Are asthma medications and management related to deaths from asthma?
There is controversy about the role of beta-agonists in asthma mortality, and the impact of asthma management plans remains unclear. We compared blood beta-agonist levels in patients dying from asthma with those in controls, and estimated the risks associated with specific classes of medication and patterns of management. We identified 89 asthma deaths and recruited 322 patients presenting to hospitals with acute asthma. A questionnaire was administered to the next of kin in 51 cases, and to 202 controls. Blood drawn from 35 cases and 229 controls was assayed for salbutamol. Smoking, drinking, and family problems were significantly more likely among the cases of asthma death than among the controls. The two groups were reasonably well matched with regard to markers of chronic asthma severity. Cases of asthma death were significantly less likely than controls to use a peak flow meter. Written action plans were associated with a 70% reduction in the risk of death. Use of nebulized bronchodilators or oral steroids was significantly more likely in cases of asthma death. Mean blood salbutamol concentrations were 2.5 times higher in cases of asthma. The use of oral steroids for an attack of asthma reduced the risk of death by 90%. More widespread adoption of written asthma management plans, with less reliance on beta-agonists and closer medical supervision, should reduce asthma mortality.


[Current status and future prospects of 3D treatment planning in radiation therapy, focusing on IMRT].
The ultimate goal of radiation therapy is to confine a high dose to the target area while sparing the surrounding normal structures in order to increase the delivered dose and decrease the likelihood of organ injuries. In Japan, the rotational conformal technique, which is a combination of gantry rotation and dynamic movement of multi-leaf collimators (MLC), has been widely used as a standard method for high-precision radiation therapy. The non-coplanar technique in which radiation beams are given in three dimensions has the advantage of dose concentration as well as organ sparing. In intensity modulated radiotherapy (IMRT), an uneven intensity map within a beam is generated with various methods such as "sliding window technique" and "stop and shoot technique". Several intensity modulated beams are combined to create arbitrary dose distribution including concave distribution. Although a substantial number of proton therapy facilities are planned in this country, IMRT should be considered as a competitive rival from the viewpoint of cost-benefit analysis as well as clinical effectiveness.


Radioimmunodetection of small human tumor xenografts in spleen of athymic mice by monoclonal antibodies.
The ability of radiolabeled monoclonal antibodies to accumulate in and image small human tumors growing in the spleen of athymic mice was assessed. The antibodies B6.2 and B72.3, which reacted against human breast (Clouser) and colon (LS174T) tumor cells in vitro and in vivo, respectively, and the isotype matched anti-horseradish peroxidase antibody which did not bind to these tumors were used in pharmacokinetic and imaging experiments. Human melanoma cells and tumors (A375) which did not react with any of the three antibodies were used as additional controls. Radioiodinated "tumor specific" and non-specific antibodies were injected i.v. into athymic mice bearing intrasplenic tumors and the mice were sacrificed at various times to assess the specificity of uptake of these antibodies into tumor and normal host tissues. The accumulation of B6.2 in the Clouser tumor was maximal at 24 h as indicated by a localization index (specific/nonspecific antibody in tumor divided by the same ratio in blood) of about 4.0. The uptake of B72.3 in LS174T tumor increased with time with a localization index of about 12.0 observed at 50 h post-antibody injection. Localization indices for the control A375 tumor and for all normal mouse tissues, including the uninvolved portion of the tumor bearing spleen, were between 0.8 and 1.0, thus indicating no specific antibody accumulation. The relative blood flows of the Clouser and A375 tumors, as determined by the 86RbCl method, were similar. The results suggested that immunospecificity was a major factor in antibody localization in vivo. Specific images of approximately 100-mg Clouser tumors with radiolabeled B6.2 and of LS174T tumor with radiolabeled B72.3 were seen by 24 h after antibody injection. Images of smaller (about 20 mg) LS174T tumors were seen by 48 h following B72.3 injection. The control antibody, anti-horseradish peroxidase, did not image either Clouser or LS174T tumor. Also the control tumor was not imaged with any of the three antibodies tested. The data generated with this novel animal model support the concept of using radiolabeled monoclonal antibodies for detecting and possibly treating small metastatic visceral tumors in cancer patients.


Enhanced Exchange Bias in Epitaxial High-Entropy Oxide Heterostructures.
High-entropy oxides (HEOs) have gained significant interest in recent years due to their unique structural characteristics and potential to tailor functional properties. However, the electronic structure of the HEOs currently remains vastly unknown. In this work, combining magnetometry measurements, scanning transmission electron microscopy, and element-specific X-ray absorption spectroscopy, the electronic structure and magnetic properties of the perovskite-HEO La(Cr0.2Mn0.2Fe0.2Co0.2Ni0.2)O3 epitaxial thin films are systemically studied. It is found that enhanced magnetic frustration emerges from competing exchange interactions of the five transition-metal cations with energetically favorable half-filled/full-filled electron configurations, resulting in an unprecedented large vertical exchange bias effect in the single-crystalline films. Furthermore, our findings demonstrate that the La(Cr0.2Mn0.2Fe0.2Co0.2Ni0.2)O3 layer with a thickness down to 1 nm can be used as a pinning layer and strongly coupled with a ferromagnetic La0.7Sr0.3MnO3 layer, leading to a notable exchange bias and coercivity enhancement in a cooling field as small as 5 Oe. Our studies not only provide invaluable insight into the electronic structure of HEOs but also pave the way for a new era of large bias materials for spintronics devices.


