Factors influencing autism spectrum disorder screening by community paediatricians.
In most cases, autism spectrum disorders (ASD) can be reliably diagnosed at two to three years of age. However, Canadian data reveal a median age at diagnosis of approximately four years. To examine general paediatricians' practices regarding ASD screening and identify factors that influence decisions regarding the use of ASD screening tools. Using a qualitative inquiry-based interpretive description approach, 12 paediatricians from four practice groups participated in four focus groups and one individual interview. These were conducted using semistructured interviews, digitally recorded and transcribed verbatim. Five main domains of themes were identified related to screening tool use: benefits; needs not addressed; elements that limit utility; elements that encourage utility; and implementation challenges. Factors influencing practice included availability of time, comfort with screening tool use, previous use and knowledge about specific tools. Systemic factors included knowledge and access to community resources, as well as the ability to provide support to the child and family. The results from the present study identified important factors that influence paediatric practice in ASD screening. As screening tools improve, it will be important to examine the implementation and effectiveness of screening tools and strategies for increased uptake. Future research will also need to attend to the practical needs of physicians and communities in the aim of earlier diagnosis and rapid access to interventional resources.


Regression of atherosclerosis: role of nitric oxide and apoptosis.
We have recently found that administration of L-arginine to hypercholesterolemic rabbits induces regression of preexisting lesions. Others have previously shown that activation of the L-arginine/nitric oxide (NO) synthase pathway can induce apoptosis of vascular cells in vitro. Accordingly, the current study was designed to determine if dietary supplementation of L-arginine induces apoptosis of intimal lesions and if this effect is mediated through the NO synthase pathway. Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 weeks and subsequently placed on 2.5% L-arginine HCl in the drinking water, and the cholesterol diet was continued for 2 weeks, at which time the aortas were harvested for histological studies. L-Arginine treatment increased the number of apoptotic cells (largely macrophages) in the intimal lesions by 3-fold (11.9+/-3.9 vs 3.9+/-1. 4 apoptotic cells/mm2, P<0.01). In subsequent studies, aortas were harvested for ex vivo studies. Aortic segments were incubated in cell culture medium for 4 to 24 hours with modulators of the NO synthase pathway. The tissues were then collected for histological studies and the conditioned medium collected for measurement of nitrogen oxides by chemiluminescence. Addition of sodium nitroprusside (10(-5) mol/L) to the medium caused a time-dependent increase in apoptosis of vascular cells (largely macrophages) in the intimal lesion. L-Arginine (10(-3) mol/L) had an identical effect on apoptosis, which was associated with an increase in nitrogen oxides released into the medium. These effects were not mimicked by D-arginine, and they were antagonized by the NO synthase inhibitor L-nitro-arginine (10(-4) mol/L). The effect of L-arginine was not influenced by an antagonist of cGMP-dependent protein kinase, nor was the effect mimicked by the agonist of protein kinase G or 8-BR cGMP. These results indicate that supplemental L-arginine induces apoptosis of macrophages in intimal lesions by its metabolism to NO, which acts through a cGMP-independent pathway. These studies are consistent with our previous observation that supplementation of dietary arginine induces regression of atheroma in this animal model. These studies provide a rationale for further investigation of the therapeutic potential of manipulating the NO synthase pathway in atherosclerosis.


Pathology of myelinated fibers in cervical and lumbar ventral spinal roots in amyotrophic lateral sclerosis.
Pathological alterations were evaluated by morphometry and by a teased-fiber study on the 6th cervical (C6) and the 4th lumbar (L4) ventral spinal roots of cases of amyotrophic lateral sclerosis (ALS). The large-diameter fibers were severely affected in both spinal segments. However, small-diameter myelinated fibers were numerically well preserved. The number of large fibers in C6 and L4 ventral roots was strongly correlated to the strength of muscles innervated by C6 or L4 segments. There was no correlation of the number of small fibers with muscle strength. Teased fiber studies revealed a marked increase in the incidence of fibers showing axonal degeneration. Fibers considered to be regenerative were rarely observed. These observations suggest that large myelinated fibers, which correspond to alpha-motoneuron fibers, are selectively affected, and that small myelinated fibers, which are considered to correspond to gamma-motoneuron fibers, are preserved to some extent in the C6 and L4 ventral spinal roots in ALS.


Immunopathology of sympathetic ophthalmia.
The long held notion that sympathetic ophthalmia represents an autoimmune reaction to uveal pigment is no longer tenable. Pigmentation influences the histopathologic picture of sympathetic ophthalmia but no evidence supports the role of uveal pigment as inciting antigen. Several recent studies have confirmed our initial report of the participation of cellular hypersensitivity to ocular tissues in the pathogenesis of this disease. Both clinical and experimental studies implicate retinal tissue as being more immunogenic than uveal antigens. The recent histopathologic observation that eosinophils concentrate near the choriocapillaris suggests that outer retina and retinal pigment epithelium should not be overlooked as a potential source of the stimulating antigen in sympathetic ophthalmia.


The Beneficial Effects of UM206 on Wound Healing After Myocardial Infarction in Mice Are Lost in Follow-Up Experiments.
Introduction: An inadequate wound healing following myocardial infarction (MI) is one of the main etiologies of heart failure (HF) development. Interventions aiming at improving this process may contribute to preserving cardiac function after MI. Our group, as well as others, have demonstrated the crucial role of Wnt/frizzled signaling in post-MI remodeling. In this overview, we provide the results of different studies aimed at confirming an initial study from our group, in which we observed beneficial effects of administration of a peptide fragment of Wnt5a, UM206, on infarct healing in a mouse MI model. Methods: Mice were subjected to permanent left coronary artery ligation, and treated with saline (control) or UM206, administered via osmotic minipumps. Cardiac function was assessed by echocardiography and hemodynamic measurements, while infarct size and myofibroblast content were characterized by (immuno)histochemistry. Results: In total, we performed seven follow-up studies, but we were unable to reproduce the beneficial effects of UM206 on infarct healing in most of them. Variations in dose and timing of UM206 administration, its manufacturer and the genetic background of the mice could not restore the phenotype. An in-depth analysis of the datasets revealed that the absence of effect of UM206 coincided with a lack of adverse cardiac remodeling and HF development in all experimental groups, irrespective of the treatment. Discussion: Irreproducibility of experimental observations is a major issue in biomedical sciences. It can arise from a relatively low number of experimental observations in the original study, a faulty hypothesis or a variation in the experimental model that cannot be controlled. In this case, the lack of adverse cardiac remodeling and lung weight increases in the follow-up studies point out to altered experimental conditions as the most likely explanation.


Does unemployment contribute to poorer health-related quality of life among Swedish adults?
Previous studies have shown that unemployment has negative impacts on various aspects of health. However, little is known about the effect of unemployment on health-related quality of life. Our aim was to examine how unemployment impacts upon health-related quality of life among Swedish adults, and to investigate these effects on population subgroups defined by education level, marital status, previous health, and gender. As part of a cross-sectional study, a questionnaire was sent to 2500 randomly selected individuals aged 20 to 64 years living in Sweden in 2016. The questionnaire included the EuroQol 5 dimensions (EQ-5D) instrument and was answered by 967 individuals (39%). Quality-adjusted life year (QALY) scores were derived from the EQ-5D responses. Of the respondents, 113 were unemployed and 724 were employed. We used inverse probability-weighted propensity scores in our analyses to estimate a risk difference. Gender, age, education level, marital status, and previous health were used as covariates in our analyses. There was a statistically significant lower QALY score by 0.096 points for the unemployed compared to the employed. There were also statistically significant more problems due to unemployment for usual activities (6.6% more), anxiety/depression (23.6% more), and EQ-5D's Visual Analogue Scale (7.5 point lower score). Grouped analyses indicated a larger negative health effect from becoming unemployed for men, those who are married, and young individuals. In our study, we show that the health deterioration from unemployment is likely to be large, as our estimated effect implies an almost 10% worse health (in absolute terms) from being unemployed compared to being employed. This further highlights that unemployment is a public health problem that needs more focus. Our study also raises further demands for determining for whom unemployment has the most negative effects and thus suggesting groups of individuals who are in greatest need for labor market measures.


HIF-prolyl hydroxylases and cardiovascular diseases.
Prolyl hydroxylases belong to the family of iron- and 2-oxoglutamate-dependent dioxygenase enzyme. Several distinct prolyl hydroxylases have been identified. The hypoxia-inducible factor (HIF) prolyl hydroxylase termed prolyl hydroxylase domain (PHD) enzymes play an important role in oxygen regulation in the physiological network. There are three isoforms that have been identified: PHD1, PHD2 and PHD3. Deletion of PHD enzymes result in stabilization of HIFs and offers potential treatment options for many ischemic disorders such as peripheral arterial occlusive disease, myocardial infarction, and stroke. All three isoforms are oxygen sensors that regulate the stability of HIFs. The degradation of HIF-1α is regulated by hydroxylation of the 402/504 proline residue by PHDs. Under hypoxic conditions, lack of oxygen causes hydroxylation to cease HIF-1α stabilization and subsequent translocation to the nucleus where it heterodimerizes with the constitutively expressed β subunit. Binding of the HIF-heterodimer to specific DNA sequences, named hypoxia-responsive elements, triggers the transactivation of target genes. PHD regulation of HIF-1α-mediated cardioprotection has resulted in considerable interest in these molecules as potential therapeutic targets in cardiovascular and ischemic diseases. In recent years, attention has been directed towards identifying small molecule inhibitors of PHD. It is postulated that such inhibition might lead to a clinically useful strategy for protecting the myocardium against ischemia and reperfusion injury. Recently, it has been reported that the orally absorbed PHD inhibitor GSK360A can modulate HIF-1α signaling and protect the failing heart following myocardial infarction. Furthermore, PHD1 deletion has been found to have beneficial effects through an increase in tolerance to hypoxia of skeletal muscle by reprogramming basal metabolism. In the mouse liver, such deletion has resulted in protection against ischemia and reperfusion. As a result of these preliminary findings, PHDs is attracting increasing interest as potential therapeutic targets in a wide range of diseases.


