Treatment of a malignant peripheral nerve sheath tumor and its complications through a multidisciplinary approach.
The authors report the case of a 14-year-old girl with a residual malignant peripheral nerve sheath tumor after thoracotomy, chemotherapy, and radiation therapy. The residual tumor, which involved the intercostal muscles, aorta, and neural foramina of T4-10, was completely resected through a costotransversectomy and multiple hemilaminotomies with the patient in the prone position and was stabilized using a T1-12 pedicle screw fusion. Postoperatively, the patient developed several infections requiring multiple washouts and prolonged antibiotics. Thirty months after surgery, she developed a bronchocutaneous fistula. The hardware was removed, and a vascularized latissimus dorsi free flap was placed over the lung. She continued to have an air leak and presented 3 weeks later with a 40° left thoracic curve. She returned to the operating room for a T2-L2 fusion with a vascularized fibular graft. On postoperative Day 1, she underwent a bronchoscopy and had her left lower lobe airways occluded with multiple novel one-way endobronchial valves. She is now 5 years out from her tumor resection and 3 years out from her definitive fusion. She has no evidence of residual tumor, infection, or pseudarthrosis and continues to remain asymptomatic.


Mechanism of action of pentagastrin on the lower esophageal sphincter.
The effects of pentagastrin on lower esophageal sphincter (LES) pressure has been studied in trained, unanesthetized dogs. LES pressure was monitored by an infusion manometric technique. Increasing doses of pentagastrin up to 3 mug/kg given as an i.v. bolus resulted in increasing rises in LES pressure; larger doses resulted in a lesser effect of shorter duration. Increasing i.v. boluses of methacholine produced greater increases in LES pressure up to a maximum of 5 mug/kg; higher doses had similar effects. Atropine (50-100 mug/kg) slightly diminished the response of the LES to 2 or 6 mug/kg of pentagastrin. In large doses (500-2,000 mug/kg), atropine did not diminish the response to pentagastrin and prolonged the response of 6 mug/kg pentagastrin. Hexamethonium (2 mg/kg i.v.) depressed the peak response to 3 mug/kg pentagastrin slightly but the response to 6 mug/kg was increased and prolonged. Propranolol (2 mg/kg i.v.) significantly prolonged the effect of 6 mug/kg pentagastrin on the LES. We conclude that the stimulatory effect of pentagastrin is mainly due to a direct action on the LES. A lesser stimulatory effect is due to an action on preganglionic cholinergic neurons. Large doses of pentagastrin have both stimulatory and inhibitory effects. The inhibitory effect is mediated at least in part via preganglionic neurons acting through adrenergic receptors. Ganglionic transmission of the effect may be through muscarinic as well as nicotinic receptors.


Wickerhamomyces arborarius f.a., sp. nov., an ascomycetous yeast species found in arboreal habitats on three different continents.
Five strains representing a novel yeast species belonging to the genus Wickerhamomyces were independently isolated from Ecuador, Taiwan and the USA. One strain (CLQCA 10-161(T)) was isolated from the white flower of an unidentified plant species collected in the Maquipucuna cloud forest reserve, near Quito, in Ecuador. A second strain (GY7L12) was isolated from the leaf of a Chinese sumac or nutgall tree (Rhus chinensis 'roxburghiana') collected in the Taoyuan mountain area, Kachsiung, in Taiwan. Three additional strains (A543, A546 and A563) were isolated from two species of wood-boring beetle (Xyleborus glabratus and Xyleborinus saxeseni) collected near Clyo, Georgia, USA. Analysis of the D1/D2 domains of the LSU rRNA gene indicated that the novel species belongs to the genus Wickerhamomyces, and is most closely related to Wickerhamomyces sydowiorum, an insect-associated species predominantly found in South Africa. The North American and Taiwanese strains have identical internal transcribed spacer (ITS) sequences and can be distinguished from the Ecuadorian strain based on a single nucleotide substitution in the ITS1 region. The species name of Wickerhamomyces arborarius f.a., sp. nov. is proposed to accommodate these strains, with CLQCA 10-161(T) ( = CBS 12941(T) = NCYC 3743(T)) designated the type strain.


Preoperative prediction of vasculogenic mimicry in lung adenocarcinoma using a CT radiomics model.
To develop and validate a non-invasive computed tomography (CT)-based radiomics model for predicting vasculogenic mimicry (VM) status in lung adenocarcinoma (LA). Two hundred and three patients with LA were enrolled retrospectively and grouped into training and test groups with a ratio of 7:3. Uni- and multivariate logistic regression analyses were performed in the training cohort to screen the independent clinical and radiological factors for VM, and the clinical model was then established. A radiomics model was established based on the rad-scores through support vector machine (SVM). A radiomics nomogram model was subsequently constructed by combining the rad-score with clinical-radiological factors. The receiver operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA) were conducted to evaluate the performance of the three models. Nine selected radiomics features were selected for the radiomics model and the maximum length and spiculation sign were constructed for the clinical model. The radiomics nomogram model integrating the maximum length, spiculation sign, and rad-score yielded the best AUC in both the training (AUC = 0.925) and test cohorts (AUC = 0.978), in comparison with the radiomics model (AUC = 0.907 and 0.964, in both the training and test cohorts) and the clinical model (AUC = 0.834 and 0.836 in both training and test cohorts). The CT-based radiomics nomogram model showed satisfying discriminating performance for preoperatively and non-invasively predicting VM expression status in LA patients.


Australian University Nursing and Allied Health Students' and Staff Physical Activity Promotion Preparedness and Knowledge: A Pre-Post Study Using an Educational Intervention.
The promotion of physical activity (PA) by health professionals is a key strategy to increase PA levels in the population. In this study, we investigated PA promotion, preparedness, and knowledge among university nursing and allied health students and staff, as well as PA resource usage within curricula, before and after an educational intervention. Students and staff from 13 health disciplines at one Australian university were invited to complete an online survey, and a curriculum audits were conducted before and after PA teaching resources were promoted by academic PA champions (n = 14). A total of 299 students and 43 staff responded to the survey pre-intervention, and 363 and 32 responded to the post-intervention, respectively. PA promotion role perception (≥93%) and confidence to provide general PA advice (≥70%) were high throughout the study. Knowledge of PA guidelines was poor (3−10%). Students of physiotherapy, sport and exercise science, as well as more active students, were more likely to be aware of the PA guidelines (p < 0.05). Over 12 months, PA promotion preparedness and knowledge did not change significantly, nor was there a change in the amount of PA content delivered, despite a significant increase in the use of the teaching resources across a number of disciplines (p = 0.007). Future research should be carried out to investigate the implementation of the resources over time and to develop additional strategies for PA promotion and education scaffolded across curricula.


Signal transduction pathways mediated by PECAM-1: new roles for an old molecule in platelet and vascular cell biology.
Recent studies of platelet endothelial cell adhesion molecule-1 (PECAM-1 [CD31])-deficient mice have revealed that this molecule plays an important role in controlling the activation and survival of cells on which it is expressed. In this review, we focus on the complex cytoplasmic domain of PECAM-1 and describe what is presently known about its structure, posttranslational modifications, and binding partners. In addition, we summarize findings that implicate PECAM-1 as an inhibitor of cellular activation via protein tyrosine kinase-dependent signaling pathways, an activator of integrins, and a suppressor of cell death via pathways that depend on damage to the mitochondria. The challenge of future research will be to bridge our understanding of the functional and biochemical properties of PECAM-1 by establishing mechanistic links between signals transduced by the PECAM-1 cytoplasmic domain and discrete cellular responses.


Risk factors and prevalence of toxocariasis in pregnant women and diabetic patients compared to healthy adults in Ilam province, western Iran.
Toxocara is one of the common intestinal nematodes in dogs and cats and is the agent of tissue migratory larvae in humans. Customarily, the prevalence of human toxocariasis hovers around 15.8 % in Iran. Furthermore, other research outcomes demonstrated a tendency for an outbreak of toxocariasis in Iran. Therefore, we carried out a cross-sectional study and assessed the seroprevalence of toxocariasis humans in Ilam Province, western of Iran. A total of 539 serum samples were collected between September 2017 and March 2018 from patients referred to the Health Centers of Ilam province, Iran. Serum samples were investigated for the presence of Toxocara using IgG antibodies, ELISA (Enzyme-Linked Immunosorbent Assay) kit. Risk factors such as contact with cats and dogs, living in rural areas were investigated among the study population. Out of 539 total samples collected, 97 cases (17.99 %) were positive for anti-toxocara IgG antibodies. These antibodies were recovered from serum samples of otherwise healthy adults (15.54 %, 49/296), pregnant women (21.16 %, 40/189) and diabetic patients (14.81 %, 8/54). This study showed significant relationship between toxocariasis and contact with animal pets in all studied groups (P value ≤ 0.05) and a significant relationship between toxocariasis and living in rural areas among pregnant women (P value ≤ 0.05).


Selective and regulated gene expression in murine Purkinje cells by in utero electroporation.
Cerebellar Purkinje cells, which convey the only output from the cerebellar cortex, play an essential role in cerebellar functions, such as motor coordination and motor learning. To understand how Purkinje cells develop and function in the mature cerebellum, an efficient method for molecularly perturbing them is needed. Here we demonstrate that Purkinje cell progenitors at embryonic day (E)11.5 could be efficiently and preferentially transfected by spatially directed in utero electroporation (IUE) with an optimized arrangement of electrodes. Electrophysiological analyses indicated that the electroporated Purkinje cells maintained normal membrane properties, synaptic responses and synaptic plasticity at postnatal days 25-28. By combining the L7 promoter and inducible Cre/loxP system with IUE, transgenes were expressed even more specifically in Purkinje cells and in a temporally controlled manner. We also show that three different fluorescent proteins could be simultaneously expressed, and that Bassoon, a large synaptic protein, could be expressed in the electroporated Purkinje cells. Moreover, phenotypes of staggerer mutant mice, which have a deletion in the gene encoding retinoid-related orphan receptor α (RORα1), were recapitulated by electroporating a dominant-negative form of RORα1 into Purkinje cells at E11.5. Together, these results indicate that this new IUE protocol, which allows the selective, effective and temporally regulated expression of multiple foreign genes transfected into Purkinje cell progenitors in vivo, without changing the cells' physiological characteristics, is a powerful tool for elucidating the molecular mechanisms underlying early Purkinje cell developmental events, such as dendritogenesis and migration, and synaptic plasticity in mature Purkinje cells.