Lipid metabolism and mobilization in the guinea pig during pregnancy.
The liver of the foetal guinea pig accumulates a large quantity of triacyglycerol late in gestation at the same time that adipose-tissue mass grows at its maximum rate and foetal adipose-tissue lipoprotein lipase activity and sensitivity to lipolytic hormones has substantially declined. The fatty acid for triacyglycerol synthesis is not synthesized in the foetal liver and it is unlikely that it originates from any of the foetal tissues. Before the accumulation of hepatic triacyglycerol the concentration of free fatty acids increases in both the umbilical vein and the maternal inferior vena cava. This occurs at a time when the triacyglycerol lipase activity in maternal adipose tissue is elevated and the rate of lipolysis, but not of fatty acid esterification, is higher than earlier in gestation or than in the non-pregnant state. It is proposed that the increase in lipolysis in maternal adipose tissue, brought about by an increase in circulating lipolytic hormones, mobilizes fatty acid, which passes to the foetus and is partly stored as hepatic triacylglycerol. The foetal liver effectively removes both long-and short-chain fatty acids from umbilical-vein blood. The rate of placental fatty acid transfer is more than adequate to account for the triacylglycerol accumulation.


The bidirectional causal association between psoriasis and psychological illnesses: a 2-sample Mendelian randomization study.
There have been reports of association between psoriasis and psychological illnesses. Nevertheless, it is not easy to draw conclusions with high quality causality from conventional observational studies. The objective of this study was to evaluate the causality of psoriasis and psychological illnesses. All summary-level data from genome-wide association studies for psoriasis and psychological illnesses were collected from Neale Lab and MRC Integrative Epidemiology Unit. Bidirectional Mendelian randomization analysis was performed to determine the random orientation with an independent genetic variation. The main estimated effects are derived using Inverse-Variance Weighted, weighted median, and MR Egger methods. Multiple data sets were validated against each other, and a series of sensitivity studies were conducted to ensure the reliability of the results. Mendelian randomization analysis revealed a causal effect of psoriasis [odds ratio (OR) 1·34, 95% confidence interval (CI) 1·21-1·46, P < 0.001; and OR 1.28, CI 1.17-1.39, P < 0.001] on psychological illnesses, and vice versa (OR 1.23, CI 1.14-1.31, P < 0.001; and OR 1.21, CI 1.11-1.31, P < 0.001). The results were supported by a series of sensitivity analyses. The findings of this Mendelian randomization study support a causal effect between psoriasis and psychological illnesses, and vice versa.


Traditional and cyber bullying and sexual harassment: A longitudinal assessment of risk and protective factors.
Adolescents engage in bullying and sexual harassment perpetration both in-person and online. Yet, little is known about the overlap of traditional (in-person) and cyber bullying and sexual harassment perpetration. The present study assessed the co-occurrence of these forms of aggression in high school and identified middle school predictors based on participants' perceptions of factors across the social ecology. Racially diverse middle and high school students (n = 3549) were surveyed over four time points from Spring 2008 to Spring 2013. A latent class analysis was used to identify classes of individuals according to endorsement of traditional and cyber bullying and sexual harassment items in high school. Four classes were identified: (1) high all, consisting of traditional and cyber bullying and sexual harassment perpetration (n = 227); (2) traditional bullying perpetration (n = 604); (3) traditional and cyber bullying perpetration (n = 450); and (4) low all (n = 1,261). Students who reported high levels of anger, self-esteem, empathy, pornographic exposure, and traditional masculinity (individual level), lower levels of social support and parental monitoring (relational level), and higher levels of school belonging (community level) had increased odds of being in the high all class when compared to the other classes. Given the co-occurrence of traditional and cyber bullying and sexual harassment, prevention programming that addresses both forms of aggression across traditional and online contexts may be beneficial. This study also suggests the importance of comprehensive prevention efforts that incorporate approaches at the different ecological levels, such as teaching adolescents healthy emotional and interpersonal skills, and engaging parents in prevention.


New phenotype with generalized platyspondyly, large mandible, hypoplastic teeth, strabismus, hyperopia and low cholesterol levels.
A sporadic, adult male patient with generalized platyspondyly, large mandible, hypoplastic teeth, strabismus, and low serum cholesterol levels is presented. Some of the patient's features resemble brachyolmia, Spondylo-epiphyseal dysplasia tarda, Kenny-Caffey and Stickler syndromes. Based on literature review, possible diagnoses are discussed. In conclusion, this patient can have a variant of brachyolmia or Spondylo-epiphyseal dysplasia tarda. However, we cannot exclude that this constellation of clinical features may represent a new syndrome.


Technical guide for genetic advancement of underdeveloped and intractable Clostridium.
In recent years, the genus Clostridium has risen to the forefront of both medical biotechnology and industrial biotechnology owing to its potential in applications as diverse as anticancer therapy and production of commodity chemicals and biofuels. The prevalence of hyper-virulent strains of C. difficile within medical institutions has also led to a global epidemic that demands a more thorough understanding of clostridial genetics, physiology, and pathogenicity. Unfortunately, Clostridium suffers from a lack of sophisticated genetic tools and techniques which has hindered the biotechnological exploitation of this important bacterial genus. This review provides a comprehensive summary of biotechnological progress made in clostridial genetic tool development, while also aiming to serve as a technical guide for the advancement of underdeveloped clostridial strains, including recalcitrant species, novel environmental samples, and non-type strains. Relevant strain engineering techniques, from genome sequencing and establishment of a gene transfer methodology through to deployment of advanced genome editing procedures, are discussed in detail to provide a blueprint for future clostridial strain construction endeavors. It is expected that a more thorough and rounded-out genetic toolkit available for use in the clostridia will bring about the construction of superior bioprocessing strains and a more complete understanding of clostridial genetics, physiology, and pathogenicity.