Spreading of a granular droplet.
The influence of controlled vibrations on the granular rheology is investigated in a specifically designed experiment in which a granular film spreads under the action of horizontal vibrations. A nonlinear diffusion equation is derived theoretically that describes the evolution of the deposit shape. A self-similar parabolic shape (the "granular droplet") and a spreading dynamics are predicted that both agree quantitatively with the experimental results. The theoretical analysis is used to extract effective friction coefficients between the base and the granular layer under sustained and controlled vibrations. A shear thickening regime characteristic of dense granular flows is evidenced at low vibration energy, both for glass beads and natural sand. Conversely, shear thinning is observed at high agitation.


Does referencing system affect the selection of implant size, position and gap balance in total knee arthroplasty?
(1) To evaluate if referencing system affects selection of implant size, position, and gap balance in total knee arthroplasty (TKA) with the use of contemporary implant designs and (2) to describe the authors' intraoperative sizing strategy using anterior referencing (AR) and posterior referencing (PR) systems. This was a retrospective review of 270 consecutive patients (397 knees) who underwent primary TKA with an AR or PR system. Selection of implant size, mediolateral and anteroposterior alignment of the femoral component, as well as gaps were compared between groups. In the AR group, more patients had femoral components which were upsized or downsized compared to those in the PR group (29.5% vs 12.0% respectively) and in patients who underwent bilateral TKA, 49.4% of those in the AR group had femur component size asymmetry. The AR group had better medio-lateral (ML) fit over the distal cutting surface area, smaller change in anterior offset but higher incidence of anterior notching when compared to the PR group. Posterior condylar offset (PCO) was restored in both groups and gap differences in flexion-extension and ML were comparable. There was also no difference in clinical scores and ROM between groups at 2-years follow-up. In this study, conventional implications related to referencing system were not observed. In practice, AR systems can restore PCO while PR systems do not result in increased anterior notching or anterior overstuffing. Differences observed in this study are most likely related to implant design specifics and surgical technique.


Localization of preganglionic neurons that innervate choroidal neurons of pterygopalatine ganglion.
The pterygopalatine ganglion (PPG) receives preganglionic input from the superior salivatory nucleus (SSN) of the facial motor complex and is the main source of parasympathetic input to the choroid in mammals. The present study was undertaken to determine in rats the location and neurotransmitters of SSN neurons innervating those PPG neurons that target the choroid and to determine the location and neurotransmitters of the PPG choroidal neurons themselves. Retrograde labeling from rat choroid using a fluorescent tracer, in combination with immunofluorescence labeling for nitric oxide synthase (NOS), vasoactive intestinal polypeptide (VIP), and choline acetyltransferase (ChAT), was used to characterize the location and neurotransmitters of choroidal PPG neurons. To identify SSN neurons that innervate the choroidal PPG neurons, the Bartha strain of the retrograde transneuronal tracer pseudorabies virus (PRV-Ba) was injected into rat choroid, and immunolabeling for NOS or ChAT was used to characterize their neurochemistry. Fluorescent retrograde labeling showed that PPG neurons projecting to the choroid contained NOS, VIP, and ChAT and were widely distributed in PPG and its preganglionic root, the greater petrosal nerve. SSN neurons were ChAT(+), and a subset of them was found to contain NOS. PRV-Ba transneuronal retrograde labeling revealed that choroidal preganglionic neurons were localized to the rostral medioventral part of the ipsilateral SSN. The choroidal SSN neurons were ChAT(+) and appeared largely to correspond to the NOS(+) neurons of the SSN. These results show that preganglionic neurons in rats that are presumed to regulate choroidal blood flow through the PPG reside within the rostral medioventral SSN, and that NOS is a marker for these SSN neurons.


Clinical tests for successful contact lens wear: relationship and predictive potential.
Although comfort is important for contact lens wearers, common clinical tests can fail to predict patients' symptoms. Lid wiper epitheliopathy (LWE) and lid parallel conjunctival folds (LIPCOF) are related to dry eye symptoms in lens wearers. This study investigates the predictive value of LWE and LIPCOF as objective measures of discomfort, and their relation to the ocular surface in soft contact lens wearers. Subjects were classified as symptomatic or asymptomatic, using the Contact Lens Dry Eye Questionnaire (CLDEQ). Pre-lens tear break-up time (PLBUT), limbal and bulbar hyperaemia, corneal staining, LWE and LIPCOF were assessed in the right eyes of 61 (23 M, 38 F; mean age 32.1 years; range = 18 to 55) experienced contact lens wearers. Differences between groups, and relationships between LWE, LIPCOF (nasal, temporal and sum) and objective signs were examined using non-parametric analyses. The positive and negative predictive values for symptoms of each objective measure were calculated. Thirty eight subjects were classified as asymptomatic, 23 symptomatic. LWE and LIPCOF severity scores were significantly increased in symptomatic patients (U-test, p < 0.03), while no significant differences were found between groups for PLBUT, corneal staining or hyperaemia (0.29 < p < 0.88). Significant positive correlations were found between LWE and LIPCOF scores (temporal r = 0.67, p < 0.001; nasal r = 0.39, p < 0.001), and between LWE and hyperaemia (bulbar, r = 0.28, p < 0.001; limbal r = 0.36, p < 0.001). Age and gender were different in the two groups (p < 0.05). The predictive value of temporal LIPCOF was positive = 56.9%, negative = 77.1% with a cutoff value of > or =2 (PPV/NPV/cutoff value), of nasal LIPCOF 70.7%/75.0%/> or =1, of LIPCOF Sum 79.8%/86.5%/> or =2, and of LWE 53.1%/81.1%/> or =1. Contact lens wearers with dryness symptoms exhibit significantly more LWE and LIPCOF, but not increased corneal staining, bulbar hyperaemia or decreased PLBUT. LWE and LIPCOF are significantly correlated: this may reflect their common frictional origin. LIPCOF Sum severity scores appear to be most predictive for symptoms.


Interference potential of personal lubricants and vaginal medications on ThinPrep pap tests.
The effects of water-based speculum lubricants on both conventional Papanicolaou smears and liquid-based Papanicolaou tests have been well documented. However, studies are lacking concerning the effects on these tests of personal lubricants and/or vaginal medications. Lubricants containing "carbomers" or "carbopol polymers" are known to interfere with ThinPrep® Papanicolaou test processing. Many over-the-counter products that advertise effects lasting several days may contain these substances. This study tests 2 popular personal lubricants (KY Warming Liquid [Johnson & Johnson, New Brunswick, NJ] and Replens [KoRa Health Care, Swords, Ireland]) and one yeast medication (Monistat 7, McNeill-PPC, Inc., Skillman, NJ) for interference on ThinPrep® Papanicolaou tests. The residual specimens from 270 ThinPrep® vials were combined to form 100 homogenous ThinPrep® Papanicolaou specimens. Nine groups of 10 vials were then contaminated with 20 μL, 100 μL, and 500 μL of each of the 3 products. One group of 10 vials served as control. Cell counts were performed after processing the specimens onto slides, and the results were recorded. KY Warming Liquid had no effect at any volume of contamination. Replens caused a drastic reduction in cellularity at even the lowest volume. Monistat 7 reduced cellularity incrementally as the volume increased. The potential exists for some over-the-counter lubricants and vaginal medications to interfere with the ThinPrep® Papanicolaou test.


Differential Role of Leptin as an Immunomodulator in Controlling Visceral Leishmaniasis in Normal and Leptin-Deficient Mice.
Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani There are no vaccines and available drugs against leishmaniasis are toxic. Immunomodulators that specifically boost the anti-microbial activities of the immune cells could alleviate several of these limitations. Therefore, finding novel immunomodulators for VL therapy is a pressing need. This study is aimed to evaluate the immunomodulatory role of leptin, an adipocyte-derived hormone capable of regulating the immune response, in L. donovani-infected mice. We observed that recombinant leptin treatment reduced splenic parasite burden compared with non-treated infected normal mice. Decrease in parasite burden correlated with an induction of innate immune response in antigen-presenting cells that showed an increase in nitric oxide, enhanced pro-inflammatory cytokine (interferon gamma [IFNγ], interleukin12 [IL]12, and IL1β) response in the splenocytes, indicating host-protecting Th1 response mediated by leptin. Moreover, in infected normal mice, leptin treatment induced IFNγ production from both CD4(+) and CD8(+) T cells, compared with non-treated infected mice. Alternatively, leptin-deficient (Ob/Ob) mice had higher splenic and liver parasite burden compared with the infected normal mice. However, leptin treatment failed to reduce the splenic parasite burden and improve a host-protective cytokine response in these mice. In addition, in contrast to dendritic cells (DCs) from a normal mouse, Ob/Ob mouse-derived DCs showed a defect in the induction of innate immune response on Leishmania infection that could not be reversed by leptin treatment. Therefore, our findings reveal that leptin has a differential immunomodulatory effect in controlling VL in normal and Ob/Ob mice.


[Perspectives of using radiofrequency surgery in operations on the major duodenal papilla].
The article presents the results of an experimental study of the possibility of using radiofrequency surgery for performing papillosphincterotomy. A generator of radiowaves of a high frequency range was used for the generation of the electromagnetic field, which when acting upon the living tissues makes a cut and destruction of the tissue. The experiment was made in 20 dogs divided into two groups for acute and chronic experiments. In the group of chronic experiments the dogs were exterminated on the 7, 14, 21 and 35th days after operations. The area of the influence in all the periods of the experiment was investigated histologically. Significant advantages of the given method as compared with the traditional ones were revealed.


Plasmid vectors designed for high-efficiency expression controlled by the portable recA promoter-operator of Escherichia coli.
A novel expression vector using the 236-bp promoter-operator fragment of the recA gene (recApo) of Escherichia coli has been constructed. This DNA fragment contains complete signals for the initiation of RNA synthesis, as well as for regulation by the lexA product, but lacks the coding sequence for the RecA protein. The strength of the recA promoter was examined by assaying beta-galactosidase activity expressed from a cro-lacZ fused gene placed downstream of the promoter. Under noninducing conditions, the promoter was regulated by the LexA protein, and the fused gene was expressed only weakly. Upon induction by nalidixic acid in a recA+ strain, high expression was observed for an extended period. After 5 h under inducing conditions, as much as 11% of the total cellular protein was cro-lacZ product. The expression level was higher than that from promoters of lac, trp, and lambda early genes.


