Effects of the Dietary Approach to Stop Hypertension (DASH) diet on blood pressure, overweight and obesity in adolescents: A systematic review.
The high prevalence of overweight/obesity, and arterial hypertension (AH) in adolescence is a public health problem worldwide. The aim of the article is to perform a systematic review looking to verify the effects of DASH diet on overweight/obesity and blood pressure (BP) in adolescents. Systematic search of the literature conducted until March 2018. Five databases were investigated. We follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) Statement. The systematic review protocol was recorded in PROSPERO (CRD42016046968). Two reviewers examined 1005 abstracts. The risk of bias was assessed using STROBE or CONSORT. Seven studies were eligible, three cross-sectional, two cohort and two randomized clinical trials (RCTs). Cross-sectional study found that a higher DASH score was associated with decreased body composition measurements; the other two did not find associations between DASH scores, body weight, and BP. Cohort studies found that the DASH diet resulted in lower levels of diastolic BP and lower body mass index gain over 10 years. One RCT showed that the DASH diet proved to be effective in improving systolic BP and another RCT observed a decrease in the prevalence of AH. The DASH diet may have beneficial effects on the alterations of BP, overweight and obesity in adolescence. However, adherence to this dietary pattern is still low. It is believed that, in the future, dietary interventions based on DASH may be part of public policies to combat AH and overweight/obesity, since all age groups of the population can adopt this dietary pattern.


Bayesian nonlinear model selection for gene regulatory networks.
Gene regulatory networks represent the regulatory relationships between genes and their products and are important for exploring and defining the underlying biological processes of cellular systems. We develop a novel framework to recover the structure of nonlinear gene regulatory networks using semiparametric spline-based directed acyclic graphical models. Our use of splines allows the model to have both flexibility in capturing nonlinear dependencies as well as control of overfitting via shrinkage, using mixed model representations of penalized splines. We propose a novel discrete mixture prior on the smoothing parameter of the splines that allows for simultaneous selection of both linear and nonlinear functional relationships as well as inducing sparsity in the edge selection. Using simulation studies, we demonstrate the superior performance of our methods in comparison with several existing approaches in terms of network reconstruction and functional selection. We apply our methods to a gene expression dataset in glioblastoma multiforme, which reveals several interesting and biologically relevant nonlinear relationships.


Genetic complementation among poliovirus mutants derived from an infectious cDNA clone.
We constructed several well-defined mutations in the nonstructural portion of the poliovirus type I (Mahoney strain) genome by making small insertions in an infectious cDNA clone. The derived viral strains carrying the mutations exhibited a variety of distinct plaque phenotypes. Thus, we were able to examine genetic complementation between different pairs of mutants by comparing the yields of progeny virus in mixed and single infections. Two mutants bearing lesions in the 2A and 3A regions of the genome, which are defective in the inhibition of host cell translation and the synthesis of viral RNA, respectively, could be rescued efficiently by genetic complementation; three replication-deficient mutants containing insertions in the 2B, 3D (replicase), and 3'-untranslated regions could not. Both the 2A and 3A mutants could be rescued by each other and by all of the other mutants tested. Because yield enhancement was apparent well before the completion of a single infectious cycle, it is likely that complementation of both mutants involved early diffusion of functional products. These data provide the first unambiguous evidence that the nonstructural portion of the poliovirus genome contains multiple complementation groups. The data also suggest that certain nonstructural functions act only in cis.


In vitro function and post-transfusion survival of granulocytes collected by continuous-flow centrifugation and by filtration leukapheresis.
The function of granulocytes collected by continuous-flow centrifugation (CFC) and by filtration leukapheresis (FL) was studied in vitro, and the post-transfusion recovery and intravascular survival of these cells was studied by autologous transfusion in normal donors. Granulocytes collected by both FL and CFC leukapheresis (CFCL) functioned normally in the quantitative nitroblue tetrazolium, oxygen consumption, and chemotaxis assays. Bacterial killing was slightly but consistently decreased in FL but not CFCL granulocytes. The post-transfusion recovery of control granulocytes collected by ordinary phlebotomy averaged 52% in eight transfusions, compared with 34% for six CFCL granulocyte concentrates and 16% for six FL concentrates. The intravascular half-times were 3.8 hr for phlebotomy and 3.0 hr for CFCL granulocytes. FL granulocytes had survival curves which were nonlinear and a single half-life could not be calculated. The average half-time 30 min after transfusion was 1.3 hr, and 3 hr after transfusion it was 2.6 hr. Granulocytes collected by FL had a mild impairment of bacterial killing, decreased post-transfusion recovery, and altered intravascular kinetics. None of these abnormalities was found in granulocytes collected by CFCL.


From voxels to knowledge: a practical guide to the segmentation of complex electron microscopy 3D-data.
Modern 3D electron microscopy approaches have recently allowed unprecedented insight into the 3D ultrastructural organization of cells and tissues, enabling the visualization of large macromolecular machines, such as adhesion complexes, as well as higher-order structures, such as the cytoskeleton and cellular organelles in their respective cell and tissue context. Given the inherent complexity of cellular volumes, it is essential to first extract the features of interest in order to allow visualization, quantification, and therefore comprehension of their 3D organization. Each data set is defined by distinct characteristics, e.g., signal-to-noise ratio, crispness (sharpness) of the data, heterogeneity of its features, crowdedness of features, presence or absence of characteristic shapes that allow for easy identification, and the percentage of the entire volume that a specific region of interest occupies. All these characteristics need to be considered when deciding on which approach to take for segmentation. The six different 3D ultrastructural data sets presented were obtained by three different imaging approaches: resin embedded stained electron tomography, focused ion beam- and serial block face- scanning electron microscopy (FIB-SEM, SBF-SEM) of mildly stained and heavily stained samples, respectively. For these data sets, four different segmentation approaches have been applied: (1) fully manual model building followed solely by visualization of the model, (2) manual tracing segmentation of the data followed by surface rendering, (3) semi-automated approaches followed by surface rendering, or (4) automated custom-designed segmentation algorithms followed by surface rendering and quantitative analysis. Depending on the combination of data set characteristics, it was found that typically one of these four categorical approaches outperforms the others, but depending on the exact sequence of criteria, more than one approach may be successful. Based on these data, we propose a triage scheme that categorizes both objective data set characteristics and subjective personal criteria for the analysis of the different data sets.


Incidence and risk factors of late rupture, conversion, and death after endovascular repair of infrarenal aortic aneurysms: the EUROSTAR experience. European Collaborators on Stent/graft techniques for aortic aneurysm repair.
The EUROSTAR (European Collaborators on Stent/graft techniques for aortic aneurysm repair) Registry was established in 1996 to collect data on the outcome of treatment of patients with infrarenal aortic aneurysms with endovascular repair. To date, 88 European centers of vascular surgery have contributed. The purpose of the study was to evaluate the results of this treatment in the medium term (up to 4 years) according to the analysis of "hard" or primary end points of rupture, late conversion, and death. Patients with aortic aneurysms suitable for endovascular aneurysm repair were notified to the EUROSTAR Data Registry Centre before treatment to eliminate bias due to selective reporting. The following information was collected on all patients: (1) demographic details and the anatomic characteristics of their aneurysms, (2) details of the endovascular device used, (3) complications encountered during the procedure and the immediate outcome, (4) results of contrast enhanced computed tomographic imaging at 3, 6, 12, and 18 months after operation and at yearly intervals thereafter, and (5) all adverse events. Life table analysis was performed to determine the cumulative rates of (1) death from all causes, (2) rupture, and (3) late conversion to open repair. Risk factors for rupture and late conversion were identified through regression analysis. By March 2000, 2464 patients had been registered, and their mean duration of follow-up was 12.19 months (SD, 12.3 months). There were 14 patients with confirmed rupture of their aneurysms. The cumulative rate (risk) of rupture was approximately 1% per year. Emergency surgery was undertaken in 12 (86%) patients, of whom five (41.6%) survived. Two patients who were not treated surgically also died, which resulted in an overall death rate of 64.5% (9/14) of the patients. Significant risk factors for rupture were proximal type I endoleak (P =.001), midgraft (type III) endoleak (P =.001), graft migration (P =.001), and postoperative kinking of the endograft (P =.001). Forty-one patients underwent late conversion to open repair with a perioperative mortality rate of 24.4% (10/41). The cumulative rate (risk) of late conversion was approximately 2.1% per year. Risk factors (indications) for late conversion were proximal type I endoleak (P =. 001), midgraft (type III) endoleak (P =.001), type II endoleak (P =. 003), graft migration (P =.001), graft kinking (P =.001), and distal type I endoleak (P =.001). Endovascular repair of infrarenal aortic aneurysms with the first- and second-generation devices that predominated in this study was associated with a risk of late failure, according to an analysis of observed hard end points of 3% per year. Action taken to address the risk factors identified by the study may improve results in the future.


Ethical decision-making for children with neuromuscular disorders in the COVID-19 crisis.
The sudden appearance and proliferation of coronavirus disease 2019 has forced societies and governmental authorities across the world to confront the possibility of resource constraints when critical care facilities are overwhelmed by the sheer numbers of grievously ill patients. As governments and health care systems develop and update policies and guidelines regarding the allocation of resources, patients and families affected by chronic disabilities, including many neuromuscular disorders that affect children and young adults, have become alarmed at the possibility that they may be determined to have less favorable prognoses due to their underlying diagnoses and thus be assigned to lower priority groups. It is important for health care workers, policymakers, and government officials to be aware that the long-term prognoses for children and young adults with neuromuscular disorders are often more promising than previously believed due to a better understanding of the natural history of these diseases, benefits of multidisciplinary supportive care, and novel molecular therapies that can dramatically improve the disease course. Although the realities of a global pandemic have the potential to require a shift from our usual, highly individualistic standards of care to crisis standards of care, shifting priorities should nonetheless be informed by good facts. Resource allocation guidelines with the potential to affect children and young adults with neuromuscular disorders should take into account the known trajectory of acute respiratory illness in this population and rely primarily on contemporary long-term outcome data.