Low oxygen tension increases mitochondrial membrane potential and enhances expression of antioxidant genes and implantation protein of mouse blastocyst cultured in vitro.
In human IVF, embryos cultured with a lower O2 tension (5%) can give rise to higher success rates when compared with normoxic conditions (20%). However, the mechanisms behind the beneficial effects of reduced oxygen tension in embryogenesis remain unclear. The aim of this study was to evaluate the expression of oxygen related and antioxidant genes and mitochondrial function in mouse embryo cultured under hypoxic and normoxic conditions, to investigate the beneficial effect of low oxygen tension in preimplantation embryogenesis. Two-cell ICR mouse embryos were cultured to blastocysts under different oxygen tension (3% and 20%). The gene expression of oxygen-related proteins (hypoxia-inducible factor, HIF), HIF targets (vascular endothelial growth factor, VEGF; glucose transporter 3, GLUT-3) and antioxidants (manganese superoxide dismutase, MnSOD; peroxiredoxin 5, PRDX5) were assessed using quantitative RT-PCR and implantation-related protein (Leukemia Inhibitory Factor Receptor, LIFR) was validated by immunofluorescence. Apoptosis, mitochondrial membrane potential (MtMP) and ROS levels were measured by TUNEL, JC-1 and DCFDA assays, respectively. Blastocyst development rate (92.3% vs. 79.4%) and hatch rate (80% vs. 70.4%) were both higher in embryos cultured in 3% O2 than in 20% O2. The transcription levels of MnSOD, PRDX5, VEGF and GLUT-3 also significantly increased in 3% O2 compared with 20% O2 (P < 0.05). Immunofluorescence showed that the intensity of staining for HIF-2α, MnSOD and LIFR were higher in 3% O2. Blastocysts cultured under 3% O2 exhibited significantly higher MtMP compared with 20% O2. ROS and Apoptosis levels were significantly higher in the 20% O2 group than in the 3% O2 group (P < 0.05). Low O2 tension may improve embryo viability by increasing expression of antioxidant enzymes and glucose transporter activities. It provides an environment conducive to viability by upregulation of LIFR/VEGF and increased MtMP which could enhance implantation potential and reduce apoptosis in mouse blastocyst. These effects may be initiated and regulated by HIF-2α, a key mediator in a hypoxic environment.


Sleep as a support for social competence, peer relations, and cognitive functioning in preschool children.
Evidence that sleep influences social and cognitive adaptation for school-age children and adolescents is accumulating rapidly, but less research focuses on the role of sleep for adaptive functioning during early childhood. We addressed these questions using actigraphy to assess sleep duration, sleep quality, and variability in sleep schedules in relation to a range of social/emotional and cognitive measures, including receptive vocabulary, emotion understanding, peer acceptance, social skills, social engagement, and temperament. Children in a convenience sample (N = 62, 40 boys, mean age = 4.15 yrs, 67% European American) wore actigraphs for 4-7 days, with sleep and wake states determined using Sadeh's scoring algorithm. Older children spent less time in bed at night and ethnic minority children (mostly African Americans) slept less at night and had lower sleep efficiency than did European American ethnic status children. Bivariate relations (controlling for sex, age, and ethnicity) between sleep variables and child adaptation scores showed that sleep duration was positively associated with peer acceptance, social skills, social engagement, receptive vocabulary, and understanding of the causes of emotions. Fewer variables were associated with nighttime sleep quality and variability and these tended to be related to outcome variables suggestive of behavioral and emotional regulation. Results suggest that sleep parameters are broadly implicated in the adjustment of preschool age children.


An unusual case of a microscopic alveolar adenoma coexisting with lung carcinoma: a case report and review of the literature.
Alveolar adenomas are extremely rare, benign, primary lung tumors of unknown histogenesis that are characterized by proliferative type II alveolar epithelium and septal mesenchyma. Mostly incidental, they are clinically important as they can imitate benign primary and secondary malignant tumors and at times are difficult to differentiate from early-stage lung cancer. We describe the case of a 59-year-old man with an incidental microscopic alveolar adenoma coexisting with poorly differentiated lung carcinoma. A 59-year-old Caucasian man with a medical history of smoking and chronic obstructive pulmonary disease was incidentally found to have a right upper lobe mass while undergoing a computed tomographic chest scan as part of a chronic obstructive pulmonary disease clinical trial. Our patient underwent a right upper lobectomy after a bronchoscopic biopsy of the mass revealed the mass to be a carcinoma. A pathological examination revealed an incidental, small, 0.2 cm, well circumscribed lesion on the staple line margin of the lobectomy in addition to the carcinoma. Histopathological and immunohistochemical examinations revealed the lesion to be an alveolar adenoma. We report the rare presentation of a microscopic alveolar adenoma coexisting with lung carcinoma. Alveolar adenoma is an entirely benign incidental neoplasm that can be precisely diagnosed using immunohistochemical analysis in addition to its unique histopathological characteristics.


Perceptions of voluntary medical male circumcision among circumcising and non-circumcising communities in Malawi.
Three randomised controlled trials in Africa indicated that voluntary medical male circumcision (VMMC) is an effective method to reduce a man's risk of becoming infected through sex with an HIV-positive female partner. The success of recent public health initiatives to increase numbers of circumcised men in Malawi has been very limited. We conducted in-depth interviews and focus group discussions (FGDs) with men, women and male adolescents from non-circumcising and circumcising communities in southern Malawi to better understand their beliefs about male circumcision and the promotion of VMMC for HIV prevention. Results revealed that beliefs about male circumcision, in general, are strongly mediated by Malawian culture and history. Participants have attempted to develop a new meaning for circumcision in light of the threat of HIV infection and the publicised risk reduction benefits of VMMC. Several study participants found it difficult to distinguish VMMC from traditional circumcision practices (jando and lupanda), despite awareness that the new form of circumcision was an expression of (western) modern medicine performed largely for public health purposes. Greater recognition of background cultural beliefs and practices could inform future efforts to promote medical male circumcision as an HIV prevention strategy in this context.


