial cell, the addition of the CFTR inhibitors, Gly H101 or CFTR_inh-172, for 24 h surprisingly results in an initial drop in membrane cholesterol measurement followed by a rebound at 72 h suggesting a feedback mechanism may be driving the increase in membrane cholesterol. <it>De novo </it>cholesterol synthesis contributes to membrane cholesterol accessibility.</p> <p>Conclusions</p> <p>The data in this study suggest that CFTR influences cholesterol trafficking to the plasma membrane, which when depleted, leads to an increase in <it>de novo </it>cholesterol synthesis to restore membrane content.</p

The semi-classical expansion and resurgence in gauge theories: new perturbative, instanton, bion, and renormalon effects

We study the dynamics of four dimensional gauge theories with adjoint fermions for all gauge groups, both in perturbation theory and non-perturbatively, by using circle compactification with periodic boundary conditions for the fermions. There are new gauge phenomena. We show that, to all orders in perturbation theory, many gauge groups are Higgsed by the gauge holonomy around the circle to a product of both abelian and nonabelian gauge group factors. Non-perturbatively there are monopole-instantons with fermion zero modes and two types of monopole-anti-monopole molecules, called bions. One type are "magnetic bions" which carry net magnetic charge and induce a mass gap for gauge fluctuations. Another type are "neutral bions" which are magnetically neutral, and their understanding requires a generalization of multi-instanton techniques in quantum mechanics - which we refer to as the Bogomolny-Zinn-Justin (BZJ) prescription - to compactified field theory. The BZJ prescription applied to bion-anti-bion topological molecules predicts a singularity on the positive real axis of the Borel plane (i.e., a divergence from summing large orders in peturbation theory) which is of order N times closer to the origin than the leading 4-d BPST instanton-anti-instanton singularity, where N is the rank of the gauge group. The position of the bion--anti-bion singularity is thus qualitatively similar to that of the 4-d IR renormalon singularity, and we conjecture that they are continuously related as the compactification radius is changed. By making use of transseries and Ecalle's resurgence theory we argue that a non-perturbative continuum definition of a class of field theories which admit semi-classical expansions may be possible.Comment: 112 pages, 7 figures; v2: typos corrected, discussion of supersymmetric models added at the end of section 8.1, reference adde

Emergency percutaneous needle decompression for tension pneumoperitoneum

<p>Abstract</p> <p>Background</p> <p>Tension pneumoperitoneum as a complication of iatrogenic bowel perforation during endoscopy is a dramatic condition in which intraperitoneal air under pressure causes hemodynamic and ventilatory compromise. Like tension pneumothorax, urgent intervention is required. Immediate surgical decompression though is not always possible due to the limitations of the preclinical management and sometimes to capacity constraints of medical staff and equipment in the clinic.</p> <p>Methods</p> <p>This is a retrospective analysis of cases of pneumoperitoneum and tension pneumoperitoneum due to iatrogenic bowel perforation. All patients admitted to our surgical department between January 2005 and October 2010 were included. Tension pneumoperitoneum was diagnosed in those patients presenting signs of hemodynamic and ventilatory compromise in addition to abdominal distension.</p> <p>Results</p> <p>Between January 2005 and October 2010 eleven patients with iatrogenic bowel perforation were admitted to our surgical department. The mean time between perforation and admission was 36 ± 14 hrs (range 30 min - 130 hrs), between ER admission and begin of the operation 3 hrs and 15 min ± 47 min (range 60 min - 9 hrs). Three out of eleven patients had clinical signs of tension pneumoperitoneum. In those patients emergency percutaneous needle decompression was performed with a 16G venous catheter. This improved significantly the patients' condition (stabilization of vital signs, reducing jugular vein congestion), bridging the time to the start of the operation.</p> <p>Conclusions</p> <p>Hemodynamical and respiratory compromise in addition to abdominal distension shortly after endoscopy are strongly suggestive of tension pneumoperitoneum due to iatrogenic bowel perforation. This is a rare but life threatening condition and it can be managed in a preclinical and clinical setting with emergency percutaneous needle decompression like tension pneumothorax. Emergency percutaneous decompression is no definitive treatment, only a method to bridge the time gap to definitive surgical repair.</p

Testing the theory of immune selection in cancers that break the rules of transplantation

Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance

How to Minimize the Attack Rate during Multiple Influenza Outbreaks in a Heterogeneous Population

<div><h3>Background</h3><p>If repeated interventions against multiple outbreaks are not feasible, there is an optimal level of control during the first outbreak. Any control measures above that optimal level will lead to an outcome that may be as sub-optimal as that achieved by an intervention that is too weak. We studied this scenario in more detail.</p> <h3>Method</h3><p>An age-stratified ordinary-differential-equation model was constructed to study infectious disease outbreaks and control in a population made up of two groups, adults and children. The model was parameterized using influenza as an example. This model was used to simulate two consecutive outbreaks of the same infectious disease, with an intervention applied only during the first outbreak, and to study how cumulative attack rates were influenced by population composition, strength of inter-group transmission, and different ways of triggering and implementing the interventions. We assumed that recovered individuals are fully immune and the intervention does not confer immunity.</p> <h3>Results/Conclusion</h3><p>The optimal intervention depended on coupling between the two population sub-groups, the length, strength and timing of the intervention, and the population composition. Population heterogeneity affected intervention strategies only for very low cross-transmission between groups. At more realistic values, coupling between the groups led to synchronization of outbreaks and therefore intervention strategies that were optimal in reducing the attack rates for each subgroup and the population overall coincided. For a sustained intervention of low efficacy, early intervention was found to be best, while at high efficacies, a delayed start was better. For short interventions, a delayed start was always advantageous, independent of the intervention efficacy. For most scenarios, starting the intervention after a certain cumulative proportion of children were infected seemed more robust in achieving close to optimal outcomes compared to a strategy that used a specified duration after an outbreak’s beginning as the trigger.</p> </div