Characterization of the quaternary amine transporters of Rhizobium leguminosarum bv. viciae 3841.
Rhizobium leguminosarum bv. viciae 3841 contains six putative quaternary ammonium transporters (Qat), of the ABC family. Qat6 was strongly induced by hyperosmosis although the solute transported was not identified. All six systems were induced by the quaternary amines choline and glycine betaine. It was confirmed by microarray analysis of the genome that pRL100079-83 (qat6) is the most strongly upregulated transport system under osmotic stress, although other transporters and 104 genes are more than threefold upregulated. A range of quaternary ammonium compounds were tested but all failed to improve growth of strain 3841 under hyperosmotic stress. One Qat system (gbcXWV) was induced 20-fold by glycine betaine and choline and a Tn5::gbcW mutant was severely impaired for both transport and growth on these compounds, demonstrating that it is the principal system for their use as carbon and nitrogen sources. It transports glycine betaine and choline with a high affinity (apparent K(m), 168 and 294 nM, respectively).


Mesenchymal stem cells and tooth engineering.
Tooth loss compromises human oral health. Although several prosthetic methods, such as artificial denture and dental implants, are clinical therapies to tooth loss problems, they are thought to have safety and usage time issues. Recently, tooth tissue engineering has attracted more and more attention. Stem cell based tissue engineering is thought to be a promising way to replace the missing tooth. Mesenchymal stem cells (MSCs) are multipotent stem cells which can differentiate into a variety of cell types. The potential MSCs for tooth regeneration mainly include stem cells from human exfoliated deciduous teeth (SHEDs), adult dental pulp stem cells (DPSCs), stem cells from the apical part of the papilla (SCAPs), stem cells from the dental follicle (DFSCs), periodontal ligament stem cells (PDLSCs) and bone marrow derived mesenchymal stem cells (BMSCs). This review outlines the recent progress in the mesenchymal stem cells used in tooth regeneration.


Feasibility, Acceptability, and Impact of a Web-based Gratitude Exercise among Individuals in Outpatient Treatment for Alcohol Use Disorder.
This mixed-methods pilot study examined the feasibility, acceptability, and impact of a web-based gratitude exercise (the 'Three Good Things' exercise (TGT)) among 23 adults in outpatient treatment for alcohol use disorder (AUD). Participants were randomized to TGT or a placebo condition. The intervention was feasible with high rates of completion. Participants found TGT acceptable and welcomed the structure of daily emails; however, they found it difficult at times and discontinued TGT when the study ended. Participants associated TGT with gratitude, although there were no observed changes in grateful disposition over time. TGT had a significant effect on decreasing negative affect and increasing unactivated (e.g., feeling calm, at ease) positive affect, although there were no differences between groups at the 8 week follow up. Qualitative results converged on quantitative findings that TGT was convenient, feasible, and acceptable, and additionally suggested that TGT was beneficial for engendering positive cognitions and reinforcing recovery.


Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization.
We sought to examine the effect of resveratrol (3,4',5-trihydroxy-trans-stilbene), a plant-derived polyphenolic compound, on the development of abdominal aortic aneurysm (AAA). AAA was induced in mice by periaortic application of CaCl(2). NaCl (0.9%)-applied mice were used as a sham group. Mice were treated with intraperitoneal injection of PBS (Sham/CON, AAA/CON, n=30 for each) or resveratrol (100 mg/kg/day) (AAA/RSVT, n=30). Six weeks after the operation, aortic tissue was excised for further examinations. Aortic diameter was enlarged in AAA/CON compared with Sham/CON. Resveratrol treatment reduced the aneurysm size and inflammatory cell infiltration in the aortic wall compared with AAA/CON. Elastica Van Gieson staining showed destruction of the wavy morphology of the elastic lamellae in AAA/CON, while it was preserved in AAA/RSVT. The increased mRNA expression of monocyte chemotactic protein-1, tumor necrosis factor-α, intercellular adhesion molecule-1, CD68, vascular endothelial growth factor-A, p47, glutathione peroxidase (GPX)1 and GPX3 were attenuated by resveratrol treatment (all p<0.05). Administration of resveratrol decreased protein expression of phospho-p65 in AAA. The increased 8-hydroxy-2'-deoxyguanosine-positive cell count and 4-hydroxy-2-nonenal-positive cell count in AAA were also reduced by resveratrol treatment. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lower in AAA/RSVT compared with AAA/CON (both p<0.05). Compared with AAA/CON, Mac-2(+) macrophages and CD31(+) vessels in the aortic wall were decreased in AAA/RSVT (both p<0.05). Treatment with resveratrol in mice prevented the development of CaCl(2)-induced AAA, in association with reduced inflammation, oxidative stress, neoangiogenesis, and extracellular matrix disruption. These findings suggest therapeutic potential of resveratrol for AAA.


Aggressive behavior, related conduct problems, and variation in genes affecting dopamine turnover.
A number of dopamine-related genes have been implicated in the etiology of violent behavior and conduct problems. Of these genes, the ones that code for the enzymes that influence the turnover of dopamine (DA) have received the most attention. In this study, we investigated 12 genetic polymorphisms in four genes involved with DA functioning (COMT, MAOA and MAOB, and DbetaH) in 179 incarcerated male Russian adolescents and two groups of matched controls: boys without criminal records referred to by their teachers as (a) "troubled-behavior-free" boys, n=182; and (b) "troubled-behavior" boys, n=60. The participants were classified as (1) being incarcerated or not, (2) having the DSM-IV diagnosis of conduct disorder (CD) or not, and (3) having committed violent or nonviolent crimes (for the incarcerated individuals only). The findings indicate that, although no single genetic variant in any of the four genes differentiated individuals in the investigated groups, various linear combinations (i.e., haplotypes) and nonlinear combinations (i.e., interactions between variants within and across genes) of genetic variants resulted in informative and robust classifications for two of the three groupings. These combinations of genetic variants differentiated individuals in incarceration vs. nonincarcerated and CD vs. no-CD groups; no informative combinations were established consistently for the grouping by crime within the incarcerated individuals. This study underscores the importance of considering multiple rather than single markers within candidate genes and their additive and interactive combinations, both with themselves and with nongenetic indicators, while attempting to understand the genetic background of such complex behaviors as serious conduct problems.


IQ-motif peptides as novel anti-microbial agents.
The IQ-motif is an amphipathic, often positively charged, α-helical, calmodulin binding sequence found in a number of eukaryote signalling, transport and cytoskeletal proteins. They share common biophysical characteristics with established, cationic α-helical antimicrobial peptides, such as the human cathelicidin LL-37. Therefore, we tested eight peptides encoding the sequences of IQ-motifs derived from the human cytoskeletal scaffolding proteins IQGAP2 and IQGAP3. Some of these peptides were able to inhibit the growth of Escherichia coli and Staphylococcus aureus with minimal inhibitory concentrations (MIC) comparable to LL-37. In addition some IQ-motifs had activity against the fungus Candida albicans. This antimicrobial activity is combined with low haemolytic activity (comparable to, or lower than, that of LL-37). Those IQ-motifs with anti-microbial activity tended to be able to bind to lipopolysaccharide. Some of these were also able to permeabilise the cell membranes of both Gram positive and Gram negative bacteria. These results demonstrate that IQ-motifs are viable lead sequences for the identification and optimisation of novel anti-microbial peptides. Thus, further investigation of the anti-microbial properties of this diverse group of sequences is merited.


Effect of peeling, cutting, or shredding of lettuce, carrot, or potato on the efficacy of chlorine disinfection.
Minimally processed vegetables are washed and subsequently disinfected by immersion in water solutions with antimicrobials which reduce the initial pathogenic or spoilage microbial load. Chlorine remains one of the most widely used disinfectants for vegetables and hence the importance of studying its properties. The aim of this study was to evaluate the effect of peeling, cutting, and shredding on the effectiveness of chlorine (200 ppm) as a disinfectant in lettuce, carrot, and potato. Three independent repetitions of each experiment were completed, and data was statistically analyzed. Results showed that the maintenance of the chlorine concentration in the disinfectant solution, over time, depended on the vegetables' preliminary processing technique (whole, peeled, cut, or shredded) (p < 0.05). In general, the disinfection treatments studied reduced Escherichia coli by 1-8 logs. The addition of chlorine in the disinfectant solution allowed greater reduction in E. coli than using water immersions (p < 0.05) and disinfection times longer than 5 min did not improve these microbiological reductions (p>0.05). The vegetables' subdivision (whole, peeled, cut, or shredded) can affect both E coli's reduction and the vegetables' residual chlorine concentration. No trend was observed in terms of sensory differences and their relationship to the vegetables' processing and disinfection. These results suggest that each facility must validate its disinfection processes, according to the conditions established on site and reduction goals related to initial microbial counts, vegetables' quality, processing operations, and other important aspects.


[Lower limb arterial disease in patients with diabetes].
Lower limb arteriopathy is a frequent and potentially serious complication of diabetes. In fact, it largely explains the high incidence of lower limb amputations in diabetic patients as well as a significant impairment of quality of life in the case of intermittent claudication or decubitus pain. The severity of the disease is also based on the associated cardiovascular morbidity and mortality. The diagnosis is primarily made by the clinical examination, completed by functional hemodynamic tests (ankle/brachial index, transcutaneous oxygen pressure and toe pressure) and possibly imaging tests (arterial Doppler and arteriography of the lower limbs). The treatment of lower limbs arterial disease will depend on the vascular symptomatology, the severity of the vascular lesions evaluated by the hemodynamic tests and by the anatomical characteristics of the vascular lesions.


Rings in the neonate.
Neonatal lupus erythematosus (NLE) is an uncommon disease of the neonate. It is believed to be caused by the transplacental passage of maternal autoantibodies to the ribonucleoproteins (Ro/SSA, La/SSB or rarely U RNP) as these are almost invariably present in NLE sera. The most common clinical manifestations include cutaneous lupus lesions and congenital complete heart block. Hepatobiliary and haematologic abnormalities are reported less frequently. We describe a patient with cutaneous NLE to illustrate and raise awareness of the characteristic annular eruption of this condition. We also emphasize the need for thorough investigation for concomitant organ involvement and for maternal education regarding risk in future pregnancies.