Manipulation of amorphous precursors to enhance zeolite nucleation.
Crystallization in media comprised of amorphous precursors is becoming a more common phenomenon for numerous synthetic, biological, and natural materials that grow by a combination of classical and nonclassical pathways. Amorphous phases can exhibit a wide range of physicochemical properties that may evolve during the course of nucleation and crystal growth. This creates challenges for establishing causal relationships between amorphous precursor properties and their effect(s) on the selection of mechanistic pathways of crystallization and ultimately the properties of the crystalline product. In this study, we examine ways to manipulate the composition and colloidal stability of amorphous (alumino)silicate precursors that are prevalent in nanoporous zeolite syntheses. Changes in the amorphous precursor properties are evaluated on the basis of their ability to enhance rates of crystal formation. Here, we use fumed silica as the primary silicon source and examine the effects of infusing the source or growth medium with additional alkali metal, which serves as an inorganic structure-directing agent to facilitate the formation of porous crystal structures. We also assess the impact of adding a polymer additive, which reduces the colloidal stability of precursors, wherein we posit that the confined pockets of solution within the interstitial spaces of the precursor aggregates play an important role in regulating the rate of zeolite crystallization. Three commercially relevant zeolites (mordenite, SSZ-13, and ZSM-5) were selected for this study based on their diverse frameworks and methods of preparation. Our findings reveal that alkali infusion significantly reduces the crystallization times for mordenite and SSZ-13, but has little impact on ZSM-5 synthesis. Conversely, we find that polymer addition markedly enhanced the rates of crystallization among all three zeolites, suggesting that this method may be a general approach to reduce zeolite synthesis times. Given the relatively high costs associated with commercial zeolite production, identifying new methods to improve the efficiency of hydrothermal syntheses can have significant practical implications beyond the fundamental benefits of developing new routes to tailor nonclassical crystallization.


Molecular interaction of cryptophycin 52 with Caspase 8 for the management of lung cancer during coronavirus outbreak : A computational study.
It has been seen that, during COVID-19 outbreak lung cancer (LC) patients are noted as a high-risk population which make a more challenging to treatment of the LC patients. The active form of caspase-8 is involved in lung carcinogenesis in both humans and mice. In this study, the virtual screening was performed among 200 compounds retrieved from several resources for the searching of potent lead against Caspase 8 (Casp8). Cryptophycin 52 was found to have a strong inhibiting efficacy based on the free energy of binding with the active site of Casp8. The lowest binding energy was found to be -8.05 kcal/mole and was further analyzed for molecular dynamic simulation. Casp8 enzyme was determined to interact with cryptophycin 52 through twelve amino acid residues, specifically ARG260, SER316, GLY318, ASP319, THR337, VAL354, PHE355, PHE356, ILE357, GLN358, ALA359 and CYS360 along with six hydrogen bond particular, ILE357:N-UNK1: O7, UNK1: O14-PHE355:O, UNK1: C25-PHE355:O, UNK1: C35-THR337:O, UNK1: H65-HE355:O and UNK1: C25-PHE356. In addition, MD simulations for 50ns were performed for optimization, flexibility estimation and assessment of Casp8-cryptophycin 52 complex stability. This complex was seen as reasonably stable according to the RMSD, RMSF, and radius of gyration graph. Results obtained indicate cryptophycin 52 may be a lead compound with significant anti-cancer ability against Casp8. Further experimental work, however, is expected to support the compound's anti-cancer viewpoint.


[Morbidity in Chagas' disease. III. Longitudinal study of 6 years, in Virgem da Lapa, MG, Brazil].
In a clinical, radiological and electrocardiographical, follow-up study of the "case control" type performed in Virgem da Lapa, Minas Gerais State, Brazil, 124 chagasic patients were followed during six years. The results of the patients, the majority in the indeterminate form, did not register any change, in 32.2% there was a progress in the disease and in 5.6% the electrocardiogram returned to normal. These results when compared to that achieved by the control group, composed of pairs of non chagasic persons with the same age and sex, was shown to be 27.4% higher than among patients with positive serology. This factor represents the excess risk or exclusively chagasic component in the development of the disease. No differences were observed by sex related to the development of the disease. It was more premature and seven times more frequent however when related to the cardiopathy than to the megaesophagus. Both conditions occurring mainly in slight or moderate degree. In 192 chagasic patients and 188 non chagasic persons observed in that area in the same period, the mortality was 3.6 times higher among the chagasic patients with a letality due to cardiopathy of 8.9% without difference between sexes but more premature among the males. Sudden death was more frequent than that one caused by cardiac insufficiency. The prognostic was good for the patients with indeterminate and digestive forms and reserved for patients with the highest degree of cardiopathy.


Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms.
The thyroid hormones (THs) 3,3',5,5'-tetraiodo-l-thyronine (T4) and 3,5,3'-triiodo-l-thyronine (T3) influence many metabolic pathways. The major physiological function of THs is to sustain basal energy expenditure, by acting primarily on carbohydrate and lipid catabolism. Beyond the mobilization and degradation of lipids, at the hepatic level THs stimulate the de novo fatty acid synthesis (de novo lipogenesis, DNL), through both the modulation of gene expression and the rapid activation of cell signalling pathways. 3,5-Diiodo-l-thyronine (T2), previously considered only a T3 catabolite, has been shown to mimic some of T3 effects on lipid catabolism. However, T2 action is more rapid than that of T3, and seems to be independent of protein synthesis. An inhibitory effect on DNL has been documented for T2. Here, we give an overview of the mechanisms of THs action on liver fatty acid metabolism, focusing on the different effects exerted by T2 and T3 on the regulation of the DNL. The inhibitory action on DNL exerted by T2 makes this compound a potential and attractive drug for the treatment of some metabolic diseases and cancer.


Prediction of a common beta-propeller catalytic domain for fructosyltransferases of different origin and substrate specificity.
The three-dimensional (3D) structure of fructan biosynthetic enzymes is still unknown. Here, we have explored folding similarities between reported microbial and plant enzymes that catalyze transfructosylation reactions. A sequence-structure compatibility search using TOPITS, SDP, 3D-PSSM, and SAM-T98 programs identified a beta-propeller fold with scores above the confidence threshold that indicate a structurally conserved catalytic domain in fructosyltransferases (FTFs) of diverse origin and substrate specificity. The predicted fold appeared related to that of neuraminidase and sialidase, of glycoside hydrolase families 33 and 34, respectively. The most reliable structural model was obtained using the crystal structure of neuraminidase (Protein Data Bank file: 5nn9) as template, and it is consistent with the location of previously identified functional residues of bacterial levansucrases (Batista et al., 1999; Song & Jacques, 1999). The sequence-sequence analysis presented here reinforces the recent inclusion of fungal and plant FTFs into glycoside hydrolase family 32, and suggests a modified sequence pattern H-x (2)-[PTV]-x (4)-[LIVMA]-[NSCAYG]-[DE]-P-[NDSC][GA]3 for this family.


