Reporting of clinically diagnosed dementia on death certificates:retrospective cohort study

Background: mortality statistics are a frequently used source of information on deaths in dementia but are limited by concerns over accuracy. Objective: to investigate the frequency with which clinically diagnosed dementia is recorded on death certificates, including predictive factors. Methods: a retrospective cohort study assembled using a large mental healthcare database in South London, linked to Office for National Statistics mortality data. People with a clinical diagnosis of dementia, aged 65 or older, who died between 2006 and 2013 were included. The main outcome was death certificate recording of dementia. Results: in total, 7,115 people were identified. Dementia was recorded on 3,815 (53.6%) death certificates. Frequency of dementia recording increased from 39.9% (2006) to 63.0% (2013) (odds ratio (OR) per year increment 1.11, 95% CI 1.07–1.15). Recording of dementia was more likely if people were older (OR per year increment 1.02, 95% CI 1.01–1.03), and for those who died in care homes (OR 1.89, 95% CI 1.50–2.40) or hospitals (OR 1.14, 95% CI 1.03–1.46) compared with home, and less likely for people with less severe cognitive impairment (OR 0.95, 95% CI 0.94–0.96), and if the diagnosis was Lewy body (OR 0.30, 95% CI 0.15–0.62) or vascular dementia (OR 0.79, 95% CI 0.68–0.93) compared with Alzheimer's disease. Conclusions: changes in certification practices may have contributed to the rise in recorded prevalence of dementia from mortality data. However, mortality data still considerably underestimate the population burden of dementia. Potential biases affecting recording of dementia need to be taken into account when interpreting mortality data

Synthetic reconstruction of extreme high hydrostatic pressure resistance in Escherichia coli

Although high hydrostatic pressure (HHP) is an interesting parameter to be applied in bioprocessing, its potential is currently limited by the lack of bacterial chassis capable of surviving and maintaining homeostasis under pressure. While several efforts have been made to genetically engineer microorganisms able to grow at sublethal pressures, there is little information for designing backgrounds that survive more extreme pressures. In this investigation, we analyzed the genome of an extreme HHP-resistant mutant of E. coli MG1655 (designated as DVL1), from which we identified four mutations (in the cra, cyaA, aceA and rpoD loci) causally linked to increased HHP resistance. Analysing the functional effect of these mutations we found that the coupled effect of downregulation of cAMP/CRP, Cra and the glyoxylate shunt activity, together with the upregulation of RpoH and RpoS activity, could mechanistically explain the increased HHP resistance of the mutant. Using combinations of three mutations, we could synthetically engineer E. coli strains able to comfortably survive pressures of 600-800 MPa, which could serve as genetic backgrounds for HHP-based biotechnological applications

Trapezius contracture and loss of strength

Musculoskeletal pathology is common in primary care, but not always have a trivial origin. According to the symptoms and comorbidities of the patient, these pathologies have to make us think if is possible to be a guiding symptom of a more severe pathology. That is why we present the case of a young woman with cardiovascular risk factors (hypertension, smoking, obesity and sleep apnea-hypopnea syndrome) with pain at left trapezius and motor and sensory clinical alterations in left upper extremity. These comorbidities have in common their relationship with cerebrovascular pathology so, given the concomitant clinical musculoskeletal, we need to suspect this cause, as was in this case

Kinetics of ventilation-induced changes in diaphragmatic metabolism by bilateral phrenic pacing in a piglet model

Citation: Breuer, T., Hatam, N., Grabiger, B., Marx, G., Behnke, B. J., Weis, J., . . . Bruells, C. S. (2016). Kinetics of ventilation-induced changes in diaphragmatic metabolism by bilateral phrenic pacing in a piglet model. Scientific Reports, 6, 10. doi:10.1038/srep35725Perioperative necessity of deep sedation is inevitably associated with diaphragmatic inactivation. This study investigated 1) the feasibility of a new phrenic nerve stimulation method allowing early diaphragmatic activation even in deep sedation and, 2) metabolic changes within the diaphragm during mechanical ventilation compared to artificial activity. 12 piglets were separated into 2 groups. One group was mechanically ventilated for 12 hrs (CMV) and in the second group both phrenic nerves were stimulated via pacer wires inserted near the phrenic nerves to mimic spontaneous breathing (STIM). Lactate, pyruvate and glucose levels were measured continuously using microdialysis. Oxygen delivery and blood gases were measured during both conditions. Diaphragmatic stimulation generated sufficient tidal volumes in all STIM animals. Diaphragm lactate release increased in CMV transiently whereas in STIM lactate dropped during this same time point (2.6 vs. 0.9 mmol L-1 after 5:20 hrs; p < 0.001). CMV increased diaphragmatic pyruvate (40 vs. 146 mu mol L-1 after 5:20 hrs between CMV and STIM; p < 0.0001), but not the lactate/pyruvate ratio. Diaphragmatic stimulation via regular electrodes is feasible to generate sufficient ventilation, even in deep sedation. Mechanical ventilation alters the metabolic state of the diaphragm, which might be one pathophysiologic origin of ventilator-induced diaphragmatic dysfunction. Occurrence of hypoxia was unlikely