Characterizing genomic alterations in cancer by complementary functional associations.
Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes.


Clinical applications of polygenic risk score for coronary artery disease through the life course.
Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, highlighting the limitations of current primary and secondary prevention frameworks. In this review, we detail how the polygenic risk score for CAD can improve our current preventive and treatment frameworks across three clinical applications that span the life course: (i) identification and treatment of people at increased risk early in the life course prior to the onset of clinical risk factors, (ii) improving the precision around risk estimation in middle age, and (ii) guiding treatment decisions and enabling more efficient clinical trials even after the onset of CAD. We end by summarizing the efforts needed as we head towards more widespread use of polygenic risk score for CAD in clinical practice.


Can We protect workers from developing the adverse respiratory effects of isocyanate exposure?
In this review, the authors have attempted to present the difficulty in defining a permissible exposure limit (PEL) to agents that act as sensitizers and may induce asthma-even at exposure levels less than the PEL. One approach to this relatively unaddressed problem may be to define the separate aspects of exposure to the specific sensitizing agent. The first effect is an accelerated rate of decline in lung function in nonsensitized individuals who are exposed to the agent (in this case the model used is isocyanates). The second effect is sensitization. Rules for developing a PEL might take this sensitizing effect into account, and this group of agents with such dual effects may be defined as "sensitizers." Exposure to agents with this designation would require special educational and surveillance initiatives to facilitate early detection. The elimination of sensitization may be a greater challenge. An important form of prevention is medical screening of exposed workers, yet it is unclear which screening approach best identifies workers with early isocyanate asthma.


Preserved Expert Object Recognition in a Case of Visual Hemiagnosia.
We examined a stroke patient (HWS) with a unilateral lesion of the right medial ventral visual stream, involving the right fusiform and parahippocampal gyri. In a number of object recognition tests with lateralized presentations of target stimuli, HWS showed significant symptoms of hemiagnosia with contralesional recognition deficits for everyday objects. We further explored the patient's capacities of visual expertise that were acquired before the current perceptual impairment became effective. We confronted him with objects he was an expert for already before stroke onset and compared this performance with the recognition of familiar everyday objects. HWS was able to identify significantly more of the specific ("expert") than of the everyday objects on the affected contralesional side. This observation of better expert object recognition in visual hemiagnosia allows for several interpretations. The results may be caused by enhanced information processing for expert objects in the ventral system in the affected or the intact hemisphere. Expert knowledge could trigger top-down mechanisms supporting object recognition despite of impaired basic functions of object processing. More importantly, the current work demonstrates that top-down mechanisms of visual expertise influence object recognition at an early stage, probably before visual object information propagates to modules of higher object recognition. Because HWS showed a lesion to the fusiform gyrus and spared capacities of expert object recognition, the current study emphasizes possible contributions of areas outside the ventral stream to visual expertise.


Brain regional α-[11C]methyl-L-tryptophan trapping in medication-free patients with obsessive-compulsive disorder.
The hypothesis of a serotonin (5-hydroxytryptamine [5-HT]) dysfunction in obsessive-compulsive disorder (OCD) stems largely from the clinical efficacy of 5-HT reuptake inhibitors. Serotonergic abnormalities in the unmedicated symptomatic state, however, remain to be fully characterized. To investigate brain regional 5-HT synthesis, as indexed by positron emission tomography and the α-[(11)C]methyl-L-tryptophan trapping constant (K*), in treatment-free adults meeting criteria for OCD. Between-group comparison. Department of Psychiatry and Montreal Neurological Institute, McGill University, and Department of Psychology, McGill University Health Centre, Quebec, Canada. Twenty-one medication-free patients with OCD (15 men with a mean [SD] age of 33.2 [9.3] years and 6 women with a mean [SD] age of 35.8 [7.1] years) and 21 healthy controls matched for age and sex (15 men with a mean [SD] age of 32.9 [10.1] years and 6 women with a mean [SD] age of 36.5.5 [8.6] years). Main Outcome Measure The α-[(11)C]methyl-L-tryptophan brain trapping constant K*, which was analyzed with Statistical Parametric Mapping (SPM8) and with proportional normalization (extent threshold of 100 voxels with a peak threshold of P ≤ .005). Compared with healthy controls, the patients with OCD exhibited significantly greater α-[(11)C]methyl-L-tryptophan trapping in the right hippocampus and left temporal gyrus (Brodmann area 20). In the larger subsample of all men, these same differences were also evident, as well as higher K* values in the caudate nucleus. Individual differences in symptom severity correlated positively with K* values sampled from the caudate and temporal lobe of the patients with OCD, respectively. There were no regions where the patients exhibited abnormally low K* values. Volumetric analyses found no morphometric alterations that would account for the group differences. The results support previous reports of greater striatal and temporal lobe activity in patients with OCD than in healthy controls and suggest that these disturbances include a serotonergic component. Previously reported glucose metabolic disturbances in OCD involving the orbitofrontal and cingulate cortices, in comparison, might reflect postsynaptic changes in the serotonergic system.


Protease Inhibitors as a Potential Target in Modulation of Postischemic Inflammation.
Prevention of ischemia-reperfusion injury represents a main objective in infarction, cardiac surgery and organ transplantation. In the context of cellular homeostasis, postischemic inflammation may be understood in part as an initial physiological response to ischemia and reperfusion, aiming at restoration of tissue integrity. Polymorphonuclear cell infiltration and subsequent protease production, however, are crucial mechanisms contributing to tissue damage, cell necrosis and subsequent functional deficits. Therefore, inhibition of protease activity appears a promising target for modulating destructive processes of postischemic inflammation, while preserving its restorative nature. Recently, effects of secretory leukocyte protease inhibitor elafin and other protease inhibitors have been investigated in vivo and in vitro, which may provide a basis for future therapeutic strategies in postischemic inflammation. (c) 2002 Prous Science. All rights reserved.


[Social psychological and sexological aspects of oral contraception (author's transl)].
An inventory is made on the hindrances to the acceptance of contraception in general and oral contraception in particular. They are grouped as hindrances related to the social and psychological significance of "making children", hindrances related to the social and psychological significance of "having children" hindrances, related to the method of oral contraception itself, to be divided in social hindrances, psychological hindrances and medical hindrances and finally hindrances related to the provision of the pill to the individual user. Each of these is amply discussed, the author expresses the hope that by identification of these hindrances, lessons may be learned for the future, when other methods of contreception become available.


The Normal Vulva, Vulvar Examination, and Evaluation Tools.
The appearance of the female external genitalia is key for understanding and diagnosing many diseases that women of all ages encounter. Alas, the normal appearance of the vulva is an elusive concept, scarcely represented in textbooks, and the growing number of vulvar cosmetic surgery calls for a review of the normal appearance of the vulva and its diversity. In this paper I will review vulvar embryology, anatomy, the current literature discussing vulvar appearance, and describe meticulous vulvar examination, including the diagnostic tools.


Response of hydroperoxidase and superoxide dismutase deficient mutants of Escherichia coli K-12 to oxidative stress.
In Escherichia coli, the coordinate action of two antioxidant enzymes, superoxide dismutase and hydroperoxidase (catalase), protect the cell from the deleterious effects of oxyradicals generated during normal aerobic respiration. To evaluate the relative importance of these two classes of enzymes, strains of E. coli deficient in superoxide dismutase and (or) hydroperoxidase were constructed by generalized transduction and their physiological responses to oxygen and oxidant stress examined. Superoxide dismutase was found to be more important than hydroperoxidase in preventing oxygen-dependent growth inhibition and mutagenesis, and in reducing sensitivity to redox-active compounds known to generate the superoxide anion. However, both types of enzymes were required for an effective defense against chemical oxidants that generate superoxide radicals and hydrogen peroxide.


Venous thromboembolism during pregnancy, postpartum or during contraceptive use.
Venous thromboembolism (VTE) is a leading cause of maternal death during pregnancy or postpartum, and in women using hormonal contraceptives. However, important issues concerning its natural history and therapy remain unsolved, and most of the protocols for treatment of VTE in this patient population are based on data extrapolated from other populations. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We examined the clinical characteristics and three-month outcome of all enrolled women with pregnancy, postpartum or using hormonal contraceptives. As of December 2008, 173 pregnant women, 135 postpartum, and 798 contraceptive users were enrolled. Of these, 438 (40%) presented with pulmonary embolism (PE) and 668 with deep-vein thrombosis (DVT). Most women with acute PE had dyspnea (72%) or chest pain (75%), but only 2.0% had hypoxaemia. During the three-month study period, five women (0.45%; 95% CI: 0.17-1.00) died (3 had fatal PE), 13 (1.18%; 95% CI: 0.66-1.95) had VTE recurrences, and seven (0.63%; 95% CI: 0.28-1.25) major bleeding. Two of the three women with fatal PE died during the first few hours after arriving at the emergency ward, with no time to start any therapy. The outcome of pregnant or postpartum women with VTE is similar to that in contraceptive users, even though the treatment is different. The non-specific nature of PE signs may have caused some delay in PE diagnosis.


[The change of some indices of coagulogram in rats in experimental pancreonecrosis under the influence of electromagnet irradiation of extremely high frequencies].
The dynamics of changes of some coagulogram indices under the influence of electromagnet irradiation of extremely high frequencies was studied in rats in conditions of experimental pancreonecrosis. Irradiation of abdominal cavity in animals, using electromagnet irradiation with the 6.5 mm wave length, reduces hypercoagulation shifts essentially and raises the plasm anticoagulant and fibrinolytic activity.