An Introduction to History of Science and the Emotions.
This essay introduces our call for an intertwined history-of-emotions/history-of science perspective. We argue that the history of science can greatly extend the history of emotions by proffering science qua science as a new resource for the study of emotions. We present and read science, in its multiple diversities and locations, and in its variegated activities, products, theories, and emotions, as constitutive of the norms, experiences, expressions, and regimes of emotions. Reciprocally, we call for a new reading of science in terms of emotions as an analytical category. Assuming emotions are intelligible and culturally learned, we extend the notion of emotion to include a nonintentional and noncausal "emotional style," which is inscribed into (and can reciprocally be generated by) technologies, disease entities, laboratory models, and scientific texts. Ultimately, we argue that emotional styles interrelate with broader emotional cultures and thus can contribute to and/or challenge grand historical narratives.


Reactive oxygen species level defines two functionally distinctive stages of inflammatory dendritic cell development from mouse bone marrow.
Reactive oxygen species (ROS) have been implicated in various physiological activities. However, their role in dendritic cell (DC) activation and generation has not been investigated. Using the bone marrow-derived GM-CSF-induced ex vivo DC model, we characterize how induction of ROS correlates with inflammatory DC functionality and expansion. We describe that the functionality of GM-CSF-induced DCs is distinct in two developmental stages. Whereas division of DC-committed hematopoietic progenitor cells (HPCs) neared completion by day 6, the level of ROS soared after day 4. Day 3 ROS(lo) DCs were highly responsive to TLR stimuli such as LPS and zymosan by rapid upregulation of CD80, CD86, and MHC class II, in contrast to the low response of day 6 ROS(hi) DCs. ROS(hi) DCs could not initiate and sustain a significant level of NF-kappaB phosphorylation in response to LPS and zymosan, although demonstrating hyperactivation of p38 MAPK by LPS, in a fashion disparate to ROS(lo) DCs. ROS(lo) DCs stimulated a higher level of allogeneic and OVA-specific T cell proliferative responses, although ROS(hi) DCs were much more proficient in processing OVA. In response to pathogenic stimuli, ROS(hi) DCs also demonstrated rapid cellular adhesion and H(2)O(2) release, indicating their role in immediate microbial targeting. Moreover, HPC expansion and DC generation were dependent on the surge of ROS in an NADPH oxidase-independent manner. These findings point to the potential role of cellular ROS in mediating functionality and development of DCs from HPCs during inflammation.


Deep tissue injury: how deep is our understanding?
Deep pressure ulcers, necessarily involving deep tissue injury (DTI), arise in the muscle layers adjacent to bony prominences because of sustained loading. They represent a serious type of pressure ulcer because they start in underlying tissues and are often not visible until they reach an advanced stage, at which time treatment becomes problematic. Underlying mechanisms of DTI require further investigation if appropriate preventive measures are to be determined. The present commentary illustrates a hierarchic research approach selected to study these mechanisms. To differentiate between the individual roles of deformation and ischemia in the onset of skeletal muscle damage, 2 complementary approaches have been selected. In an in vivo animal model, the effects of ischemia combined with deformation and ischemia per se were studied. An in vitro muscle model was used to study the separate effects of deformation and several aspects of ischemia, including hypoxia, glucose depletion, and tissue acidification, in more detail. Based on the results of both models a sequence of events leading to cell necrosis is proposed. Deformation levels exceeding a threshold value can result in rapid tissue damage that may persist, whereas ischemia has a more gradual effect as a result of glucose depletion and tissue acidification.


Frightfully funny: combining threat and humour in health messages for men and women.
It is imperative for public health to investigate what factors may reduce defensive responses and increase the effectiveness of health information. The present research investigated gender differences in responses to threatening health-promoting information communicated with humour. Male and female participants were exposed to a health message stressing the negative consequences of binge drinking (Experiment 1; N = 209) or caffeine consumption (Experiment 2; N = 242), that did or did not contain a funny visual metaphor (Experiment 1) or a slapstick cartoon (Experiment 2). Message evaluation, message attention, and attitudes and intentions towards the behaviour were measured. Results showed that health messages were more persuasive when communicated with humour, although humour played a different role for men and women. Whereas men responded more in line with message goals when the message combined high threat with humour, women preferred the low threat humour messages. By uncovering the moderating role of gender as a key audience characteristic, this research contributes to designing effective future health campaigns and provides important insights for future studies investigating the underlying mechanisms responsible for the different effects of threat and humour appeals for men and women.


Ocular manifestations in Down syndrome.
Down syndrome patients have characteristic ocular findings and associated problems and should have periodic ophthalmologic examinations. The ocular abnormalities of Down syndrome are, for the most part, amenable to treatment and significant visual loss should rarely occur in these patients. Early recognition and treatment will minimize added problems of visual deprivation and permit the patient with Down syndrome to function at his or her highest level of potential.