Intravascular clotting activation and bleeding in patients with hematologic malignancies.
The association between thrombosis, bleeding and neoplastic disease is well recognized. There are distinctive features of the thrombotic and bleeding complications associated with specific hematologic malignancies. A number of procoagulants can initiate intravascular clotting including tissue factor, cancer procoagulant and interleukin-1. The hematologic malignancy most often associated with intravascular clotting and bleeding is acute promyelocytic leukemia. The pathogenesis of the life-threatening bleeding disorder associated with this uncommon subtype of acute myeloid leukemia (AML) is complex and involves disseminated intravascular coagulation, fibrinolysis and proteolysis. Both all-trans retinoic acid and arsenic trioxide result in relatively rapid resolution of the coagulopathy. Intravascular clotting may also be induced by hyperleukocytosis in AML and by the hyperviscosity syndrome observed in multiple myeloma and Waldenström's macroglobulinemia. In the setting of hematologic malignancies, when thromboembolic complications occur, the presence of comorbid thrombophilic conditions should be excluded. Abnormal platelet production and function contribute to the development of thrombosis in patients with myeloproliferative disorders. The Budd-Chiari syndrome may be observed in patients with myeloproliferative disorders. A number of medications have thrombogenic potential, including corticosteroids, thalidomide, L-asparaginase, all-trans retinoic acid and arsenic trioxide.


Effects of A-23187 and verapamil on the active transport enzymes in turtle bladder epithelial cells.
These experiments were designed to examine the effects of A-23187 (5 x 10(-4) M) and verapamil (100 microM) on membrane transport, 45Ca fluxes, and adenosine-triphosphatase (ATPase) activities in turtle bladder. In the intact membrane, the calcium ionophore decreased proton secretion and sodium transport [short-circuit current (SCC)] to approximately the same degree (by approximately 55% at 30 min). During the same period of time, verapamil decreased SCC (by approximately 58%), but proton secretion was unaffected. The turtle bladder membrane is composed predominantly of two cell types: 1) the mitochondrial-rich cells (MR cells) thought to be involved in proton (and bicarbonate) secretion containing significant H(+)-ATPase and Ca(2+)-ATPase and 2) the granular cells (G cells), postulated important in sodium reabsorption, having abundant Na(+)-K(+)-ATPase. That Na(+)-K(+)-ATPase activity was unchanged by either a calcium ionophore or a calcium channel blocker suggests that the decrease in SCC noted in the intact membrane is not directly mediated by changes in the sodium "pump." The decrease of H(+)-ATPase in MR cells, which resulted after the A-23187, suggests that it probably exerts a direct action on the proton pump, which decreases hydrogen ion secretion. The increase in ATP-dependent 45Ca transport seen after the ionophore (or the decrease in ATP-independent 45Ca transport after verapamil) most likely reflects increased (or decreased) Ca2+ availability within the cytosol, and the high (or low) cell calcium could decrease the SCC. These results thus suggest that cytosolic Ca2+ reciprocally sets, by different mechanisms, the rate of proton secretion in MR cells and the sodium reabsorption in G cells.


A geostatistical framework for combining spatially referenced disease prevalence data from multiple diagnostics.
Multiple diagnostic tests are often used due to limited resources or because they provide complementary information on the epidemiology of a disease under investigation. Existing statistical methods to combine prevalence data from multiple diagnostics ignore the potential overdispersion induced by the spatial correlations in the data. To address this issue, we develop a geostatistical framework that allows for joint modelling of data from multiple diagnostics by considering two main classes of inferential problems: (a) to predict prevalence for a gold-standard diagnostic using low-cost and potentially biased alternative tests; (b) to carry out joint prediction of prevalence from multiple tests. We apply the proposed framework to two case studies: mapping Loa loa prevalence in Central and West Africa, using miscroscopy, and a questionnaire-based test called RAPLOA; mapping Plasmodium falciparum malaria prevalence in the highlands of Western Kenya using polymerase chain reaction and a rapid diagnostic test. We also develop a Monte Carlo procedure based on the variogram in order to identify parsimonious geostatistical models that are compatible with the data. Our study highlights (a) the importance of accounting for diagnostic-specific residual spatial variation and (b) the benefits accrued from joint geostatistical modelling so as to deliver more reliable and precise inferences on disease prevalence.


Lead-position dependent regular oscillations and random fluctuations of conductance in graphene quantum dots.
Quantum interference causes a wavefunction to have sensitive spatial dependence, and this has a significant effect on quantum transport. For example, in a quantum-dot system, the conductance can depend on the lead positions. We investigate, for graphene quantum dots, the conductance variations with the lead positions. Since for graphene the types of boundaries, e.g., zigzag and armchair, can fundamentally affect the quantum transport characteristics, we focus on rectangular graphene quantum dots, for which the effects of boundaries can be systematically studied. For both zigzag and armchair horizontal boundaries, we find that changing the positions of the leads can induce significant conductance variations. Depending on the Fermi energy, the variations can be either regular oscillations or random conductance fluctuations. We develop a physical theory to elucidate the origin of the conductance oscillation/fluctuation patterns. In particular, quantum interference leads to standing-wave-like-patterns in the quantum dot which, in the absence of leads, are regulated by the energy-band structure of the corresponding vertical graphene ribbon. The observed 'coexistence' of regular oscillations and random fluctuations in the conductance can be exploited for the development of graphene-based nanodevices.


Proximal femoral medullary canal diameters in Indians: correlation between anatomic, radiographic, and computed tomographic measurements.
To compare anatomic, radiographic, and computed tomographic (CT) measurements of the proximal femur in an Indian population. 26 left and 24 right dried cadaveric femurs were obtained. Each femur was divided into segments at 10 cross-sectional levels from proximal to distal. At each level, anteroposterior (AP), lateral, 45-degree internal oblique, and 45-degree external oblique diameters of the medullary canal were measured using radiography and CT. To minimise magnification, the femur was placed over the film/board. The neck shaft angle, femoral head offset, neck length, and femoral head diameter were also measured. For anatomic measurements, the cross-sections of the medullary canal at levels 3 to 10 were measured using a calliper. Anatomic measurements were compared with radiographic and CT measurements, and the distortion calculated. Correlation between the 3 modalities was calculated using the Pearson correlation coefficient. Accuracy index of the 2 diagnostic modalities was measured, based on the differences between anatomic and radiographic/CT measurements. Lower accuracy indices indicated higher accuracy. On AP radiographs of all femurs, the mean femoral head diameter was 45 mm, the mean neck shaft angle was 132 degrees, the mean femoral head offset was 42 mm, and the mean neck length was 63 mm. With regard to medullary canal diameters, the radiographic and CT measurements were smaller than anatomic measurements at proximal levels, but similar at distal levels. Variations between femurs and between the 4 diameters at the same level were greater at proximal levels. Combined use of radiography and CT is recommended for preoperative assessment of implant size, particularly in uncemented arthroplasty where an optimal fit is essential for biological fixation.


Individualizing therapy for early, middle-of-the-night and late-night insomnia.
Many patients with insomnia describe their sleep problems as an inability to remain asleep throughout the night, resulting in next-day fatigue that may adversely affect daytime functioning. To be most effective, insomnia treatment should be tailored to resolving underlying causes of the condition and managing specific sleep complaints. Therefore, hypnotic therapy administered prior to bedtime, as is currently recommended for most compounds, is not appropriate for all insomnia patients. Ideally, behavioral interventions should be combined with a rapid-acting agent that can be administered at virtually any time during the night without producing residual effects the following day. Zaleplon, a new non-benzodiazepine sleep medication, provides the clinician with an effective and safe pharmacotherapeutic option for insomnia management. Its rapid rates of absorption and elimination allow for treatment of symptoms when they occur, either at bedtime or later at night, without incurring significant risk for the development of next-day impairment of psychomotor and cognitive functioning.


Novel mutations in the GPIHBP1 gene identified in 2 patients with recurrent acute pancreatitis.
Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) has been demonstrated to be essential for the in vivo function of lipoprotein lipase (LPL), the major triglyceride (TG)-hydrolyzing enzyme involved in the intravascular lipolysis of TG-rich lipoproteins. Recently, loss-of-function mutations of GPIHBP1 have been reported as the cause of type I hyperlipoproteinemia in several patients. Two unrelated patients were referred to our Lipid Units because of a severe hypertriglyceridemia and recurrent pancreatitis. We measured LPL activity in postheparin plasma and serum ApoCII and sequenced LPL, APOC2, and GPIHBP1. The 2 patients exhibited very low LPL activity not associated with mutations in LPL gene or with ApoCII deficiency. The sequence of GPIHBP1 revealed 2 novel point mutations. One patient (proband 1) was found to be homozygous for a C>A transversion in exon 3 resulting in the conversion of threonine to lysine at position 80 (p.Thr80Lys). The other patient (proband 2) was found to be homozygous for a G>T transversion in the third base of the ATG translation initiation codon in exon 1, resulting in the conversion of methionine to isoleucine (p.Met1Ile). In conclusion, we have identified 2 novel GPIHBP1 missense mutations in 2 unrelated patients as the cause of their severe hypertriglyceridemia.


