Downregulating Aberrant Motor Evoked Potential Synergies of the Lower Extremity Post Stroke During TMS of the Contralesional Hemisphere.
Growing evidence demonstrates unique synergistic signatures in the lower limb (LL) post-stroke, with specific across-plane and across-joint representations. While the inhibitory role of the ipsilateral hemisphere in the upper limb (UL) has been widely reported, examination of the contralesional hemisphere (CON-H) in modulating LL expressions of synergies following stroke is lacking. We hypothesize that stimulation of lesioned and contralesional motor cortices will differentially regulate paretic LL motor outflow. We propose a novel TMS paradigm to identify synergistic motor evoked potential (MEP) patterns across multiple muscles. Amplitude and background activation matched adductor MEPs were elicited using single pulse TMS of L-H and CON-H (control ipsilateral) during an adductor torque matching task from 11 stroke and 10 control participants. Associated MEPs of key synergistic muscles were simultaneously observed. By quantifying CON-H/L-H MEP ratios, we characterized a significant targeted inhibition of aberrant MEP coupling between ADD and VM (p = 0.0078) and VL (p = 0.047) exclusive to the stroke group (p = 0.028) that was muscle dependent (p = 0.039). We find TA inhibition in both groups following ipsilateral hemisphere stimulation (p = 0.0014; p = 0.015). We argue that ipsilaterally mediated attenuation of abnormal synergistic activations post stroke may reflect an adaptive intracortical inhibition. The predominance of sub 3ms interhemispheric MEP latency differences implicates LL ipsilateral corticomotor projections. These findings provide insight into the association between CON-H reorganization and post-stroke LL recovery. While a prevailing view of driving L-H disinhibition for UL recovery seems expedient, presuming analogous LL neuromodulation may require further examination for rehabilitation. This study provides a step toward this goal.


Psychiatric emergencies (part I): psychiatric disorders causing organic symptoms.
Psychiatric emergencies are conditions that mostly destabilize the already frenetic activity of the Emergency Department. Sometimes the emergency is clearly referable to primitive psychiatric illness. Other times, psychiatric and organic symptoms can independently coexist (comorbidity), or develop together in different conditions of substance abuse, including alcohol and prescription drugs. Differentiating between substance induced and pre-existing psychiatric disorder (dual diagnosis) may be difficult, other than controversial issue. Finally, an organic disease can hide behind a psychiatric disorder (pseudopsychiatric emergency). In this review (part I), psychiatric disorders that occur with organic symptoms are discussed. They include: (1) anxiety, conversion and psychosomatic disorders, and (2) simulated diseases. The physiologic mechanisms of the stress reaction, divided into a dual neuro-hormonal response, are reviewed in this section: (1) activation of the sympathetic nervous system and adrenal medulla with catecholamine production (rapid response), and (2) activation of the hypothalamic-pituitary-adrenal axis with cortisol production (slow response). The concept of the fight-or-flight response, its adaptive significance and the potential evolution in paralyzing response, well showing by Yerkes-Dodson curve, is explained. Abnormal short- and long-term reactions to stress evolving toward well codified cluster of trauma and stressor-related disorders, including acute stress disorder, adjustment disorder and post-traumatic stress disorder, are examined. A brief review of major psychiatric disorder and related behaviour abnormalities, vegetative symptoms and cognitive impairment, according to DMS IV-TR classification, are described. Finally, the reactive psychic symptoms and behavioral responses to acute or chronic organic disease, so called "somatopsychic disorders", commonly occurring in elderly and pediatric patients, are presented. The specific conditions of post-operative and intensive care unit patients, and cancer and HIV positive population are emphasized.


Prediction of the severity of aortic stenosis by Doppler aortic valve area determination: prospective Doppler-catheterization correlation in 100 patients.
Two-dimensional and Doppler echocardiography was performed prospectively in 100 patients with aortic stenosis who were undergoing clinically indicated cardiac catheterization. The purpose of this study procedure was to determine various Doppler variables predictive of the severity of aortic stenosis and to compare Doppler- and catheterization-derived aortic valve areas. Doppler-derived mean gradient correlated well with corresponding gradient by catheterization (r = 0.86). Peak Doppler aortic flow velocity greater than or equal to 4.5 m/s and Doppler-derived mean aortic gradient greater than or equal to 50 mm Hg were specific (93 and 94%, respectively) for severe aortic stenosis (defined as catheterization-derived aortic valve area less than or equal to 0.75 cm2) but were not sensitive (44 and 48%, respectively). Doppler-derived aortic valve area calculated by the continuity equation correlated well with catheterization-derived aortic valve area calculated by the Gorlin equation when either the time-velocity integral ratio (r = 0.83) or the peak flow velocity ratio (r = 0.80) between the left ventricular outflow tract and the aortic valve was used in the continuity equation. A velocity ratio of less than or equal to 0.25 alone was sensitive (92%) in detecting severe aortic stenosis. Therefore, use of various Doppler-derived values allows reliable noninvasive estimation of the severity of aortic stenosis.


Where is God in my dying? A qualitative investigation of faith reflections among hospice patients in a secularized society.
Despite increased focus on the role of spiritual care in palliative care, there is limited knowledge about spirituality/religiosity among dying patients in secularized cultures such as Denmark. This study aims through semi-structured interviews with Danish hospice patients and participant observation to elucidate how hospice patients reflect and act upon their potential faith. The results demonstrate three dimensions of faith: (1) "Knowing" (cognition), (2) "doing" (praxis) and (3) "being" (meaning). The article concludes that most patients had a hesitant, but according to their situation, important faith although it was not something they knew much about, let alone discussed or practiced much.


Comparison of two adult mosquito sampling methods with human landing catches in south-central Ethiopia.
The human landing catch (HLC) is the standard reference method for measuring human exposure to mosquito bites. However, HLC is labour-intensive, exposes collectors to infectious mosquito bites and is subjected to collector bias. These necessitate local calibration and application of alternative methods. This study was undertaken to determine the relative sampling efficiency (RSE) of light traps with or without yeast-produced carbon dioxide bait vs. HLC in south-central Ethiopia. The experiment was conducted for 39 nights in a 3 × 3 Latin square randomized design with Anopheles arabiensis as the target species in the period between July and November 2014 in Edo Kontola village, south-central Ethiopia. Center for Disease Control and Prevention light trap catches (LTC) and yeast-generated carbon dioxide-baited light trap catches (CB-LTC) were each evaluated against HLC. The total nightly mosquito catches for each Anopheles species in either method was compared with HLC by Pearson correlation and simple linear regression analysis on log-transformed [log10(x + 1)] values. To test if the RSE of each alternative method was affected by mosquito density, the ratio of the number of mosquitoes in each method to the number of mosquitoes in HLC was plotted against the average mosquito abundance. Overall, 7606 Anopheles females were collected by the three sampling methods. Among these 5228 (68.7%) were Anopheles ziemanni, 1153 (15.2%) An. arabiensis, 883 (11.6%) Anopheles funestus s.l., and 342 (4.5%) Anopheles pharoensis. HLC yielded 3392 (44.6%), CB-LTC 2150 (28.3%), and LTC 2064 (27.1%) Anopheles females. The RSEs of LTC and HLC for An. arabiensis were significantly correlated (p < 0.001) and density independent (p = 0.65). However, for outdoor collection of the same species, RSEs of LTC and CB-LTC were density dependent (p < 0.001). It was estimated that on average, indoor LTC and CB-LTC each caught 0.35 and 0.44 times that of indoor HLC for An. arabiensis respectively. Results showed that HLC was the most efficient method for sampling An. arabiensis. LTC can be used for large-scale indoor An. arabiensis surveillance and monitoring when it is difficult to use HLC. CB-LTC does not substantially improve sampling of this major vector compared to LTC in this setting. Trial registration PACTR201411000882128 (retrospectively registered 8 September, 2014).


Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial.
The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit.


The effect of the dual Src/Abl kinase inhibitor AZD0530 on Philadelphia positive leukaemia cell lines.
Imatinib mesylate, a selective inhibitor of Abl tyrosine kinase, is efficacious in treating chronic myeloid leukaemia (CML) and Ph+ acute lymphoblastic leukaemia (ALL). However, most advanced-phase CML and Ph+ ALL patients relapse on Imatinib therapy. Several mechanisms of refractoriness have been reported, including the activation of the Src-family kinases (SFK). Here, we investigated the biological effect of the new specific dual Src/Abl kinase inhibitor AZD0530 on Ph+ leukaemic cells. Cell lines used included BV173 (CML in myeloid blast crisis), SEM t(4;11), Ba/F3 (IL-3 dependent murine pro B), p185Bcr-Abl infected Ba/F3 cells, p185Bcr-Abl mutant infected Ba/F3 cells, SupB15 (Ph+ ALL) and Imatinib resistant SupB15 (RTSupB15) (Ph+ ALL) cells. Cells were exposed to AZD0530 and Imatinib. Cell proliferation, apoptosis, survival and signalling pathways were assessed by dye exclusion, flow cytometry and Western blotting respectively. AZD0530 specifically inhibited the growth of, and induced apoptosis in CML and Ph+ ALL cells in a dose dependent manner, but showed only marginal effects on Ph- ALL cells. Resistance to Imatinib due to the mutation Y253F in p185Bcr-Abl was overcome by AZD0530. Combination of AZD0530 and Imatinib showed an additive inhibitory effect on the proliferation of CML BV173 cells but not on Ph+ ALL SupB15 cells. An ongoing transphosphorylation was demonstrated between SFKs and Bcr-Abl. AZD0530 significantly down-regulated the activation of survival signalling pathways in Ph+ cells, resistant or sensitive to Imatinib, with the exception of the RTSupB15. Our results indicate that AZD0530 targets both Src and Bcr-Abl kinase activity and reduces the leukaemic maintenance by Bcr-Abl.