Plate Versus Tension-Band Wire Fixation for Olecranon Fractures: A Prospective Randomized Trial.
The aim of this single-center, single-blinded, prospective randomized trial was to compare the outcomes of tension-band wire (TBW) and plate fixation for simple isolated, displaced fractures of the olecranon. We performed a prospective randomized trial involving 67 patients who were ≥16 to <75 years of age and had an acute isolated, displaced fracture of the olecranon. Patients were randomized to either TBW (n = 34) or plate fixation (n = 33) and were evaluated at 6 weeks, 3 months, 6 months, and 1 year following surgery. The primary outcome measure was the Disabilities of the Arm, Shoulder and Hand (DASH) score at 1 year. The baseline demographic and fracture characteristics of the 2 groups were comparable, except for age, which was lower in the TBW group. The 1-year follow-up rate was 85% (n = 57), with 84% (n = 56) completing the DASH. There was a significant improvement in the DASH score over the 1-year period following surgery (p < 0.001). At 1 year, the DASH score for the TBW group (12.8) did not differ significantly from that of the plate group (8.5) (p = 0.315). The groups also did not differ significantly in terms of range of motion, the Broberg and Morrey score, the Mayo Elbow Score, or the DASH at all assessment points over the 1 year (all p ≥ 0.05). Complication rates were significantly higher in the TBW group (63% compared with 38%; p = 0.042), predominantly because of a significantly higher rate of metalwork removal in symptomatic patients (50.0% compared with 22%; p = 0.021). Four infections occurred, all in the plate group (0% versus 13%; p = 0.114), as did 3 revision surgeries (0% versus 9.4%; p = 0.238). Among active patients with a simple isolated, displaced fracture of the olecranon, no difference was found between TBW and plate fixation in the patient-reported outcome at 1 year following surgery. The complication rate was higher following TBW fixation and was due to a higher rate of implant removal in symptomatic patients. However, the more serious complications of infection and the need for revision surgery occurred exclusively following plate fixation in this trial. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


A comparison of transanal excision and endoscopic resection for early rectal cancer.
To compare the outcomes of endoscopic resection with transanal excision in patients with early rectal cancer. Thirty-two patients with early rectal cancer were treated by transanal excision or endoscopic resection between May 1999 and December 2007. The patients were regularly re-examined by means of colonoscopy and abdominal computed tomography after resection of the early rectal cancer. Complications, length of hospital-stay, disease recurrence and follow up outcomes were assessed. Sixteen patients were treated by endoscopic resection and 16 patients were treated by transanal excision. No significant differences were present in the baseline characteristics. The rate of complete resection in the endoscopic resection group was 93.8%, compared to 87.5% in the transanal excision group (P = 0.544). The mean length of hospital-stay in the endoscopic resection group was 2.7 ± 1.1 d, compared to 8.9 ± 2.7 d in the transanal excision group (P = 0.001). The median follow up was 15.0 mo (range 6-99). During the follow up period, there was no case of recurrent disease in either group. Endoscopic resection was a safe and effective method for the treatment of early rectal cancers and its outcomes were comparable to those of transanal excision procedures.


Toward a perceptual theory of transparency.
Theories of perceptual transparency have typically been developed within the context of a physical model that generates the percept of transparency (F. Metelli's episcotister model, 1974b). Here 2 fundamental questions are investigated: (a) When does the visual system initiate the percept of one surface seen through another? (b) How does it assign surface properties to a transparent layer? Results reveal systematic deviations from the predictions of Metelli's model, both for initiating image decomposition into multiple surfaces and for assigning surface attributes. Specifically, results demonstrate that the visual system uses Michelson contrast as a critical image variable to initiate percepts of transparency and to assign transmittance to transparent surfaces. Findings are discussed in relation to previous theories of transparency, lightness, brightness, and contrast-contrast.


Small airway morphometry and improvement in pulmonary function after lung volume reduction surgery.
We examined small airway morphometry from resected lung specimens in 25 patients with severe emphysema undergoing lung volume reduction surgery (LVRS) and correlated their pathologic findings to changes in FEV(1) 6 months after LVRS. Patients were classified into two groups: responders had a more than 12% and a more than 200-ml change in FEV(1) at 6 months, and nonresponders had 12% or less and/or 200 ml or less change in FEV(1). Epithelial height (EH) and perimeters and areas of peribronchial smooth muscle, epithelium, and subepithelial space were measured quantitatively. The degrees of interstitial fibrosis, vascular sclerosis, goblet cell hyperplasia, squamous metaplasia, chronic inflammation, peribronchial fibrosis, and bullous disease were assessed semiquantitatively. Despite similar baseline characteristics, nonresponders had a greater EH (0.045 vs. 0.035 mm, p = 0.025), greater EH adjusted for basement membrane perimeter (0.040 vs. 0.011, p = 0.016), greater epithelial area adjusted for basement membrane area (0.561 vs. 0.499, p = 0.040), and less bullous disease (1.7 vs. 2.6, p = 0.011) compared with responders. We found a linear relationship between percentage change in FEV(1) and bullous disease and inverse relationships between percentage change in FEV(1) and interstitial fibrosis, goblet cell hyperplasia, peribronchial fibrosis, and vascular sclerosis. We conclude that small airway morphometry and lung histopathology in patients with severe emphysema have an important influence on changes in FEV(1) 6 months after LVRS.


Evaluation of a colorimetric method for canine glycosylated hemoglobin.
Glycosylated hemoglobins can be used to monitor glucose status and the effectiveness of insulin therapy in canine diabetes mellitus. We have compared a colorimetric method with a time-consuming chromatographic method for measuring glycosylated hemoglobins in canine blood. Although the colorimetric method is sensitive to hemoglobin concentration, its convenience and sample size make it a possible alternative to other methods.