Black Community Conversations About Opposing Ethnically Targeted Marketing of Unhealthy Foods and Beverages.
Efforts to reduce disparities in obesity prevalence affecting Black Americans are having limited success. One reason for this may be the disproportionate, ethnically targeted marketing of foods and beverages high in fat and sugar (FBHFS) to Black consumers. Such marketing promotes high consumption of FBHFS, leading to excess caloric intake and unintentional weight gain. We convened focus groups with Black men and women (total n = 57) in collaboration with community groups in three localities to elicit their views, as consumers and parents/caregivers, about targeted FBHFS marketing and potential ways to combat it. At each location, trained community members facilitated two sets of focus groups: one for adults aged 18 to 25 years and another for adults aged 26 to 55 years who had a 3-to-17-year-old child at home. Each group met twice to discuss food and beverage marketing practices to Black communities and reviewed a booklet about ethnically targeted marketing tactics in between. A directed content analysis of participant comments identified and explored salient themes apparent from initial summarization of results. Results show how parents are concerned with and critical of pervasive FBHFS marketing. In particular, comments emphasize the involvement of Black celebrities in FBHFS marketing-how and why they engage in such marketing and whether this could be shifted towards healthier foods. These findings suggest a potential role for counter marketing efforts focused on Black celebrity endorsements of FBHFS, possibly with a youth focus. They also underscore the need for additional, qualitative exploration of Black consumer views of ethnically targeted FBHFS marketing more generally.


Can the risk of gadolinium be extrapolated to lanthanum?
The recent recognition of gadolinium (Gd) administration as a cause of nephrogenic systemic fibrosis (NSF) is a growing concern. The similarity of Gd and lanthanum (La), based on their place in the table of Mendeljev, has led to assumptions that the NSF risk of Gd in patients with kidney disease can de extrapolated to La. However, Gd and La, two trivalent cations, differ substantially in their metabolism, pharmacokinetics, and most importantly in their clinical use and toxicity. Thus, it is extremely unlikely that La can cause NSF.


Analytical Validation and Capabilities of the Epic CTC Platform: Enrichment-Free Circulating Tumour Cell Detection and Characterization.
The Epic Platform was developed for the unbiased detection and molecular characterization of circulating tumour cells (CTCs). Here, we report assay performance data, including accuracy, linearity, specificity and intra/inter-assay precision of CTC enumeration in healthy donor (HD) blood samples spiked with varying concentrations of cancer cell line controls (CLCs). Additionally, we demonstrate clinical feasibility for CTC detection in a small cohort of metastatic castrate-resistant prostate cancer (mCRPC) patients. The Epic Platform demonstrated accuracy, linearity and sensitivity for the enumeration of all CLC concentrations tested. Furthermore, we established the precision between multiple operators and slide staining batches and assay specificity showing zero CTCs detected in 18 healthy donor samples. In a clinical feasibility study, at least one traditional CTC/mL (CK+, CD45-, and intact nuclei) was detected in 89 % of 44 mCRPC samples, whereas 100 % of samples had CTCs enumerated if additional CTC subpopulations (CK-/CD45- and CK+ apoptotic CTCs) were included in the analysis. In addition to presenting Epic Platform's performance with respect to CTC enumeration, we provide examples of its integrated downstream capabilities, including protein biomarker expression and downstream genomic analyses at single cell resolution.


Molecular surface chemistry by metal single crystals and nanoparticles from vacuum to high pressure.
Model systems for studying molecular surface chemistry have evolved from single crystal surfaces at low pressure to colloidal nanoparticles at high pressure. Low pressure surface structure studies of platinum single crystals using molecular beam surface scattering and low energy electron diffraction techniques probe the unique activity of defects, steps and kinks at the surface for dissociation reactions (H-H, C-H, C-C, O=O bonds). High-pressure investigations of platinum single crystals using sum frequency generation vibrational spectroscopy have revealed the presence and the nature of reaction intermediates. High pressure scanning tunneling microscopy of platinum single crystal surfaces showed adsorbate mobility during a catalytic reaction. Nanoparticle systems are used to determine the role of metal-oxide interfaces, site blocking and the role of surface structures in reactive surface chemistry. The size, shape and composition of nanoparticles play important roles in determining reaction activity and selectivity and is covered in this tutorial review.


Neuronal synchrony and the relation between the blood-oxygen-level dependent response and the local field potential.
The most widespread measures of human brain activity are the blood-oxygen-level dependent (BOLD) signal and surface field potential. Prior studies report a variety of relationships between these signals. To develop an understanding of how to interpret these signals and the relationship between them, we developed a model of (a) neuronal population responses and (b) transformations from neuronal responses into the functional magnetic resonance imaging (fMRI) BOLD signal and electrocorticographic (ECoG) field potential. Rather than seeking a transformation between the two measures directly, this approach interprets each measure with respect to the underlying neuronal population responses. This model accounts for the relationship between BOLD and ECoG data from human visual cortex in V1, V2, and V3, with the model predictions and data matching in three ways: across stimuli, the BOLD amplitude and ECoG broadband power were positively correlated, the BOLD amplitude and alpha power (8-13 Hz) were negatively correlated, and the BOLD amplitude and narrowband gamma power (30-80 Hz) were uncorrelated. The two measures provide complementary information about human brain activity, and we infer that features of the field potential that are uncorrelated with BOLD arise largely from changes in synchrony, rather than level, of neuronal activity.


Furan levels in coffee as influenced by species, roast degree, and brewing procedures.
Brazilian green coffee beans of Coffea arabica and Coffea canephora species were roasted to light, medium, and dark roast degrees and analyzed in relation to furan content by using an in-house validated method based on gas chromatography coupled to mass spectrometry preceded by headspace solid-phase microextraction. Furan was not detected in green coffees, whereas levels between 911 and 5852 μg/kg were found in the roasted samples. Higher concentrations were found in Coffea canephora species and darker ground coffees. Some of the potential furan precursors were observed in significant amounts in green coffee, especially sucrose and linoleic acid, but their concentrations could not be correlated to furan formation. Additionally, coffee brews were prepared from roasted ground coffees by using two different procedures, and furan levels in the beverages varied from <10 to 288 μg/kg. The factor that most influenced the furan content in coffee brew was the brewing procedure.


High-speed particle separation and steric inversion in thin flow field-flow fractionation channels.
The performance of thin (down to 71 microns thick) flow field-flow fractionation (flow FFF) channels was examined at both high channel flow-rates (up to approximately 47 ml/min) and cross flow-rates (up to approximately 11 ml/min). High levels of retention were observed, suggestive of good performance characteristics. Supporting this expectation, four sizes (0.04-0.30 microns) of polystyrene latex microbeads were baseline separated in under 3 min. Nonetheless, a plate height analysis showed that performance was still less than theoretically expected. Fast steric-hyperlayer separations of larger latex beads were observed in the same systems. Furthermore, it was shown that the steric inversion diameter was shifted down to approximately 0.23 micron thus expanding the size range to which this FFF mode is applicable. The steric inversion phenomenon observed using narrow latex standards was shown to be consistent with that found for a polydisperse polyvinylchloride latex.


Scientific evidence of diets for weight loss: Different macronutrient composition, intermittent fasting, and popular diets.
New dietary strategies have been created to treat overweight and obesity and have become popular and widely adopted. Nonetheless, they are mainly based on personal impressions and reports published in books and magazines, rather than on scientific evidence. Animal models and human clinical trials have been employed to study changes in body composition and metabolic outcomes to determine the most effective diet. However, the studies present many limitations and should be carefully analyzed. The aim of this review was to discuss the scientific evidence of three categories of diets for weight loss. There is no one most effective diet to promote weight loss. In the short term, high-protein, low-carbohydrate diets and intermittent fasting are suggested to promote greater weight loss and could be adopted as a jumpstart. However, owing to adverse effects, caution is required. In the long term, current evidence indicates that different diets promoted similar weight loss and adherence to diets will predict their success. Finally, it is fundamental to adopt a diet that creates a negative energy balance and focuses on good food quality to promote health.


[Molecular mechanisms of autophagy in regulating renal aging and interventional effects of Chinese herbal medicine].
Aging is the gradual functional recession of the living tissues or organs caused by a variety of genetic and environmental factors together. Autophagy is a process of degrading cytoplasmic components mediated by lysosomes in eukaryotic cells. Kidney is a typical target organ of aging. Autophagy regulates renal aging. Decrease in autophagy can accelerate renal aging,whereas,increase in autophagy can delay renal aging. During the process of regulating renal aging,the mammalian target of rapamycin (mTOR) and its related signaling pathways including the adenosine monophosphate activated protein kinase (AMPK)/mTOR,the phosphatidylinositol 3-kinase (PI3K)/ serine-threonine kinase(Akt)/mTOR,the AMPK/silent information regulation 1 (Sirt1) and transforming growth factor β (TGF-β) play the important roles in renal aging. Regulating the key signaling molecules in these pathways in vivo can control renal aging. Some Chinese herbal medicine (CHM) and their extracts with the effects of nourishing kidney or activating stasis, such as Cordyceps sinensis, curcumin and resveratrol have the beneficial effects on renal aging and/or autophagy. Therefore,revealing the pharmacological effects of CHM in anti-renal aging based on the molecular mechanisms of autophagy will become one of the development trends in the future study.


Acetaminophen or Nonsteroidal Anti-Inflammatory Drugs in Acute Musculoskeletal Trauma: A Multicenter, Double-Blind, Randomized, Clinical Trial.
We determine whether pain treatment with acetaminophen was not inferior to nonsteroidal anti-inflammatory drugs or the combination of both in minor musculoskeletal trauma. The Paracetamol or NSAIDs in Acute Musculoskeletal Trauma Study was a double-blind, randomized, clinical trial conducted in 2 general practices and 2 emergency departments in the Netherlands. A total of 547 adults, aged 18 years and older, with acute blunt minor musculoskeletal extremity trauma were randomly assigned in a 1:1:1 ratio to acetaminophen 4,000 mg/day, diclofenac 150 mg/day, or acetaminophen 4,000 mg/day+diclofenac 150 mg/day during 3 consecutive days. Patients, health care staff, and outcome assessors were blinded for treatment allocation. Follow-up for each patient was 30 days. Primary outcome measures were between-group differences in mean numeric rating scale (NRS) pain scores in rest and with movement at 90 minutes after initial drug administration compared with baseline pain scores with a predefined noninferiority margin of 0.75 NRS points. Secondary outcomes included NRS pain scores during 3 consecutive days and need for additional analgesia. One hundred eighty-two patients were treated with acetaminophen, 183 with diclofenac, and 182 with combination treatment. Intention-to-treat analysis revealed mean NRS reduction in rest -1.23 (95% confidence interval [CI] -1.50 to -0.95) and -1.72 (95% CI -2.01 to -1.44) with movement, both for acetaminophen at 90 minutes compared with baseline. Pairwise comparison in rest with diclofenac showed a difference of -0.027 (97.5% CI -0.45 to 0.39) and -0.052 (97.5% CI -0.46 to 0.36) for combination treatment. With movement, these numbers were -0.20 (97.5% CI -0.64 to 0.23) and -0.39 (97.5% CI -0.80 to 0.018), respectively. All differences were well below the predefined noninferiority margin. Pain treatment with acetaminophen was not inferior to that with diclofenac or the combination of acetaminophen and diclofenac in acute minor musculoskeletal extremity trauma, both in rest and with movement.