The Electronic Health Insurance Card for Asylum-Seekers in Berlin: Effects on the Local Health System.
In debates on asylum-seekers' access to healthcare it is frequently claimed that restrictions are necessary to prevent unduly high health service utilization and costs. Within Germany, healthcare provision for asylum-seekers varies across the different states. Berlin's authorities removed some barriers to healthcare for asylum-seekers by introducing an electronic health insurance card (HIC) in 2016. We used the HIC introduction in Berlin as an opportunity to investigate the effects of improved healthcare access for asylum-seekers on the local health system. The study applied a mixed-methods design. A cost analysis compared expenses for outpatient and inpatient health services for asylum-seekers before and after the HIC introduction, based on aggregate claims data and information on expenses for humanitarian healthcare provision that were retrieved from the Berlin authorities. Semi-structured interviews with 12 key informants explored organizational effects like administrative workloads and ethical dilemmas for staff. We performed a content analysis and used respondent validation to enhance the accuracy and trustworthiness of our results. The HIC has reduced bureaucratic complexity and administrative workloads; it has enabled unprecedented financial transparency and control; and it has mitigated ethical tensions. All the while, average per person expenses for outpatient health services have declined since the HIC introduction. However, our cost analysis also indicates a rise in the utilization and costs of inpatient care. The HIC introduction in Berlin suggests that the removal of barriers to healthcare for asylum-seekers can create win-win-situations by reducing administrative workloads, advancing financial transparency, and mitigating ethical tensions, whilst cutting the costs of outpatient healthcare provision. Removing barriers to healthcare thus appears to be a more prudent policy choice than maintaining mechanisms of restriction and control. However, high inpatient care utilization and costs warrant further research.


Monitoring Chewing and Eating in Free-Living Using Smart Eyeglasses.
We propose to 3-D-print personal fitted regular-look smart eyeglasses frames equipped with bilateral electromyography recording to monitor temporalis muscles' activity for automatic dietary monitoring. Personal fitting supported electrode-skin contacts are at temple ear bend and temple end positions. We evaluated the smart monitoring eyeglasses during in-lab and free-living studies of food chewing and eating event detection with ten participants. The in-lab study was designed to explore three natural food hardness levels and determine parameters of an energy-based chewing cycle detection. Our free-living study investigated whether chewing monitoring and eating event detection using smart eyeglasses is feasible in free-living. An eating event detection algorithm was developed to determine intake activities based on the estimated chewing rate. Results showed an average food hardness classification accuracy of 94% and chewing cycle detection precision and recall above 90% for the in-lab study and above 77% for the free-living study covering 122 hours of recordings. Eating detection revealed the 44 eating events with an average accuracy above 95%. We conclude that smart eyeglasses are suitable for monitoring chewing and eating events in free-living and even could provide further insights into the wearer's natural chewing patterns.


Molecular epidemiology of Mycobacterium avium complex isolated from patients with and without AIDS in Brazil and England.
Mycobacterium avium complex (MAC) is ubiquitous throughout the world. It is an opportunistic pathogen in AIDS patients but the number of cases in HIV negative patients is also increasing. The aim of this study was to determine whether patients were being infected with different MAC strains or whether one strain was dominant. DNA obtained from isolates in Brazil and England were compared using pulsed field gel electrophoresis (PFGE). Strains from 22 Brazilian patients clustered into 7 groups but 68/90 patients had a unique strain. In all patients, Brazilian and English, the same strain was isolated repeatedly over time, some over several years. This study shows that it is most likely that Man is infected from the environment and that one strain can survive without change for many years both in the environment and in Man.


Effect of early antibiotic treatment strategy on prognosis of acute pancreatitis.
Antibiotic use in the early stages of acute pancreatitis is controversial. The purpose of this study was to investigate the effect of early antibiotic application on the prognosis of acute pancreatitis (AP). Clinical data of patients with primary AP admitted to our emergency ward within 72 hours of onset were retrospectively collected from January 2016 to December 2020. We classified patients with acute pancreatitis according to etiology and disease severity, and compared the differences in hospital stay, laparotomy rate, and in-hospital mortality among AP patients who received different antibiotic treatment strategies within 72 hours of onset. A total of 1134 cases were included, with 681 (60.1%) receiving early antibiotic treatment and 453 (39.9%) not receiving it. There were no significant differences in baseline values and outcomes between the two groups. In subgroup analysis, patients with biliary severe acute pancreatitis (SAP) who received early antibiotics had lower rates of laparotomy and invasive mechanical ventilation, as well as shorter hospital stays compared to those who did not receive antibiotics. In logistic regression analysis, the early administration of carbapenem antibiotics in biliary SAP patients was associated with a lower in-hospital mortality rate. Early antibiotic use in biliary moderate-severe acute pancreatitis (MSAP) reduced hospital stays and in-hospital mortality. Quinolone combined with metronidazole treatment in biliary mild acute pancreatitis (MAP) shortened hospital stays. Early antibiotic use does not benefit patients with non-biliary AP. Strategies for antibiotic use in the early stages of AP need to be stratified according to cause and disease severity.


Systematic characterization of the local evolutionary space available to human PKR and vaccinia virus K3.
The interfaces between host and viral proteins can be dynamic spaces in which genetic variants are continually pursued, giving rise to evolutionary arms races. One such scenario is found between the mammalian innate immunity protein PKR (protein kinase R) and the poxvirus antagonist K3. Once activated, PKR phosphorylates the natural substrate eIF2α, which halts protein synthesis within the cell and prevents viral replication. K3 acts as a pseudosubstrate antagonist against PKR by directly antagonizing this halt in protein synthesis, enabling poxviruses to replicate in the cell. Exploring the impact of genetic variants in both PKR and K3 is necessary not only to highlight residues of evolutionary constraint and opportunity but also to elucidate the mechanism by which human PKR is able to subvert a rapidly evolving viral antagonist. To systematically explore this dynamic interface, we have generated a combinatorial library of PKR and K3 missense variants to be co-expressed and characterized in a high-throughput yeast selection assay. This assay allows us to characterize hundreds of thousands of unique PKR-K3 genetic combinations in a single pooled experiment. Our results highlight specific missense variants available to PKR that subvert the K3 antagonist. We find that improved PKR variants are readily available at sites under positive selection, with limited opportunity at sites interfacing with K3 and eIF2α. Additionally, we find many variants that improve and disable K3 antagonism, suggesting a pliable interface. We reason that this approach can be leveraged to explore the evolutionary plasticity of many other host-virus interfaces.


[Methodological aspects of the analysis of the effects of drugs (diazepam and caffeine) on contingent negative variation].
The paper discusses the importance and implications of the event-related-potentials in the analysis of effects of centrally acting drugs. This is illustrated using a study on the influence of diazepam and caffeine on the contingent-negative-variation (CNV) as an example. Special emphasis is placed on methodological problems and their possible solutions. A linear robust fitting technique was used for quantification of the slow-rising, ramp-like CNV potentials as an alternative to conventional baseline-to-peak measures. Results obtained by this method were validated by a second analysis taking slow superimposed DC-shifts into account. This was achieved by defining a reference line from the data for CNV-development and -resolution. The possibilities of single-trial potential evaluation were explored by using a pattern recognition algorithm. The average CNV-waveform was used as a reference-signal to which the single-trial potentials were correlated. Since pattern recognition techniques are sensitive to morphological changes of the potentials they are adding a new aspect to event-related-potential analysis.


Understanding the adaptive growth strategy of Lactobacillus plantarum by in silico optimisation.
In the study of metabolic networks, optimization techniques are often used to predict flux distributions, and hence, metabolic phenotype. Flux balance analysis in particular has been successful in predicting metabolic phenotypes. However, an inherent limitation of a stoichiometric approach such as flux balance analysis is that it can predict only flux distributions that result in maximal yields. Hence, previous attempts to use FBA to predict metabolic fluxes in Lactobacillus plantarum failed, as this lactic acid bacterium produces lactate, even under glucose-limited chemostat conditions, where FBA predicted mixed acid fermentation as an alternative pathway leading to a higher yield. In this study we tested, however, whether long-term adaptation on an unusual and poor carbon source (for this bacterium) would select for mutants with optimal biomass yields. We have therefore adapted Lactobacillus plantarum to grow well on glycerol as its main growth substrate. After prolonged serial dilutions, the growth yield and corresponding fluxes were compared to in silico predictions. Surprisingly, the organism still produced mainly lactate, which was corroborated by FBA to indeed be optimal. To understand these results, constraint-based elementary flux mode analysis was developed that predicted 3 out of 2669 possible flux modes to be optimal under the experimental conditions. These optimal pathways corresponded very closely to the experimentally observed fluxes and explained lactate formation as the result of competition for oxygen by the other flux modes. Hence, these results provide thorough understanding of adaptive evolution, allowing in silico predictions of the resulting flux states, provided that the selective growth conditions favor yield optimization as the winning strategy.


Physiological and transcriptomic characterization of submergence and reoxygenation responses in soybean seedlings.
Complete inundation at the early seedling stage is a common environmental constraint for soybean production throughout the world. As floodwaters subside, submerged seedlings are subsequently exposed to reoxygenation stress in the natural progression of a flood event. Here, we characterized the fundamental acclimation responses to submergence and reoxygenation in soybean at the seedling establishment stage. Approximately 90% of seedlings succumbed during 3 d of inundation under constant darkness, whereas 10 d of submergence were lethal to over 90% of seedlings under 12 h light/12 h dark cycles, indicating the significance of underwater photosynthesis in seedling survival. Submergence rapidly decreased the abundance of carbohydrate reserves and ATP in aerial tissue of seedlings although chlorophyll breakdown was not observed. The carbohydrate and ATP contents were recovered upon de-submergence, but sudden exposure to oxygen also induced lipid peroxidation, confirming that reoxygenation induced oxidative stress. Whole transcriptome analysis recognized genome-scale reconfiguration of gene expression that regulates various signalling and metabolic pathways under submergence and reoxygenation. Comparative analysis of differentially regulated genes in shoots and roots of soybean and other plants defines conserved, organ-specific and species-specific adjustments which enhance adaptability to submergence and reoxygenation through different metabolic pathways.


Isoniazid protects mice against endotoxin lethality without influencing tumor necrosis factor synthesis and release.
Treatment of NMRI mice with isoniazid (INH; 25 mg/kg) intraperitoneally induced significant protection when it was injected before or after a lethal intravenous challenge with endotoxin. The INH preparation used was not contaminated with endotoxin. Tumor necrosis factor (TNF) was not elevated in sera from NMRI mice 2 h after the injection of INH. INH did not influence TNF synthesis or release determined in human monocytes in vitro. Therefore, it is concluded that the protective effect of INH against lethal endotoxin is not due to a suppressive effect of INH on TNF production.