Urea-Hydroxyapatite Nanohybrids for Slow Release of Nitrogen

While slow release of chemicals has been widely applied for drug delivery, little work has been done on using this general nanotechnology-based principle for delivering nutrients to crops. In developing countries, the cost of fertilizers can be significant and is often the limiting factor for food supply. Thus, it is important to develop technologies that minimize the cost of fertilizers through efficient and targeted delivery. Urea is a rich source of nitrogen and therefore a commonly used fertilizer. We focus our work on the synthesis of environmentally benign nanoparticles carrying urea as the crop nutrient that can be released in a programmed manner for use as a nanofertilizer. In this study, the high solubility of urea molecules has been reduced by incorporating it into a matrix of hydroxyapatite nanoparticles. Hydroxyapatite nanoparticles have been selected due to their excellent biocompatibility while acting as a rich phosphorus source. In addition, the high surface area offered by nanoparticles allows binding of a large amount of urea molecules. The method reported here is simple and scalable, allowing the synthesis of a urea-modified hydroxyapatite nanohybrid as fertilizer having a ratio of urea to hydroxyapatite of 6:1 by weight. Specifically, a nanohybrid suspension was synthesized by $\textit{in situ}$ coating of hydroxyapatite with urea at the nanoscale. In addition to the stabilization imparted due to the high surface area to volume ratio of the nanoparticles, supplementary stabilization leading to high loading of urea was provided by flash drying the suspension to obtain a solid nanohybrid. This nanohybrid with a nitrogen weight of 40% provides a platform for its slow release. Its potential application in agriculture to maintain yield and reduce the amount of urea used is demonstrated.Authors thank Hayleys Agro Ltd., Sri Lanka for initiating this research programme at SLINTEC and Nagarjuna Fertilizer and Chemical Ltd (NFCL), India for providing further support. Authors acknowledge Mr Sunanda Gunesekara of SLINTEC for assistance with scaling up the production process to enable the field trials. ARK acknowledges the financial support received from ICTPELETTRA Users Program, Trieste, Italy to conduct photoemission experiments at Materials Science beam line (MSB) and ELETTRA SRS on HA and urea coated HA samples. ARK further acknowledges Dr. R.G. Acres of MSB beam line for his extensive support to conduct photoemission experiments. We acknowledge the Department of Agriculture and Rice Research and Development Institute of Sri Lanka, in particular Dr Priyantha Weerasinghe, Mr D Sirisena and Dr Amitha Benthota for the assistance in carrying out pot and farmers filed trials. NFCL and Central Salt & Marine Chemicals Research Institute, Gujarat, India for TEM and BET analysis

Copper-Heparin Inhalation Therapy To Repair Emphysema: A Scientific Rationale

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration

Copper-Heparin Inhalation Therapy To Repair Emphysema:A Scientific Rationale

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration

Greenspace and Atopic Sensitization in Children and Adolescents-A Systematic Review

In the last decade, studies investigating greenspace have highlighted several benefits to human health. However, the effect of greenspace on allergies and atopic sensitization in children was not clear. While several studies have investigated this link, the evidence has not been systematically synthesized. We conducted a systematic search of eight databases. Study characteristics and findings were extracted from five articles covering 11 cohorts published between 2012 and 2016, and study quality assessments were performed. Due to significant heterogeneity, meta-analysis was not conducted. Findings were not consistent, possibly due to variations in exposure measurements, study populations and location, the specific allergens tested, and inclusion of confounders. Protective effects from greenspace were reported in four cohorts, while two cohorts showed an increase in sensitization related to greenspace. The other five cohorts found no significant effect of greenspace on atopic sensitization. There is limited understanding of the contributions of greenspace to specific allergens. Future research should consider amount and type of greenspace, as well as the specific allergens tested

Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis:A multi-national multi-database case-control study

Background: Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk. Methods: A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from ele

The combination of smoking with vitamin D deficiency impairs skeletal muscle fiber hypertrophy in response to overload in mice

Vitamin D deficiency, which is highly prevalent in the general population, exerts similar deleterious effects on skeletal muscles to those induced by cigarette smoking. We examined whether cigarette smoke (CS) exposure and/or vitamin D deficiency impairs the skeletal muscle hypertrophic response to overload. Male C57Bl/6JolaH mice on a normal or vitamin D-deficient diet were exposed to CS or room air for 18 wk. Six weeks after initiation of smoke or air exposure, sham surgery or denervation of the agonists of the left plantaris muscle was performed. The right leg served as internal control. Twelve weeks later, the hypertrophic response was assessed. CS exposure instigated loss of body and muscle mass, and increased lung inflammatory cell infiltration (P < 0.05), independently of diet. Maximal exercise capacity, whole body strength, in situ plantaris muscle force, and key markers of hypertrophic signaling (Akt, 4EBP1, and FoxO1) were not significantly affected by smoking or diet. The increase in plantaris muscle fiber cross-sectional area in response to overload was attenuated in vitamin D-deficient CS-exposed mice (smoking × diet interaction for hypertrophy, P = 0.03). In situ fatigue resistance was elevated in hypertrophied plantaris, irrespective of vitamin D deficiency and/or CS exposure. In conclusion, our data show that CS exposure or vitamin D deficiency alone did not attenuate the hypertrophic response of overloaded plantaris muscles, but this hypertrophic response was weakened when both conditions were combined. These data suggest that current smokers who also present with vitamin D deficiency may be less likely to respond to a training program