Minireview: translational animal models of human menopause: challenges and emerging opportunities.
Increasing importance is placed on the translational validity of animal models of human menopause to discern risk vs. benefit for prediction of outcomes after therapeutic interventions and to develop new therapeutic strategies to promote health. Basic discovery research conducted over many decades has built an extensive body of knowledge regarding reproductive senescence across mammalian species upon which to advance animal models of human menopause. Modifications to existing animal models could rapidly address translational gaps relevant to clinical issues in human menopausal health, which include the impact of 1) chronic ovarian hormone deprivation and hormone therapy, 2) clinically relevant hormone therapy regimens (cyclic vs. continuous combined), 3) clinically relevant hormone therapy formulations, and 4) windows of opportunity and optimal duration of interventions. Modifications in existing animal models to more accurately represent human menopause and clinical interventions could rapidly provide preclinical translational data to predict outcomes regarding unresolved clinical issues relevant to women's menopausal health. Development of the next generation of animal models of human menopause could leverage advances in identifying genotypic variations in estrogen and progesterone receptors to develop personalized menopausal care and to predict outcomes of interventions for protection against or vulnerability to disease. Key to the success of these models is the close coupling between the translational target and the range of predictive validity. Preclinical translational animal models of human menopause need to keep pace with changes in clinical practice. With focus on predictive validity and strategic use of advances in genetic and epigenetic science, new animal models of human menopause have the opportunity to set new directions for menopausal clinical care for women worldwide.


Aerobic fitness, hippocampal viscoelasticity, and relational memory performance.
The positive relationship between hippocampal structure, aerobic fitness, and memory performance is often observed among children and older adults; but evidence of this relationship among young adults, for whom the hippocampus is neither developing nor atrophying, is less consistent. Studies have typically relied on hippocampal volumetry (a gross proxy of tissue composition) to assess individual differences in hippocampal structure. While volume is not specific to microstructural tissue characteristics, microstructural differences in hippocampal integrity may exist even among healthy young adults when volumetric differences are not diagnostic of tissue health or cognitive function. Magnetic resonance elastography (MRE) is an emerging noninvasive imaging technique for measuring viscoelastic tissue properties and provides quantitative measures of tissue integrity. We have previously demonstrated that individual differences in hippocampal viscoelasticity are related to performance on a relational memory task; however, little is known about health correlates to this novel measure. In the current study, we investigated the relationship between hippocampal viscoelasticity and cardiovascular health, and their mutual effect on relational memory in a group of healthy young adults (N=51). We replicated our previous finding that hippocampal viscoelasticity correlates with relational memory performance. We extend this work by demonstrating that better aerobic fitness, as measured by VO2max, was associated with hippocampal viscoelasticity that mediated the benefits of fitness on memory function. Hippocampal volume, however, did not account for individual differences in memory. Therefore, these data suggest that hippocampal viscoelasticity may provide a more sensitive measure to microstructural tissue organization and its consequences to cognition among healthy young adults.


[Characterization of an endogenous factor with digitalis-like activity in the heart of the guinea pig (I): Inhibition of Na,K-ATPase)].
The purpose of this work is to study the presence of an endogenous inhibitor of the sodium pump in mammals. A water extract was prepared from guinea pig heart and partially purified by liquid chromatography. The extract inhibited the activity of Na,K-ATPase but had no effect on Mg-ATPase nor on Ca-ATPase. The inhibition was similar to that produced by cardiac glycosides since it was dose-dependent, antagonised by potassium and the Na,K-ATPase prepared from brain was more sensitive than the one from heart. These results support the hypothesis on an endogenous factor exhibiting digitalis-like activity that could be a physiological regulator of the sodium pump.


Effect of vagal tone on airway smooth muscle force and peribronchial pressure in dogs.
The main lobar bronchi were isolated airtight from the rest of the lung in excised dog lung. In the relaxed isolated lobar bronchi in excised dog lung, we simulated the percent narrowing of bronchial diameter which was observed with vagus nerves intact and stimulated relative to that with vagus nerves cut (relaxed state). The percent narrowing of bronchi with vagus nerve intact and stimulated were adapted from the data by Hahn et al. (J. appl. Physiol., 41, 581-589, 1976). The forces of airway smooth muscle (Psm) were obtained as the negative intrabronchial pressure (Pbr) when the isolated bronchi were narrowed to the same diameter as those with vagus intact and stimulated, and they were 5 to 10 cmH20 and 10 to 30 cmH20, respectively. Peribronchial pressure (Px) was obtained as the difference of Pbr in the conditions of intact and dissected parenchyma when the diameter of the isolated bronchi were simulated to those with vagus intact and stimulated, and they were positive relative to pleural pressure (Ppl) with vagus cut, negative to Ppl with vagus stimulated and near zero relative to Ppl with vagus intact. It was suggested that smooth muscle tone which narrowed the bronchi to the same extent as the diameter with vagus intact made homogeneous expansion between bronchi and lung parenchyma.


Probabilities of transversions and transitions.
The values of the mean relative probabilities of transversions and transitions have been refined on the basis of the data collected by Jukes and found to be equal to 0.34 and 0.66, respectively. Evolutionary factors increase the probability of transversions to 0.44. The relative probabilities of individual substitutions have been determined, and a detailed classification of the nonsense mutations has been given. Such mutations are especially probable in the UGG (Trp) codon. The highest probability of AG, GA transitions correlates with the lowest mean change in the hydrophobic nature of the amino acids coded.


Innovation in Bereavement Care: Research Circles as a Framework for Translation of Research-Based Knowledge.
This article aims to contribute to the research-practice gap in bereavement care by exploring Research Circles as a collaborative approach to implementation of research-based knowledge into bereavement care. Particularly the article discusses key dimensions for translating research concerning bereaved after drug-related deaths into practice-relevant knowledge, as a first step of implementation. This co-created knowledge translation took place in the first phase of a Research Circle including bereaved mothers, practitioners and researchers. Data were collected via semi-structured interviews with Research Circle participants and field notes. Data were analyzed using reflexive thematic analysis. Results showed two key dimensions with the Research Circle approach influencing the translation process: (1) multiple and long-lasting arenas for translation: (2) multiple stakeholders and perspectives. Research Circles appear to be a promising framework for translating research-based knowledge in bereavement care, but there are some barriers to fully realizing the democratic ideal that underlines the Research Circle framework.


ΔNp63α induces the expression of FAT2 and Slug to promote tumor invasion.
Tumor invasion can be induced by changes in gene expression that alter cell phenotype. The transcription factor ΔNp63α promotes basal-like breast cancer (BLBC) migration by inducing the expression of the mesenchymal genes Slug and Axl, which confers cells with a hybrid epithelial/mesenchymal state. However, the extent of the ΔNp63α regulated genes that support invasive behavior is not known. Here, using gene expression analysis, ChIP-seq, and functional testing, we find that ΔNp63α promotes BLBC motility by inducing the expression of the atypical cadherin FAT2, the vesicular binding protein SNCA, the carbonic anhydrase CA12, the lipid binding protein CPNE8 and the kinase NEK1, along with Slug and Axl. Notably, lung squamous cell carcinoma migration also required ΔNp63α dependent FAT2 and Slug expression, demonstrating that ΔNp63α promotes migration in multiple tumor types by inducing mesenchymal and non-mesenchymal genes. ΔNp63α activation of FAT2 and Slug influenced E-cadherin localization to cell-cell contacts, which can restrict spontaneous cell movement. Moreover, live-imaging of spheroids in organotypic culture demonstrated that ΔNp63α, FAT2 and Slug were essential for the extension of cellular protrusions that initiate collective invasion. Importantly, ΔNp63α is co-expressed with FAT2 and Slug in patient tumors and the elevated expression of ΔNp63α, FAT2 and Slug correlated with poor patient outcome. Together, these results reveal how ΔNp63α promotes cell migration by directly inducing the expression of a cohort of genes with distinct cellular functions and suggest that FAT2 is a new regulator of collective invasion that may influence patient outcome.


[Effect of changes in intracellular calcium concentration on the response of isolated frog retina photoreceptors].
The role of Ca++ in photoreception was studied by releasing these ions in rod cytoplasma from mitochondrias under 2,4 DNP/10(-4) M/action or blocking the transmembrane Ca++ transport by LaCl3 application (0.1; 0.5; 4 mM). The late receptor potential of the frog retina in response to the repeating stimuli after adding 2.4-DNP in the strophantine--containing saline decreases more slowly than in the control. After adding La+++ ions rods and cones generate the receptor potentials of the same amplitude in the Ca++-free solution as in the Ca++--containing medium. La+++ seems to block calcium permeability of the photoreceptor membrane. These results are incompatible with Ca++ inward current as supposed for cones by the Hagins hypothesis. Ca++ seems to act inside photoreceptor as a modulator rather than the transmitter.


Two cases of fractured esophageal nitinol stents.
We report here on two cases of fractured nitinol stents in the esophagus. In case 1, the correctly inserted stent broke spontaneously shortly after insertion. In a second case, a nitinol stent broke after laser application due to tumor ingrowth with massive bleeding. In both cases, a second stent was implanted in order to reestablish food passage. The fracture of the stent in case 1 seemed to be caused by defective material, whilst in case 2 the stent broke because of thermal overstrain during laser application. The use of electrocoagulation or laser in the stent area should therefore be avoided; argon plasma coagulation may offer an effective alternative in treating tumor ingrowth. As there was a risk from piercing broken filaments with the second stent, covering a fracture using stents with tight walls or plastic tubes seems to be a more effective approach than the inserting an uncovered stent type.