Deficiency of hormone receptor-adenylate cyclase coupling protein: basis for hormone resistance in pseudohypoparathyroidism.
Pseudohypoparathyroidism is an inherited disorder associated with resistance to the action of several hormones, including parathyroid hormone, thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone. The disorders described under this designation are heterogeneous in regard to the underlying genetic defects, the phenotypic manifestation, and the severity of the defects in hormone action. The majority of affected individuals who also have the characteristic skeletal changes (heredity osteodystrophy) have a defect in the guanine nucleotide regulatory protein (G protein) that is essential for coupling certain cell-surface hormone receptors to the adenylate cyclase system. This defect is probably the cause for resistance to the action of multiple hormones. In the remaining patients the cause for hormone resistance has not been identified.


Metabolism of theanine, gamma-glutamylethylamide, in rats.
The metabolism of theanine, one of the major amino acid components in tea (Camellia sinensis), was studied in rats. High-performance liquid chromatography (HPLC) with fluorometric detection was used to evaluate the nature of theanine's metabolites in plasma, urine, and tissues. In the urine samples collected after administration of 100, 200, and 400 mg each of theanine, intact theanine, L-glutamic acid, and ethylamine, these compounds were detected in a dose-dependent manner. When 200 mg of theanine was orally administered to rats, the plasma concentrations of theanine and ethylamine reached their highest levels about 0.5 and 2 h after administration, respectively. It seems most likely that the enzymatic hydrolysis of theanine to glutamic acid and ethylamine was accomplished in the kidney. These results indicate that orally administered theanine is absorbed through the intestinal tract and hydrolyzed to glutamic acid and ethylamine in the rat kidney.


Detecting schizophrenia at the level of the individual: relative diagnostic value of whole-brain images, connectome-wide functional connectivity and graph-based metrics.
Previous studies using resting-state functional neuroimaging have revealed alterations in whole-brain images, connectome-wide functional connectivity and graph-based metrics in groups of patients with schizophrenia relative to groups of healthy controls. However, it is unclear which of these measures best captures the neural correlates of this disorder at the level of the individual patient. Here we investigated the relative diagnostic value of these measures. A total of 295 patients with schizophrenia and 452 healthy controls were investigated using resting-state functional Magnetic Resonance Imaging at five research centres. Connectome-wide functional networks were constructed by thresholding correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based methods. Single-subject classification was performed using three machine learning (ML) approaches associated with varying degrees of complexity and abstraction, namely logistic regression, support vector machine and deep learning technology. Connectome-wide functional connectivity allowed single-subject classification of patients and controls with higher accuracy (average: 81%) than both whole-brain images (average: 53%) and graph-based metrics (average: 69%). Classification based on connectome-wide functional connectivity was driven by a distributed bilateral network including the thalamus and temporal regions. These results were replicated across the three employed ML approaches. Connectome-wide functional connectivity permits differentiation of patients with schizophrenia from healthy controls at single-subject level with greater accuracy; this pattern of results is consistent with the 'dysconnectivity hypothesis' of schizophrenia, which states that the neural basis of the disorder is best understood in terms of system-level functional connectivity alterations.


Mobile phone use among Medical Reserve Corps coordinators and volunteers: an exploratory study.
To better understand how mobile phones can be used during emergency response, this study identifies a) current mobile phone use among Medical Reserve Corps (MRC) volunteers and coordinators in their daily lives and during response; b) challenges for mobile phone use during response; and c) areas for capacity building. In 2012, 459 MRC volunteers and coordinators responded to a 35-question survey conducted online through SurveyMonkey. Respondents were asked how they use their mobile phones in their daily lives and during response, and how they would like to use them during response. Frequencies were calculated using SurveyMonkey and Excel. Respondents reported frequent and varied mobile phone use in their daily lives, with 99 percent of respondents owning a phone, 82 percent texting, and 87 percent of smartphone owners using apps. Although 80 percent of respondents who had been deployed used mobile phones during response, use of sophisticated mobile phone features was low; only 10 percent accessed emergency preparedness apps and 23 percent browsed the Internet for emergency response information. Respondents indicated a desire to use more features during response, such as emergency preparedness apps (72 percent) and e-mail to send or receive response instructions (80 percent). Results indicate that given access to mobile technology and training, emergency responders would like to increase their mobile phone use during response. Implications of these findings show a need for organizations to improve their support of mobile phone use.


Barium complexes with crown-ether-functionalised amidinate and iminoanilide ligands for the hydrophosphination of vinylarenes.
The detailed multistep syntheses of two nitrogen-based sterically congested iminoanilidine and amidine proligands bearing a tethered 15-member aza-ether-crown macrocycle, namely {I^Acrown}H and {Amcrown}H, are reported. These proligands react with [Ba{N(SiMe2H)2}2·(thf)n] to generate the heteroleptic barium complexes [{I^Acrown}BaN(SiMe2H)2] (5) and [{Amcrown}BaN(SiMe2H)2] (6) in high yields. These complexes exhibit high coordination numbers (resp. eight and seven) and are in addition stabilised by mild BaH-Si interactions. Unusually for oxophilic elements such as barium, the amidinate ligand in 6 is only η1-coordinated. Complexes 5 and 6 mediate the intermolecular hydrophosphination of styrene with primary (PhPH2) and secondary (HPPh2) phosphines. Their catalytic performance compares favourably with those of other barium precatalysts for these reactions. During the course of the hydrophosphination of styrene with HPPh2 catalysed by 5, the phosphide complex [{I^Acrown}BaPPh2] (7) could be intercepted and crystallographically characterised.


The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes.
HACE1 is a HECT family E3 ubiquitin-protein ligase with broad but incompletely understood tumor suppressor activity. Here, we report a previously unrecognized link between HACE1 and signaling complexes containing mammalian target of rapamycin (mTOR). HACE1 blocks mTORC1 and mTORC2 activities by reducing mTOR stability in an E3 ligase-dependent manner. Mechanistically, HACE1 binds to and ubiquitylates Ras-related C3 botulinum toxin substrate 1 (RAC1) when RAC1 is associated with mTOR complexes, including at focal adhesions, leading to proteasomal degradation of RAC1. This in turn decreases the stability of mTOR to reduce mTORC1 and mTORC2 activity. HACE1 deficient cells show enhanced mTORC1/2 activity, which is reversed by chemical or genetic RAC1 inactivation but not in cells expressing the HACE1-insensitive mutant, RAC1K147R . In vivo, Rac1 deletion reverses enhanced mTOR expression in KRasG12D -driven lung tumors of Hace1-/- mice. HACE1 co-localizes with mTOR and RAC1, resulting in RAC1-dependent loss of mTOR protein stability. Together, our data demonstrate that HACE1 destabilizes mTOR by targeting RAC1 within mTOR-associated complexes, revealing a unique ubiquitin-dependent process to control the activity of mTOR signaling complexes.


Global updates in the treatment of gastric cancer: a systematic review. Part 2: perioperative management, multimodal therapies, new technologies, standardization of the surgical treatment and educational aspects.
Gastric cancer is the fifth malignancy and the third cause of cancer death worldwide, according to the global cancer statistics presented in 2018. Its definition and staging have been revised in the eight edition of the AJCC/TNM classification, which took effect in 2018. Novel molecular classifications for GC have been recently established and the process of translating these classifications into clinical practice is ongoing. The cornerstone of GC treatment is surgical, in a context of multimodal therapy. Surgical treatment is being standardized, and is evolving according to new anatomical concepts and to the recent technological developments. This is leading to a massive improvement in the use of mini-invasive techniques. Mini-invasive techniques aim to be equivalent to open surgery from an oncologic point of view, with better short-term outcomes. The persecution of better short-term outcomes also includes the optimization of the perioperative management, which is being implemented on large scale according to the enhanced recovery after surgery principles. In the era of precision medicine, multimodal treatment is also evolving. The long-time-awaited results of many trials investigating the role for preoperative and postoperative management have been published, changing the clinical practice. Novel investigations focused both on traditional chemotherapeutic regimens and targeted therapies are currently ongoing. Modern platforms increase the possibility for further standardization of the different treatments, promote the use of big data and open new possibilities for surgical learning. This systematic review in two parts assesses all the current updates in GC treatment.


Child and Parent Perceived Determinants of Children's Inadequate Sleep Health. A Concept Mapping Study.
Many children do not meet the recommendations for healthy sleep, which is concerning given the potential negative effects on children's health. To promote healthy sleep, it is crucial to understand its determinants. This concept mapping study therefore explores perspectives of children and parents on potential determinants of children's inadequate sleep. The focus lies on 9-12 year old children (n = 45), and their parents (n = 33), from low socioeconomic neighbourhoods, as these children run a higher risk of living in a sleep-disturbing environment (e.g., worries, noise). All participants generated potential reasons (i.e., ideas) for children's inadequate sleep. Next, participants sorted all ideas by relatedness and rated their importance. Subsequently, multidimensional scaling and hierarchical cluster analyses were performed to create clusters of ideas for children and parents separately. Children and parents both identified psychological (i.e., fear, affective state, stressful situation), social environmental (i.e., sleep schedule, family sleep habits), behavioural (i.e., screen behaviour, physical activity, diet), physical environmental (i.e., sleep environment such as temperature, noise, light), and physiological (i.e., physical well-being) determinants. These insights may be valuable for the development of future healthy sleep interventions.


Long-term retention of kinship recognition established during infancy in the domestic dog.
The ability of the domestic dog to recognise its kin, and to retain this information once acquired, was studied in this paper. Dogs were examined for their ability to recognise their siblings, offspring to recognise their mother, and mothers to recognise their offspring, using a series of two choice tests. The results revealed that, at 4-5.5 weeks of age, pups can recognise their siblings and their mother, and mothers can recognise their offspring. The preference of pups at this age appears to be strongest for their mother. Olfactory cues are sufficient for this recognition to take place. At approximately 2 years of age, and having been separated from their offspring from 8-12 weeks after their birth, mothers were able to recognise their now adult offspring and these adult offspring could recognise their mothers. Siblings could only recognise one another if they had been living with a sibling (not the test animal). Dogs living on their own were unable to recognise their siblings. Thus dogs can recognise their kin, retaining this information for a period of two years in the case of mother-offspring. It is suggested that mother-offspring and siblings are recognised by different mechanisms.