New techniques for determining the longitudinal effects of local hemodynamics on the intima-media thickness in arteriovenous fistulae in an animal model.
Remodeling in the arteriovenous fistulas (AVFs) is believed to be a hemodynamic-driven process, which results in extreme changes in the diameter and intima-media thickening (IMT) of vessels over time. This study aims to describe the successful development of techniques that enabled correlation of changes in local and longitudinal wall shear stress (WSS) with the temporal variations of the diameter and IMT in the venous segment of AVFs. An AVF was created between the femoral artery and vein of a 50-kg pig. We have previously shown the successful use of CT-scan and ultrasound techniques for anatomical and flow measurements in AVFs, respectively. In this study, we developed new techniques involving markers (both in vivo and ex vivo), casting (ex vivo), and micro-MRI (ex vivo; 7 Tesla). A radiopaque marker (ROM) was sutured to the AVF at the day of surgery, which was visible in the CT-scan images, micro-MRI, and histology sections. Therefore, ROM served as a fixed local reference for both in vivo and ex vivo states of AVFs. Immediately after sacrificing the pig, a procedure was developed to create a cast from the AVF and thus, maintaining the in vivo state of the AVF during the histology process. Then, micro-MRI and histology techniques were conducted on the AVF to measure IMT in the vein. Along the ROM, the local changes in WSS levels for two cross-sections were tracked at 2D (D: days) and 28D post surgery. WSS levels reduced from 2D to 28D for both cross-sections. Also, the recirculation zones, which formed at 2D for both sections, became smaller in size at 28D. These hemodynamic changes were then mapped onto the corresponding IMT measurements from histology and micro-MRI. It was observed that the recirculation zones at 2D and 28D corresponded to the largest IMT in the two sections. In summary, the new methodologies allowed us to define a fixed local reference at all time points in the AVF, which enabled accurate tracking of local changes in hemodynamics (WSS), configuration (diameter), and structure (IMT) of the venous segment over time. This also empowered study of the interactions between these parameters, which could improve our understanding about the hemodynamic-driven remodeling in AVFs. From a clinical point of view, this information could be translated into local and early therapeutic interventions for dialysis patients.


Dissecting Motor Neuron Disease With Drosophila melanogaster.
Motor Neuron Disease (MND) typically affects patients during the later stages of life, and thus, MND is having an increasingly devastating impact on diagnosed individuals, their families and society. The umbrella term MND refers to diseases which cause the progressive loss of upper and/or lower motor neurons and a subsequent decrease in motor ability such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). The study of these diseases is complex and has recently involved the use of genome-wide association studies (GWAS). However, in the case of MND, it has been difficult to identify the complex genetics involved in subtypes, and functional investigation of new candidate disease genes is warranted. Drosophila is a powerful model for addressing these complex diseases. The UAS/Gal4/Gal80 system allows for the upregulation of Drosophila genes, the "knockdown" of genes and the ectopic expression of human genes or mutations in a tissue-specific manner; often resulting in Drosophila models which exhibit typical MND disease pathologies. These can then be further interrogated to identify disease-modifying genes or mutations and disease pathways. This review will discuss two common MNDs and the current Drosophila models which are being used to research their genetic basis and the different pathologies of MND.


Dynamic, spatial models of parasite transmission in wildlife: Their structure, applications and remaining challenges.
Individual differences in contact rate can arise from host, group and landscape heterogeneity and can result in different patterns of spatial spread for diseases in wildlife populations with concomitant implications for disease control in wildlife of conservation concern, livestock and humans. While dynamic disease models can provide a better understanding of the drivers of spatial spread, the effects of landscape heterogeneity have only been modelled in a few well-studied wildlife systems such as rabies and bovine tuberculosis. Such spatial models tend to be either purely theoretical with intrinsic limiting assumptions or individual-based models that are often highly species- and system-specific, limiting the breadth of their utility. Our goal was to review studies that have utilized dynamic, spatial models to answer questions about pathogen transmission in wildlife and identify key gaps in the literature. We begin by providing an overview of the main types of dynamic, spatial models (e.g., metapopulation, network, lattice, cellular automata, individual-based and continuous-space) and their relation to each other. We investigate different types of ecological questions that these models have been used to explore: pathogen invasion dynamics and range expansion, spatial heterogeneity and pathogen persistence, the implications of management and intervention strategies and the role of evolution in host-pathogen dynamics. We reviewed 168 studies that consider pathogen transmission in free-ranging wildlife and classify them by the model type employed, the focal host-pathogen system, and their overall research themes and motivation. We observed a significant focus on mammalian hosts, a few well-studied or purely theoretical pathogen systems, and a lack of studies occurring at the wildlife-public health or wildlife-livestock interfaces. Finally, we discuss challenges and future directions in the context of unprecedented human-mediated environmental change. Spatial models may provide new insights into understanding, for example, how global warming and habitat disturbance contribute to disease maintenance and emergence. Moving forward, better integration of dynamic, spatial disease models with approaches from movement ecology, landscape genetics/genomics and ecoimmunology may provide new avenues for investigation and aid in the control of zoonotic and emerging infectious diseases.


Thromboembolic disease in renal allograft recipients. What is its clinical significance?
Detailed analysis of the clinical data and autopsy material of 100 consecutive renal transplant recipients revealed significant thromboembolic disease in 25 patients and a total of 41 complications. In six of them, thromboembolism was associated with sepsis. Nine patients died (20% of total number of deaths) due to a primary thromboembolic event. The incidence of pulmonary embolism was 14%; myocardial infarction, 3%; cerebrovascular disease, 4%; renal artery thrombosis, 2%; renal vein thrombosis, 3%; thrombophlebitis/deep vein thrombosis, 13%; and miscellaneous, 2%. The incidence of thromboembolism was higher in patients older than 40 years of age (P = .02) and during the earlier months after transplantation. We summarize the general incidence and mortality related to thromboembolism and discuss the factors predisposing the graft recipient to thromboembolic disease. Prevention and therapy of this complication should decrease the morbidity and mortality in graft recipients and enhance the success of renal transplantation.