Oral health studies in the 1982 Pelotas (Brazil) birth cohort: methodology and principal results at 15 and 24 years of age.
The aim of this study was to describe the methodology and results of oral health studies nested in a birth cohort in Pelotas, Southern Brazil. For the oral health studies a sub-sample (n = 900) was selected from the cohort and dental examinations and interviews were performed at ages 15 (n = 888) and 24 years (n = 720; 81.1%). Data collection included dental outcomes, dental care, oral health behaviors, and use of dental services. Mean DMF-T varied from 5.1 (SD = 3.8) to 5.6 (SD = 4.1) in the study period. The proportion of individuals with at least one filled tooth increased from 51.9% to more than 70%. Individuals who had always been poor used dental services less and had fewer healthy teeth on average than those who had never been poor. Individuals with decreasing or increasing family income trajectories showed intermediate values. An increase was seen in the number of healthy teeth from age 15 to 24 only among those who had never been poor. A history of at least one experience with poverty had a negative impact on oral health in adulthood.


Improved Electrostatic Embedding for Fragment-Based Chemical Shift Calculations in Molecular Crystals.
Fragment-based methods predict nuclear magnetic resonance (NMR) chemical shielding tensors in molecular crystals with high accuracy and computational efficiency. Such methods typically employ electrostatic embedding to mimic the crystalline environment, and the quality of the results can be sensitive to the embedding treatment. To improve the quality of this embedding environment for fragment-based molecular crystal property calculations, we borrow ideas from the embedded ion method to incorporate self-consistently polarized Madelung field effects. The self-consistent reproduction of the Madelung potential (SCRMP) model developed here constructs an array of point charges that incorporates self-consistent lattice polarization and which reproduces the Madelung potential at all atomic sites involved in the quantum mechanical region of the system. The performance of fragment- and cluster-based 1H, 13C, 14N, and 17O chemical shift predictions using SCRMP and density functionals like PBE and PBE0 are assessed. The improved embedding model results in substantial improvements in the predicted 17O chemical shifts and modest improvements in the 15N ones. Finally, the performance of the model is demonstrated by examining the assignment of the two oxygen chemical shifts in the challenging γ-polymorph of glycine. Overall, the SCRMP-embedded NMR chemical shift predictions are on par with or more accurate than those obtained with the widely used gauge-including projector augmented wave (GIPAW) model.


The putative role of transforming viruses in childhood acute lymphoblastic leukemia.
Epidemiological evidence suggests that infection is involved in the etiology of common acute lymphoblastic leukemia, either by stimulating an inappropriate immune response or in the form of a classical transforming agent. In an attempt to elucidate the role that infection is playing in this disease, we used representational difference analysis (RDA) to examine tumor samples for the presence of exogenous genomes. Twenty RDA experiments were carried out, using four different restriction enzymes, but no exogenous sequences were identified within leukemic cells. These results suggest that it is unlikely that a single, direct transforming agent is involved in the pathogenesis of common acute lymphoblastic leukemia.


Crass: identification and reconstruction of CRISPR from unassembled metagenomic data.
Clustered regularly interspaced short palindromic repeats (CRISPR) constitute a bacterial and archaeal adaptive immune system that protect against bacteriophage (phage). Analysis of CRISPR loci reveals the history of phage infections and provides a direct link between phage and their hosts. All current tools for CRISPR identification have been developed to analyse completed genomes and are not well suited to the analysis of metagenomic data sets, where CRISPR loci are difficult to assemble owing to their repetitive structure and population heterogeneity. Here, we introduce a new algorithm, Crass, which is designed to identify and reconstruct CRISPR loci from raw metagenomic data without the need for assembly or prior knowledge of CRISPR in the data set. CRISPR in assembled data are often fragmented across many contigs/scaffolds and do not fully represent the population heterogeneity of CRISPR loci. Crass identified substantially more CRISPR in metagenomes previously analysed using assembly-based approaches. Using Crass, we were able to detect CRISPR that contained spacers with sequence homology to phage in the system, which would not have been identified using other approaches. The increased sensitivity, specificity and speed of Crass will facilitate comprehensive analysis of CRISPRs in metagenomic data sets, increasing our understanding of phage-host interactions and co-evolution within microbial communities.


Visual Mementos: Reflecting Memories with Personal Data.
In this paper we discuss the creation of visual mementos as a new application area for visualization. We define visual mementos as visualizations of personally relevant data for the purpose of reminiscing, and sharing of life experiences. Today more people collect digital information about their life than ever before. The shift from physical to digital archives poses new challenges and opportunities for self-reflection and self-representation. Drawing on research on autobiographical memory and on the role of artifacts in reminiscing, we identified design challenges for visual mementos: mapping data to evoke familiarity, expressing subjectivity, and obscuring sensitive details for sharing. Visual mementos can make use of the known strengths of visualization in revealing patterns to show the familiar instead of the unexpected, and extend representational mappings beyond the objective to include the more subjective. To understand whether people's subjective views on their past can be reflected in a visual representation, we developed, deployed and studied a technology probe that exemplifies our concept of visual mementos. Our results show how reminiscing has been supported and reveal promising new directions for self-reflection and sharing through visual mementos of personal experiences.


Severe case and literature review of primary erythromelalgia: novel SCN9A gene mutation.
Erythromelalgia is a rare clinical syndrome characterized by intermittent heat, redness, swelling and pain more commonly affecting the lower extremities. Symptoms are mostly aggravated by warmth and are eased by a cold temperature. In some cases, symptoms can be very severe and disabling. Erythromelalgia can be classified as either familial or sporadic, with the familial form inherited in an autosomal dominant manner. Recently, there has been a lot of progress in studying Na(v)1.7 sodium channels (expressed mostly in the sympathetic and nociceptive small-diameter sensory neurons of the dorsal root ganglion) and different mutations affecting the encoding SCN9A gene that leads to channelopathies responsible for some disorders, including primary erythromelalgia. We present a severe case of progressive primary erythromelalgia caused by a new de novo heterozygous missense mutation (c.2623C>G) of the SCN9A gene which substitutes glutamine 875 by glutamic acid (p.Q875E). To our knowledge, this mutation has not been previously reported in the literature. We also provided a short literature review about erythromelalgia and Na(v) sodium channelopathies.


Land-atmosphere energy exchange in Arctic tundra and boreal forest: available data and feedbacks to climate.
This paper summarizes and analyses available data on the surface energy balance of Arctic tundra and boreal forest. The complex interactions between ecosystems and their surface energy balance are also examined, including climatically induced shifts in ecosystem type that might amplify or reduce the effects of potential climatic change. High latitudes are characterized by large annual changes in solar input. Albedo decreases strongly from winter, when the surface is snow-covered, to summer, especially in nonforested regions such as Arctic tundra and boreal wetlands. Evapotranspiration (QE ) of high-latitude ecosystems is less than from a freely evaporating surface and decreases late in the season, when soil moisture declines, indicating stomatal control over QE , particularly in evergreen forests. Evergreen conifer forests have a canopy conductance half that of deciduous forests and consequently lower QE and higher sensible heat flux (QH ). There is a broad overlap in energy partitioning between Arctic and boreal ecosystems, although Arctic ecosystems and light taiga generally have higher ground heat flux because there is less leaf and stem area to shade the ground surface, and the thermal gradient from the surface to permafrost is steeper. Permafrost creates a strong heat sink in summer that reduces surface temperature and therefore heat flux to the atmosphere. Loss of permafrost would therefore amplify climatic warming. If warming caused an increase in productivity and leaf area, or fire caused a shift from evergreen to deciduous forest, this would increase QE and reduce QH . Potential future shifts in vegetation would have varying climate feedbacks, with largest effects caused by shifts from boreal conifer to shrubland or deciduous forest (or vice versa) and from Arctic coastal to wet tundra. An increase of logging activity in the boreal forests appears to reduce QE by roughly 50% with little change in QH , while the ground heat flux is strongly enhanced.


Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study.
We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device. We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin]. Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71-48.8; p < 0.001). The administration of on-demand medication through tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.


Anesthetic type and risk of myocardial infarction after carotid endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).
Carotid endarterectomy (CEA) is usually performed under general anesthesia (GA), although some advocate regional anesthesia (RA) to reduce hemodynamic instability and allow neurologic monitoring and selective shunting. RA does not reduce risk of periprocedural stroke or death, although some series show a reduction in myocardial infarction (MI). We investigated the association of anesthesia type and periprocedural MI among patients receiving GA or RA for CEA and patients undergoing carotid artery stenting (CAS) in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Between 2000 and 2008, 1151 patients underwent CEA (anesthetic type available for 1149 patients), and 1123 patients underwent CAS ≤30 days of randomization in CREST. CEA patients were categorized by anesthetic type (GA vs RA). CREST defined protocol MI as chest pain or electrocardiogram change plus biomarker evidence of MI, and total MI was defined as protocol MI plus biomarker-positive (+)-only MI. The incidence of protocol MI and total MI in patients undergoing CEA under GA and RA were compared with those undergoing CAS. Other study end points were similarly compared. Differences in baseline characteristics and periprocedural events were evaluated among the three groups. Logistic regression, adjusting for age and symptomatic status, was used to assess group differences. The three groups had similar demographic risk factors, except for prevalence of symptomatic carotid stenosis, which was lowest in the CEA-RA group (P = .03). Of the 111 patients in the CEA-RA group, no protocol MIs occurred and only two biomarker+-only MIs, for an overall incidence of 1.8%, similar to the 1.7% overall incidence in patients undergoing CAS. In contrast, the combined incidence of protocol and biomarker+-only MIs in the 1038 patients in the CEA-GA group was significantly higher at 3.4% (P = .04), twice the risk of protocol MI and biomarker+-only MI compared with those undergoing CAS (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.14-3.54). Direct comparison of the MI incidence between CEA-RA and CEA-GA showed no statistical difference. Patients undergoing CEA-GA had lower odds of a periprocedural stroke (OR, 0.48; 95% CI, 0.28-0.79) and stroke or death (OR, 0.46; 95% CI, 0.27-0.76) compared with those undergoing CAS but were not significantly different from those undergoing CEA-RA. Patients in CREST undergoing CEA-RA had a similar risk of periprocedural MI as those undergoing CAS, whereas the risk for CEA-GA was twice that compared with patients undergoing CAS. Nevertheless, because periprocedural MI is one of the few variables favoring CAS over CEA and has been associated with decreased long-term survival, RA should be seriously considered for patients undergoing CEA.


Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.
Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).


Spatially extensive microbial biogeography of the Indian Ocean provides insights into the unique community structure of a pristine coral atoll.
Microorganisms act both as drivers and indicators of perturbations in the marine environment. In an effort to establish baselines to predict the response of marine habitats to environmental change, here we report a broad survey of microbial diversity across the Indian Ocean, including the first microbial samples collected in the pristine lagoon of Salomon Islands, Chagos Archipelago. This was the first large-scale ecogenomic survey aboard a private yacht employing a 'citizen oceanography' approach and tools and protocols easily adapted to ocean going sailboats. Our data highlighted biogeographic patterns in microbial community composition across the Indian Ocean. Samples from within the Salomon Islands lagoon contained a community which was different even from adjacent samples despite constant water exchange, driven by the dominance of the photosynthetic cyanobacterium Synechococcus. In the lagoon, Synechococcus was also responsible for driving shifts in the metatranscriptional profiles. Enrichment of transcripts related to photosynthesis and nutrient cycling indicated bottom-up controls of community structure. However a five-fold increase in viral transcripts within the lagoon during the day, suggested a concomitant top-down control by bacteriophages. Indeed, genome recruitment against Synechococcus reference genomes suggested a role of viruses in providing the ecological filter for determining the β-diversity patterns in this system.


Changes in GIP gene expression following bariatric surgery.
After bariatric surgery, there is a significant improvement in type 2 diabetes (T2D). T2D has been linked to incretins, including glucose-dependent insulinotropic polypeptide (GIP). Analysis of bariatric surgery patients may help to understand the link between GIP and T2D. Twenty-three morbidly obese patients underwent Roux-en-Y gastric bypass (RYGB) or gastric banding. Overall, there were 12 RYGB (5 T2D; 7 nondiabetic) patients and 11 gastric band (7 T2D; 4 nondiabetic) patients. Preoperative and postoperative blood samples were collected. Total RNA was extracted, cDNA synthesized, and real-time quantitative PCR were used to quantify gene expression. Student's t test was used for statistical analysis. Postoperatively, T2D resolved or improved in 83.3 % (10/12) of the diabetic patients. Six (4 RYGB, 2 bands) patients discontinued hypoglycemic medications and four (3 RYGB, 1 band) patients discontinued the majority of their hypoglycemic agents. The remaining two diabetic patients (bands) showed no improvement. Postoperative GIP gene expression increased 4.36-fold (p = 0.02) in diabetic RYGB patients, whereas diabetic band patients increased 1.4-fold (p = 0.25). All diabetic patients with either resolution or improvement of T2D, had a 3.4-fold increase (p = 0.01) but nonresponders decreased 0.69-fold (p = 0.41). Nondiabetic RYGB patients increased 2.21-fold (p = 0.07) versus a 0.81-fold (p = 0.37) decrease of nondiabetic band patients. This is one of the initial studies that show a significant increase in GIP gene expression following a RYGB. This increase correlates with the clinical resolution of T2D. The anatomical changes after RYGB may account for these changes. Based on this data, GIP may be a key peptide in the "foregut hypothesis" for resolution of T2D.


HIV epidemic among men who have sex with men in the Czech Republic, 2016: high time for targeted action.
Reported incidence of human immunodeficiency virus (HIV) infection in the Czech Republic increased steeply over the past decade from 90 new cases in 2005 to 266 in 2015. This increase is almost exclusively attributed to sexual transmissions between men who have sex with men (MSM). In 2015, there were 79% (n=210) newly diagnosed cases among MSM, 17% (n=45) were attributed to heterosexual transmission and 1% (n=3) to people who inject drugs. Interventions targeted at MSM have not yet been prioritised in the broadly focused national HIV prevention strategy which this is envisaged to change in the programme set out for 2018 to 2022. The national budget for HIV prevention has been reduced, however, and this remains. Availability of voluntary counselling and testing has decreased substantially in the past decade. Post- and pre-exposure prophylaxis for sexual intercourse among MSM are not part of the HIV prevention policy and the concept of treatment as prevention is not fully recognised. Provision of a combined prevention strategy with a focus on MSM, reflecting the above factors including stigmatisation, should contribute to reverse the development of a concentrated HIV epidemic among MSM in the Czech Republic.


Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modelling studies.
To establish the clinical effectiveness and cost-effectiveness of electroconvulsive therapy (ECT) for depressive illness, schizophrenia, catatonia and mania. Electronic bibliographic databases. The reference lists of relevant articles and health services research-related resources were consulted via the Internet. Identified studies were examined to ascertain whether they met the inclusion criteria for the review. The study quality of relevant articles was assessed using standard checklists and data were abstracted using standardised forms into a database. Where relevant, results from studies were pooled for meta-analysis. Two economic models were developed primarily based on evidence from the clinical effectiveness analysis and limited quality of life studies. Two good-quality systematic reviews of randomised evidence of the efficacy and safety of ECT in people with depression, schizophrenia, catatonia and mania were identified. Four systematic reviews on non-randomised evidence were also identified, although only one of these could be described as good quality. There was no randomised evidence of the effectiveness of ECT in specific subgroups including older people, children and adolescents, people with catatonia and women with postpartum exacerbations of depression or schizophrenia. The economic modelling results for depression did not demonstrate that any of the scenarios had a clear economic benefit over the others, mainly because of the uncertainty surrounding the clinical effectiveness of the different treatments and the quality of life utility gains. Sensitivity analysis surrounding the cost of ECT and the quality of life utility values had little effect on the overall results. The results of the model for schizophrenia adapted to include ECT suggest that clozapine is a cost-effective treatment compared with ECT. For patients who fail to respond to clozapine, ECT treatment may be preferred to the comparative treatment of haloperidol/chlorpromazine. Real ECT is probably more effective than sham ECT, but as stimulus parameters have an important influence on efficacy, low-dose unilateral ECT is no more effective than sham ECT. ECT is probably more effective than pharmacotherapy in the short term and limited evidence suggests that ECT is more effective than repetitive transcranial magnetic stimulation. Tricyclic antidepressants (TCAs) may improve the antidepressant effect of ECT during the course of treatment. Continuation pharmacotherapy with TCAs combined with lithium in people who have responded to ECT reduces the rate of relapses. Overall, gains in the efficacy of the intervention depending on the stimulus parameters of ECT are achieved only at the expense of an increased risk of cognitive side-effects. Limited evidence suggests these effects do not last beyond 6 months, but there is no evidence examining the longer term cognitive effects of ECT. There is little evidence of the long-term efficacy of ECT. ECT either combined with antipsychotic medication or as a monotherapy is not more effective than antipsychotic medication in people with schizophrenia. More research is needed to examine the long-term efficacy of ECT and the effectiveness of post-ECT pharmacotherapy, the short-term and longer term cognitive side-effects of ECT, and the impact of ECT on suicide and all-cause mortality. Further work is needed to examine the information needs of people deciding whether to accept ECT and how their decision-making can be facilitated. More research is also needed on the mechanism of action of ECT. Finally, the quality of reporting of trials in this area would be vastly improved by strict adherence to the Consolidated Standards of Reporting Trials recommendations. Economic analysis may identify areas in which research would be best targeted by identifying parameters where reducing the level of uncertainty would have the most effect in helping to make the decision on whether ECT is a cost-effective treatment.


Preferential horizontal growth of tungsten sulfide on carbon and insight into active sulfur sites for the hydrogen evolution reaction.
Transition metal dichalcogenides (TMDs) have attracted considerable attention as active electrocatalysts for the hydrogen evolution reaction (HER). Since TMD catalysts are commonly supported on carbon to endow electrical conductivity, understanding the growth behaviour of TMDs on carbon surfaces is crucial, and yet remains to be explored. In this work, we investigated the growth behaviour of tungsten sulfide (WSx) on carbon surfaces inside the confined nanopores. Experimental and computational studies revealed the preferential bonding between the basal planes of WSx and carbon surfaces, as well as the subsequent horizontal growth of WSx. As a result, subnanometer WSx clusters were formed at a low WSx loading, and grew into monolayer WS2 nanoplates with increased WSx loadings. In contrast, a TMD analogue, MoS2, favors edge plane bonding with carbon surfaces and subsequent stacking of nanoplate layers, leading to multilayer MoS2 nanoplates with increased MoS2 loadings. A time-dependent growth of WSx further corroborated the formation of WS2 nanoplates at the expense of ultrasmall WSx nanoclusters. Interestingly, the sample prepared with a short sulfidation time, which was mainly comprised of WSx nanoclusters, showed higher HER activity compared to the sample prepared with a prolonged sulfidation time, which mostly contained WS2 nanoplates. The higher HER activity of WSx nanoclusters is attributed to the larger density of active bridging S22- sites, compared to the WS2 nanoplates. These findings may provide important insights into the growth behaviour of layered TMD materials at the nanoscale, as well as potential active species in WSx for the HER.