Antifungal activity of linalool in cases of Candida spp. isolated from individuals with oral candidiasis.
This study analyzed the antifungal activity of phytoconstituents from linalool on Candida spp. strains, in vitro, isolated from patients with clinical diagnoses of oral candidiasis associated with the use of a dental prosthesis. Biological samples were collected from 12 patients using complete dentures or removable partial dentures and who presented mucous with diffuse erythematous or stippled features, indicating a clinical diagnosis of candidiasis. To identify fungal colonies of the genus Candida, samples were plated onto CHROMagar Candida®. The antifungal activity of linalool, a monoterpene unsaturated constituent of basil oil, was performed using the broth microdilution technique. Then, the minimum inhibitory concentration (MIC), the two subsequent stronger concentrations and the positive controls were subcultured on Sabouraud Dextrose Agar plates to determine the minimum fungicidal concentration (MFC). The experiments were performed in triplicate and nystatin was used as a positive control in all tests. Diagnoses of oral candidiasis were verified in eight patients (66.6%) and the most prevalent fungal species was Candida albicans (37.5%), followed by Candida krusei (25.0%); and Candida tropicalis (4.2%). The best antifungal activity of linalool was observed on Candida tropicalis (MIC = 500 mg/mL), followed by Candida albicans (MIC = 1.000 mg/mL), and Candida krusei (MIC = 2.000 mg/mL).Under the study conditions and based on the results obtained, it can be concluded that the Candida strains tested were susceptible to linalool.


Monitoring of DNA breakage in embryonic stages of the African catfish Clarias gariepinus (Burchell, 1822) after exposure to lead nitrate using alkaline comet assay.
Increasing lead contamination in Egyptian ecosystems and high lead concentrations in food items have raised concern for human health and stimulated studies on monitoring ecotoxicological impact of lead-caused genotoxicity. In this work, the alkaline comet assay was modified for monitoring DNA strand breakage in sensitive early life stages of the African catfish Clarias gariepinus. Following exposure to 100, 300, and 500 microg/L lead nitrate, DNA strand breakage was quantified in embryos at 30, 48, 96, 144, and 168 h post-fertilization (PFS). For quantitative analysis, four commonly used parameters (tail % DNA, %TDNA; head % DNA, %HDNA; tail length, TL; tail moment, TM) were analyzed in 96 nuclei (in triplicates) at each sampling point. The parameter %TDNA revealed highest resolution and lowest variation. A strong correlation between lead concentration, time of exposure, and DNA strand breakage was observed. Here, genotoxicity detected by comet assay preceded the manifested malformations assessed with conventional histology. Qualitative evaluation was carried out using five categories are as follows: undamaged (%TDNA < or = 10%), low damaged (10% < %TDNA < or = 25%), median damaged (25 < %TDNA < or = 50%), highly damaged (50 < %TDNA < or = 75%), and extremely damaged (%TDNA > 75%) nuclei confirming a dose and time-dependent shift towards increased frequencies of highly and extremely damaged nuclei. A protective capacity provided by a hardened chorion is a an interesting finding in this study as DNA damage in the prehatching stages 30 h-PFS and 48 h-PFS was low in all treatments (qualitative and quantitative analyses). These results clearly show that the comet assay is a sensitive tool for the detection of genotoxicity in vulnerable early life stages of the African catfish and is a method more sensitive than histological parameters for monitoring genotoxic effects.


Temporal proteomic analysis reveals continuous impairment of intestinal development in neonatal piglets with intrauterine growth restriction.
Efficiency of nutrient utilization is reduced in neonates with intrauterine growth restriction (IUGR) compared with those with a normal birth weight (NBW). However, the underlying mechanisms are largely unknown. In this study, we applied temporal proteomic approach, coupled with histological and biochemical analyses, to study dynamic changes of the proteome in the small intestinal mucosa of IUGR piglets during the nursing period (Days 1, 7 and 21). We identified 56 differentially expressed protein spots between IUGR and NBW piglets. These proteins participate in key biological processes, including (1) absorption, digestion and transport of nutrients; (2) cell structure and motility; (3) glucose and energy metabolism; (4) lipid metabolism; (5) amino acid metabolism; (6) mineral and vitamin metabolism; (7) cellular redox homeostasis; (8) stress response; and (9) apoptosis. The results of our temporal proteomics analysis reveal continuous impairment of intestinal development in neonatal piglets with IUGR. The findings have important implications for understanding metabolic defects in the small intestine of IUGR neonates and are expected to provide new strategies to improve their survival and growth.


Image Captioning for the Visually Impaired and Blind: A Recipe for Low-Resource Languages.
Visually impaired and blind people often face a range of socioeconomic problems that can make it difficult for them to live independently and participate fully in society. Advances in machine learning pave new venues to implement assistive devices for the visually impaired and blind. In this work, we combined image captioning and text-to-speech technologies to create an assistive device for the visually impaired and blind. Our system can provide the user with descriptive auditory feedback in the Kazakh language on a scene acquired in real-time by a head-mounted camera. The image captioning model for the Kazakh language provided satisfactory results in both quantitative metrics and subjective evaluation. Finally, experiments with a visually unimpaired blindfolded participant demonstrated the feasibility of our approach.


Biosynthesis of carnitine and 4-N-trimethylaminobutyrate from 6-N-trimethyl-lysine.
The conversion of 6-N-[Me-(14)C]trimethyl-lysine into carnitine and 4-N-trimethylaminobutyrate (butyrobetaine) was demonstrated in rats kept on a lysine-deficient diet. After the rats were given [(14)C]trimethyl-lysine for 4 days, a total of 17% of the injected label was recovered as carnitine from carcass and urine extracts. Another 8% of the trimethyl-lysine label was converted into 4-N-trimethylaminobutyrate, most of which was recovered from the urine. The conversion of trimethyl-lysine into the above two metabolites supports the pathway of carnitine biosynthesis as lysine+methionine --> 6-N-trimethyl-lysine --> 4-N-trimethylaminobutyrate --> carnitine. In addition, three other metabolites representing 2% of the injected dose were recovered. Only an insignificant portion of the label was recovered as free trimethyl-lysine from the carcass, whereas 22% of the injected label was recovered in the urine. A relatively low specific radioactivity in carnitine was found when 5-N-[Me-(14)C]trimethylaminopentanoate and 6-N-[Me-(14)C]trimethylaminohexanoate were administered to rats in amounts similar to the [(14)C]trimethyl-lysine, suggesting that they were not free intermediates.


Perforated Concave Earplug (pCEP): A Proof-of-Concept Earplug to Improve Sound Localization without Compromising Noise Attenuation.
Combat soldiers are currently faced with using a hearing-protection device (HPD) at the cost of adequately detecting critical signals impacting mission success. The current study tested the performance of the Perforated-Concave-Earplug (pCEP), a proof-of-concept passive HPD consisting of a concave bowl-like rigid structure attached to a commercial roll-down earplug, designed to improve sound localization with minimal compromising of noise attenuation. Primarily intended for combat/military training settings, our aim was an evaluation of localization of relevant sound sources (single/multiple gunfire, continuous noise, spoken word) compared to 3M™-Combat-Arms™4.1 earplugs in open-mode and 3M™-E-A-R™-Classic™ earplugs. Ninety normal-hearing participants, aged 20-35 years, were asked to localize stimuli delivered from monitors evenly distributed around them in no-HPD and with-HPD conditions. The results showed (1) localization abilities worsened using HPDs; (2) the spoken word was localized less accurately than other stimuli; (3) mean root mean square errors (RMSEs) were largest for stimuli emanating from rear monitors; and (4) localization abilities corresponded to HPD attenuation levels (largest attenuation and mean RMSE: 3M™-E-A-R™-Classic™; smallest attenuation and mean RMSE: 3M™-Combat-Arms™4.1; pCEP was mid-range on both). These findings suggest that the pCEP may benefit in military settings by providing improved sound localization relative to 3M™ E-A-R™-Classic™ and higher attenuation relative to 3M™-Combat Arms™-4.1, recommending its use in noisy environments.


Exploring evidence for behavioral risk compensation among participants in an HIV vaccine clinical trial.
HIV vaccine trial participants may engage in behavioral risk compensation due to a false sense of protection. We conducted an ancillary study of an HIV Vaccine Trials Network (HVTN) vaccine efficacy trial to explore risk compensation among trial participants compared to persons who were willing to participate but ineligible based on previous exposure to the Ad5 virus (Ad5+) across three timepoints. Participants were drawn from the Atlanta, GA site of the HVTN 505 vaccine trial. From 2011-2013, all persons who met prescreening criteria for the clinical trial and presented for Ad5 antibody testing were invited to participate in the ancillary study. Data were collected from vaccine trial participants (n=51) and Ad5+ participants (n=60) via online surveys across three timepoints: baseline, T2 (after trial participants received 2/4 injections) and T3 (after trial participants received 4/4 injections). Data analyses assessed demographic, psychosocial, and behavioral differences at baseline and changes at each timepoint. At baseline, Ad5+ participants were less likely to have some college education (p=0.024) or health insurance (p=0.008), and were more likely to want to participate in the vaccine trial "to feel safer having unprotected sex" (p=0.005). Among vaccine trial participants, unprotected anal sex with a casual partner (p=0.05), HIV transmission worry (p=0.033), and perceived chance of getting HIV (p=0.027), decreased across timepoints. Study findings suggest that persons with previous exposure to Ad5 may be systematically different from their Ad5-negative peers. Unprotected anal sex with a casual partner significantly decreased among HIV vaccine trial participants, as did HIV worry and perceived chance of getting HIV. Findings did not support evidence of risk compensation among HIV vaccine trial participants compared to Ad5+ participants.


Ten-armed fossil cephalopod from the Pennsylvanian of Illinois.
Jeletzkya douglassae Johnson and Richardson is described as the oldest known representative of an extant squid group. The species is known from a single specimen from the Middle Pennsylvanian of Illinois. This very unusual fossil consists of the complete tentacular crown and a fragile shell. The arms bear hooks in double rows.