The Advantages and Disadvantages of Online and Blended Therapy: Survey Study Amongst Licensed Psychotherapists in Austria.
Web-based and blended (face-to-face plus Web-based) interventions for mental health disorders are gaining significance. However, many licensed psychotherapists still have guarded attitudes toward computer-assisted therapy, hindering dissemination efforts. The objective of this study was to provide a therapist-oriented evaluation of Web-based and blended therapies and identify commonalities and differences in attitudes toward both formats. Furthermore, it aimed to test the impact of an information clip on expressed attitudes. In total, 95 Austrian psychotherapists were contacted and surveyed via their listed occupational email address. An 8-minute information video was shown to half of the therapists before 19 advantages and 13 disadvantages had to be rated on a 6-point Likert scale. The sample resembled all assessed properties of Austrian psychotherapists (age, theoretical orientation, and region). Therapists did not hold a uniform overall preference. Instead, perceived advantages of both interventions were rated as neutral (t94=1.89, P=.06; d=0.11), whereas Web-based interventions were associated with more disadvantages and risks (t94=9.86, P<.001; d=0.81). The information clip did not excerpt any detectable effect on therapists' attitudes (r95=-.109, P=.30). The application of modern technologies in the own therapeutic practice and cognitive behavioral orientation were positively related to the given ratings. This study is the first to directly compare therapists' attitudes toward Web-based and blended therapies. Positive attitudes play a pivotal role in the dissemination of new technologies, but unexperienced therapists seem to lack knowledge on how to benefit from technology-aided treatments. To speed up implementation, these aspects need to be addressed in the development of new interventions. Furthermore, the preference of blended treatments over Web-based interventions seems to relate to avoidance of risks. Although this study is likely to represent therapists' attitudes in countries with less advanced electronic health services, therapists' attitudes in more advanced countries might present differently.


Comparative Three-Dimensional Morphology of Baleen: Cross-Sectional Profiles and Volume Measurements Using CT Images.
Baleen whales are obligate filter feeders, straining prey-laden seawater through racks of keratinized baleen plates. Despite the importance of baleen to the ecology and natural history of these animals, relatively little work has been done on baleen morphology, particularly with regard to the three-dimensional morphology and structure of baleen. We used computed tomography (CT) scanning to take 3D images of six baleen specimens representing five species, including three complete racks. With these images, we described the three-dimensional shape of the baleen plates using cross-sectional profiles from within the gum tissue to the tip of the plates. We also measured the percentage of each specimen that was composed of either keratinized plate material or was void space between baleen plates, and thus available for seawater flow. Baleen plates have a complex three-dimensional structure with curvature that varies across the anterior-posterior, proximal-distal, and medial-lateral (lingual-labial) axes. These curvatures also vary with location along the baleen rack, and between species. Cross-sectional profiles resemble backwards-facing airfoils, and some specimens display S-shaped, or reflexed, camber. Within a baleen specimen, the intra-baleen void volume correlates with the average bristle diameter for a species, suggesting that essentially, thinner plates (with more space between them for flow) have thinner bristles. Both plate curvature and the relative proportions of plate and void volumes are likely to have implications for the mechanics of mysticete filtration, and future studies are needed to determine the particular functions of these morphological characters. Anat Rec, 300:1942-1952, 2017. © 2017 The Authors The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.


Optics-based compressibility parameter for pharmaceutical tablets obtained with the aid of the terahertz refractive index.
The objective of this study is to propose a novel optical compressibility parameter for porous pharmaceutical tablets. This parameter is defined with the aid of the effective refractive index of a tablet that is obtained from non-destructive and contactless terahertz (THz) time-delay transmission measurement. The optical compressibility parameter of two training sets of pharmaceutical tablets with a priori known porosity and mass fraction of a drug was investigated. Both pharmaceutical sets were compressed with one of the most commonly used excipients, namely microcrystalline cellulose (MCC) and drug Indomethacin. The optical compressibility clearly correlates with the skeletal bulk modulus determined by mercury porosimetry and the recently proposed terahertz lumped structural parameter calculated from terahertz measurements. This lumped structural parameter can be used to analyse the pattern of arrangement of excipient and drug particles in porous pharmaceutical tablets. Therefore, we propose that the optical compressibility can serve as a quality parameter of a pharmaceutical tablet corresponding with the skeletal bulk modulus of the porous tablet, which is related to structural arrangement of the powder particles in the tablet.


Study of Asymmetric Margins in Prostate Cancer Radiation Therapy Using Fuzzy Logic.
The purpose of present study is to estimate asymmetric margins of prostate target volume based on biological limitations with help of knowledge based fuzzy logic considering the effect of organ motion and setup errors. A novel application of fuzzy logic modelling technique considering radiotherapy uncertainties including setup, delineation and organ motion was used in this study to derive margins. The new margin was applied in prostate cancer treatment planning and the results compared very well to current techniques Here volumetric modulated arc therapy treatment plans using stepped increments of asymmetric margins of planning target volume (PTV) were performed to calculate the changes in prostate radiobiological indices and results were used to formulate the rule based and membership function for Mamdani-type fuzzy inference system. The optimum fuzzy rules derived from input data, the clinical goals and knowledge-based conditions imposed on the margin limits. The PTV margin obtained using the fuzzy model was compared to the commonly used margin recipe. For total displacement standard errors ranging from 0 to 5 mm the fuzzy PTV margin was found to be up to 0.5 mm bigger than the vanHerk derived margin, however taking the modelling uncertainty into account results in a good match between the PTV margin calculated using our model and the one based on van Herk et al. formulation for equivalent errors of up to 5 mm standard deviation (s. d.) at this range. When the total displacement standard errors exceed 5 mm s. d., the fuzzy margin remained smaller than the van Herk margin. The advantage of using knowledge based fuzzy logic is that a practical limitation on the margin size is included in the model for limiting the dose received by the critical organs. It uses both physical and radiobiological data to optimize the required margin as per clinical requirement in real time or adaptive planning, which is an improvement on most margin models which mainly rely on physical data only.


Mental health of African Americans and Caribbean blacks in the United States: results from the National Epidemiological Survey on Alcohol and Related Conditions.
Previous epidemiological studies have found lower mood, anxiety, and substance use disorder prevalence in Black Americans, in general, compared with White Americans. We estimated the prevalence and persistence of psychiatric disorders in African Americans, Caribbean Blacks, and non-Hispanic Whites. We drew data from wave 1 (2001-2002) of the National Epidemiological Survey of Alcohol and Related Conditions, a nationally representative sample of US adults, which included 7529 African Americans, 469 Caribbean Blacks, and 24 502 non-Hispanic Whites. Blacks had equal or lower prevalence than Whites of lifetime (adjusted odds ratio [AOR] =0.6 for African Americans; 0.3 for Caribbean Blacks) and 12-month (AOR =0.7 for African Americans; 0.4 for Caribbean Blacks) Axis I psychiatric disorders, but higher prevalence of several personality disorders. Among Blacks, Caribbean Blacks had higher prevalence of 12-month psychotic disorders and lower lifetime prevalence of major depressive disorder, alcohol dependence, and drug abuse than African Americans. There were no differences in persistence of disorders between Caribbean Blacks and African Americans. This study yielded new data on prevalence of mental disorders in these groups, which has important implications for clinical work with US Blacks.


Calcium and neurodegeneration.
When properly controlled, Ca2+ fluxes across the plasma membrane and between intracellular compartments play critical roles in fundamental functions of neurons, including the regulation of neurite outgrowth and synaptogenesis, synaptic transmission and plasticity, and cell survival. During aging, and particularly in neurodegenerative disorders, cellular Ca2+-regulating systems are compromised resulting in synaptic dysfunction, impaired plasticity and neuronal degeneration. Oxidative stress, perturbed energy metabolism and aggregation of disease-related proteins (amyloid beta-peptide, alpha-synuclein, huntingtin, etc.) adversely affect Ca2+ homeostasis by mechanisms that have been elucidated recently. Alterations of Ca2+-regulating proteins in the plasma membrane (ligand- and voltage-gated Ca2+ channels, ion-motive ATPases, and glucose and glutamate transporters), endoplasmic reticulum (presenilin-1, Herp, and ryanodine and inositol triphosphate receptors), and mitochondria (electron transport chain proteins, Bcl-2 family members, and uncoupling proteins) are implicated in age-related neuronal dysfunction and disease. The adverse effects of aging on neuronal Ca2+ regulation are subject to modification by genetic (mutations in presenilins, alpha-synuclein, huntingtin, or Cu/Zn-superoxide dismutase; apolipoprotein E isotype, etc.) and environmental (dietary energy intake, exercise, exposure to toxins, etc.) factors that may cause or affect the risk of neurodegenerative disease. A better understanding of the cellular and molecular mechanisms that promote or prevent disturbances in cellular Ca2+ homeostasis during aging may lead to novel approaches for therapeutic intervention in neurological disorders such as Alzheimer's and Parkinson's diseases and stroke.


Classical Swine Fever Virus Biology, Clinicopathology, Diagnosis, Vaccines and a Meta-Analysis of Prevalence: A Review from the Indian Perspective.
: Classical swine fever (CSF) is an economically significant, multi-systemic, highly contagious viral disease of swine world over. The disease is notifiable to the World Organization for Animal Health (OIE) due to its enormous consequences on porcine health and the pig industry. In India, the pig population is 9.06 million and contributes around 1.7% of the total livestock population. The pig industry is not well organized and is mostly concentrated in the eastern and northeastern states of the country (~40% of the country's population). Since the first suspected CSF outbreak in India during 1944, a large number of outbreaks have been reported across the country, and CSF has acquired an endemic status. As of date, there is a scarcity of comprehensive information on CSF from India. Therefore, in this review, we undertook a systematic review to compile and evaluate the prevalence and genetic diversity of the CSF virus situation in the porcine population from India, targeting particular virus genes sequence analysis, published reports on prevalence, pathology, and updates on indigenous diagnostics and vaccines. The CSF virus (CSFV) is genetically diverse, and at least three phylogenetic groups are circulating throughout the world. In India, though genotype 1.1 predominates, recently published reports point toward increasing evidence of co-circulation of sub-genotype 2.2 followed by 2.1. Sequence identities and phylogenetic analysis of Indian CSFV reveal high genetic divergence among circulating strains. In the meta-analysis random-effects model, the estimated overall CSF prevalence was 35.4%, encompassing data from both antigen and antibody tests, and region-wise sub-group analysis indicated variable incidence from 25% in the southern to nearly 40% in the central zone, eastern, and northeastern regions. A country-wide immunization approach, along with other control measures, has been implemented to reduce the disease incidence and eliminate the virus in time to come.