Papillorenal syndrome-causing missense mutations in PAX2/Pax2 result in hypomorphic alleles in mouse and human.
Papillorenal syndrome (PRS, also known as renal-coloboma syndrome) is an autosomal dominant disease characterized by potentially-blinding congenital optic nerve excavation and congenital kidney abnormalities. Many patients with PRS have mutations in the paired box transcription factor gene, PAX2. Although most mutations in PAX2 are predicted to result in complete loss of one allele's function, three missense mutations have been reported, raising the possibility that more subtle alterations in PAX2 function may be disease-causing. To date, the molecular behaviors of these mutations have not been explored. We describe a novel mouse model of PRS due to a missense mutation in a highly-conserved threonine residue in the paired domain of Pax2 (p.T74A) that recapitulates the ocular and kidney findings of patients. This mutation is in the Pax2 paired domain at the same location as two human missense mutations. We show that all three missense mutations disrupt potentially critical hydrogen bonds in atomic models and result in reduced Pax2 transactivation, but do not affect nuclear localization, steady state mRNA levels, or the ability of Pax2 to bind its DNA consensus sequence. Moreover, these mutations show reduced steady-state levels of Pax2 protein in vitro and (for p.T74A) in vivo, likely by reducing protein stability. These results suggest that hypomorphic alleles of PAX2/Pax2 can lead to significant disease in humans and mice.


Compression Angle of Ossification of the Posterior Longitudinal Ligament and Its Clinical Significance in Cervical Myelopathy.
The correction of clinical and radiologic abnormalities in patients with symptomatic ossification of the posterior longitudinal ligament (OPLL) is the current mainstay of treatment. This study aimed to identify radiographic predictors of severity of myelopathy in patients with symptomatic OPLL. Fifty patients with symptomatic cervical OPLL were enrolled. Based on Japanese Orthopedic Association (JOA) scores, patients were divided into either the mild myelopathy (n=31) or severe myelopathy (n=19) group. All subjects underwent preoperative plain cervical roentgenogram, computed tomography (CT), and MR imaging (MRI). Radiological parameters (C2-7 sagittal vertical axis, SVA; C2-7 Cobb angle; C2-7 range of motion, ROM; OPLL occupying ratio; and compression angle) were compared. Compression angle of OPLL was defined as the angle between the cranial and caudal surfaces of OPLL at the maximum level of cord compression. The occupying ratio of the spinal canal, C2-7 Cobb angle, C2-7 SVA, types of OPLL, and C2-7 ROM of the cervical spine were not statistically different between the two groups. However, the OPLL compression angle was significantly greater (p=0.003) in the severe myelopathy group than in the mild myelopathy group and was inversely correlated with JOA score (r=-0.533, p<0.01). Furthermore, multivariate regression analysis demonstrated that the compression angle (B=-0.069, p<0.001) was significantly associated with JOA scores (R=0.647, p<0.005). Higher compression angles of OPLL have deleterious effects on the spinal cord and decrease preoperative JOA scores.


Arteriosclerosis obliterans and associated risk factors in insulin-dependent and non-insulin-dependent diabetes.
The prevalence of arteriosclerosis obliterans (ASO) of the legs was determined by a battery of noninvasive tests in 141 insulin-dependent and 289 non-insulin-dependent diabetic subjects and in 64 other subjects. The prevalence of detectable ASO ranges from 18% in the younger IDDM group to 41% in the diet-treated NIDDM group. The prevalence of ASO increases 7.5% per decade, appears to increase 6.5% in the age-adjusted IDDM group, 9% in males, 19% in those with hypertension, and 12% in smokers. No consistently significant correlations with fasting glucose, glycosylated hemoglobin, or obesity were found. After accounting for the effect of smoking, the increased risk for ASO in males becomes nonsignificant.


Fiber-optic liquid-level sensor using a long-period grating.
A liquid-level sensor based on the refractive-index sensitivity of long-period fiber-optic gratings is proposed and demonstrated. The form of the transmission spectrum of the long-period grating is dependent on the fraction of the length of the long-period grating that is surrounded by the liquid. The sensor shows a large linear range, with sensitivity of 4.8% change in transmission per millimeter, for a long-period grating with a length of 40 mm and a periodicity of 400mu;m .


Clinical features and surgical outcomes following closed reduction of arytenoid dislocation.
Arytenoid dislocation is a rare condition characterized by vocal fold immobility and is easily mistaken as recurrent laryngeal nerve paralysis. To describe the presenting features, multimodal diagnostic evaluation, and surgical outcomes following closed reduction (CR) of arytenoid dislocation. Prospective case series at a single academic medical center. Evaluation and treatment data were obtained from 22 consecutive patients with arytenoid dislocation over a 7-year period. Patients underwent direct laryngoscopy and CR of the dislocated arytenoid, with adjunct injection laryngoplasty or botulinum toxin administration in select cases. Initial diagnosis was confirmed using flexible laryngeal endoscopy with stroboscopy, computed tomography, electromyography, and interoperative palpation. Arytenoid motion (primary outcome measure) and vocal function data (secondary outcome measures) were collected before treatment and up to 6 months after treatment. Key history features included emergent intubation, elective intubation, and external laryngeal trauma. Sixteen patients (73%) had anterior and 6 patients (27%) posterior dislocation. One patient experienced spontaneous recovery. Following CR, with or without adjunct therapy, 18 of the remaining patients (86%) exhibited arytenoid motion recovery with concomitant voice improvement. Recovery was sustained at 6 months after CR. Closed reduction performed within 21 days of the presumed dislocation event was associated with a superior arytenoid motion recovery rate. These data represent the largest clinical series on arytenoid dislocation with complete vocal function data and follow-up at 6 months after CR. These findings also corroborate existing evidence for early surgical intervention.


Do parents who smoke underutilize health care services for their children? A cross sectional study within the longitudinal PIAMA study.
A higher prevalence of respiratory symptoms and an associated increase in health care utilization among children with parents who smoke is to be expected. From previous studies however, it appears that parents who smoke may underutilize health services for their children, especially with respect to respiratory care. This study explores the validity and generalizability of the previous assumption. Data were obtained from a Dutch birth-cohort study; the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) project. Information regarding parental smoking, the child's respiratory symptoms and health care use and potential confounders were obtained by postal questionnaires. Multivariate logistic models were used to relate parental smoking to the child's respiratory symptoms and health care use. The study comprised 3,564, 4-year old children. In the crude analysis, respiratory symptoms were more frequent among children with a parent who smoked, while health care utilization for respiratory symptoms was not significantly different between children with or without a parent who smoked. In the multivariate analyses, maternal smoking had a larger impact on the child's respiratory symptoms and health care use as compared to paternal smoking. Maternal smoking was positively associated with mild respiratory symptoms of the child, adjusted odds ratio [AOR] 1.50 (1.19-1.91), but not with severe respiratory symptoms AOR 1.03 (0.75-1.40). Among children with mild respiratory symptoms, children with a mother who smoked were less likely to be taken to the general practitioner (GP) for respiratory symptoms, than children with mothers who did not smoke, AOR 0.58 (0.33-1.01). This finding was less pronounced among children with severe respiratory symptoms AOR 0.86 (0.49-1.52). Neither GP visits for non-respiratory symptoms nor specialized care for respiratory disease were significantly associated with parental smoking. Mothers who smoke appear to underutilize health care for their children with mild respiratory symptoms. Health care workers should be informed about this phenomenon. Inquiring after the respiratory health of the children during regular visits to healthy baby clinics may help to track potential underutilization of care.


Motion contrast classification is a linearly nonseparable problem.
Sensitivity to image motion contrast, that is, the relative motion between different parts of the visual field, is a common and computationally important property of many neurons in the visual pathways of vertebrates. Here we illustrate that, as a classification problem, motion contrast detection is linearly nonseparable. In order to do so, we prove a theorem stating a sufficient condition for linear nonseparability. We argue that nonlinear combinations of local measurements of velocity at different locations and times are needed in order to solve the motion contrast problem.


Detection and measurement of middle-distillate fuel vapors by use of tunable diode lasers.
A sensor for the rapid (10-ms response time) measurement of vapors from the hydrocarbon-based fuels JP-8, DF-2, and gasoline is described. The sensor is based on a previously reported laser-mixing technique that uses two tunable diode lasers emitting in the near-infrared spectral region [Appl. Opt. 39, 5006 (2000)] to measure concentrations of gases that have unstructured absorption spectra. The fiber-mixed laser beam consists of two wavelengths: one that is absorbed by the fuel vapor and one that is not absorbed. Sinusoidally modulating the power of the two lasers at the same frequency but 180 degrees out of phase allows a sinusoidal signal to be generated at the detector (when the target gas is present in the line of sight). The signal amplitude, measured by use of standard phase-sensitive detection techniques, is proportional to the fuel-vapor concentration. Limits of detection at room temperature are reported for the vapors of the three fuels studied. Improvements to be incorporated into the next generation of the sensor are discussed.


Laparoscopic resection of single site pelvic side wall recurrence 6 years after stage IIIc high grade serous primary peritoneal cancer.
The findings of the DESKTOP 3 (Du Bois et al., 2017) study advocate secondary cytoreduction in patients with disease relapse of ovarian or peritoneal malignancy meeting specified criteria. We present a surgical video demonstrating the technique of laparoscopic resection of single site pelvic side wall recurrence 6 years after stage IIIc high grade serous primary peritoneal cancer. In 2014, our patient underwent 3 cycles of neo-adjuvant Cisplatin/Paclitaxel, followed by interval debulking surgery - achieving R0 - for stage IIIc high grade serous primary peritoneal carcinoma. Six years later, at aged 81 years, routine surveillance identified a rising CA 125 level of 91. CT imaging confirmed single site recurrence, reporting an isolated enlarged (3.5 × 2 cm) external iliac lymph node. Given the prolonged disease-free interval, absence of ascites, resectability of recurrent disease and fitness for surgery - secondary cytoreduction was undertaken. Our surgical video demonstrates gaining laparoscopic retroperitoneal access and the subsequent development of the lateral pelvic spaces to facilitate safe excision of disease relapse with a clear surgical margin, Our surgical video demonstrates the feasibility of minimal access surgery for single site recurrence of peritoneal carcinoma, highlighting the importance of understanding and exposing pelvic sidewall anatomy to enable safe and adequate resection - systematically identifying and preserving the ureter, iliac vessels and obturator nerve.