Peromyscus mice as a model for studying natural variation.
The deer mouse (genus Peromyscus) is the most abundant mammal in North America, and it occupies almost every type of terrestrial habitat. It is not surprising therefore that the natural history of Peromyscus is among the best studied of any small mammal. For decades, the deer mouse has contributed to our understanding of population genetics, disease ecology, longevity, endocrinology and behavior. Over a century's worth of detailed descriptive studies of Peromyscus in the wild, coupled with emerging genetic and genomic techniques, have now positioned these mice as model organisms for the study of natural variation and adaptation. Recent work, combining field observations and laboratory experiments, has lead to exciting advances in a number of fields-from evolution and genetics, to physiology and neurobiology.


Antipsychotics for delirium in the general hospital setting in consecutive 2453 inpatients: a prospective observational study.
Attention to risk of antipsychotics for older patients with delirium has been paid. A clinical question was whether risk of antipsychotics for older patients with delirium would exceed efficacy of those even in the general hospital setting. A prospective observational study proceeded over a 1-year period at 33 general hospitals, where at least one psychiatrist worked full time. Subjects were patients who developed delirium during their admission due to acute somatic diseases or surgery, and who received antipsychotics for delirium. The primary outcome was rates and kinds of serious adverse events. Among 2834 patients who developed delirium, 2453 patients received antipsychotics, such as risperidone (34%), quetiapine (32%), and parenteral haloperidol (20%), for delirium. Out of 2453 patients, 22 serious adverse events (0.9%) were reported. Aspiration pneumonia was the most frequent (17 patients, 0.7%), followed by cardiovascular events (4 patients, 0.2%) and venous thromboembolism (1 patient, 0.0%). There was no patient with a fracture or intracranial injury due to a fall. No one died because of antipsychotic side effects. The mean Clinical Global Impressions-Improvement Scale score was 2.02 (SD 1.09). Delirium was resolved within 1 week in more than half of the patients (54%). In the general hospital setting under management including fine dosage adjustment and early detection of side effects, risk of antipsychotics for older patients with delirium might be low, in contrast to antipsychotics for dementia in the nursing home or outpatient settings. A point may be not how to avoid using antipsychotics but how to monitor their risk.


Improving the visualization of cryo-EM density reconstructions.
Cryo-electron microscopy yields 3D density maps of macromolecules from single-particle images, tomograms, or 2D crystals. An optimal visualization of the density map is important for its proper interpretation. We have developed a method to improve the visualization of density maps by using general statistical information about proteins for the sharpening process. In particular, the packing density of atoms is highly similar between different proteins, which allows for building a pseudo-atomic model to approximate the true mass distribution. From this model the radial structure factor and density value histogram are estimated and applied as constraints to the 3D reconstruction in reciprocal- and real-space, respectively. Interestingly, similar improvements are obtained when using the correct radial structure factor and density value histogram from a crystal structure. Thus, the estimated pseudo-atomic model yields a sufficiently accurate mass distribution to optimally sharpen a density map.


Whole Exome Sequencing Reveals Homozygous Mutations in RAI1, OTOF, and SLC26A4 Genes Associated with Nonsyndromic Hearing Loss in Altaian Families (South Siberia).
Hearing loss (HL) is one of the most common sensorineural disorders and several dozen genes contribute to its pathogenesis. Establishing a genetic diagnosis of HL is of great importance for clinical evaluation of deaf patients and for estimating recurrence risks for their families. Efforts to identify genes responsible for HL have been challenged by high genetic heterogeneity and different ethnic-specific prevalence of inherited deafness. Here we present the utility of whole exome sequencing (WES) for identifying candidate causal variants for previously unexplained nonsyndromic HL of seven patients from four unrelated Altaian families (the Altai Republic, South Siberia). The WES analysis revealed homozygous missense mutations in three genes associated with HL. Mutation c.2168A>G (SLC26A4) was found in one family, a novel mutation c.1111G>C (OTOF) was revealed in another family, and mutation c.5254G>A (RAI1) was found in two families. Sanger sequencing was applied for screening of identified variants in an ethnically diverse cohort of other patients with HL (n = 116) and in Altaian controls (n = 120). Identified variants were found only in patients of Altaian ethnicity (n = 93). Several lines of evidences support the association of homozygosity for discovered variants c.5254G>A (RAI1), c.1111C>G (OTOF), and c.2168A>G (SLC26A4) with HL in Altaian patients. Local prevalence of identified variants implies possible founder effect in significant number of HL cases in indigenous population of the Altai region. Notably, this is the first reported instance of patients with RAI1 missense mutation whose HL is not accompanied by specific traits typical for Smith-Magenis syndrome. Presumed association of RAI1 gene variant c.5254G>A with isolated HL needs to be proved by further experimental studies.


Parameters of humoral and cellular immunity following vaccination of pigs with a European modified-live strain of porcine reproductive and respiratory syndrome virus (PRRSV).
Parameters of humoral and cellular immunity were investigated in pigs experimentally infected with a modified-live European porcine reproductive and respiratory syndrome virus (PRRSV, strain DV). PRRSV was detected by real-time RT-PCR and PRRSV-specific antibodies by a commercial ELISA test-kit, respectively. Interleukins IL-1alpha, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF-alpha) and interferon-gamma (IFN-gamma) as well as IL-2 receptor (IL-2R) were quantified at mRNA level using RT-PCR. Subpopulations of blood lymphocytes were assayed using flow cytometry. No significant changes neither in cytokine expression nor in shifts of CD4 and CD8 markers could be found, but similar curve diagrams concerning CD8 single positive T cells could be observed in all vaccinated animals with an initial decrease and an increase between post-infection days (PIDs) 7 and 14. In the vaccination group, TNF-alpha and IL-6 tended to be increased at PIDs 22 and 40, whereas no increase could be seen in IFN-gamma. When comparing the in vivo immune response to that being seen in in vitro experiments, similar shifts of CD4/CD8 lymphocyte subpopulations may be seen. Cytokine curve diagrams, however, do not reflect the in vitro findings to that extent.


Disclosing and Reporting of Consent Violations Among Kink Practitioners in the United States.
Kink practitioners are marginalized and experience adverse health and social outcomes, which are exacerbated by consent violations. This study aims to understand experiences of reporting consent violations within a kink context. Kink practitioners (N = 2,888) completed a survey focused on consent violations, reporting, and recommendations, with 767 (25.56%) of them reporting consent violations in the kink context. The type of consent violation (sexual assault or kink-related behaviors), disclosure, and reporting significantly differed based on gender, sexual orientation, and injury status, but not age. Additionally, recommended steps included avoidance of police and others in positions of power and increased accountability.


First hominine remains from a ~1.0 million year old bone bed at Cornelia-Uitzoek, Free State Province, South Africa.
We report here on evidence of early Homo around 1.0 Ma (millions of years ago) in the central plains of southern Africa. The human material, a first upper molar, was discovered during the systematic excavation of a densely-packed bone bed in the basal part of the sedimentary sequence at the Cornelia-Uitzoek fossil vertebrate locality. We dated this sequence by palaeomagnetism and correlated the bone bed to the Jaramillo subchron, between 1.07 and 0.99 Ma. This makes the specimen the oldest southern African hominine remains outside the dolomitic karst landscapes of northern South Africa. Cornelia-Uitzoek is the type locality of the Cornelian Land Mammal Age. The fauna contains an archaic component, reflecting previous biogeographic links with East Africa, and a derived component, suggesting incipient southern endemism. The bone bed is considered to be the result of the bone collecting behaviour of a large predator, possibly spotted hyaenas. Acheulian artefacts are found in small numbers within the bone bed among the fossil vertebrates, reflecting the penecontemporaneous presence of people in the immediate vicinity of the occurrence. The hominine tooth was recovered from the central, deeper part of the bone bed. In size, it clusters with southern African early Homo and it is also morphologically similar. We propose that the early Homo specimen forms part of an archaic component in the fauna, in parallel with the other archaic faunal elements at Uitzoek. This supports an emergent pattern of archaic survivors in the southern landscape at this time, but also demonstrates the presence of early Homo in the central plains of southern Africa, beyond the dolomitic karst areas.


Efficient Dynamic Correspondence Network.
We tackle the problem of establishing dense correspondences between a pair of images in an efficient way. Most existing dense matching methods use 4D convolutions to filter incorrect matches, but 4D convolutions are highly inefficient due to their quadratic complexity. Besides, these methods learn features with fixed convolutions which cannot make learnt features robust to different challenge scenarios. To deal with these issues, we propose an Efficient Dynamic Correspondence Network (EDCNet) by jointly equipping preseparate convolution (Psconv) and dynamic convolution (Dyconv) to establish dense correspondences in a coarse-to-fine manner. The proposed EDCNet enjoys several merits. First, two welldesigned modules including a neighbourhood aggregation (NA) module and a dynamic feature learning (DFL) module are combined elegantly in the coarse-to-fine architecture, which is efficient and effective to establish both reliable and accurate correspondences. Second, the proposed NA module maintains linear complexity, showing its high efficiency. And our proposed DFL module has better flexibility to learn features robust to different challenges. Extensive experimental results show that our algorithm performs favorably against state-of-the-art methods on three challenging datasets including HPatches, Aachen Day-Night and InLoc.


Evaluation of Staphylococcal Bacteriophage Sb-1 as an Adjunctive Agent to Antibiotics Against Rifampin-Resistant Staphylococcus aureus Biofilms.
Rifampin plays a crucial role in the treatment of staphylococcal implant-associated infection, as it is the only antibiotic capable of eradicating Staphylococcus aureus biofilms. However, the emergence of rifampin resistance strongly limits its use. Combinatorial therapy of antibiotics and bacteriophages may represent a strategy to overcome the resistance. Here, we evaluated the activity of staphylococcal bacteriophage Sb-1 in combination with different antibiotics against the biofilms of 10 rifampin-resistant S. aureus clinical strains, including MRSA and MSSA. S. aureus biofilms formed on porous glass beads were exposed to antibiotics alone or combined with Sb-1 simultaneously or staggered (first Sb-1 for 24 h followed by antibiotic). Recovered bacteria were detected by measuring growth-related heat production at 37°C (isothermal microcalorimetry) and the biofilm eradication was assessed by sonication of beads and plating of the resulting sonication fluid. Minimum biofilm eradication concentration (MBEC) was defined as the lowest concentration of antibiotic required to kill all adherent bacteria, resulting in absence of growth after plating the sonication fluid. Tested antibiotics presented high MBEC values when administered alone (64 to > 1,024 μg/ml). The simultaneous or staggered combination of Sb-1 with daptomycin showed the highest activity against all MRSA biofilms, whereas the exposure to Sb-1 with vancomycin showed no improved anti-biofilm activity. Staggered administration of Sb-1 and flucloxacillin, cefazolin, or fosfomycin improved the antibiofilm activity in four out of six MSSA, whereas simultaneous exposure exhibited similar or lesser synergy. In conclusion, the combinatorial effect of Sb-1 and antibiotics enabled to eradicate rifampin-resistant S. aureus biofilms in vitro.