Comparison of treatment effects during en-masse retraction of upper anterior teeth placed using mini-implants placed at infrazygomatic crest and interradicular sites: A randomized controlled trial.
The objective of this prospective study was to examine the efficacy of posterior interradicular and infrazygomatic crest mini-implants for en-masse anterior retraction. The 22 patients were divided into two groups. In group 1 (IZC n = 11), mini-implants were placed in the infrazygomatic crests and in group 2 (IR, n = 11), mini-implants were placed in the molar-premolar interradicular sites. Soft tissue, skeletal, and dental treatment effects between two groups were compared using lateral cephalometric measurements. The average angle between the cranial base and A point was 1.01 degrees (P = .004), and the linear distance between the upper incisor and A point was 2.67 to 5.2 millimetres (P = .00). In IZC group the maxillary incisor to the palatal plane moved upward by a mean of -5.20 mm (P = .059), whereas in IR group the incisor movement changed by -2.67 mm (P = .068). There was no significant difference between groups IZC and IR while comparing overall treatment changes on upper incisor position change, angle, and overjet. Mini-implants placed in between the molar and premolar as well as the infrazygomatic crest can withstand the deepening of the bite during retraction. Mini-implants in IZC are capable of causing intrusion of the anterior teeth and preventing intrusion of the molars, thereby providing absolute anchoring in all planes. Placement of the mini-implants in the infrazygomatic crest resulted in more linear retraction.


Medical malpractice and sarcoma care--a thirty-three year review of case resolutions, inciting factors, and at risk physician specialties surrounding a rare diagnosis.
We reviewed medico-legal cases related to extremity sarcoma malpractice in order to recognize those factors most commonly instigating sarcoma litigation. Over one million legal cases available in a national legal database were searched for malpractice verdicts and settlements involving extremity sarcoma spanning 1980-2012. We categorized verdict/settlement resolutions by state, year, award amount, nature of the complaint/injury, specialty of the physician defendant, and academic affiliation of defendant-amongst other variables. Of the 216 cases identified, 57% of case resolutions favored the plaintiff, with a mean indemnity payment of $2.30 million (range $65,076-$12.66 million). Delay in diagnosis (81%), unnecessary amputation (11%), and misdiagnosis (7%) accounted for the majority of complaints. The greatest numbers of claims were filed against primary care specialties (34%), orthopaedic surgeons (23%), and radiologists (12%). Individual state tort reform measures were not protective against case resolution outcome. Reported medico-legal claims involving sarcoma care continue to rise, with mean indemnity payments approaching 10 times that for other reported medical/surgical specialties. Primary care and orthopaedic specialties are the most commonly named physician defendants, citing a delay in diagnosis. This suggests further education in the front line diagnosis and management of sarcomas is needed.


Targeting the COPD exacerbation.
Exacerbations of COPD have a profound detrimental effect on the patient and impose a significant burden on healthcare resource utilization. Prevention and treatment of exacerbations are major objectives of the clinical management of COPD. For this approach to be successful, clinicians must combine both pharmacologic approaches and non-pharmacologic strategies aimed at improving the patient's disease management. Non-pharmacologic approaches include those that can be incorporated into the office setting as well as intervention strategies that are integrated into the lifelong management of COPD. These strategies include developing a partnership with the patient and their social supports, encouraging and facilitating smoking cessation, immunizations, proper use of supplemental oxygen, and most importantly, giving the patient the tools to manage their illness appropriately. Moreover there is clear evidence of an irrevocable decline in pulmonary function after each exacerbation, usually resulting in reduced physical activity and impaired skeletal muscle function. Not surprisingly, pulmonary rehabilitation after such events has been shown to prevent relapse, improve survival and enhance patients' overall function after acute exacerbations.


Circadian variation in ischemic stroke subtypes.
While previous studies suggest that the peak time period for the occurrence of ischemic stroke is in the mid- to late-morning hours, detailed information pertaining to circadian variations among the various stroke subtypes has been limited. The purpose of our study was to define the circadian patterns of symptom onset in an acute stroke trial with an established system for stroke subtype classification. An analysis was conducted on 1272 patients enrolled in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) study. All patients had a documented time of stroke symptom onset, and all stroke subtype determinations were made by a single rater. The Greatest portion of atherothrombotic strokes (25.7%), cardioembolic strokes (30.5%), and strokes of other/unknown mechanism (27.1%) occurred between 6:01 AM and 12:00 noon. The greatest portion of lacunar strokes (31.6%) were present on awakening. More than one half of the infarcts in this series were either present on awakening or occurred in the mid- to late-morning hours. The correlation between stroke subtype and time of symptom onset did not reach statistical significance (P=0.07, Pearson's chi(2) method). Although there is a trend for clustering of ischemic stroke in the morning hours, there is insufficient specificity to predict with any reasonable likelihood the stroke subtype according to the circadian pattern of symptom onset.


[Natural and UV-induced variability of the producer of telavimycin Streptomyces levoris, Krass, strain 243].
The experimental data showed that the morphological variation of the culture of strain 243 of Streptomyces levoris, Krass, producing telavimycin (antibiotic 243) resulted in the formation of three morphological types differing in some features from the initial culture. Cultures of the type I and II colonies were most promising for selection. Strains producing higher yields of the antibiotic as compared to the initial strain 243 were selected from these cultures. After exposure of the spores of strain 243-96 to UV light in a dose of 500 erg/mm2 a highly productive strain 243-197 was isolated. The activity of this strain is 51 per cent higher than that of strain 243-96.


From intermodulation components to visual perception and cognition-a review.
Perception results from complex interactions among sensory and cognitive processes across hierarchical levels in the brain. Intermodulation (IM) components, used in frequency tagging neuroimaging designs, have emerged as a promising direct measure of such neural interactions. IMs have initially been used in electroencephalography (EEG) to investigate low-level visual processing. In a more recent trend, IMs in EEG and other neuroimaging methods are being used to shed light on mechanisms of mid- and high-level perceptual processes, including the involvement of cognitive functions such as attention and expectation. Here, we provide an account of various mechanisms that may give rise to IMs in neuroimaging data, and what these IMs may look like. We discuss methodologies that can be implemented for different uses of IMs and we demonstrate how IMs can provide insights into the existence, the degree and the type of neural integration mechanisms at hand. We then review a range of recent studies exploiting IMs in visual perception research, placing an emphasis on high-level vision and the influence of awareness and cognition on visual processing. We conclude by suggesting future directions that can enhance the benefits of IM-methodology in perception research.


Surgical approach to synchronous colorectal liver metastases: staged, combined, or reverse strategy.
An increasing number of patients with colorectal cancer (CRC) are presenting with synchronous disease to the liver. The optimal surgical approach for this complex patient group is controversial, but ultimately depends on individual patient characteristics and institutional practices. Surgical strategies include the traditional staged approach, a combined colorectal and liver resection, or a liver-first reverse approach. In this review, the authors will provide an overview of each strategy, including case examples demonstrating the benefits of the more recently described liver-first approach, while arguing for individualized planning and multidisciplinary discussion for every patient.


Reduction in mortality from implantable cardioverter-defibrillators in non-ischaemic cardiomyopathy patients is dependent on the presence of left ventricular scar.
In patients with non-ischaemic cardiomyopathy (NICM), the mortality benefit of a primary prevention implantable cardioverter-defibrillator (ICD) has been challenged. Left ventricular (LV) scar identified by cardiac magnetic resonance (CMR) imaging is associated with a high risk of malignant arrhythmia in NICM. We aimed to determine the impact of LV scar on the mortality benefit from a primary prevention ICD in NICM. We recruited 452 consecutive heart failure patients [New York Heart Association (NYHA) Class II/III] with NICM and LV ejection fraction ≤35% from a state-wide CMR service. All patients fulfilled European Society of Cardiology guidelines for primary prevention ICD implantation; however, the decision to implant was at the treating physician's discretion. Baseline clinical and CMR data were recorded prospectively and heart failure mortality risk (MAGGIC score) was calculated. The primary study outcome measurement was all-cause mortality based on presence or absence of ICD, stratified by LV scar. Median follow-up was 37.9 months and there was no difference in MAGGIC score between those who did and did not receive a primary prevention ICD (19.30 ± 5.46 vs. 18.90 ± 5.67, P = 0.50). In patients without LV scar, ICD implantation was not associated with improved mortality [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 0.53-2.78, P = 0.64]. In patients with LV scar, ICD implantation was independently associated with reduced mortality (HR = 0.45, 95% CI: 0.26-0.77, P = 0.003). In patients with NICM, primary prevention ICD implantation is only associated with reduced mortality in patients with LV scar. This may enable more effective selection of NICM patients for ICD implantation compared with current guidelines.