Rainbows, water droplets, and seeing--slow motion analysis of experiments in atmospheric optics.
Many physics processes underlying phenomena in atmospheric optics happen on a rather short time scale such that neither the human eye nor video cameras are able to analyze the details. We report applications of high-speed imaging of laboratory experiments in atmospheric optics with subsequent slow motion analysis. The potential to study respective transient effects is investigated in general and for a few phenomena in detail, in particular for rainbow scattering due to single oscillating droplets during free fall, and for light propagation effects through atmospheric paths with turbulences, leading, e.g., to scintillation of stars or shimmering of mirage images.


Modulation of erbB kinase activity and oncogenic potential by single point mutations in the glycine loop of the catalytic domain.
Avian c-erbB is activated to a leukemia oncogene following truncation of its amino-terminal ligand-binding domain by retroviral insertion. The insertionally activated transcripts encode protein products which have constitutive tyrosine kinase activity and can induce erythroleukemia but not sarcomas. We have previously found that a valine-to-isoleucine point mutation at position 157 (V157I mutant) within the tyrosine kinase domain of this truncated erbB can dramatically activate the sarcomagenic potential of the oncogene and increase the kinase activity of this oncoprotein. This mutation lies at position 157 of the insertionally activated c-erbB product, affecting a highly conserved valine residue of the glycine loop involved in ATP binding and phosphate transfer. To investigate the functional importance of this residue in the catalytic activity of kinases, we have introduced at this position, by site-directed mutagenesis, codons representing the remaining 18 amino acid residues. Most of the mutants have diminished activity, with six of them completely devoid of kinase activity, indicating the sensitivity of this region to conformational changes. Some of these mutants displayed increased kinase activity and greater transforming potential in comparison with IA c-erbB, but none had levels as high as those of the V157I mutant. In general, the sarcomagenic potential of the various erbB mutants correlated with their autophosphorylation state and their ability to cause phosphorylation of MAP kinase. However, there are important exceptions such as the V157G mutant, which lacks enhanced autophosphorylation but is highly sarcomagenic. Studies of this and other autophosphorylation site mutants point to the existence of an autophosphorylation-independent pathway in sarcomagenesis. The requirement for leukemogenic potential is much less stringent and correlates with positivity of kinase activity. When the valine-to-isoleucine substitution was put in context of the full-length erbB protein, the mutation relaxed the ligand dependence and had a positive effect on the transforming potential of the full-length c-erbB.


Management of respiratory motion in PET/computed tomography: the state of the art.
Combined PET/computed tomography (CT) is of value in cancer diagnosis, follow-up, and treatment planning. For cancers located in the thorax or abdomen, the patient's breathing causes artifacts and errors in PET and CT images. Many different approaches for artifact avoidance or correction have been developed; most are based on gated acquisition and synchronization between the respiratory signal and PET acquisition. The respiratory signal is usually produced by an external sensor that tracks a physiological characteristic related to the patient's breathing. Respiratory gating is a compensation technique in which time or amplitude binning is used to exclude the motion in reconstructed PET images. Although this technique is performed in routine clinical practice, it fails to adequately correct for respiratory motion because each gate can mix several tissue positions. Researchers have suggested either selecting PET events from gated acquisitions or performing several PET acquisitions (corresponding to a breath-hold CT position). However, the PET acquisition time must be increased if adequate counting statistics are to be obtained in the different gates after binning. Hence, other researchers have assessed correction techniques that take account of all the counting statistics (without increasing the acquisition duration) and integrate motion information before, during, or after the reconstruction process. Here, we provide an overview of how motion is managed to overcome respiratory motion in PET/CT images.


Congenital perilymphatic fistula: computed tomography appearance of middle ear and inner ear anomalies.
Congenital perilymphatic fistula is an abnormal communication between the inner ear and middle ear. Inner ear anomalies have been described on computed tomography scans. Middle ear anomalies have been found at surgery; the most frequent are anomalies of the stapes and round window. This retrospective study describes the appearance of the inner and middle ear on computed tomography scans, and of the middle ear at surgery, in 10 patients (15 ears) in whom perilymphatic fistula was found at surgery. Twelve of 15 stapes were abnormal at surgery; 4 of these 12 (33%) could be seen on computed tomography scans. Two stapes normal at surgery were normal on computed tomography. Three round windows were abnormal at surgery; none of these was seen on computed tomography scans. There were also four dysplastic cochleas, four dysplastic vestibules, and three dilated vestibular aqueducts. Computed tomography scans identified an abnormal inner ear, middle ear, or both in 8 (53%) of the 15 ears with perilymphatic fistula. An inner ear or middle ear anomaly on computed tomography may heighten clinical suspicion of congenital perilymphatic fistula.


Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer.
We evaluated the efficacy and tolerability of gemcitabine monotherapy in heavily pretreated, breast cancer patients as salvage chemotherapy. A weekly infusion of gemcitabine at 850 mg/m2 for 30 min, for 3 of every 4 weeks, was introduced in advanced breast cancer patients who had failed previous doxorubicin and taxane based chemotherapy. There was no dose modification, and the treatment was delayed until the leukopenia was recovered with G-CSF support. The efficacy was evaluated every three cycles and the treatment was continued until either disease progression or 12 cycles. Of 41 enrolled patients, 38 were evaluable with a median age of 47. Total 178 cycles of gemcitabine was administered and the relative dose intensity was 89. The toxicity was mild with 12 of grade III neutropenia and 14 of grade III/IV thrombocytopenia without clinical symptoms. The response rate was 20 (8/38), comprising two complete and six partial responses. The median response duration and overall survival were 9 (2-25) and 11 months, respectively. The overall survival of 12 months was better in the third line patients than the 7 months in the fourth line treatment group. Gemcitabine monotherapy is effective and safe as salvage treatment in heavily pretreated, breast cancer patients.


Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients.
Widespread use of computed tomography and ultrasound has led to the identification of increasing numbers of patients with asymptomatic cystic lesions of the pancreas. Retrospective case series of patients with pancreatic cystic lesions. University-affiliated tertiary care referral center. Two hundred twelve patients with pancreatic cystic lesions seen in our surgical practice during 5 years (April 1997-March 2002). Presence or absence of symptoms, cyst size and location, cytologic or pathologic diagnosis, surgical treatment, and outcome. Seventy-eight (36.7%) of 212 patients were asymptomatic. Incidental cysts were smaller (3.3 +/- 1.9 vs 4.6 +/- 2.7 cm; P<.001) and were found in older patients (65 +/- 13 vs 56 +/- 15 years; P<.001). Seventy-eight percent of the asymptomatic patients and 87% of those with symptoms underwent surgery, with a single operative death in the entire group (0.5%). Seventeen percent of asymptomatic cysts were serous cystadenomas; 28%, mucinous cystic neoplasms; 27%, intraductal papillary mucinous neoplasms; and 2.5%, ductal adenocarcinomas. The respective numbers for symptomatic cysts were 7%, 16%, 40%, and 9%. Ten percent of asymptomatic patients had a variety of other cystic lesions, and in 12%, no definitive cytologic or pathologic diagnosis was obtained. Overall, 17% of asymptomatic patients had in situ or invasive cancer, and 42% had a premalignant lesion. When evaluated as a function of size, only 1 (3.5%) of 28 asymptomatic cysts smaller than 2 cm had cancer compared with 13 (26%) of 50 cysts larger than 2 cm (P =.04). The proportion of premalignant lesions, however, remained high in both groups (46% and 38%, respectively). Pseudocysts comprised only 3.8% of asymptomatic cysts compared with 19.4% of symptomatic cysts (P =.003). Incidental pancreatic cysts are common, occur in older patients, are smaller than symptomatic cysts, and are unlikely to be pseudocysts. More than half of them are either malignant or premalignant lesions and therefore cannot be dismissed.


Serotonin as a modulator of skeletal muscle oxygenation: effects of ketanserin and ritanserin on oxygen pressure distributions.
Hyperoxemia induces disturbances in tissue oxygenation. The purpose of this study was to examine the influence of serotonin (5-HT) on skeletal muscle oxygenation during hyperoxemia. Two highly selective and pure 5-HT2 receptor antagonists with different T1/2, ketanserin (90 min). and ritanserin (40 h), were employed during measurements of skeletal muscle oxygenation, blood gases and hemoglobin oxygenation in a rabbit model. Surface oxygen pressure measurements were performed on the medial vastus muscle using an MDO oxygen electrode. The results are presented as oxygen pressures distributions (OPD's). Ketanserin was used in one group of 7 rabbits (K-group), and ritanserin in another 7 (R-group). Normal near-Gaussian OPD shapes during normoxemia (paO2 11 kPa) changed to abnormal (scattered) shapes during hyperoxemia (paO2 approx. 50 kPa). After injection of ketanserin (0.07 mg.kg-1 bw) or ritanserin (0.035 mg.kg-1 bw) OPD shapes normalized in 13/14 cases. In the K-group, after ninety minutes, OPD shapes had rescattered and were not completely normalized after an additional half dose of ketanserin (0.035 mg/kg-1 bw). In the R-group, OPD shapes remained normal without additional ritanserin administration. There was poor correlation between normalization of muscle tissue oxygenation and venous pO2 (PvO2) or avDO2. Hyperoxemia-induced disturbance in OPD shape was normalized both by ketanserin and ritanserin in a fashion possibly related to the T1/2 time of the respective 5-HT2 receptor antagonist. These results suggest that serotonin modulates skeletal muscle oxygenation.