Dengue Deaths in Puerto Rico: Lessons Learned from the 2007 Epidemic

Dengue is a major public health problem in the tropics and subtropics; an estimated 50 million cases occur annually and 40 percent of the world's population lives in areas with dengue virus (DENV) transmission. Dengue has a wide range of clinical presentations from an undifferentiated acute febrile illness, classic dengue fever, to severe dengue (i.e., dengue hemorrhagic fever or dengue shock syndrome). About 5% of patients develop severe dengue, which is more common with second or subsequent infections. No vaccines are available to prevent dengue, and there are no specific antiviral treatments for patients with dengue. However, early recognition of shock and intensive supportive therapy can reduce risk of death from ∼10% to less than 1% among severe dengue cases. Reviewing dengue deaths is one means to identify issues in clinical management. These findings can be used to develop healthcare provider education to minimize dengue morbidity and mortality

Lipoprotein (a), C-reactive protein and some metabolic cardiovascular risk factors in type 2 DM

<p>Abstract</p> <p>Background</p> <p>Lipoprotein (a) (LP (a) is an independent cardiovascular risk factor that is not widely studied in people of sub-Saharan African origin. The aim of this report is to determine the frequency of occurrence of elevated Lp (a) and possible relationship with total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), C reactive protein (CRP) and serum uric acid (SUA).</p> <p>Methods</p> <p>This is a cross sectional study carried out in 200 Nigerian patients with type 2 DM and 100 sex and age matched healthy Controls aged between 32-86 years. We determined the frequency of occurrence of elevated Lp (a) levels in the study subjects and compared clinical and biochemical variables between type 2 diabetic patients and non-diabetic patients. Clinical and biochemical parameters were also compared between subjects with type 2 DM who had elevated LP (a) and normal LP (a) levels. Long term glycaemic control using glycosylated haemoglobin was determined and compared in the study subjects. Test statistics used include chi square, correlation coefficient analysis and Student's t test.</p> <p>Results</p> <p>The mean Lp(a) concentration differed significantly between type 2 diabetic patients and the Control subjects (18.7 (5.8) mg/dl vs 23 (6.8) mg/dl, 0.00001). Similarly, the prevalence of high LP (a) levels in type 2 DM patients was significantly higher than that of the Control subjects (12.5% vs 4%, p-0.019). The mean levels of the lipid profile parameters (TCHOL, LDL-C, TG, LDL/HDL) and CRP were significantly higher in DM patients than in the Control subjects. The mean LP (a) levels were comparable in both sexes and in DM subjects with and without hypertension. TG was the only parameter that differed significantly between subjects with elevated Lp (a) levels and those with normal Lp (a) levels. There was a significant positive correlation (r) between Lp(a) levels and TG, LDL-C. TCHOL, LDL/HDL and uric acid. No association was found between Lp(a) and clinical parameters such as age and anthropometric indices.</p> <p>Conclusion</p> <p>We have showed that Lp (a), CRP and other CVS risk factors cluster more in patients with DM than non DM patients. Serum Lp (a) levels are not associated with anthropometric and glycaemic indices.</p

Encoding Odorant Identity by Spiking Packets of Rate-Invariant Neurons in Awake Mice

Background: How do neural networks encode sensory information? Following sensory stimulation, neural coding is commonly assumed to be based on neurons changing their firing rate. In contrast, both theoretical works and experiments in several sensory systems showed that neurons could encode information as coordinated cell assemblies by adjusting their spike timing and without changing their firing rate. Nevertheless, in the olfactory system, there is little experimental evidence supporting such model. Methodology/Principal Findings: To study these issues, we implanted tetrodes in the olfactory bulb of awake mice to record the odorant-evoked activity of mitral/tufted (M/T) cells. We showed that following odorant presentation, most M/T neurons do not significantly change their firing rate over a breathing cycle but rather respond to odorant stimulation by redistributing their firing activity within respiratory cycles. In addition, we showed that sensory information can be encoded by cell assemblies composed of such neurons, thus supporting the idea that coordinated populations of globally rateinvariant neurons could be efficiently used to convey information about the odorant identity. We showed that different coding schemes can convey high amount of odorant information for specific read-out time window. Finally we showed that the optimal readout time window corresponds to the duration of gamma oscillations cycles. Conclusion: We propose that odorant can be encoded by population of cells that exhibit fine temporal tuning of spiking activity while displaying weak or no firing rate change. These cell assemblies may transfer sensory information in spikin