Intermittent hypoxia activates temporally coordinated transcriptional programs in visceral adipose tissue.
Obstructive sleep apnea (OSA) is a prevalent disorder characterized by intermittent hypoxia (IH) during sleep. OSA is strongly associated with obesity and dysregulation of metabolism-yet the molecular pathways linking the effects of IH on adipocyte biology remain unknown. We hypothesized that exposure to IH would activate distinct, time-dependent transcriptional programs in visceral adipose tissue of mice. We exposed 36 mice to IH or normoxia for up to 13 days. We transcriptionally profiled visceral fat tissue harvested from the animals and performed functional enrichment and network analysis on differentially expressed genes. We identified over 3,000 genes with significant expression patterns during the time course of IH exposure. The most enriched pathways mapped to metabolic processes, mitochondrion, and oxidative stress responses. We confirmed the pathophysiological relevance of these findings by demonstrating that mice exposed to chronic IH developed dyslipidemia and underwent significant lipid and protein oxidation within their visceral adipose depots. We applied gene-gene interaction network analysis to identify critical controllers of IH-induced transcriptional programs in adipocytes-these network hubs represent putative targets to modulate the effects of chronic IH on adipose tissue. Our approach to integrate computational methods with gene expression profiling of visceral fat tissue during IH exposure shows promise in helping unravel the mechanistic links between OSA and adipocyte biology.


The Translational Repressor 4E-BP1 Contributes to Diabetes-Induced Visual Dysfunction.
The translational repressor 4E-BP1 interacts with the mRNA cap-binding protein eIF4E and thereby promotes cap-independent translation of mRNAs encoding proteins that contribute to diabetic retinopathy. Interaction of 4E-BP1 with eIF4E is enhanced in the retina of diabetic rodents, at least in part, as a result of elevated 4E-BP1 protein expression. In the present study, we examined the role of 4E-BP1 in diabetes-induced visual dysfunction, as well as the mechanism whereby hyperglycemia promotes 4E-BP1 expression. Nondiabetic and diabetic wild-type and 4E-BP1/2 knockout mice were evaluated for visual function using a virtual optomotor test (Optomotry). Retinas were harvested from nondiabetic and type 1 diabetic mice and analyzed for protein abundance and posttranslational modifications. Similar analyses were performed on cells in culture exposed to hyperglycemic conditions or an O-GlcNAcase inhibitor (Thiamet G [TMG]). Diabetes-induced visual dysfunction was delayed in mice deficient of 4E-BP1/2 as compared to controls. 4E-BP1 protein expression was enhanced by hyperglycemia in the retina of diabetic rodents and by hyperglycemic conditions in retinal cells in culture. A similar elevation in 4E-BP1 expression was observed with TMG. The rate of 4E-BP1 degradation was significantly prolonged by either hyperglycemic conditions or TMG. A PEST motif in the C-terminus of 4E-BP1 regulated polyubiquitination, turnover, and binding of an E3 ubiquitin ligase complex containing CUL3. The findings support a model whereby elevated 4E-BP1 expression observed in the retina of diabetic rodents is the result of O-GlcNAcylation of 4E-BP1 within its PEST motif.


[Role of lymphofluoroscopy in the management of lymphedema].
The lymphatic vascular system is essential for maintaining a healthy balance between interstitial fluid production and transport. Dysregulation of this balance can lead to the formation of lymphedema, a pathology that is disabling and bothersome in the daily lives of the patients. Lymphofluoroscopy is an invaluable tool that provides static and dynamic images of the superficial lymphatic vessels, with diagnostic and therapeutic implications. This diagnostic tool is beginning to take its place in the field of lymphology, as it is minimally invasive and has virtually no side effects.


Occupational health hazards in a prosthodontic practice: review of risk factors and management strategies.
The intent of this article was to analyze the potential hazards and risks involved in persons exposed to prosthodontic practice. These risks include exposure to physical and chemical hazards, dental materials, infectious environment, inappropriate working pattern and psychosocial stress. The potential harm of these hazards and its prevention is highlighted. Prosthodontists, students, dental technicians, and others working in the prosthodontic clinics and laboratory should be aware of the specific risk factors and take measures to prevent and overcome these hazards.


[Arterio-ureteral fistula, report of three cases].
On connection with four cases of arterio-uro-enteric fistula in three patients and after a review of the literature, the authors propose to make light on this extremely rare complication describing aetiologies factors and the diagnostic means and therapeutics. Two patients had had a pelvic exenteration with respectively Bricker and Kock pouch. The third patient had had an anterior resection in block with the right deferent duct and right seminal gland. All three received high doses of radiotherapy. These fistulas had appeared by abundant haemorrhages. The surgical operation in urgency had made it possible to treat these fistulas with success in two patients. The other patient had deceased of cataclysmic haemorrhage.


Sepsis and septic shock.
Sepsis is a common condition that is associated with unacceptably high mortality and, for many of those who survive, long-term morbidity. Increased awareness of the condition resulting from ongoing campaigns and the evidence arising from research in the past 10 years have increased understanding of this problem among clinicians and lay people, and have led to improved outcomes. The World Health Assembly and WHO made sepsis a global health priority in 2017 and have adopted a resolution to improve the prevention, diagnosis, and management of sepsis. In 2016, a new definition of sepsis (Sepsis-3) was developed. Sepsis is now defined as infection with organ dysfunction. This definition codifies organ dysfunction using the Sequential Organ Failure Assessment score. Ongoing research aims to improve definition of patient populations to allow for individualised management strategies matched to a patient's molecular and biochemical profile. The search continues for improved diagnostic techniques that can facilitate this aim, and for a pharmacological agent that can improve outcomes by modifying the disease process. While waiting for this goal to be achieved, improved basic care driven by education and quality-improvement programmes offers the best hope of increasing favourable outcomes.


Effector proteins for methylated histones: an expanding family.
Methylation of histone lysine residues in eukaryotic chromatin has been an exciting area of research ever since the first histone methyltransferase enzyme, Suv39h, was found to methylate lysine 9 of histone H3 in 2000. Only a year later, the HP1 chromodomain polypeptide was identified as a recognition module for this histone modification. Similar to bromodomain-containing proteins that recognize histone acetylation sites and subsequently stabilize large complexes to chromatin, effector proteins can also be recruited and stabilized by histone methylation. Although histone acetylation generally correlates with active transcription, histone methylation is associated with both the activation and silencing of transcription, depending on which lysine residue is modified. The list of proteins that may in fact directly associate with specific methylated histone lysines is expanding. Since the finding of HP1, many additional proteins have been shown to bind methylated histone residues. For instance, Polycomb, Chd1, 53BP1, and Crb2/Rad9 proteins all associate with methylated chromatin in a unique manner governed by their respective recognition motifs. Here we highlight recent data on the recognition specificity and biological significance of proteins that associate with methylated histone lysines.


Onchocerciasis in Gilgel Ghibe River Valley southwest Ethiopia.
To determine the prevalence of onchocerciasis and the entomological transmission indices such as the parous rate and annual transmission potential (ATP). Gilgel Ghibe village, Gilgel Ghibe River Valley Southwest Ethiopia between April 1994 and March 1995. Two hundred twenty eight subjects of the total 400 population in Gilgel Ghibe village were subjected to parasitological and clinical examinations. Two skin snips per person were taken and examined for microfilariae of Onchocerca volvulus. Fly collections were done from dawn to dusk from human baits seated in pairs at four representative sites at the river bank and away from the river bank. Flies were dissected for parity and infections with O. volvulus larvae. Among the 228 people examined, the prevalence of the disease was low (17%), being higher in males (19%) than in females (14%). The geometric mean of microfilarial density was 11.1 (range, 1-132) mf per skin snip. Itching followed by pigmentary changes were the most common clinical signs and symptoms. The predominant anthropophilic blackfly species was Simulium (Edwardsellum) damnosum s.l. The annual parous rate and ATP were 74.7% and 1669.5, respectively, being higher at the river bank than at sites further away suggesting a greater risk of infection by the river side. The low prevalence of onchocerciasis in Gilgel Ghibe area vis-a-vis the high ATP level could be due to the possible presence of bovine onchocerciasis in the area. Further studies employing molecular techniques are thus required to identify O. volvulus from other filariae in flies.


PLETHORA gradient formation mechanism separates auxin responses.
During plant growth, dividing cells in meristems must coordinate transitions from division to expansion and differentiation, thus generating three distinct developmental zones: the meristem, elongation zone and differentiation zone. Simultaneously, plants display tropisms, rapid adjustments of their direction of growth to adapt to environmental conditions. It is unclear how stable zonation is maintained during transient adjustments in growth direction. In Arabidopsis roots, many aspects of zonation are controlled by the phytohormone auxin and auxin-induced PLETHORA (PLT) transcription factors, both of which display a graded distribution with a maximum near the root tip. In addition, auxin is also pivotal for tropic responses. Here, using an iterative experimental and computational approach, we show how an interplay between auxin and PLTs controls zonation and gravitropism. We find that the PLT gradient is not a direct, proportionate readout of the auxin gradient. Rather, prolonged high auxin levels generate a narrow PLT transcription domain from which a gradient of PLT protein is subsequently generated through slow growth dilution and cell-to-cell movement. The resulting PLT levels define the location of developmental zones. In addition to slowly promoting PLT transcription, auxin also rapidly influences division, expansion and differentiation rates. We demonstrate how this specific regulatory design in which auxin cooperates with PLTs through different mechanisms and on different timescales enables both the fast tropic environmental responses and stable zonation dynamics necessary for coordinated cell differentiation.