The Egocentric Nature of Action-Sound Associations.
Actions that produce sounds infuse our daily lives. Some of these sounds are a natural consequence of physical interactions (such as a clang resulting from dropping a pan), but others are artificially designed (such as a beep resulting from a keypress). Although the relationship between actions and sounds has previously been examined, the frame of reference of these associations is still unknown, despite it being a fundamental property of a psychological representation. For example, when an association is created between a keypress and a tone, it is unclear whether the frame of reference is egocentric (gesture-sound association) or exocentric (key-sound association). This question is especially important for artificially created associations, which occur in technology that pairs sounds with actions, such as gestural interfaces, virtual or augmented reality, and simple buttons that produce tones. The frame of reference could directly influence the learnability, the ease of use, the extent of immersion, and many other factors of the interaction. To explore whether action-sound associations are egocentric or exocentric, an experiment was implemented using a computer keyboard's number pad wherein moving a finger from one key to another produced a sound, thus creating an action-sound association. Half of the participants received egocentric instructions to move their finger with a particular gesture. The other half of the participants received exocentric instructions to move their finger to a particular number on the keypad. All participants were performing the same actions, and only the framing of the action varied between conditions by altering task instructions. Participants in the egocentric condition learned the gesture-sound association, as revealed by a priming paradigm. However, the exocentric condition showed no priming effects. This finding suggests that action-sound associations are egocentric in nature. A second part of the same session further confirmed the egocentric nature of these associations by showing no change in the priming effect after moving to a different starting location. Our findings are consistent with an egocentric representation of action-sound associations, which could have implications for applications that utilize these associations.


Prolonged Exclusive Breastfeeding Duration Is Positively Associated with Risk of Anemia in Infants Aged 12 Months.
The association between exclusive breastfeeding duration and infant anemia is not clear. This study aimed to assess the association of exclusive breastfeeding duration with risk of anemia in infants at 12 mo of age and in children aged 48-71 mo in mainland China. Detailed breastfeeding information and anthropometric data were obtained for 65,256 children enrolled in the Jiaxing Birth Cohort at 1, 3, and 6 mo of age. Hemoglobin was measured in 25,549 children at 12 mo and in 32,770 children between the ages of 48 and 71 mo. Anemia was defined as hemoglobin concentrations <110 g/L in children aged <60 mo and <115 g/L in children aged ≥60 mo. The associations between exclusive breastfeeding duration and risk of anemia were assessed as adjusted ORs by using multiple logistic regression. Overall anemia prevalences at 12 and 48-71 mo were 24.9% and 9.9%, respectively. Exclusive breastfeeding for ≥6 mo, but not for 3-5 mo, was significantly associated with a higher risk of anemia in infants at age 12 mo (OR: 1.15; 95% CI: 1.02, 1.29; P = 0.02) compared with exclusive breastfeeding for <3 mo. For young children aged 48-71 mo, this finding was only marginally significant (OR: 1.13; 95% CI: 0.99, 1.29; P = 0.08). Prolonged duration of exclusive breastfeeding was also significantly associated with decreased hemoglobin concentrations of -0.56 g/L (95% CI: -1.10, -0.03; P = 0.04) in infants and -0.99 g/L (95% CI: -1.44, -0.55; P < 0.001) in young children. Exclusive breastfeeding for ≥6 mo was associated with an increased risk of anemia in infants aged 12 mo and with lower hemoglobin concentrations in both infants aged 12 mo and young children aged 48-71 mo. Parents should provide infants with an adequate source of iron after 6 mo of exclusive breastfeeding.


RICE MORPHOLOGY DETERMINANT encodes the type II formin FH5 and regulates rice morphogenesis.
Multicellular organisms contain a large number of formins; however, their physiological roles in plants remain poorly understood. Here, we reveal that formin homology 5 (FH5), a type II formin mutated in rice morphology determinant (rmd), plays a crucial role in determining rice (Oryza sativa) morphology. FH5/RMD encodes a formin-like protein consisting of an N-terminal phosphatase tensin (PTEN)-like domain, an FH1 domain, and an FH2 domain. The rmd mutants display a bending growth pattern in seedlings, are stunted as adult plants, and have aberrant inflorescence (panicle) and seed shape. Cytological analysis showed that rmd mutants have severe cell elongation defects and abnormal microtubule and microfilament arrays. FH5/RMD is ubiquitously expressed in rice tissues, and its protein localization to the chloroplast surface is mediated by the PTEN domain. Biochemical assays demonstrated that recombinant FH5 protein can nucleate actin polymerization from monomeric G-actin or actin/profilin complexes, cap the barbed end of actin filaments, and bundle actin filaments in vitro. Moreover, FH5 can directly bind to and bundle microtubules through its FH2 domain in vitro. Our findings suggest that the rice formin protein FH5 plays a critical role in determining plant morphology by regulating actin dynamics and proper spatial organization of microtubules and microfilaments.


Extracellular respiration.
Although it has long been known that microbes can generate energy using diverse strategies, only recently has it become clear that a growing number involve electron transfer to or from extracellular substrates. The best-known example of what we will term 'extracellular respiration' is electron transfer between microbes and minerals, such as iron and manganese (hydr)oxides. This makes sense, given that these minerals are sparingly soluble. What is perhaps surprising, however, is that a number of substrates that might typically be classified as 'soluble' are also respired at the cell surface. There are several reasons why this might be the case: the substrate, in its ecological context, might be associated with a solid surface and thus effectively insoluble; the substrate, while soluble, might simply be too large to transport inside the cell; or the substrate, while benign in one redox state, might become toxic after it is metabolized. In this review, we discuss various examples of extracellular respiration, paying particular attention to what is known about the molecular mechanisms underlying these processes. As will become clear, much remains to be learned about the biochemistry, cell biology and regulation of extracellular respiration, making it a rich field of study for molecular microbiologists.


Differential and developmental expression of beta-tubulins in a higher plant.
By using two-dimensional gel electrophoresis and immunoblotting, we have analyzed the expression of beta-tubulin isotypes in the higher plant, carrot. We report a complex expression of beta-tubulins that is dependent on the developmental stage of the tissues analyzed. Consequently, each tissue examined can be identified by its unique composition of beta-tubulins. In total, there are six electrophoretically separable beta-tubulins. In no tissue, however, is there less than two or more than five beta-tubulins. Within this framework we have detected a beta-tubulin specific to seedling tissue beta 6, and a beta-tubulin, beta 5, that is found only in the vegetative tissues of the mature plant. Traced from stem to midrib to leaf lamina, the beta 5 isotype becomes progressively dominant relative to beta 1. Another beta-tubulin isotype, beta 4, appears in marked abundance in immature and mature stamens. In isolated mature pollen the beta 4-tubulin overwhelmingly predominates the ubiquitously expressed beta 2-tubulin isotype. The remaining beta-tubulin isotypes also have specific expression programs with beta 1 present in all tissues except pollen and beta 3 absent only from pollen and leafy tissues.


Advances in the diagnosis and excision of breast cancer.
Until recently little advance in the diagnosis and excision of breast cancer has been made since the inception of needle localization breast biopsy (NLBB). Stereotactic core needle breast biopsy (SCNBB) can avoid most NLBB especially for calcifications. However, when open biopsy is necessary NLBB has been the standard of care. As many as 50 per cent of nonpalpable lesions can be seen by ultrasound (US) to avoid the unpleasantness and complications associated with NLBB. Further SCNBB leaves a blood-filled cavity that can be easily seen by US. Intraoperative US can be used to direct the excision while improving margin negativity. MRI has improved sensitivity in detecting suspicious breast lesions and techniques such as hematoma-directed US-guided breast biopsy can facilitate excision of such masses. Clearly new technologies have improved the ability to diagnosis and excise breast cancer. The onus on the surgeon is to incorporate them into standard practice to improve outcomes.


The Role of Additives in Warm Mix Asphalt Technology: An Insight into Their Mechanisms of Improving an Emerging Technology.
The asphalt industry's incentive to reduce greenhouse gas emissions has increased since the 1990s due to growing concerns on environmental issues such as global warming and carbon footprint. This has stimulated the introduction of Warm Mix Asphalt (WMA) and its technologies which serve the purpose of reducing greenhouse gas emissions by reducing the mixing and compaction temperatures of asphalt mix. WMA gained popularity due to the environmental benefit it offers without compromising the properties, performance and quality of the asphalt mix. WMA is produced at significantly lower temperatures (slightly above 100 °C) and thus results in less energy consumption, fewer emissions, reduced ageing, lower mixing and compaction temperatures, cool weather paving and better workability of the mix. The latter of these benefits is attributed to the incorporation of additives into WMA. These additives can also confer even better performance of WMA in comparison to conventional Hot Mix Asphalt (HMA) methods. Even though there are recommended dosages of several WMA additives, there is no general standardized mixture design procedure and this makes it challenging to characterize the mechanism(s) of action of these additives in the warm mix. The effects of the addition of additives into WMA are known to a reasonable extent but not so much is known about the underlying interactions and phenomena which bring about the mechanism(s) by which these additives confer beneficial features into the warm mix. Additives in a certain way are being used to bridge the gap and minimize or even nullify the effect of the mixing temperature deficit involved in WMA processes while improving the general properties of the mix. This review presents WMA technologies such as wax, chemical additives and foaming processes and the mechanisms by which they function to confer desired characteristics and improve the durability of the mix. Hybrid techniques are also briefly mentioned in this paper in addition to a detailed description of the specific modes of action of popular WMA technologies such as Sasobit, Evotherm and Advera. This paper highlights the environmental and technical advantages of WMA over the conventional HMA methods and also comprehensively analyzes the mechanism(s) of action of additives in conferring desirable characteristics on WMA, which ultimately improves its durability.