Technical Note: Characterization of x-ray beam profiles for a fluoroscopic system incorporating copper filtration.
The goal of this study was to investigate x-ray beam profiles at various water depths to characterize the two-dimensional x-ray dose distribution, allowing for off-axis and out-of-field radiation dose estimation for a wide range of x-ray beam spectra commonly encountered in fluoroscopically guided interventional procedures. A Siemens Artis interventional fluoroscope was operated in a service mode to generate a continuous x-ray beam at fixed x-ray beam spectra, defined by their kVp and the thickness of additional copper filtration. A PTW scanning water tank with a diode detector was used to measure the x-ray beam profiles at several depths in water at various fields of view and x-ray beam spectra, both parallel and perpendicular to the anode-cathode axis direction. X-ray beam profiles, including out-of-field tails, were characterized for a wide range of beam qualities. The anode heel effect was pronounced even at depth, resulting in large dose variations across the x-ray field; this effect was even more definite at large fields of view, at higher kVps, and in the absence of additional copper filtration. This study investigated and characterized 2D radiation dose deposition in water from x-ray beam spectra commonly used by modern fluoroscopes in interventional procedures. This knowledge can be applied to manual dosimetry calculations or can be used to refine the accuracy of automated dose mapping tools or Monte Carlo simulations of the radiation dose to soft tissue within the x-ray field and to tissue adjacent to the primary beam. Additionally, this study illustrates a substantial reduction of the anode heel effect by using moderate amounts of additional copper filtration to harden the x-ray beam spectrum.


Motor and behavioral phenotype in conditional mutants with targeted ablation of cortical D1 dopamine receptor-expressing cells.
D1-dopamine receptors (Drd1a) are highly expressed in the deep layers of the cerebral cortex and the striatum. A number of human diseases such as Huntington disease and schizophrenia are known to have cortical pathology involving dopamine receptor expressing neurons. To illuminate their functional role, we exploited a Cre/Lox molecular paradigm to generate Emx-1(tox) MUT mice, a transgenic line in which cortical Drd1a-expressing pyramidal neurons were selectively ablated. Emx-1(tox) MUT mice displayed prominent forelimb dystonia, hyperkinesia, ataxia on rotarod testing, heightened anxiety-like behavior, and age-dependent abnormalities in a test of social interaction. The latter occurred in the context of normal working memory on testing in the Y-maze and for novel object recognition. Some motor and behavioral abnormalities in Emx-1(tox) MUT mice overlapped with those in CamKIIα(tox) MUT transgenic mice, a line in which both striatal and cortical Drd1a-expressing cells were ablated. Although Emx-1(tox) MUT mice had normal striatal anatomy, both Emx-1(tox) MUT and CamKIIα(tox) MUT mice displayed selective neuronal loss in cortical layers V and VI. This study shows that loss of cortical Drd1a-expressing cells is sufficient to produce deficits in multiple motor and behavioral domains, independent of striatal mechanisms. Primary cortical changes in the D1 dopamine receptor compartment are therefore likely to model a number of core clinical features in disorders such as Huntington disease and schizophrenia.


Calving intervals in beef cows at 2, 3, and 4 years of age when breeding is not restricted after calving.
The objective of this study was to evaluate calving intervals and repeatability of calving intervals of young beef cows when breeding seasons were initiated immediately after calving. Average calving date at 2, 3, and 4 yr of age was recorded, and duration of calving interval between the first and second and second and third parities was compared in 178 crossbred beef cows calving between 1981 and 1988. Cows were placed in paddocks with intact bulls immediately after calving so they had the opportunity to conceive at the estrus associated with the initial estrous cycles after calving. Average Gregorian date of calving for cows was progressively earlier with older age (March 9, March 5, and February 14 at 2, 3, and 4) yr of age, respectively). Repeatability of calving intervals within individual cows was also evaluated. There was an interaction between year and parity on calving interval between 2 and 3 (P < .001) and 3 and 4 (P < .004) yr of age. Repeatability of calving interval was low and negative during 5 of the 6 yr. In young beef cows, year and parity interact to influence calving interval, and this average interval is less than 365 d when initiation of the breeding season is not restricted after calving.


Stereoelectroencephalography in the setting of a previously implanted responsive neural stimulation device: illustrative case.
Responsive neural stimulation (RNS) is a relatively novel procedure for drug-resistant epilepsy, which involves implantation of a device into the skull and brain. As more devices are implanted, there may be an increasing need to perform intracranial electrocorticography in implant patients with persistent seizures. Given the device location, imaging difficulties with implanted devices, and other technical hurdles, stereoelectroencephalography (SEEG) could be especially challenging. The authors describe the first reported SEEG investigation in a patient with an RNS device, highlighting the technical challenges and clinical data ascertained. A 41-year-old male with drug-resistant epilepsy presented several years after a local surgeon had placed an RNS device with two electrodes in the bilateral parieto-occipital lobes. Because of inadequate seizure control, the patient was offered a repeat SEEG investigation to characterize his epilepsy better. Although more technically challenging than a traditional SEEG implantation, the SEEG investigation was successfully performed, which led to a confirmation of bilateral hippocampal seizure onset. The patient underwent repositioning of his RNS leads with a significant decrease in his seizure frequency. Concurrent implantation of SEEG electrodes in a functioning RNS device can be safely performed and can augment our understanding of a patient's seizures.


Purified aged garlic extract modulates allergic airway inflammation in BALB/c mice.
Garlic is known as a potent spice and a medicinal herb with broad therapeutic properties ranging from antibacterial to anticancer and anticoagulant. Our previous studies have shown some immunoregulatory effects for aged garlic extract, suggesting a key role for 14-kD glycoprotein of garlic in shifting the cytokine pattern to T helper-1. In present study, we investigated the effect of 1, 2, and 3 times intraperitoneal injections of aged garlic extract on an established allergic airway inflammation in murine model (BALB/c mice). The garlic extract, isolated by biochemical method, includes proteins precipitation by ammonium sulfate. After injection of the aged garlic extract, IFN-, anti allergen specific IgE and IgG1 were measured in lavage and serum by ELISA and histological assessment was performed on the lung tissues. The results indicated that three-time intra peritoneal injections of the aged garlic extract caused a significant decrease in the hallmark criteria of allergic airway inflammation levels which included eosinophil percentage in lavage, peribronchial lung eosinophils, IgG1 level in lavage and serum, mucous producing goblet cells grade and peribronchial and perivascular inflammation. Our findings in the present research suggested that aged garlic extract has the potential of attenuation of inflammatory features of allergic airway inflammation in murine model.


Changes in the glutathione system of lung cell lines after treatment with hydrocortisone.
Administration of anti-inflammatory glucocorticoids is a drug option in the therapy of acute respiratory distress syndrome (ARDS), according to present pathophysiological concepts. Surprisingly, glucocorticoids failed to show beneficial effects. This failure is not understood. In this investigation changes in the glutathione system due to hydrocortisone were found to consist of glutathione depletion and lowered glutathione reductase activities in alveolar epithelial type II cells, contrasted with unchanged activities in a fibroblast-like lung cell line. The glutathione system is thought to be the most important cellular antioxidative system and therefore alveolar epithelial type II cells might be more susceptible to oxidative stress after glucocorticoid treatment. As alveolar epithelial type II cells may be important targets in ARDS, because of their functions (stem cells of type I epithelial cells; surfactant synthesis), these changes might provide an explanation for the failure of glucocorticoids. In the present experiments the capability of hydrocortisone-treated alveolar epithelial type II cells to synthesise glutathione was found to be cysteine dependent at physiological concentrations. Transposing this observation to the in vivo situation, it might be expected that glucocorticoid efficacy in ARDS therapy requires co-administration of substances that increase glutathione synthesis, e.g. N-acetylcysteine.


Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes.
Differentiation of intestinal T helper 17 (Th17) cells, which contribute to mucosal barrier protection from invasive pathogens, is dependent on colonization with distinct commensal bacteria. Segmented filamentous bacteria (SFB) are sufficient to support Th17 cell differentiation in mouse, but the molecular and cellular requirements for this process remain incompletely characterized. Here, we show that intestine-draining mesenteric lymph nodes (MLNs), not intestine proper, are the dominant site of SFB-induced intestinal Th17 cell differentiation. Subsequent migration of these cells to the intestinal lamina propria is dependent on their upregulation of integrin β7. Stat3-dependent induction of RORγt, the Th17 cell-specifying transcription factor, largely depends on IL-6, but signaling through the receptors for IL-21 and IL-23 can compensate for absence of IL-6 to promote SFB-directed Th17 cell differentiation. These results indicate that redundant cytokine signals guide commensal microbe-dependent Th17 cell differentiation in the MLNs and accumulation of the cells in the lamina propria.


Islet allograft survival after a single course of treatment of recipient with antibody to L3T4.
Allografts of pancreatic islets of Langerhans were induced to survive for an indefinite period in diabetic mice if, at the time of engraftment, the mice received a single course of treatment with a monoclonal antibody directed against the L3T4 determinant, a nonpolymorphic cell surface glycoprotein present on the cell surface of the murine T helper-inducer lymphocyte subset. This treatment allowed the survival of islets of Langerhans transplanted across a major histocompatibility barrier without additional immunosuppression. The results demonstrate that the lymphocyte subset defined by the expression of the L3T4 molecules is central to the induction of allograft rejection and provides a model for tolerance induction for organ allograft transplantation.


Serine requirement in leukemic and normal blood cells.
In a serine-deficient medium, cells from humangt chronic granulocytic leukemia and normal human bone marrow exhibited a marked inhibition of incorporation of-radioactive precursors of DNA, RNA, and protein into an acid insoluble cell fraction. Normal diploid human fibroblasts did not exhibit inhibition without serine. Chronic granulocytic leukemia and normal marrow cells were essentially unable to synthesize C(14)-serine from C(14)-glucose, while human diploid fibroblasts were highly capable of this synthesis.