∆4-3-oxo-5β-reductase deficiency: favorable outcome in 16 patients treated with cholic acid.
Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Δ4-3-oxosteroid 5β-reductase (Δ4-3-oxo-R) deficiency. Sixteen patients with Δ4-3-oxo-R deficiency confirmed by AKR1D1 gene sequencing who received oral cholic acid were retrospectively analyzed. First symptoms were reported early in life (median 2 months of age), with 14 and 3 patients having cholestatic jaundice and severe bleeding respectively. Fifteen patients received ursodeoxycholic acid before diagnosis, with partial improvement in 8 patients. Four patients had liver failure at the time of cholic acid initiation. All 16 patients received cholic acid from a median age of 8.1 months (range 3.1-159) and serum liver tests normalized in all within 6-12 months of treatment. After a median cholic acid therapy of 4.5 years (range 1.1-24), all patients were alive with their native liver. Median daily cholic acid dose at last follow-up was 8.3 mg/kg of body weight. All patients, but one, had normal physical examination and all had normal serum liver tests. Fibrosis, evaluated using liver biopsy (n = 4) or liver elastography (n = 9), had stabilized or improved. Cholic acid therapy enabled a 12-fold decrease of 3-oxo-∆4 derivatives in urine. Patients had normal growth and quality of life. The treatment was well tolerated without serious adverse events and signs of hepatotoxicity. Oral cholic acid therapy is a safe and effective treatment for patients with Δ4-3-oxo-R deficiency.


On the stability of shared near neighbor clustering.
This correspondence concentrates on the detection of stable clustering results when using the nonparmetric clustering technique of Jarvis and Patrick. This technique incorporates the concept of similarity based on sharing of near neighbors. Essentially, in this clustering scheme, two parameters are involved: neighborhood depth and similarity threshold. Combining a penalty for chaining with the detection of so-called hierarchical stable solutions in the field of all possible solutions, due to the setting of the two parameters, is experimentally shown to provide a powerful method for discriminating between reliable and unreliable results.


Evaluation of wrought Zn-Al alloys (1, 3, and 5 wt % Al) through mechanical and in vivo testing for stent applications.
Special high grade zinc and wrought zinc-aluminum (Zn-Al) alloys containing up to 5.5 wt % Al were processed, characterized, and implanted in rats in search of a new family of alloys with possible applications as bioabsorbable endovascular stents. These materials retained roll-induced texture with an anisotropic distribution of the second-phase Al precipitates following hot-rolling, and changes in lattice parameters were observed with respect to Al content. Mechanical properties for the alloys fell roughly in line with strength (190-240 MPa yield strength; 220-300 MPa ultimate tensile strength) and elongation (15-30%) benchmarks, and favorable elastic ranges (0.19-0.27%) were observed. Intergranular corrosion was observed during residence of Zn-Al alloys in the murine aorta, suggesting a different corrosion mechanism than that of pure zinc. This mode of failure needs to be avoided for stent applications because the intergranular corrosion caused cracking and fragmentation of the implants, although the composition of corrosion products was roughly identical between non- and Al-containing materials. In spite of differences in corrosion mechanisms, the cross-sectional reduction of metals in murine aorta was nearly identical at 30-40% and 40-50% after 4.5 and 6 months, respectively, for pure Zn and Zn-Al alloys. Histopathological analysis and evaluation of arterial tissue compatibility around Zn-Al alloys failed to identify areas of necrosis, though both chronic and acute inflammatory indications were present. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 245-258, 2018.


Efficacy of the Olyset Duo net against insecticide-resistant mosquito vectors of malaria.
Olyset Duo is a new long-lasting insecticidal net treated with permethrin (a pyrethroid) and pyriproxyfen, an insect growth regulator that disrupts the maturation of oocytes in mosquitoes exposed to the net. We tested the Olyset Duo net against pyrethroid-resistant Anopheles gambiae mosquitoes, which transmit malaria parasites, in laboratory bioassays and in a trial in Benin using experimental huts that closely resemble local habitations. Host-seeking mosquitoes that entered to feed were free to contact the occupied nets and were collected the next morning from exit traps. Surviving blood-fed mosquitoes were observed for effects on reproduction. Control nets were treated with pyrethroid only or pyriproxyfen only, and nets were tested unwashed and after 20 standardized washes. The Olyset Duo net showed improved efficacy and wash resistance relative to the pyrethroid-treated net in terms of mosquito mortality and prevention of blood feeding. The production of offspring among surviving blood-fed A. gambiae in the hut trial was reduced by the pyriproxyfen-treated net and the Olyset Duo net both before washing (90 and 71% reduction, respectively) and after washing (38 and 43% reduction, respectively). The degree of reproductive suppression in the hut trial was predicted by laboratory tunnel tests but not by cone bioassays. The overall reduction in reproductive rate of A. gambiae with the Olyset Duo net in the trial was 94% with no washing and 78% after 20 washes. The Olyset Duo net has the potential to provide community control of mosquito populations and reduce malaria transmission in areas of high insecticide resistance.


Accommodating religious beliefs in the ICU: a narrative account of a disputed death.
Despite widespread acceptance in the United States of neurological criteria to determine death, clinicians encounter families who object, often on religious grounds, to the categorization of their loved ones as "brain dead." The concept of "reasonable accommodation" of objections to brain death, promulgated in both state statutes and the bioethics literature, suggests the possibility of compromise between the family's deeply held beliefs and the legal, professional and moral values otherwise directing clinicians to withdraw medical interventions. Relying on narrative to convey the experience of a family and clinical caregivers embroiled in this complex dilemma, the case analyzed here explores the practical challenges and moral ambiguities presented by the concept of reasonable accommodation. Clarifying the term's meaning and boundaries, and identifying guidelines for its clinical implementation, could help to reduce uncertainty for both health care professionals and families and, thereby, the incremental moral distress such uncertainty creates.


Strain-specific differences in Neisseria gonorrhoeae associated with the phase variable gene repertoire.
There are several differences associated with the behaviour of the four main experimental Neisseria gonorrhoeae strains, FA1090, FA19, MS11, and F62. Although there is data concerning the gene complements of these strains, the reasons for the behavioural differences are currently unknown. Phase variation is a mechanism that occurs commonly within the Neisseria spp. and leads to switching of genes ON and OFF. This mechanism may provide a means for strains to express different combinations of genes, and differences in the strain-specific repertoire of phase variable genes may underlie the strain differences. By genome comparison of the four publicly available neisserial genomes a revised list of 64 genes was created that have the potential to be phase variable in N. gonorrhoeae, excluding the opa and pilC genes. Amplification and sequencing of the repeat-containing regions of these genes allowed determination of the presence of the potentially unstable repeats and the ON/OFF expression state of these genes. 35 of the 64 genes show differences in the composition or length of the repeats, of which 28 are likely to be associated with phase variation. Two genes were expressed differentially between strains causing disseminated infection and uncomplicated gonorrhoea. Further study of one of these in a range of clinical isolates showed this association to be due to sample size and is not maintained in a larger sample. The results provide us with more evidence as to which genes identified through comparative genomics are indeed phase variable. The study indicates that there are large differences between these four N. gonorrhoeae strains in terms of gene expression during in vitro growth. It does not, however, identify any clear patterns by which previously reported behavioural differences can be correlated with the phase variable gene repertoire.


[Alcohol drinking-related disorders in 1901 patients treated at Taubaté's Municipal Emergency room in 2000: a contribution to sociocentric education in neurology].
Medical education must focus prevalent themes in communities; alcohol consumption is one of these themes. Our objective was to determine the frequency of the alcohol consumption related disorders and verify if a patient had more than one disease diagnosed, contributing to sociocentric education. It was a transversal retrospective study made by collection of medical records that had any reference to alcohol in a emergency room in 2000 (1901 cases). Alcohol direct effects were found in 80.38% of the patients, trauma in 28.56%, digestive and/or metabolic diseases in 27%, infections in 6.42% and nutritional disorders in 5.94%. Only one diagnosis was attributed in 46.6% of the cases and more than one in 48.67%. The most frequent disturbs were: intoxication, abstinence syndrome, gastritis, cirrhosis, dehydration, low or high glucose levels and trauma. Alcohol related disturbances are frequent and often associated; thus, alcohol abuse is an important content in a medical education.


Uniformity of stratum-ventilated thermal environment and thermal sensation.
Three human test series were conducted to evaluate the uniformity of the thermal environments in a stratum-ventilated chamber with dimensions of 8.8 m (L) × 5.1 m (W) × 2.4 m (H). In all, nineteen conditions were generated by adjusting the room temperature, supply airflow rate, and supply terminal type. An air diffuser performance index (ADPI) of at least 80% was achieved for most cases. This result shows that the air velocity and temperature in the occupied zone are reasonably uniform. Subjective assessments using the ASHRAE 7-point scale indicate that the thermal sensations of the subjects in stratum ventilation are also uniform. This study examines the applicability of the predicted mean vote (PMV) model for evaluating stratum ventilation. When compared to the actual mean thermal sensation votes (ATS), the PMV values are acceptable. The PMV results at a height of 1.1 m above the floor show better agreement with the ATS than at a height of 0.1 m.


Selection of highly informative and user-friendly microsatellites (SSRs) for genotyping of cultivated potato.
Characterization of nearly 1,000 cultivated potato accessions with simple sequence repeats (SSRs; also referred to as microsatellites) has allowed the identification of a reference set of SSR markers for accurate and efficient genotyping. In addition, 31 SSRs are reported here for a potato genetic map, including new map locations for 24 of them. A first criterion for this proposed reference set was ubiquity of the SSRs in the eight landrace cultivar groups of the potato, Solanum tuberosum. All SSRs tested in the present study displayed the same allele phenotypes and allele size range in the diverse germplasm set as in the advanced potato cultivar germplasm in which they were originally discovered. Thirteen of 13 SSR products from all cultivar groups are shown to cross-hybridize with the corresponding SSR product of the source cultivar to ascertain sequence homology. Other important SSR selection criteria are quality of amplification products, locus complexity, polymorphic index content, and well-dispersed location on a potato genetic map. Screening of 156 SSRs allowed the identification of a highly informative and user-friendly set comprising 18 SSR markers for use in characterization of potato genetic resources. In addition, we have identified true- and pseudo-multiplexing SSRs for even greater efficiency.