Decoding immunogenic cell death from a dendritic cell perspective.
Dendritic cells (DCs) are myeloid cells bridging the innate and adaptive immune system. By cross-presenting tumor-associated antigens (TAAs) liberated upon spontaneous or therapy-induced tumor cell death to T cells, DCs occupy a pivotal position in the cancer immunity cycle. Over the last decades, the mechanisms linking cancer cell death to DC maturation, have been the focus of intense research. Growing evidence supports the concept that the mere transfer of TAAs during the process of cell death is insufficient to drive immunogenic DC maturation unless this process is coupled with the release of immunomodulatory signals by dying cancer cells. Malignant cells succumbing to a regulated cell death variant called immunogenic cell death (ICD), foster a proficient interface with DCs, enabling their immunogenic maturation and engagement of adaptive immunity against cancer. This property relies on the ability of ICD to exhibit pathogen-mimicry hallmarks and orchestrate the emission of a spectrum of constitutively present or de novo-induced danger signals, collectively known as damage-associated molecular patterns (DAMPs). In this review, we discuss how DCs perceive and decode danger signals emanating from malignant cells undergoing ICD and provide an outlook of the major signaling and functional consequences of this interaction for DCs and antitumor immunity.


The decision to treat: profiling benefit.
The decision to treat a hypertensive patient is usually based on the level of the blood pressure and some consideration of epidemiological risk factors. The implicit assumption is that all patients derive the same benefit from a particular type of drug. Recent evidence suggests that benefits are influenced by many factors, both positive and negative, which include age, sex, race, tobacco smoking and many diseases that can be provoked or aggravated by commonly used drugs, e.g. asthma, claudication, diabetes and gout. Risk factor analysis no longer seems the most appropriate technique on which to base treatment decisions. Analysis of potential benefits from different treatment strategies in an individual patient seems a better way.


[Expression and Clinical Significance of NAMPT in Bone Marrow of Patients with Multiple Myeloma].
To study the expression level of nicotinamide phosphoribosyltransferase (NAMPT) in multiple myeloma (MM), its relationship with clinical indicators, prognosis and potential role. Immunohistochemical staining was used to detect the expression of NAMPT in bone marrow biopsies of patients with newly diagnosed multiple myeloma (NDMM) and patients with iron deficiency anemia (IDA) hospitalized during the same period. According to the median expression level of NAMPT, NDMM patients were divided into high expression group and low expression group. The correlation between NAMPT expression level and clinical baseline data was analyzed, and survival analysis was performed to evaluate the relationship between NAMPT expression level and prognosis. The GSE24080 and GSE19784 datasets were used to analyze the effect of NAMPT on the prognosis. Gene set enrichment analysis (GSEA) explored the possible mechanism of NAMPT involved in MM cell function. The mean staining intensity of NAMPT in bone marrow tissue of 31 NDMM patients was 0.007±0.002, and that of 10 IDA patients was 0.002±0.002 (P < 0.05). The median expression level of NAMPT was 0.0041 in NDMM patients, and the mean staining intensity of high expression group and low expression group was 0.007±0.005 and 0.002±0.001, respectively (P < 0.001). There were certain differences in lactate dehydrogenase (LDH), C-reactive protein (CRP) and ISS staging between high expression group and low expression group (P < 0.001), while no significant differences in other indicators. The overall response rate (ORR) of high expression group was significantly lower than that of low expression group (P < 0.001). The median survival time of patients in high expression group was significantly shorter than that in low expression group (P =0.024). The results of bioinformatics analysis showed that the event-free survival (EFS) rate and overall survival (OS) rate of low NAMPT group were both higher than high NAMPT group (P =0.037, P =0.009), and NAMPT was an independent prognostic factor for EFS and OS (P =0.006, P =0.020). GSEA suggested that NAMPT might affect MM cell function through mTORC1 signaling pathway. The expression level of NAMPT in bone marrow of NDMM patients is significantly higher than that of IDA patients, and the high expression of NAMPT may be correlated with late ISS stage, and high level of LDH and CRP. Patients with high expression of NAMPT have worse response to bortezomib and survival time may be shorter. NAMPT may be involved in the occurrence and development of MM through mTORC1 signaling pathway.


Mass Effect After Flow Diversion for Unruptured Large and Giant Cavernous or Paraclinoid Internal Carotid Artery Aneurysm.
The mass effect associated with large or giant intracranial aneurysms is difficult for traditional endovascular treatment. This study investigated whether flow diverters can relieve the aneurysmal mass effect caused by aneurysmal compression symptoms. Fifty-five patients with unruptured large and giant intracranial aneurysms treated by a flow diverter at our institution from January 2014 to February 2022 were retrospectively evaluated. In this study, 53 patients were included. Initially, 27 patients (51.9%), including 10 with compressive optic neuropathy, 12 with third nerve palsy, 2 with facial hyperesthesia, and 11 with sixth nerve palsy, were symptomatic. The symptom duration was shorter in the improved group (n = 2.2 ± 4.0 vs. n = 3.1 ± 3.9, P = 0.49). Thrombus formation following the flow diversion procedure was typically observed on magnetic resonance imaging (MRI) performed immediately and was not significantly associated with symptomatic improvement (OR = 0.395; 95% CI (0.058-2.698), P = 0.343). However, symptomatic improvement was seen in most patients when the aneurysm size decreased on MRI. A reduction in the aneurysm size on the MRI at the 3-month follow-up was correlated with symptomatic improvement in the multivariate analysis (OR = 0.08, 95% CI (0.013-0.485), P < 0.05). A flow diverter might help alleviate compression symptoms caused by large or giant intracranial aneurysms. Shrinkage of the aneurysm within 3 months postoperatively and a shorter duration of symptoms contribute to the favorable outcomes of mass effect. Ultimately, prompt treatment is crucial for improving symptomatic intracranial artery aneurysms.


Kinetic properties and role of bacterial chitin deacetylase in the bioconversion of chitin to chitosan.
Chitin is an extremely insoluble material with very limited industrial use; however it can be deacetylated to soluble chitosan which has a wide range of applications. The enzymatic deacetylation of various chitin samples was investigated using the bacterial chitin deacetylase (CDA), which was partially purified from Alcaligenes sp. ATCC 55938 growth medium and the kinetic parameters of the enzyme were determined. Also, the efficiency of biocatalyst recycling by immobilization technique was examined. CDA activity reached its maximum (0.419 U/ml) after 18 h of bacterial cultivation. When glycol chitin was used as a substrate, the optimum pH of the enzyme was estimated to be 6 after checking a pH range between 3 and 9, while the optimum temperature was found to be 35°C. Addition of acetate (100 mM) in the assay mixture resulted in 50% loss of enzyme activity. The Km value of the enzyme is 1.6 × 10(-4) µM and Vmax is 24.7 µM/min. The average activity of CDA was 0.38 U/ml for both of immobilized and freely suspended cells after 18 h of bacterial growth. Some related patents are also discussed here.


Small RNA deep sequencing discriminates subsets of extracellular vesicles released by melanoma cells--Evidence of unique microRNA cargos.
Melanoma cells release different types of extracellular vesicles (EVs) into the extracellular milieu that are involved with communication and signaling in the tumor microenvironment. Subsets of EVs include exosomes, microvesicles, and apoptotic bodies that carry protein and genetic (RNA) cargos. To define the contribution of the RNA cargo of melanoma cell derived EVs we performed small RNA sequencing to identify different small RNAs in the EV subsets. Using validated centrifugation protocols, we separated these EV subsets released by the melanoma cell line MML-1, and performed RNA sequencing with the Ion Torrent platform. Various, but different, non-coding RNAs were detected in the EV subsets, including microRNA, mitochondrial associated tRNA, small nucleolar RNA, small nuclear RNA, Ro associated Y-RNA, vault RNA and Y-RNA. We identified in total 1041 miRNAs in cells and EV subsets. Hierarchical clustering showed enrichment of specific miRNAs in exosomes, including hsa-miR-214-3p, hsa-miR-199a-3p and hsa-miR-155-5p, all being associated with melanoma progression. Comparison of exosomal miRNAs with miRNAs in clinical melanoma samples indicate that multiple miRNAs in exosomes also are expressed specifically in melanoma tissues, but not in benign naevi. This study shows for the first time the presence of distinct small RNAs in subsets of EVs released by melanoma cells, with significant similarities to clinical melanoma tissue, and provides unique insights into the contribution of EV associated extracellular RNA in cancer.


Dimeric Organization of Blood Coagulation Factor VIII bound to Lipid Nanotubes.
Membrane-bound Factor VIII (FVIII) has a critical function in blood coagulation as the pro-cofactor to the serine-protease Factor IXa (FIXa) in the FVIIIa-FIXa complex assembled on the activated platelet membrane. Defects or deficiency of FVIII cause Hemophilia A, a mild to severe bleeding disorder. Despite existing crystal structures for FVIII, its membrane-bound organization has not been resolved. Here we present the dimeric FVIII membrane-bound structure when bound to lipid nanotubes, as determined by cryo-electron microscopy. By combining the structural information obtained from helical reconstruction and single particle subtomogram averaging at intermediate resolution (15-20 Å), we show unambiguously that FVIII forms dimers on lipid nanotubes. We also demonstrate that the organization of the FVIII membrane-bound domains is consistently different from the crystal structure in solution. The presented results are a critical step towards understanding the mechanism of the FVIIIa-FIXa complex assembly on the activated platelet surface in the propagation phase of blood coagulation.