SID-1 protein of Caenorhabditis elegans mediates uptake of dsRNA into Bombyx cells.
RNA interference is one of the most revolutionary tools in the study of gene function, particularly in non-model systems. However, in Bombyx mori, as with many lepidopteran species, attempts at systemic RNAi have had mixed success. Gene identification and phylogenetic analyses suggest that Bombyx has the core RNAi machinery, which is necessary to undergo RNAi as a cellular response. We introduced sid genes from Caenorhabditis elegans into Bombyx BmN4 cells to enhance the uptake of dsRNA and revealed that the SID-1 protein, but not SID-2, has the ability to endow the RNAi effect with the addition of dsRNA to the medium. Observed RNAi effect was dependent on both the levels of sid-1 expression and the concentration of the dsRNA. These results suggest that SID-1 promotes the uptake of dsRNA from the medium into Bombyx cells. We generated transgenic animals that express sid-1 but have not detected significant enhancements of in vivo phenotype in response to the injection of the dsRNA into hemocoel.


Evidence-based psychosocial treatments for phobic and anxiety disorders in children and adolescents.
The article reviews psychosocial treatments for phobic and anxiety disorders in youth. Using criteria from Nathan and Gorman (2002), 32 studies are evaluated along a continuum of methodological rigor. In addition, the treatments evaluated in each of the 32 studies are classified according to Chambless et al.'s (1996) and Chambless and Hollon's (1998) criteria. Findings from a series of meta-analyses of the studies that used waitlists also are reported. In accordance with Nathan and Gorman, the majority of the studies were either methodologically robust or fairly rigorous. In accordance with Chambless and colleagues, although no treatment was well-established, Individual Cognitive Behavior Therapy, Group Cognitive Behavior Therapy (GCBT), GCBT with Parents, GCBT for social phobia (SOP), and Social Effectiveness Training for children with SOP each met criteria for probably efficacious. The other treatments were either possibly efficacious or experimental. Meta-analytic results revealed no significant differences between individual and group treatments on diagnostic recovery rates and anxiety symptom reductions, as well as other youth symptoms (i.e., fear, depression, internalizing and externalizing problems). Parental involvement was similarly efficacious as parental noninvolvement in individual and group treatment formats. The article also provides a summary of the studies that have investigated mediators, moderators, and predictors of treatment outcome. The article concludes with a discussion of the clinical representativeness and generalizability of treatments, practice guidelines, and future research directions.


Plasmacytoid dendritic cells and Toll-like receptor 7-dependent signalling promote efficient protection of mice against highly virulent influenza A virus.
Types I and III interferons (IFNs) elicit protective antiviral immune responses during influenza virus infection. Although many cell types can synthesize IFN in response to virus infection, it remains unclear which IFN sources contribute to antiviral protection in vivo. We found that mice carrying functional alleles of the Mx1 influenza virus resistance gene partially lost resistance to infection with a highly pathogenic H7N7 influenza A virus strain if Toll-like receptor 7 (TLR7) signalling was compromised. This effect was achieved by deleting either the TLR7 gene or the gene encoding the TLR7 adaptor molecule MyD88. A similar decrease of influenza virus resistance was observed when animals were deprived of plasmacytoid dendritic cells (pDCs) at day 1 post-infection. Our results provide in vivo proof that pDCs contribute to the protection of the lung against influenza A virus infections, presumably via signals from TLR7.


Nerve loop around the axillary vessels by the roots of the median nerve a rare variation in a south Indian male cadaver: a case report.
Median nerve is normally formed by the union of medial and lateral root arising from the medial and the lateral cords of the brachial plexus respectively. However, variations in the formation and its relation with the axillary vessels are not uncommon. Therefore, knowledge of the variations in the nerve formation and course is useful for the clinicians during surgery and for differential diagnosis of uncommon clinical conditions. During the routine dissection in the department of anatomy, Kasturba Medical Collage, Manipal, India, we found unique anatomical variations in the formation and the course of the roots of the median nerve forming the neural loops around the axillary artery and vein. Here we report the detailed description of these variations along with its clinical, embryological relevance and review of literature.


The effect of radiation on the immune response to cancers.
In cancer patients undergoing radiation therapy, the beneficial effects of radiation can extend beyond direct cytotoxicity to tumor cells. Delivery of localized radiation to tumors often leads to systemic responses at distant sites, a phenomenon known as the abscopal effect which has been attributed to the induction and enhancement of the endogenous anti-tumor innate and adaptive immune response. The mechanisms surrounding the abscopal effect are diverse and include trafficking of lymphocytes into the tumor microenvironment, enhanced tumor recognition and killing via up-regulation of tumor antigens and antigen presenting machinery and, induction of positive immunomodulatory pathways. Here, we discuss potential mechanisms of radiation-induced enhancement of the anti-tumor response through its effect on the host immune system and explore potential combinational immune-based strategies such as adoptive cellular therapy using ex vivo expanded NK and T cells as a means of delivering a potent effector population in the context of radiation-enhanced anti-tumor immune environment.


Food product tracing technology capabilities and interoperability.
Despite the best efforts of food safety and food defense professionals, contaminated food continues to enter the food supply. It is imperative that contaminated food be removed from the supply chain as quickly as possible to protect public health and stabilize markets. To solve this problem, scores of technology companies purport to have the most effective, economical product tracing system. This study sought to compare and contrast the effectiveness of these systems at analyzing product tracing information to identify the contaminated ingredient and likely source, as well as distribution of the product. It also determined if these systems can work together to better secure the food supply (their interoperability). Institute of Food Technologists (IFT) hypothesized that when technology providers are given a full set of supply-chain data, even for a multi-ingredient product, their systems will generally be able to trace a contaminated product forward and backward through the supply chain. However, when provided with only a portion of supply-chain data, even for a product with a straightforward supply chain, it was expected that interoperability of the systems will be lacking and that there will be difficulty collaborating to identify sources and/or recipients of potentially contaminated product. IFT provided supply-chain data for one complex product to 9 product tracing technology providers, and then compared and contrasted their effectiveness at analyzing product tracing information to identify the contaminated ingredient and likely source, as well as distribution of the product. A vertically integrated foodservice restaurant agreed to work with IFT to secure data from its supply chain for both a multi-ingredient and a simpler product. Potential multi-ingredient products considered included canned tuna, supreme pizza, and beef tacos. IFT ensured that all supply-chain data collected did not include any proprietary information or information that would otherwise identify the supply-chain partner who provided the information prior to sharing this information with product tracing technology providers. The 9 traceability solution providers who agreed to participate in this project have their systems deployed in a wide range of sectors within the food industry including, but not limited to, livestock, dairy, produce, fruits, seafood, meat, and pork; as well as in pharmaceutical, automotive, retail, and other industries. Some have also been implemented across the globe including Canada, China, USA, Norway, and the EU, among others. This broad commercial use ensures that the findings of this work are applicable to a broad spectrum of the food system. Six of the 9 participants successfully completed the data entry phase of this test. To verify successful data entry for these 6, a demo or screenshots of the data set from each system's user interface was requested. Only 4 of the 6 were able to provide us with this evidence for verification. Of the 6 that completed data entry and moved on to the scenarios phase of the test, 5 were able to provide us with the responses to the scenarios. Time metrics were useful for evaluating the scalability and usability of each technology. Scalability was derived from the time it took to enter the nonstandardized data set into the system (ranges from 7 to 11 d). Usability was derived from the time it took to query the scenarios and provide the results (from a few hours to a week). The time was measured in days it took for the participants to respond after we supplied them all the information they would need to successfully execute each test/scenario. Two of the technology solution providers successfully implemented and participated in a proof-of-concept interoperable framework during Year 2 of this study. While not required, they also demonstrated this interoperability capability on the FSMA-mandated food product tracing pilots for the U.S. FDA. This has significant real-world impact since the demonstration of interoperability enables U.S. FDA to obtain evidence on the importance and impact of data-sharing moving forward. Another real-world accomplishment is the modification or upgrade of commercial technology solutions to enhance or implement interoperability. As these systems get deployed by clients in the food industry, interoperability will no longer be an afterthought but will be built into their traceability systems. In turn, industry and regulators will better understand the capabilities of the currently available technologies, and the technology provider community will identify ways in which their systems may be further developed to increase interoperability and utility.


Using Appreciative Inquiry to explore the effect of COVID-19 on student trust: medical students' perspective.
This article was migrated. The article was marked as recommended. Background Students' anxiety due to the COVID-19 pandemic was expressed by some medical students in the form of anger and mistrust. This study aims to explore the reasons for mistrust between students and faculty among medical schools in Egypt that have flared during the pandemic. Methodology This is a three-phase exploratory qualitative study depending on thematic emergence from appreciative interviews (AI) sessions. Phase 1 online Appreciative Inquiry (AI) session followed by thematic content analysis. Phase 2 The themes were approached by a smaller cohort of students using a design that relied mostly on the psychometric free association test. Phase 3 The themes were tested on a larger number of students through an online survey. Results Students are revealed to be very well educated regarding contemporary medical education concepts. The most important factors from the student perspective were the presence of a well-designed assessment system aligned with the learning outcomes and teaching methodologies and the presence of extracurricular activities and soft skills, respectively. A balanced student life respecting their mental health was found important to increase trust. Conclusion A roadmap to enhance the student trust must be planned on several pivots: curriculum structure, extracurricular life, communication strategies, and identifying student roles in their learning and decision-making.


