Fly piRNA biogenesis: tap dancing with Tej

Piwi-interacting RNAs (piRNAs) protect animal germlines from the deleterious effects of transposon activity. Unlike other small RNA classes like microRNAs (miRNAs) and small interfering RNAs (siRNAs), an exceptionally large number of factors are implicated in the biogenesis of piRNAs. Kai et al. have now added another one to this growing list, which we discuss in the overall context of our current knowledge of the piRNA biogenesis pathway in the Drosophila ovarian germline. See research article: http://www.biomedcentral.com/1741-7007/12/61

A randomised, controlled crossover comparison of the C-MAC videolaryngoscope with direct laryngoscopy in 150 patients during routine induction of anaesthesia

<p>Abstract</p> <p>Background</p> <p>The C-MAC^®(Karl Storz, Tuttlingen, Germany) has recently been introduced as a new device for videolaryngoscopy guided intubation. The purpose of the present study was to compare for the first time the C-MAC with conventional direct laryngoscopy in 150 patients during routine induction of anaesthesia.</p> <p>Methods</p> <p>After approval of the institutional review board and written informed consent, 150 patients (ASA I-III) with general anaesthesia were enrolled. Computer-based open crossover randomisation was used to determine the sequence of the three laryngoscopies: Conventional direct laryngoscopy (HEINE Macintosh classic, Herrsching, Germany; blade sizes 3 or 4; <it>DL </it>group), C-MAC size 3 (<it>C-MAC3 </it>group) and C-MAC size 4 (<it>C-MAC4 </it>group) videolaryngoscopy, respectively. After 50 patients, laryngoscopy technique in the C-MAC4 group was changed to the straight blade technique described by Miller (C-MAC4/SBT).</p> <p>Results</p> <p>Including all 150 patients (70 male, aged (median [range]) 53 [20-82] years, 80 [48-179] kg), there was no difference of glottic view between DL, C-MAC3, C-MAC4, and C-MAC4/SBT groups; however, worst glottic view (C/L 4) was only seen with DL, but not with C-MAC videolaryngoscopy. In the subgroup of patients that had suboptimal glottic view with DL (C/L≥2a; n = 24), glottic view was improved in the C-MAC4/SBT group; C/L class improved by three classes in 5 patients, by two classes in 2 patients, by one class in 8 patients, remained unchanged in 8 patients, or decreased by two classes in 1 patient. The median (range) time taken for tracheal intubation in the DL, C-MAC3, C-MAC4 and C-MAC4/SBT groups was 8 sec (2-91 sec; n = 44), 10 sec (2-60 sec; n = 37), 8 sec (5-80 sec; n = 18) and 12 sec (2-70 sec; n = 51), respectively.</p> <p>Conclusions</p> <p>Combining the benefits of conventional direct laryngoscopy and videolaryngoscopy in one device, the C-MAC may serve as a standard intubation device for both routine airway management and educational purposes. However, in patients with suboptimal glottic view (C/L≥2a), the C-MAC size 4 with straight blade technique may reduce the number of C/L 3 or C/L 4 views, and therefore facilitate intubation. Further studies on patients with difficult airway should be performed to confirm these findings.</p

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Can cognitive psychological research on reasoning enhance the discussion around moral judgments?

In this article we will demonstrate how cognitive psychological research on reasoning and decision making could enhance discussions and theories of moral judgments. In the first part, we will present recent dual-process models of moral judgments and describe selected studies which support these approaches. However, we will also present data that contradict the model predictions, suggesting that approaches to moral judgment might be more complex. In the second part, we will show how cognitive psychological research on reasoning might be helpful in understanding moral judgments. Specifically, we will highlight approaches addressing the interaction between intuition and reflection. Our data suggest that a sequential model of engaging in deliberation might have to be revised. Therefore, we will present an approach based on Signal Detection Theory and on intuitive conflict detection. We predict that individuals arrive at the moral decisions by comparing potential action outcomes (e.g., harm caused and utilitarian gain) simultaneously. The response criterion can be influenced by intuitive processes, such as heuristic moral value processing, or considerations of harm caused

Overstimulation of NMDA Receptors Impairs Early Brain Development in vivo

BACKGROUND: Brains of patients with schizophrenia show both neurodevelopmental and functional deficits that suggest aberrant glutamate neurotransmission. Evidence from both genetic and pharmacological studies suggests that glutamatergic dysfunction, particularly with involvement of NMDARs, plays a critical role in the pathophysiology of schizophrenia. However, how prenatal disturbance of NMDARs leads to schizophrenia-associated developmental defects is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Glutamate transporter GLAST/GLT1 double-knockout (DKO) mice carrying the NMDA receptor 1 subunit (NR1)-null mutation were generated. Bouin-fixed and paraffin-embedded embryonic day 16.5 coronal brain sections were stained with hematoxylin, anti-microtubule-associated protein 2 (MAP2), and anti-L1 antibodies to visualize cortical, hippocampal, and olfactory bulb laminar structure, subplate neurons, and axonal projections. NR1 deletion in DKO mice almost completely rescued multiple brain defects including cortical, hippocampal, and olfactory bulb disorganization and defective corticothalamic and thalamocortical axonal projections. CONCLUSIONS/SIGNIFICANCE: Excess glutamatergic signaling in the prenatal stage compromises early brain development via overstimulation of NMDARs