Mitochondrial AIF loss causes metabolic reprogramming, caspase-independent cell death blockade, embryonic lethality, and perinatal hydrocephalus.
Apoptosis-Inducing Factor (AIF) is a protein involved in mitochondrial electron transport chain assembly/stability and programmed cell death. The relevant role of this protein is underlined because mutations altering mitochondrial AIF properties result in acute pediatric mitochondriopathies and tumor metastasis. By generating an original AIF-deficient mouse strain, this study attempted to analyze, in a single paradigm, the cellular and developmental metabolic consequences of AIF loss and the subsequent oxidative phosphorylation (OXPHOS) dysfunction. We developed a novel AIF-deficient mouse strain and assessed, using molecular and cell biology approaches, the cellular, embryonic, and adult mice phenotypic alterations. Additionally, we conducted ex vivo assays with primary and immortalized AIF knockout mouse embryonic fibroblasts (MEFs) to establish the cell death characteristics and the metabolic adaptive responses provoked by the mitochondrial electron transport chain (ETC) breakdown. AIF deficiency destabilized mitochondrial ETC and provoked supercomplex disorganization, mitochondrial transmembrane potential loss, and high generation of mitochondrial reactive oxygen species (ROS). AIF-/Y MEFs counterbalanced these OXPHOS alterations by mitochondrial network reorganization and a metabolic reprogramming toward anaerobic glycolysis illustrated by the AMPK phosphorylation at Thr172, the overexpression of the glucose transporter GLUT-4, the subsequent enhancement of glucose uptake, and the anaerobic lactate generation. A late phenotype was characterized by the activation of P53/P21-mediated senescence. Notably, approximately 2% of AIF-/Y MEFs diminished both mitochondrial mass and ROS levels and spontaneously proliferated. These cycling AIF-/Y MEFs were resistant to caspase-independent cell death inducers. The AIF-deficient mouse strain was embryonic lethal between E11.5 and E13.5 with energy loss, proliferation arrest, and increased apoptotic levels. Contrary to AIF-/Y MEFs, the AIF KO embryos were unable to reprogram their metabolism toward anaerobic glycolysis. Heterozygous AIF+/- females displayed progressive bone marrow, thymus, and spleen cellular loss. In addition, approximately 10% of AIF+/- females developed perinatal hydrocephaly characterized by brain development impairment, meningeal fibrosis, and medullar hemorrhages; those mice died 5 weeks after birth. AIF+/- with hydrocephaly exhibited loss of ciliated epithelium in the ependymal layer. This phenotype was triggered by the ROS excess. Accordingly, it was possible to diminish the occurrence of hydrocephalus AIF+/- females by supplying dams and newborns with an antioxidant in drinking water. In a single knockout model and at 3 different levels (cell, embryo, and adult mice) we demonstrated that by controlling the mitochondrial OXPHOS/metabolism, AIF is a key factor regulating cell differentiation and fate. Additionally, by providing new insights into the pathological consequences of mitochondrial OXPHOS dysfunction, our new findings pave the way for novel pharmacological strategies.


Is a cancer diagnosis associated with subsequent risk of transient global amnesia?
Psychological stress has been associated with transient global amnesia (TGA). Whether a cancer diagnosis, a severely stressful life event, is associated with subsequent risk of TGA has not been studied. Based on the Swedish Cancer Register and Patient Register, we conducted a prospective cohort study including 5,365,608 Swedes at age 30 and above during 2001-2009 to examine the relative risk of TGA among cancer patients, as compared to cancer-free individuals. Incidence rate ratios (IRRs) and their 95% confidence intervals (CIs) derived from Poisson regression were used as estimates of the association between cancer diagnosis and the risk of TGA. During the study 322,558 individuals (6.01%) received a first diagnosis of cancer. We identified 210 cases of TGA among the cancer patients (incidence rate, 0.22 per 1000 person-years) and 4,887 TGA cases among the cancer-free individuals (incidence rate, 0.12 per 1000 person-years). Overall, after adjustment for age, sex, calendar year, socioeconomic status, education and civil status, cancer patients had no increased risk of TGA than the cancer-free individuals (IRR, 0.99; 95% CI, 0.86-1.13). The IRRs did not differ over time since cancer diagnosis or across individual cancer types. The null association was neither modified by sex, calendar period or age. Our study did not provide support for the hypothesis that patients with a new diagnosis of cancer display a higher risk of TGA than cancer-free individuals.


[Mechanisms of early changes in water-electrolyte metabolism in man in various ground-based models of the effects of microgravity].
Analysed was an array of data amassed in 4 series of experiments with simulated microgravity effects (HDT (-6 degrees); dry and suited immersions in horizontal and vertical position). Water-electrolyte turnover in blood and urine and hormonal controls have been under study. It was demonstrated that irrespective of the body axis position relative to the gravity vector in the immersion models, reactions of the active regulation of the water--electrolyte metabolism were noted already within the initial hours, i.e. more rapidly than in HDT. During the early phase of adaptation to the immersion models, some ostensibly similar responses were governed by different hormonal controls. Unlike the dry immersion, the suited immersion tests with various body positioning modified not only the strength but the dynamics of the water-electrolyte regulation, too. Findings also included differences in the dynamics osmo- and volumoregulation in the vertical and horizontal suited immersion tests which are, possibly, reflective of recruitment of different stimulating mechanisms and efficiency of organs-targets.


Successful Pulmonary Artery Embolization for the Management of Hemoptysis in a Patient with Eisenmenger Syndrome Caused by Patent Ductus Arteriosus.
The patient was a 19-year-old woman who was diagnosed with patent ductus arteriosus complicating Eisenmenger syndrome at a previous medical institution. She was referred to our hospital and arranged for lung transplantation. She developed hemoptysis after the introduction of i.v. epoprostenol, which was administered as a bridging treatment while the patient awaited lung transplantation. She continued to suffer from recurrent hemoptysis, even after switching from i.v. epoprostenol to i.v. treprostinil. Angiography of the systemic and pulmonary arteries revealed the vessel responsible for the recurrent hemoptysis and pulmonary artery embolization was successfully performed. It is essential to identify the culprit vessel and physicians must not hesitate in performing embolization when patients develop lethal hemoptysis.


The proliferation of plasma cells from mouse bone marrow in vitro. I. The role of thymus.
An in vitro proliferative system for immunoglobulin-G-forming plasma cells from the bone marrow of mice was established by the addition of antigenic protein and thymic cells or their homogenate to bone marrow cultures. The promoting activity of the thymus on plasma cells was independent from mouse strain, but it differed in strength with the variations of donor strains. Synthesis of immunoglobulin-G in proliferating plasma cells and its antibody reactivity against the administered antigen were demonstrated by immunocytological analyses.


Gene duplication and phylogeography of North American members of the Hart Park serogroup of avian rhabdoviruses.
Flanders virus (FLAV) and Hart Park virus (HPV) are rhabdoviruses that circulate in mosquito-bird cycles in the eastern and western United States, respectively, and constitute the only two North American representatives of the Hart Park serogroup. Previously, it was suggested that FLAV is unique among the rhabdoviruses in that it contains two pseudogenes located between the P and M genes, while the cognate sequence for HPV has been lacking. Herein, we demonstrate that FLAV and HPV do not contain pseudogenes in this region, but encode three small functional proteins designated as U1-U3 that apparently arose by gene duplication. To further investigate the U1-U3 region, we conducted the first large-scale evolutionary analysis of a member of the Hart Park serogroup by analyzing over 100 spatially and temporally distinct FLAV isolates. Our phylogeographic analysis demonstrates that although FLAV appears to be slowly evolving, phylogenetically divergent lineages co-circulate sympatrically.


[Professional development and entering the labor market: the perceptions of nursing graduates].
The professional history of nursing graduates allows for understanding and reflecting on higher education and the characteristics inherent in the job market. The objectives of the present study were to analyze the perceptions that nursing graduates of a private university have regarding their development process, focusing on the conditions of entering the job market and the demands they deal with in their professional life. The Collective Subject Discourse was the method of choice used in this study. Participants included 104 graduates who were divided into three groups according to their position after graduation. Discourse analysis allowed for deep reflection regarding their preparation, indicating the need to review the pedagogical project, particularly in terms of developing competencies in the four dimensions of care: management, healthcare, education, and research.


Six-month outcome following a relapse of schizophrenia.
To analyse clinical data on patients with schizophrenia on admission to acute care and 6 months later in order to identify factors associated with frequent hospitalisations and poor outcome. Information was collected from the medical records of 99 patients with schizophrenia consecutively admitted to acute care in hospital or by community based 24 h Crisis Teams and prospectively studied for 6 months. One-quarter of patients were being admitted to acute care within 3 months of their last hospital discharge and only 34 patients were compliant with their neuroleptic medication 3 months prior to the index admission. Twenty-one patients were managed entirely by the Crisis Teams, 27 patients received inpatient care only and the remainder (n = 51) had both types of acute care. Six months after admission, 42 patients had been discharged and did not require further acute care, 29 patients had been re-admitted at least once and three patients had been transferred to an inpatient rehabilitation unit and, therefore, remained in hospital over the entire period. Of the remaining 25 patients, one committed suicide 2 months after discharge and the other patients were not contactable by Community Mental Health Teams at the 2 and/or 6 month follow up. Some of the factors associated with relapse identified in the present study were non-compliance with medication, stress, inadequate social support and substance abuse. The poor outcome in patients with frequent relapses emphasises the need to reduce the occurrences of schizophrenic symptoms to provide a better quality of life. The 25% of patients dropping out of care soon after a relapse indicates that more should be done to engage these people in long-term treatment programs.


Microbial oxidation of arsenite in a subarctic environment: diversity of arsenite oxidase genes and identification of a psychrotolerant arsenite oxidiser.
Arsenic is toxic to most living cells. The two soluble inorganic forms of arsenic are arsenite (+3) and arsenate (+5), with arsenite the more toxic. Prokaryotic metabolism of arsenic has been reported in both thermal and moderate environments and has been shown to be involved in the redox cycling of arsenic. No arsenic metabolism (either dissimilatory arsenate reduction or arsenite oxidation) has ever been reported in cold environments (i.e. < 10 degrees C). Our study site is located 512 kilometres south of the Arctic Circle in the Northwest Territories, Canada in an inactive gold mine which contains mine waste water in excess of 50 mM arsenic. Several thousand tonnes of arsenic trioxide dust are stored in underground chambers and microbial biofilms grow on the chamber walls below seepage points rich in arsenite-containing solutions. We compared the arsenite oxidisers in two subsamples (which differed in arsenite concentration) collected from one biofilm. 'Species' (sequence) richness did not differ between subsamples, but the relative importance of the three identifiable clades did. An arsenite-oxidising bacterium (designated GM1) was isolated, and was shown to oxidise arsenite in the early exponential growth phase and to grow at a broad range of temperatures (4-25 degrees C). Its arsenite oxidase was constitutively expressed and functioned over a broad temperature range. The diversity of arsenite oxidisers does not significantly differ from two subsamples of a microbial biofilm that vary in arsenite concentrations. GM1 is the first psychrotolerant arsenite oxidiser to be isolated with the ability to grow below 10 degrees C. This ability to grow at low temperatures could be harnessed for arsenic bioremediation in moderate to cold climates.


Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development.
Interactions between the Wnt (wingless) and hedgehog signaling pathways were first described as playing a role in establishing boundaries between ectodermal cells in Drosophila segmentation. During the initiation of mammalian tooth development, boundaries that distinguish oral from dental ectoderm must be formed to correctly position the sites of tooth formation. We describe a reciprocal relationship between the expression of Wnt-7b in presumptive oral ectoderm and Shh in presumptive dental ectoderm in mouse embryos that mark boundaries between these cells with different developmental fates. By using a murine retrovirus to ectopically express Wnt-7b in presumptive dental ectoderm in mandibular arch explants, we show that Shh expression in the ectoderm and Ptc expression in the underlying ectomesenchyme are down-regulated, and tooth development is subsequently arrested. This suggests that Wnt-7b acts to repress Shh expression in oral ectoderm, thus maintaining the boundaries between oral and dental ectodermal cells. Implantation of beads soaked in Shh protein into Wnt-7b-infected explants resulted in complete rescue of tooth development, confirming that the repressive action of Wnt-7b specifically affects Shh signaling.


Crop management system and carrot genotype affect endophyte composition and Alternaria dauci suppression.
Managing pests in carrot production is challenging. Endophytic microbes have been demonstrated to improve the health and productivity of many crops, but factors affecting endophyte dynamics in carrot is still not well understood. The goal of this study was to determine how crop management system and carrot genotype interact to affect the composition and potential of endophytes to mitigate disease caused by Alternaria dauci, an important carrot pathogen. Twenty-eight unique isolates were collected from the taproots of nine diverse genotypes of carrot grown in a long-term trial comparing organic and conventional management. Antagonistic activity was quantified using an in vitro assay, and potential for individual isolates to mitigate disease was evaluated in greenhouse trials using two carrot cultivars. Results confirm that carrot taproots are colonized by an abundant and diverse assortment of bacteria and fungi representing at least distinct 13 genera. Soils in the organic system had greater total organic matter, microbial biomass and activity than the conventional system and endophyte composition in taproots grown in this system were more abundant and diverse, and had greater antagonistic activity. Carrot genotype also affected endophyte abundance as well as potential for individual isolates to affect seed germination, seedling growth and tolerance to A. dauci. The benefits of endophytes on carrot growth were greatest when plants were subject to A. dauci stress, highlighting the importance of environmental conditions in the functional role of endophytes. Results of this study provide evidence that endophytes can play an important role in improving carrot performance and mediating resistance to A. dauci, and it may someday be possible to select for these beneficial plant-microbial relationships in carrot breeding programs. Implementing soil-building practices commonly used in organic farming systems has potential to promote these beneficial relationships and improve the health and productivity of carrot crops.


Insulin reversal of biochemical changes in hearts from diabetic rats.
Reversal of myocardial biochemical changes with insulin treatment (4 and 8 wk) was studied in 8 and 12 wk streptozotocin (STZ)-diabetic rats. STZ-induced diabetes was characterized by elevations in blood glucose, serum cholesterol, and triglycerides and depressed serum insulin levels. Insulin treatment for 4 and 8 wk completely restored the serum alterations to control values. The polyuria, polydipsia, and polyphagia were also markedly diminished by the insulin treatment. Diabetic rats had pronounced decreases in body, heart, and left ventricular weights, all of which were completely reversed by the insulin treatment. Hydroxyproline accumulation in diabetic rat hearts was only reversed by the 8-wk and not by the 4-wk insulin treatment. STZ produced a significant depletion of left ventricular magnesium content as well as depression of K+-stimulated sarcoplasmic reticulum and myofibrillar ATPase activities. Both the 4- and 8-wk insulin treatment produced a complete recovery of the myocardial magnesium content. No significant changes in sarcolemmal Na+-K+-ATPase and K+-stimulated p-nitrophenyl phosphatase activities were observed in diabetic animals compared with control. The decreased latency of the lysosomal hydrolase, N-acetyl-beta-glucosaminidase, and the increased collagen deposition observed in the diabetic hearts were only partially reversed by the 4-wk insulin treatment, but completely reversed by the 8-wk treatment period.


Is Coffee the Cause or the Cure? Conflicting Nutrition Messages in Two Decades of Online New York Times' Nutrition News Coverage.
Two-thirds of US adults report hearing news stories about diet and health relationships daily or a few times a week. These stories have often been labeled as conflicting. While public opinion suggests conflicting nutrition messages are widespread, there has been limited empirical research to support this belief. This study examined the prevalence of conflicting information in online New York Times' news articles discussing published nutrition research between 1996-2016. It also examined the contextual differences that existed between conflicting studies. The final sample included 375 news articles discussing 416 diet and health relationships (228 distinct relationships). The most popular dietary items discussed were alcoholic beverages (n = 51), vitamin D (n = 26), and B vitamins (n = 23). Over the 20-year study period, 12.7% of the 228 diet and health relationships had conflicting reports. Just under three-fourths of the conflicting reports involved changes in study design, 79% involved changes in study population, and 31% involved changes in industry funding. Conflicting nutrition messages can have negative cognitive and behavioral consequences for individuals. To help effectively address conflicting nutrition news coverage, a multi-pronged approach involving journalists, researchers, and news audiences is needed.


Signaling of need, sibling competition, and the cost of honesty.
Young birds and mammals frequently solicit food by means of extravagant and apparently costly begging displays. Much attention has been devoted to the idea that these displays are honest signals of need, and that their apparent cost serves to maintain their honesty. Recent analyses, however, have shown that the cost needed to maintain a fully informative, honest signal may often be so great that both offspring (signaler) and parent (receiver) would do better to refrain from communication. This apparently calls into question the relevance of the costly signaling hypothesis. Here, I show that this argument overlooks the impact of sibling competition. When multiple signalers must compete for the attention of a receiver (as is commonly the case in parent-offspring interactions), I show that (all other things being equal) individual equilibrium signal costs will typically be lower. The greater the number of competitors, the smaller the mean cost, though the maximum level of signal intensity employed by very needy signalers may actually increase with the number of competitors. At the same time, costs become increasingly sensitive to relatedness among signalers as opposed to relatedness between signalers and receivers. As a result of these trends, signaling proves profitable for signalers under a much wider range of conditions when there is competition (though it is still likely to be unprofitable for receivers).


Body parts and early-learned verbs.
This article reports the structure of associations among 101 common verbs and body parts. The verbs are those typically learned by children learning English prior to 3 years of age. In a free association task, 50 adults were asked to provide the single body part that came to mind when they thought of each verb. Analyses reveal highly systematic and structured patterns of associations that are also related to the normative age of acquisition of the verbs showing a progression from verbs associated with actions by the mouth, to verbs strongly associated with actions by hand and arm, to verbs not so strongly associated with any one body part. The results have implications for proposals about embodied verb meaning and also for processes of early verb learning.


Perceptions of social capital and sexual behaviour among youth in South Africa.
With about one quarter of new human immunodeficiency virus (HIV) infections occuring in young people, there is an on-going debate regarding the role of social capital on youth sexual behaviour. Some studies have suggested that high levels of family and community social capital may act as protective factors that lessen the likelihood of negative consequences; while others have concluded that social capital may be a risk factor for risky sexual behaviour among youth. Using data from the Third National Communications Survey (2012) conducted in South Africa, we examined the relationship between perceptions of social capital and youth sexual behaviour measured by age at first sex and condom use among 3 399 males and females (aged between 16 and 24 years). We assessed community perceptions of social capital with questions that measured trust, social participation, and support. The Cox proportional hazards regression model was used to predict the risk for early sexual debut. Logistic regression was used to predict the odds of condom use. There was no association between perceptions of social capital and youth sexual behaviour. This work reveals that youth sexual behaviour in South Africa may be influenced by socio-economic characteristics, especially at the individual level.


Role of fetal 1,25-dihydroxyvitamin D production in intrauterine phosphorus and calcium homeostasis.
During intrauterine life, fetal mineral accretion depends on active transfer from mother to fetus by the placenta. To evaluate the role of fetal production of 1,25-dihydroxyvitamin D in regulation of fetal phosphorus, calcium, and parathyroid homeostasis, studies were performed in ewes and their fetal lambs. Fetal nephrectomy caused a rise in fetal serum phosphorus and a fall in total calcium 5 days after nephrectomy. Fetal blood ionized calcium also fell and serum parathyroid hormone rose. In sham-nephrectomized fetuses, all four measurements were unchanged compared to control values. Simultaneous maternal values of ionized calcium were normal in control and nephrectomized fetuses. Fetal ureteral severance and drainage of urine into the fetal peritoneal cavity produced none of the effects of fetal nephrectomy. Daily intravenous injection of 1,25-dihydroxyvitamin D into fetuses after nephrectomy prevented the rise in serum phosphate, and serum calcium did not fall. The results suggest that fetal 1,25-dihydroxyvitamin D regulates fetal phosphate homeostasis, perhaps by the placenta, which in turn regulates blood-ionized calcium concentration.


Acute bacterial rhinosinusitis in adults: part I. Evaluation.
Acute rhinosinusitis is one of the most common conditions that physicians treat in ambulatory practice. Although often caused by viruses, it sometimes is caused by bacteria, a condition that is called acute bacterial rhinosinusitis. The signs and symptoms of acute bacterial rhinosinusitis and prolonged viral upper respiratory infection are similar, which makes accurate clinical diagnosis difficult. Because two thirds of patients with acute bacterial rhinosinusitis improve without antibiotic treatment and most patients with viral upper respiratory infection improve within seven d antibiotic therapy should be reserved for use in patients who have had symptoms for more than seven days and meet clinical criteria. Four signs and symptoms are the most helpful in predicting acute bacterial rhinosinusitis: purulent nasal discharge, maxillary tooth or facial pain (especially unilateral), unilateral maxillary sinus tenderness, and worsening symptoms after initial improvement. Sinus radiography and ultrasonography are not recommended in the diagnosis of uncomplicated acute bacterial rhinosinusitis, although computed tomography has a role in the care of patients with recurrent or chronic symptoms.