Legal but limited? Abortion service availability and readiness assessment in Nepal.
The government of Nepal revised its law in 2002 to allow women to terminate a pregnancy up to 12 weeks gestation for any indication on request, and up to 18 weeks if certain conditions are met. We evaluated the readiness of facilities in Nepal to provide three abortion services, manual vacuum aspiration (MVA), medication abortion (MA) and post-abortion care (PAC), using the service availability and readiness assessment (SARA) framework. The framework consists broadly of three domains; service availability, general service readiness and service readiness specific to individual services (i.e. service-specific readiness). We applied the framework to data from the Nepal Health Facility Survey 2015, a nationally representative survey of 992 health facilities. Overall, we find that access to safe abortion remains limited in Nepal. Of the facilities that reported offering delivery services and were thus eligible to provide safe abortion services, 44.5, 36.0 and 25.6% had provided any MVA, MA or PAC services, respectively, in the 3 months prior to the survey, and <2% were 'ready' to provide any abortion service based on our application of the SARA criteria for service-specific readiness. Among only the facilities that reported providing an abortion service in the 3 months prior to the survey, 3.2% of facilities that provided MVA, 1.5% of facilities that provided MA and 1.1% of the facilities that provided PAC had all the components of care required. Although the private sector conducted approximately half of all abortion services provided in the 3 months prior to the survey, no private sector facilities had all the abortion service-specific readiness components. Results suggest that accessing safe abortion services remains a significant challenge for Nepalese women, despite a set of permissive laws.


Induction of molecular chaperones by hyperosmotic stress in mouse inner medullary collecting duct cells.
The extreme hyperosmotic conditions that exist in the renal inner medulla enable the urinary concentrating mechanism to function. In this study, we evaluated whether stress-related molecular chaperones are induced in response to hyperosmotic stress in mouse inner medullary collecting duct (mIMCD3) cells. Exposure of cells to medium supplemented with 100 mM NaCl for 4 or 24 h resulted in an increase in heat shock protein-72 (HSP-72) (inducible form) by Western blot. Immunocytochemistry confirmed the increase of HSP-72 and showed that hyperosmotic stress resulted in a localization of HSP-72 predominantly to the nucleoplasm that surrounds the nucleoli and to the cytoplasm, a subcellular distribution pattern different from that seen with heat shock. Using a denatured protein (casein)-affinity column with ATP elution, we identified a number of putative molecular chaperones (46, 60, 78, and 200 kDa) that are upregulated in response to 4 h of hyperosmotic NaCl treatment. Microsequencing identified one of these proteins to be the mitochondrial chaperone mtHSP-70, a member of HSP-70 family, and another to be similar to beta-actin. We also found high levels of HSP-72 in cells chronically adapted to hypertonicity, indicating that chaperones are still required to maintain certain cellular functions even after nonperturbing organic osmolytes are known to accumulate. These results suggest an important role for molecular chaperones in the adaptation of renal medullary epithelial cells to the hyperosmotic conditions that exist in the inner medulla in vivo.


A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh in vitro.
The floor plate plays important roles in ventral pattern formation and axonal guidance within the neural tube of vertebrate embryos. A critical event for floor plate development is the induction of a winged helix transcription factor, Hepatocyte Nuclear Factor-3beta (HNF-3beta). The enhancer for floor plate expression of HNF-3beta is located 3' of the transcription unit and consists of multiple elements. HNF-3beta induction depends on the notochord-derived signal, Sonic hedgehog (Shh). Genetic analysis in Drosophila has led to the identification of genes involved in the Hh signalling pathway, and cubitus interruptus (ci), encoding a protein with five zinc finger motifs, was placed downstream. In the present work, we test the involvement of Gli proteins, the mouse homologues of Ci, in activation of the floor plate enhancer of HNF-3beta. Transgenic analysis shows that a Gli-binding site is required for the activity of the minimal floor plate enhancer of HNF-3beta in vivo. Three Gli genes are differentially expressed in the developing neural tube. Gli expression is restricted to the ventral part, while Gli2 and Gli3 are expressed throughout the neural tube and dorsally, respectively. Strong Gli and Gli2, and weak Gli3 expressions transiently overlap with HNF-3beta at the time of its induction. Consistent with ventrally localized expression, Gli expression can be up-regulated by Shh in a cell line. Finally, the Gli-binding site acts as a Shh responsive element, and human GLI, but not GLI3, can activate this binding site in tissue culture. Taken together, these findings suggest that Gli, and probably also Gli2, are good candidates for transcriptional activators of the HNF-3beta floor plate enhancer, and the binding site for Gli proteins is a key element for response to Shh signalling. These results also support the idea that Gli/Ci are evolutionary conserved transcription factors in the Hedgehog signalling pathway.


Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.
Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.


Nanoscale direct mapping of localized and induced noise sources on conducting polymer films.
The localized noise-sources and those induced by external-stimuli were directly mapped by using a conducting-AFM integrated with a custom-designed noise measurement set-up. In this method, current and noise images of a poly(9,9-dioctylfluorene)-polymer-film on a conducting-substrate were recorded simultaneously, enabling the mapping of the resistivity and noise source density (NT). The polymer-films exhibited separate regions with high or low resistivities, which were attributed to the ordered or disordered phases, respectively. A larger number of noise-sources were observed in the disordered-phase-regions than in the ordered-phase regions, due to structural disordering. Increased bias-voltages on the disordered-phase-regions resulted in increased NT, which is explained by the structural deformation at high bias-voltages. On photo-illumination, the ordered-phase-regions exhibited a rather large increase in the conductivity and NT. Presumably, the illumination released carriers from deep-traps which should work as additional noise-sources. These results show that our methods provide valuable insights into noise-sources and, thus, can be powerful tools for basic research and practical applications of conducting polymer films.


Size and deformability based separation of circulating tumor cells from castrate resistant prostate cancer patients using resettable cell traps.
The enumeration and capture of circulating tumor cells (CTCs) are potentially of great clinical value as they offer a non-invasive means to access tumor materials to diagnose disease and monitor treatment efficacy. Conventional immunoenrichment of CTCs may fail to capture cells with low surface antigen expression. Micropore filtration presents a compelling label-free alternative that enriches CTCs using their biophysical rather than biochemical characteristics. However, this strategy is prone to clogging of the filter microstructure, which dramatically reduces the selectivity after processing large numbers of cells. Here, we use the resettable cell trap (RCT) mechanism to separate cells based on their size and deformability using an adjustable aperture that can be periodically cleared to prevent clogging. After separation, the output sample is stained and analyzed using multi-spectral analysis, which provides a more sensitive and unambiguous method to identify CTC biomarkers than traditional immunofluorescence. We tested the RCT device using blood samples obtained from 22 patients with metastatic castrate-resistant prostate cancer while comparing the results with the established CellSearch® system. The RCT mechanism was able to capture ≥5 CTCs in 18/22 (82%) patients with a mean count of 257 in 7.5 ml of whole blood, while the CellSearch system found ≥5 CTCs in 9/22 (41%) patients with a mean count of 25. The ~10× improvement in the CTC capture rate provides significantly more materials for subsequent analysis of these cells such as immunofluorescence, propagation by tissue culture, and genetic profiling.


Psychosocial Outcomes Among Users and Nonusers of Open-Source Automated Insulin Delivery Systems: Multinational Survey of Adults With Type 1 Diabetes.
Emerging research suggests that open-source automated insulin delivery (AID) may reduce diabetes burden and improve sleep quality and quality of life (QoL). However, the evidence is mostly qualitative or uses unvalidated, study-specific, single items. Validated person-reported outcome measures (PROMs) have demonstrated the benefits of other diabetes technologies. The relative lack of research investigating open-source AID using PROMs has been considered a missed opportunity. This study aimed to examine the psychosocial outcomes of adults with type 1 diabetes using and not using open-source AID systems using a comprehensive set of validated PROMs in a real-world, multinational, cross-sectional study. Adults with type 1 diabetes completed 8 validated measures of general emotional well-being (5-item World Health Organization Well-Being Index), sleep quality (Pittsburgh Sleep Quality Index), diabetes-specific QoL (modified DAWN Impact of Diabetes Profile), diabetes-specific positive well-being (4-item subscale of the 28-item Well-Being Questionnaire), diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire), diabetes distress (20-item Problem Areas in Diabetes scale), fear of hypoglycemia (short form of the Hypoglycemia Fear Survey II), and a measure of the impact of COVID-19 on QoL. Independent groups 2-tailed t tests and Mann-Whitney U tests compared PROM scores between adults with type 1 diabetes using and not using open-source AID. An analysis of covariance was used to adjust for potentially confounding variables, including all sociodemographic and clinical characteristics that differed by use of open-source AID. In total, 592 participants were eligible (attempting at least 1 questionnaire), including 451 using open-source AID (mean age 43, SD 13 years; n=189, 41.9% women) and 141 nonusers (mean age 40, SD 13 years; n=90, 63.8% women). Adults using open-source AID reported significantly better general emotional well-being and subjective sleep quality, as well as better diabetes-specific QoL, positive well-being, and treatment satisfaction. They also reported significantly less diabetes distress, fear of hypoglycemia, and perceived less impact of the COVID-19 pandemic on their QoL. All were medium-to-large effects (Cohen d=0.5-1.5). The differences between groups remained significant after adjusting for sociodemographic and clinical characteristics. Adults with type 1 diabetes using open-source AID report significantly better psychosocial outcomes than those not using these systems, after adjusting for sociodemographic and clinical characteristics. Using validated, quantitative measures, this real-world study corroborates the beneficial psychosocial outcomes described previously in qualitative studies or using unvalidated study-specific items.