Exercise-induced skeletal muscle remodeling and metabolic adaptation: redox signaling and role of autophagy.
Skeletal muscle is a highly plastic tissue. Exercise evokes signaling pathways that strongly modify myofiber metabolism and physiological and contractile properties of skeletal muscle. Regular physical activity is beneficial for health and is highly recommended for the prevention of several chronic conditions. In this review, we have focused our attention on the pathways that are known to mediate physical training-induced plasticity. An important role for redox signaling has recently been proposed in exercise-mediated muscle remodeling and peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) activation. Still more currently, autophagy has also been found to be involved in metabolic adaptation to exercise. Both redox signaling and autophagy are processes with ambivalent effects; they can be detrimental and beneficial, depending on their delicate balance. As such, understanding their role in the chain of events induced by exercise and leading to skeletal muscle remodeling is a very complicated matter. Moreover, the study of the signaling induced by exercise is made even more difficult by the fact that exercise can be performed with several different modalities, with this having different repercussions on adaptation. Unraveling the complexity of the molecular signaling triggered by exercise on skeletal muscle is crucial in order to define the therapeutic potentiality of physical training and to identify new pharmacological compounds that are able to reproduce some beneficial effects of exercise. In evaluating the effect of new "exercise mimetics," it will also be necessary to take into account the involvement of reactive oxygen species, reactive nitrogen species, and autophagy and their controversial effects.


Retracted: Price development in important anesthesia and critical care medicine journals in comparison to journals of other disciplines.
In today's climate of financial restrictions, libraries and individual subscribers complain about the price increase of scientific journals. The development in prices of anesthesia/critical care journals was analysed over the past 6 years and compared to prices of some journals of other disciplines. Important journals in the categories Anesthesiology, Emergency Medicine & Critical Care, Surgery, Medicine (General), and Cardiac & Cardiovascular Systems listed in the 1999 Science Citation Index of Journal Citation Report were included and prices for the years 1995 to 2000 were analysed. Increase in prices ranged from +13% to +199%. The mean increase in journal prices was lowest in the category Anesthesiology (+61%), higher in the category Critical Care (+73%), and highest in the category Medicine, General (+101%). Changes in the impact factor (IF) varied widely, ranging from a decrease (Lancet: -43%; J Neurosurg Anesth: -44%) to a tremendous increase (e.g. Reg Anesth +165%; Ann Emerg Med +149%). The journals' size (number of articles or pages) did not increase proportionally with the increase in prices. A disproportionate rise in journal prices was seen over the past 6 years. The large increase in cost may have multiple reasons. The rapidly increasing cost of research journals may affect research quality because economic pressure may result in reduction in availibility of information due to cancellation of subscriptions to journals.


Euglycemic Diabetic Ketoacidosis in Pregnancy: A Case Report and Review of Current Literature.
Diabetic ketoacidosis (DKA) in pregnancy is associated with high fetal mortality rates. A small percentage of DKA occurs in the absence of high glucose levels seen in traditional DKA. Prompt recognition and management is crucial. We report a case of a 30-year-old pregnant woman with type 1 diabetes mellitus admitted with euglycemic DKA (blood glucose <200 mg/dL). Initial laboratory testing revealed a severe anion gap acidosis with pH 7.11, anion gap 23, elevated β-hydroxybutyric acid of 9.60 mmol/L, and a blood glucose of 183 mg/dL-surprisingly low given her severe acidosis. The ketoacidosis persisted despite high doses of glucose and insulin infusions. Due to nonresolving acidosis, her hospital course was complicated by spontaneous intrauterine fetal demise. Euglycemia and severe acidosis continued to persist until delivery of fetus and placenta occurred. It was observed that the insulin sensitivity dramatically increased after delivery of fetus and placenta leading to rapid correction of ketoacidosis. This case highlights that severe ketonemia can occur despite the absence of severely elevated glucose levels. We discuss the mechanism that leads to this pathophysiologic state and summarize previously published case reports about euglycemic DKA in pregnancy.


A resistive mesh phantom for assessing the performance of EIT systems.
Assessing the performance of electrical impedance tomography (EIT) systems usually requires a phantom for validation, calibration, or comparison purposes. This paper describes a resistive mesh phantom to assess the performance of EIT systems while taking into account cabling stray effects similar to in vivo conditions. This phantom is built with 340 precision resistors on a printed circuit board representing a 2-D circular homogeneous medium. It also integrates equivalent electrical models of the Ag/AgCl electrode impedances. The parameters of the electrode models were fitted from impedance curves measured with an impedance analyzer. The technique used to build the phantom is general and applicable to phantoms of arbitrary shape and conductivity distribution. We describe three performance indicators that can be measured with our phantom for every measurement of an EIT data frame: SNR, accuracy, and modeling accuracy. These performance indicators were evaluated on our EIT system under different frame rates and applied current intensities. The performance indicators are dependent on frame rate, operating frequency, applied current intensity, measurement strategy, and intermodulation distortion when performing simultaneous measurements at several frequencies. These parameter values should, therefore, always be specified when reporting performance indicators to better appreciate their significance.


Reversible effects of photodamage directed toward mitochondria.
When the initial effect of photodynamic therapy (PDT) involves mitochondrial photodamage, an early effect is loss of the mitochondrial membrane potential (ΔΨm ). Using murine hepatoma 1c1c7 cells and a photosensitizing agent known to target mitochondria, we examined loss of ΔΨm , initiation of apoptosis and loss of viability as a function of time and light dose. There was a correlation between loss of viability and the rapid disappearance of ΔΨm, as detected by the potential-sensitive probe Mitotracker Orange (MTO). Loss of ΔΨm was, however, reversible even with a substantial loss of viability. Unless there was a supralethal level of photodamage, 1c1c7 cells recovered their mitochondrial membrane potential, even if the cell population was on the pathway to apoptosis and cell death. These results indicate that when mitochondria are the initial PDT target, a qualitative estimate of photokilling can be provided by assessing the initial loss of ΔΨm.


Dexamethasone base conserves hearing from electrode trauma-induced hearing loss.
Local treatment of the cochlea after electrode insertion trauma with dexamethasone base conserves hearing against trauma-induced loss. Laboratory animal study. A guinea pig model of electron insertion trauma (EIT)-induced hearing loss (HL) used 44 guinea pigs sub-divided into four groups: 1) unoperated, controls (Controls, n = 44); 2) EIT, untreated (EIT, n = 15); 3) EIT plus artificial perilymph (EIT + AP, n = 15); and 4) EIT plus dexamethasone base (EIT + DXMb, n = 14). Cochleae that received EIT were randomly selected with contralateral, unoperated cochleae as internal controls. Auditory brainstem responses (ABRs) in response to 0.5 to 16 kHz pure tones were obtained before surgery, immediately after surgery (0 day), and on post-EIT days 3, 7, 14, and 30. Hair cell counts were obtained from stained organ of Corti specimens from all four groups (n = 3/group). Data were analyzed using analysis of variance and a Tukey-Kramer honestly significant difference post hoc test with significance alpha set at <0.05 (hearing) and <0.001 (hair cells). There were significant differences (<0.05) between the ABR thresholds of unoperated (control) and contralateral operated (experimental) ears of EIT and of EIT + AP groups for all tested frequencies. There was no statistical difference (>0.05) in ABR thresholds in the EIT + DXMb versus control groups for 0.5 to 4 kHz tones. DXMb treatment protected hair cells from EIT-induced damage and loss while AP treatment did not. The absence of significant differences in hearing thresholds between the EIT + DXMb group and control ears in response to 0.5 to 4 kHz tones demonstrates that DXMb is as effective as the aqueous form of dexamethasone in conserving hearing against EIT-induced loss.


How Do Risk Environment Factors Influence Perpetration of Partner Violence among Male Migrant and Non-migrant Market Workers in Central Asia?
Intimate partner violence (IPV) has emerged as a serious public health issue in migrant communities in Central Asia and globally. To date, however, research on risk factors associated with male perpetration of IPV among migrants remains scant. This study aims to examine risk environment theory-driven factors associated with male perpetration of IPV in the prior 6 months. We recruited, enrolled, and surveyed a respondent-driven sample of 1342 male market workers in Almaty, Kazakhstan, that included 562 (42%) non-migrants defined as Kazakhstan citizens who reside in Almaty; 502 (37%) external migrants from Kyrgyzstan, Tajikistan, or Uzbekistan; and 278 (21%) internal migrants from other areas of Kazakhstan. We conducted multivariate logistic regressions to estimate the effects of physical, economic, and political risk environment factors on IPV perpetration by migration status after controlling for potentially confounding socio-demographic and psychosocial variables. A total of 170 participants (12.7%) reported ever perpetrating physical or sexual IPV and 6.7% perpetrated such IPV in the prior 6 months. Multiple logistic regression results suggest that the risk environment factors of poor living conditions, exposure to political violence, and deportation experiences are associated with IPV perpetration among external and internal migrants, but not among non-migrants. Food insecurity is associated with IPV perpetration among external migrants and non-migrants, but not among internal migrants. Homelessness and arrests by police are associated with IPV perpetration among internal migrants, but not among external migrants or non-migrants. These findings underscore the need to consider the unique combination of risk environment factors that contribute to male IPV perpetration in the design of programs and policies to address IPV perpetration among external and internal migrant and non-migrant men in Central Asia.


Role of flexibility in entanglement.
Entanglement is essential to the function of many physical systems. Flexibility and length determine the extent to which the system can become entangled. Given a perfectly flexible unit-radius tube, several researchers have studied the minimum length needed to tie different types of knots. Can one obtain the same configurations with less flexible tubing? Does more flexibility always yield tighter knots? We demonstrate a phase change in flexibility beyond which more flexibility adds very little entanglement. This level of flexibility is surprisingly low and appears to have a global bound. Since tensile strength and flexibility act inversely, this level of flexibility provides the maximal tensile strength for materials that need to pack tightly. This is a basic design principle that should be observable in nature.


Mortality among retired fur workers. Dyers, dressers (tanners) and service workers.
A retrospective cohort mortality study was conducted on 807 fur dyers, fur dressers (tanners), and fur service workers who were pensioned between 1952 and 1977 by the Fur, Leather and Machine Workers Union of New York City. Workplace exposures of fur workers varied with job category. Dyers were exposed to oxidative dyes used in commercial hair dyes; dressers and service workers were exposed to tanning chemicals. In a comparison with the New York City population, no significant increases in mortality were observed among the fur dyers. Among fur dressers, mortality from all malignant neoplasms [standardized mortality ratio (SMR) 151] and lung cancer (SMR 232) was significantly elevated, as was mortality from cardiovascular disease (SMR 126) among fur service workers. When examined by ethnic origin, the elevated SMR values and directly age-adjusted rate ratios suggested that foreign-born fur dressers and eastern European-born fur workers experienced the highest risks for lung and colorectal cancers, respectively. These data support previous findings of increased mortality from colorectal cancer in the foreign-born population of the United States and suggest a possible occupational etiology for the observed lung cancer excess.