Innovations in total knee replacement: new trends in operative treatment and changes in peri-operative management

The human knee joint can sustain damage due to injury, or more usually osteoarthritis, to one, two or all three of the knee compartments: the medial femorotibial, the lateral femorotibial and the patellofemoral compartments. When pain associated with this damage is unmanageable using nonsurgical techniques, knee replacement surgery might be the most appropriate course of action. This procedure aims to restore a pain-free, fully functional and durable knee joint. Total knee replacement is a well-established treatment modality, and more recently, partial knee replacement—more commonly known as bi- or unicompartmental knee replacement—has seen resurgence in interest and popularity. Combined with the use of minimally invasive surgery (MIS) techniques, gender-specific prosthetics and computer-assisted navigation systems, orthopaedic surgeons are now able to offer patients knee replacement procedures that are associated with (1) minimal risks during and after surgery by avoiding fat embolism, reducing blood loss and minimising soft tissue disruption; (2) smaller incisions; (3) faster and less painful rehabilitation; (4) reduced hospital stay and faster return to normal activities of daily living; (5) an improved range of motion; (6) less requirement for analgesics; and (7) a durable, well-aligned, highly functional knee. With the ongoing advancements in surgical technique, medical technology and prosthesis design, knee replacement surgery is constantly evolving. This review provides a personal account of the recent innovations that have been made, with a particular emphasis on the potential use of MIS techniques combined with computer-assisted navigation systems to treat younger, more physically active patients with resurfacing partial/total implant knee arthroplasty

How Much Remains Undetected? Probability of Molecular Detection of Human Plasmodia in the Field

BACKGROUND: In malaria endemic areas, most people are simultaneously infected with different parasite clones. Detection of individual clones is hampered when their densities fluctuate around the detection limit and, in case of P. falciparum, by sequestration during part of their life cycle. This has important implications for measures of levels of infection or for the outcome of clinical trials. This study aimed at measuring the detectability of individual P. falciparum and P. vivax parasite clones in consecutive samples of the same patient and at investigating the impact of sampling strategies on basic epidemiological measures such as multiplicity of infection (MOI). METHODS: Samples were obtained in a repeated cross-sectional field survey in 1 to 4.5 years old children from Papua New Guinea, who were followed up in 2-monthly intervals over 16 months. At each follow-up visit, two consecutive blood samples were collected from each child at intervals of 24 hours. Samples were genotyped for the polymorphic markers msp2 for P. falciparum and msp1F3 and MS16 for P. vivax. Observed prevalence and mean MOI estimated from single samples per host were compared to combined data from sampling twice within 24 h. FINDINGS AND CONCLUSION: Estimated detectability was high in our data set (0.79 [95% CI 0.76-0.82] for P. falciparum and, depending on the marker, 0.61 [0.58-0.63] or 0.73 [0.71-0.75] for P. vivax). When genotyping data from sequential samples, collected 24 hours apart, were combined, the increase in measured prevalence was moderate, 6 to 9% of all infections were missed on a single day. The effect on observed MOI was more pronounced, 18 to 31% of all individual clones were not detected in a single bleed. Repeated sampling revealed little difference between detectability of P. falciparum and P. vivax

Analyzing the regulation of metabolic pathways in human breast cancer

<p>Abstract</p> <p>Background</p> <p>Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer.</p> <p>Methods</p> <p>For this, we mapped gene expression data from microarrays onto the corresponding enzymes and their metabolic reaction network. We used Haar Wavelet transforms on optimally arranged grid representations of metabolic pathways as a pattern recognition method to detect orchestrated regulation of neighboring enzymes in the network. Significant combined expression patterns were used to select metabolic pathways showing shifted regulation of the aggressive tumors.</p> <p>Results</p> <p>Besides up-regulation for energy production and nucleotide anabolism, we found an interesting cellular switch in the interplay of biosynthesis of steroids and bile acids. The biosynthesis of steroids was up-regulated for estrogen synthesis which is needed for proliferative signaling in breast cancer. In turn, the decomposition of steroid precursors was blocked by down-regulation of the bile acid pathway.</p> <p>Conclusion</p> <p>We applied an intelligent pattern recognition method for analyzing the regulation of metabolism and elucidated substantial regulation of human breast cancer at the interplay of cholesterol biosynthesis and bile acid metabolism pointing to specific breast cancer treatment.</p