Remote magnetic with open-irrigated catheter vs. manual navigation for ablation of atrial fibrillation: a systematic review and meta-analysis.
The aim of this study was to determine the efficacy and safety of remote magnetic navigation (RMN) with open-irrigated catheter vs. manual catheter navigation (MCN) in performing atrial fibrillation (AF) ablation. We searched in PubMed (1948-2013) and EMBASE (1974-2013) studies comparing RMN with MCN. Outcomes considered were AF recurrence (primary outcome), pulmonary vein isolation (PVI), procedural complications, and data on procedure's performance. Odds ratios (OR) and mean difference (MD) were extracted and pooled using a random-effect model. Confidence in the estimates of the obtained effects (quality of evidence) was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. We identified seven controlled trials, six non-randomized and one randomized, including a total of 941 patients. Studies were at high risk of bias. No difference was observed between RMN and MCN on AF recurrence [OR 1.18, 95% confidence interval (CI) 0.85 to 1.65, P = 0.32] or PVI (OR 0.41, 95% CI 0.11-1.47, P = 0.17). Remote magnetic navigation was associated with less peri-procedural complications (Peto OR 0.41, 95% CI 0.19-0.88, P = 0.02). Mean fluoroscopy time was reduced in RMN group (-22.22 min; 95% CI -42.48 to -1.96, P = 0.03), although the overall duration of the procedure was longer (60.91 min; 95% CI 31.17 to 90.65, P < 0.0001). In conclusion, RMN is not superior to MCN in achieving freedom from recurrent AF at mid-term follow-up or PVI. The procedure implies less peri-procedural complications, requires a shorter fluoroscopy time but a longer total procedural time. For the low quality of the available evidence, a proper designed randomized controlled trial could turn the direction and the effect of the dimensions explored.


Relationship between chewing ability and high-level functional capacity in an 80-year-old population in Japan.
To evaluate the association between high-level functional capacity and chewing in a middle-old community-based population. Although basic and instrumental activities of daily living are known to be associated with chewing ability in the elderly, an association between higher levels of competence and chewing ability has not been evaluated in the elderly. The association between chewing ability using a number of different foods and high-level functional capacity by the Tokyo Metropolitan Institute of Gerontology was evaluated in 694, 80-year-old people residing in Fukuoka Prefecture, Japan. A significant correlation was found, using multiple regression or logistic regression analyses adjusted for various confounding factors, between the number of total chewable foods, hard foods or moderately hard foods, and total functional capacity, instrumental activity, intellectual activity or social role ability. In contrast, the number of slightly hard foods, easily chewable foods and remaining teeth were only partly related to total functional capacity and intellectual activity. High-level functional capacity including intellectual activity and social role in middle-old elderly was associated with the ability to chew hard foods than to chew easily chewable foods. Maintenance of chewing ability in elderly might result in better intellectual activity and social role.


A typology of community violence perpetration and victimization among adults with mental illnesses.
The primary objective of this article was to evaluate the overlap between community violence perpetration and victimization in a large, heterogeneous sample of adults with mental illnesses (N = 4,474). We also explored participant characteristics differentiating four categories of perpetration and victimization: non-victim/non-perpetrators, victims only, perpetrators only, and victim-perpetrators. Results indicated that adults with mental illnesses were unlikely to report violent outcomes but, when they did, were more likely to report perpetration and victimization, rather than perpetration alone. In addition, bivariate and multivariable analyses showed that sex, age, race/ethnicity, and primary diagnosis differed across categories. Victim-perpetrators, for example, were more likely to be young, Black, and have a primary diagnosis of bipolar disorder, major depressive disorder, substance use disorder, or "other." Altogether, our findings provide evidence for a victim-perpetrator overlap in this population and suggest that preventive measures targeting violence and victimization may be more effective than those with separate strategies for each.


Four stage liquid chromatographic selection of methionyl peptides for peptide-centric proteome analysis: the proteome of human multipotent adult progenitor cells.
Serial application of strong cation-exchange and diagonal reversed-phase chromatography selecting methionyl peptides by stepwise shifting them from their reduced to their sulfoxide and sulfone forms generates a four-stage fractionation system, allowing high coverage analysis of complex proteome digests by LC-MALDI-MS/MS. Application to the proteome of a human multipotent adult progenitor cell line (MAPC) identified 2151 proteins with high confidence as on average four MS/MS-spectra were linked to each protein. Our dataset contains several novel, potential marker proteins that may be evaluated as affinity-anchors for isolating different adult stem cells in further studies. Furthermore, at least 2 tyrosine kinases that were previously linked to the self-renewal potential of stem cells were identified, validating the stemness of the analyzed cells. We also present data hinting at possible involvement of the ubiquitin/proteasome machinery in steering proliferation and/or differentiation of MAPC. Finally, following comparison of the MAPC proteome with proteomes of four human differentiated cell lines reveals differential usage of chromosomal information: compared to differentiated cells, MAPC do not appear to hold any preference for expressing genes located on specific chromosomes.


Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia.
Postinfluenza methicillin-resistant Staphylococcus aureus (MRSA) infection can quickly develop into severe, necrotizing pneumonia, causing over 50% mortality despite antibiotic treatments. In this study, we investigated the efficacy of antibiotic therapies and the impact of S. aureus alpha-toxin in a model of lethal influenza virus and MRSA coinfection. We demonstrate that antibiotics primarily attenuate alpha-toxin-induced acute lethality, even though both alpha-toxin-dependent and -independent mechanisms significantly contribute to animal mortality after coinfection. Furthermore, we found that the protein synthesis-suppressing antibiotic linezolid has an advantageous therapeutic effect on alpha-toxin-induced lung damage, as measured by protein leak and lactate dehydrogenase (LDH) activity. Importantly, using a Panton-Valentine leucocidin (PVL)-negative MRSA isolate from patient sputum, we show that linezolid therapy significantly improves animal survival from postinfluenza MRSA pneumonia compared with vancomycin treatment. Rather than improved viral or bacterial control, this advantageous therapeutic effect is associated with a significantly attenuated proinflammatory cytokine response and acute lung damage in linezolid-treated mice. Together, our findings not only establish a critical role of alpha-toxin in the extreme mortality of secondary MRSA pneumonia after influenza but also provide support for the possibility that linezolid could be a more effective treatment than vancomycin to improve disease outcomes.


Disorders of glucose metabolism among HIV-infected women.
Abnormal glucose metabolism in HIV-infected patients has largely been attributed to the use of protease inhibitors. However, most studies of glucose metabolism in HIV-infected patients have focused on men or have lacked appropriate control groups. We assessed the factors associated with previously diagnosed diabetes among 620 middle-aged women with or at risk for HIV infection. For a subset of 221 women without previously diagnosed diabetes, we performed an oral glucose tolerance test (OGTT) to measure glucose and insulin levels, and we assessed factors associated with abnormal glucose tolerance, insulin resistance, and insulin secretion. Thirteen percent of the women in the present study had previously diagnosed diabetes. Among women without previously diagnosed diabetes who underwent an OGTT, 6% had previously undiagnosed diabetes, and 12% had impaired glucose tolerance (IGT). According to multivariate analysis, factors that were associated with previously diagnosed diabetes included current methadone treatment, body mass index of > or =25, family history of diabetes, and physical inactivity. Factors that were independently associated with an abnormal result of an OGTT (i.e., a result consistent with IGT or diabetes) included age > or =50 years, family history of diabetes, physical inactivity, and a high number of pack-years of smoking. Factors independently associated with insulin resistance included waist circumference, Hispanic ethnicity, physical inactivity, and, among HIV-infected women, use of HAART that did not include protease inhibitors. Factors associated with lower levels of insulin secretion included current opiate use (i.e., methadone or heroin) and older age. Abnormal glucose metabolism is highly prevalent among middle-aged women with or at risk for HIV infection, particularly women who use opiates. Screening for diabetes in the HIV primary care setting should occur for women who have classic risk factors for diabetes, rather than solely for women who are taking PIs. Interventions that target modifiable risk factors, including obesity and physical inactivity, are also warranted.


A review of enteric outbreaks in child care centers: effective infection control recommendations.
Child care environments facilitate the spread of enteric infections because of diapering, confined spaces, and children's unhygienic habits. This study reviews documented outbreaks of enteric illness in daycare centers (DCCs) to identify infectious agents, modes of transmission, morbidity/mortality, ages, secondary cases, and practices found effective by investigators. A systematic review of the literature, including peer-reviewed journals and public health records, identified reports of DCC enteric outbreaks published in English occurring between January 1996 and November 2006. In the 75 studies reviewed, 1,806 children were reported ill and 104 were reported hospitalized (mainly associated with Escherichia coli O157:H7). For bacterial outbreaks, the modes of transmission were person-to-person (43%), food (29%), and animal contact (11%). The mode of transmission was largely unknown (51%) for viral outbreaks. One hundred twenty-six staff cases and at least 212 additional ill household contacts were identified. The most frequently identified effective management practices included management of symptomatic cases, enhanced hand hygiene, safe food handling practices, and improved environmental cleaning. Although most children recover quite uneventfully from enteric illness, some can be seriously affected, especially by E. coli O157:H7. Staff, family members, and the community may become ill from secondary spread; therefore, it is important for DCCs to have effective infection control procedures in place to prevent and control outbreaks.