Cardiorespiratory dynamics during respiratory maneuver in athletes.
Introduction: The modern practice of sports medicine and medical rehabilitation requires the search for subtle criteria for the development of conditions and recovery of the body after diseases, which would have a prognostic value for the prevention of negative effects of training and rehabilitation tools, and also testify to the development and course of mechanisms for counteracting pathogenetic processes in the body. The purpose of this study was to determine the informative directions of the cardiorespiratory system parameters dynamics during the performing a maneuver with a change in breathing rate, which may indicate the body functional state violation. Methods: The results of the study of 183 healthy men aged 21.2 ± 2.3 years who regularly engaged in various sports were analyzed. The procedure for studying the cardiorespiratory system included conducting combined measurements of indicators of activity of the respiratory and cardiovascular systems in a sitting position using a spiroarteriocardiograph device. The duration of the study was 6 min and involved the sequential registration of three measurements with a change in breathing rate (spontaneous breathing, breathing at 0.1 Hz and 0.25 Hz). Results: Performing a breathing maneuver at breathing 0.1 Hz and breathing 0.25 Hz in comparison with spontaneous breathing leads to multidirectional significant changes in heart rate variability indicators-TP (ms2), LF (ms2), LFHF (ms2/ms2); of blood pressure variability indicators-TPDBP (mmHg2), LFSBP (mmHg2), LFDBP (mmHg2), HFSBP (mmHg2); of volume respiration variability indicators - LFR, (L×min-1)2; HFR, (L×min-1)2; LFHFR, (L×min-1)2/(L×min-1)2; of arterial baroreflex sensitivity indicators - BRLF (ms×mmHg-1), BRHF (ms×mmHg-1). Differences in indicators of systemic hemodynamics and indicators of cardiovascular and respiratory systems synchronization were also informative. Conclusion: According to the results of the study, it is shown that during performing a breathing maneuver with a change in the rate of breathing, there are significant changes in cardiorespiratory parameters, the analysis of which the increments made it possible to determine of the changes directions dynamics, their absolute values and informative limits regarding the possible occurrence of the cardiorespiratory interactions dysregulation.


Sub-decibel silicon grating couplers based on L-shaped waveguides and engineered subwavelength metamaterials.
The availability of low-loss optical interfaces to couple light between standard optical fibers and high-index-contrast silicon waveguides is essential for the development of chip-integrated nanophotonics. Input and output couplers based on diffraction gratings are attractive coupling solutions. Advanced grating coupler designs, with Bragg or metal mirror underneath, low- and high-index overlays, and multi-level or multi-layer layouts, have proven less useful due to customized or complex fabrication, however. In this work, we propose a rather simpler in design of efficient off-chip fiber couplers that provide a simulated efficiency up to 95% (-0.25 dB) at a wavelength of 1.55 µm. These grating couplers are formed with an L-shaped waveguide profile and synthesized subwavelength grating metamaterials. This concept jointly provides sufficient degrees of freedom to simultaneously control the grating directionality and out-radiated field profile of the grating mode. The proposed chip-to-fiber couplers promote robust sub-decibel coupling of light, yet contain device dimensions (> 120 nm) compatible with standard lithographic technologies presently available in silicon nanophotonic foundries. Fabrication imperfections are also investigated. Dimensional offsets of ± 15 nm in shallow-etch depth and ± 10 nm in linewidth's and mask misalignments are tolerated for a 1-dB loss penalty. The proposed concept is meant to be universal, which is an essential prerequisite for developing reliable and low-cost optical couplers. We foresee that the work on L-shaped grating couplers with sub-decibel coupling efficiencies could also be a valuable direction for silicon chip interfacing in integrated nanophotonics.


Theoretical perspectives on language and communication problems in mental retardation and developmental disabilities.
We argue that researchers interested in language and communication problems in mental retardation or any other developmental disorder should view such problems as emerging within the broader context of the behavioral profile, or phenotype, associated with a particular genetic condition. This will require understanding the direct and indirect effects of genes on the development of language and communication and thereby an understanding of the complex relations that exist between language and other dimensions of psychological and behavioral functioning as well as an understanding of the environments in which the developing person acts and is acted upon. We believe that the dominant model for understanding language and communication problems--the nativist approach, which emphasizes the child's innate capacity for acquiring language and characterizes language as consisting of a set of context-free deterministic rules that operate on abstract representations--is inconsistent with an emphasis on indirect genetic effects. We review recent evidence that undermines the nativist approach--evidence concerning the initial state of the language-learning child, the role of environmental input, the competence-performance distinction, and modularity. In place of nativism, we argue for Emergentism, which is a model in which language is seen to emerge from the interaction between the child's biological abilities to map statistical properties of the language input into a distributed representation and the characteristics of the language learning environment and for the purpose of engaging in real-time, meaningful language use.


Communication methods and production techniques in fixed prosthesis fabrication: a UK based survey. Part 1: communication methods.
The General Dental Council (GDC) states that members of the dental team have to 'communicate clearly and effectively with other team members and colleagues in the interest of patients'. A number of studies from different parts of the world have highlighted problems and confirmed the need for improved communication methods and production techniques between dentists and dental technicians. The aim of this study was to identify the communication methods and production techniques used by dentists and dental technicians for the fabrication of fixed prostheses within the UK from the dental technicians' perspective. The current publication reports on the communication methods. Seven hundred and eighty-two online questionnaires were distributed to the Dental Laboratories Association membership and included a broad range of topics. Statistical analysis was undertaken to test the influence of various demographic variables. The number of completed responses totalled 248 (32% response rate). The laboratory prescription and the telephone were the main communication tools used. Statistical analysis of the results showed that a greater number of communication methods were used by large laboratories. Frequently missing items from the laboratory prescription were the shade and the date required. The majority of respondents (73%) stated that a single shade was selected in over half of cases. Sixty-eight percent replied that the dentist allowed sufficient laboratory time. Twenty-six percent of laboratories felt either rarely involved or not involved at all as part of the dental team. This study suggests that there are continuing communication and teamwork issues between dentists and dental laboratories.


Metastatic melanoma cells evade immune detection by silencing STAT1.
Transcriptional activation of major histocompatibility complex (MHC) I and II molecules by the cytokine, interferon γ (IFN-γ), is a key step in cell-mediated immunity against pathogens and tumors. Recent evidence suggests that suppression of MHC I and II expression on multiple tumor types plays important roles in tumor immunoevasion. One such tumor is malignant melanoma, a leading cause of skin cancer-related deaths. Despite growing awareness of MHC expression defects, the molecular mechanisms by which melanoma cells suppress MHC and escape from immune-mediated elimination remain unknown. Here, we analyze the dysregulation of the Janus kinase (JAK)/STAT pathway and its role in the suppression of MHC II in melanoma cell lines at the radial growth phase (RGP), the vertical growth phase (VGP) and the metastatic phase (MET). While RGP and VGP cells both express MHC II, MET cells lack not only MHC II, but also the critical transcription factors, interferon response factor (IRF) 1 and its upstream activator, signal transducer and activator of transcription 1 (STAT1). Suppression of STAT1 in vitro was also observed in patient tumor samples, suggesting STAT1 silencing as a global mechanism of MHC II suppression and immunoevasion.


Face-Free Chest Detection Using Convolutional Neural Networks for Non-Contact Respiration Monitoring.
Non-contact methods for monitoring respiration face limitations when it comes to selecting the chest region of interest. The semi-automatic method, which requires the user to select the chest region in the first frame, is not suitable for real-time applications. The automatic method, which tracks the face first and then detects the chest region based on the face's position, can be inaccurate if the face is not visible or is rotated. Moreover, using the face region to track the chest region can under-utilize camera pixels since the face is not essential for monitoring respiration. This approach may adversely affect the quality of the respiration signal being measured. To address these issues, we propose a face-free chest detection model based on Convolutional Neural Networks. Our model enhances the measured non-contact respiration signal quality and utilizes more pixels for the chest region alone. In our quantitative study, we demonstrate that our method outperforms traditional methods that require the presence of the face. This approach offers potential benefits for real-time, non-contact respiration monitoring applicationsClinical relevance- This work enhances the performance of non-contact respiration monitoring techniques by precisely detecting the chest region without the need of face in it through a CNN-based model. The use of the CNN-based chest detection model also enhances the real-time monitoring capabilities of non-contact respiration monitoring techniques.


Frontal alpha asymmetry: A potential biomarker of approach-withdrawal motivation towards pain.
Pain-related catastrophising is a maladaptive coping strategy known to have a strong influence on clinical pain outcomes and treatment efficacy. Notwithstanding, little is known about its neurophysiological correlates. There is evidence to suggest catastrophising is associated with resting-state EEG frontal alpha asymmetry (FAA) patterns reflective of greater relative right frontal activity, which is known to be linked to withdrawal motivation and avoidance of aversive stimuli. The present study aims to investigate whether such a relationship occurs in the situational context of experimental pain. A placebo intervention was also included to evaluate effects of a potential pain-relieving intervention on FAA. 35 participants, including both chronic pain patients and healthy subjects, completed the Pain Catastrophising Scale (PCS) questionnaire followed by EEG recordings during cold pressor test (CPT)-induced tonic pain with or without prior application of placebo cream. There was a negative correlation between FAA and PCS-subscale helplessness scores, but not rumination or magnification, during the pre-placebo CPT condition. Moreover, FAA scores were shown to increase significantly in response to pain, indicative of greater relative left frontal activity that relates to approach-oriented behaviours. Placebo treatment elicited a decrease in FAA in low helplessness scorers, but no significant effects in individuals scoring above the mean on PCS-helplessness. These findings suggest that, during painful events, FAA may reflect the motivational drive to obtain reward of pain relief, which may be diminished in individuals who are prone to feel helpless about their pain. This study provides valuable insights into biomarkers of pain-related catastrophising and prospects of identifying promising targets of brain-based therapies for chronic pain management.