Fast hyperbaric decompression after heliox saturation altered the brain proteome in rats.
Better understanding of the physiological mechanisms and neurological symptoms involved in the development of decompression sickness could contribute to improvements of diving procedures. The main objective of the present study was to determine effects on the brain proteome of fast decompression (1 bar/20 s) compared to controls (1 bar/10 min) after heliox saturation diving, using rats in a model system. The protein S100B, considered a biomarker for brain injury, was not significantly different in serum samples from one week before, immediately after, and one week after the dive. Alterations in the rat brain proteome due to fast decompression were investigated using both iontrap and orbitrap LC-MS, and 967 and 1062 proteins were quantified, respectively. Based on the significantly regulated proteins in the iontrap (56) and orbitrap (128) datasets, the networks "synaptic vesicle fusion and recycling in nerve terminals" and "translation initiation" were significantly enriched in a system biological database analysis (Metacore). Ribosomal proteins (RLA2, RS10) and the proteins hippocalcin-like protein 4 and proteasome subunit beta type-7 were significantly upregulated in both datasets. The heat shock protein 105 kDa, Rho-associated protein kinase 2 and Dynamin-1 were significantly downregulated in both datasets. Another main effect of hyperbaric fast decompression in our experiment is inhibition of endocytosis and stimulation of exocytosis of vesicles in the presynaptic nerve terminal. In addition, fast decompression affected several proteins taking parts in these two main mechanisms of synaptic strength, especially alteration in CDK5/calcineurin are associated with a broad range of neurological disorders. In summary, fast decompression after heliox saturation affected the brain proteome in a rat model for diving, potentially disturbing protein homeostasis, e.g. in synaptic vesicles, and destabilizing cytoskeletal components. Data are available via ProteomeXchange with identifier PXD006349.


A Phytase-Based Reporter System for Identification of Functional Secretion Signals in Bifidobacteria.
Health-promoting effects have been attributed to a number of Bifidobacterium sp. strains. These effects as well as the ability to colonise the host depend on secreted proteins. Moreover, rational design of protein secretion systems bears the potential for the generation of novel probiotic bifidobacteria with improved health-promoting or therapeutic properties. To date, there is only very limited data on secretion signals of bifidobacteria available. Using in silico analysis, we demonstrate that all bifidobacteria encode the major components of Sec-dependent secretion machineries but only B. longum strains harbour Tat protein translocation systems. A reporter plasmid for secretion signals in bifidobacteria was established by fusing the coding sequence of the signal peptide of a sialidase of Bifidobacterium bifidum S17 to the phytase gene appA of E. coli. The recombinant strain showed increased phytase activity in spent culture supernatants and reduced phytase levels in crude extracts compared to the control indicating efficient phytase secretion. The reporter plasmid was used to screen seven predicted signal peptides in B. bifidum S17 and B. longum E18. The tested signal peptides differed substantially in their efficacy to mediate protein secretion in different host strains. An efficient signal peptide was used for expression and secretion of a therapeutically relevant protein in B. bifidum S17. Expression of a secreted cytosine deaminase led to a 100-fold reduced sensitivity of B. bifidum S17 to 5-fluorocytosine compared to the non-secreted cytosine deaminase suggesting efficient conversion of 5-fluorocytosine to the cytotoxic cancer drug 5-fluorouracil by cytosine deaminase occurred outside the bacterial cell. Selection of appropriate signal peptides for defined protein secretion might improve therapeutic efficacy as well as probiotic properties of bifidobacteria.


The effects of plastic spectacles on the condition and behaviour of pheasants.
Plastic spectacles are often fitted to pheasants in laying pens to reduce feather pecking and egg eating. This study examined the effects of spectacles on the physiological condition and behaviour of pheasants in harem and flock laying pens. In 2006 and 2007, data were collected from 21 game farms across England. On each site, two identical pens were randomly allocated a treatment, with or without spectacles. The physiological condition of pheasants in each treatment pen was assessed before and after the laying season. In flock pens, the behaviour of spectacled and non-spectacled pheasants was also assessed weekly. Detailed records of egg collections and mortality were also kept. Spectacles had no effect on the behaviour of male pheasants but affected the behaviour of females by reducing pecking and increasing head shaking/scratching. Although spectacles halved feather damage in females, and at least halved incidences of skin damage in both sexes, they increased bill and nostril damage in females while causing no detectable damage in males. Egg collections and mortality rates did not differ between spectacled and non-spectacled pens.


The outcome of phagocytic cell division with infectious cargo depends on single phagosome formation.
Given that macrophages can proliferate and that certain microbes survive inside phagocytic cells, the question arises as to the post-mitotic distribution of microbial cargo. Using macrophage-like cells we evaluated the post-mitotic distribution of intracellular Cryptococcus yeasts and polystyrene beads by comparing experimental data to a stochastic model. For beads, the post-mitotic distribution was that expected from chance alone. However, for yeast cells the post-mitotic distribution was unequal, implying preferential sorting to one daughter cell. This mechanism for unequal distribution was phagosomal fusion, which effectively reduced the intracellular particle number. Hence, post-mitotic intracellular particle distribution is stochastic, unless microbial and/or host factors promote unequal distribution into daughter cells. In our system unequal cargo distribution appeared to benefit the microbe by promoting host cell exocytosis. Post-mitotic infectious cargo distribution is a new parameter to consider in the study of intracellular pathogens since it could potentially define the outcome of phagocytic-microbial interactions.


Proteomic analysis of protein expression and oxidative modification in r6/2 transgenic mice: a model of Huntington disease.
Huntington disease (HD) is a hereditary neurodegenerative disorder characterized by motor, psychiatric, and cognitive symptoms. The genetic defect responsible for the onset of the disease, expansion of CAG repeats in exon 1 of the gene that codes for huntingtin on chromosome 4, has been unambiguously identified. On the other hand, the mechanisms by which the mutation causes the disease are not completely understood yet. However, defects in energy metabolism of affected cells may cause oxidative damage, which has been proposed as one of the underlying molecular mechanisms that participate in the etiology of the disease. In our effort to investigate the extent of oxidative damage occurring at the protein level, we used a parallel proteomic approach to identify proteins potentially involved in processes upstream or downstream of the disease-causing huntingtin in a well established HD mouse model (R6/2 transgenic mice). We have demonstrated that the expression levels of dihydrolipoamide S-succinyltransferase and aspartate aminotransferase increase consistently over the course of disease (10-week-old mice). In contrast, pyruvate dehydrogenase expression levels were found to be decreased in 10-week-old HD transgenic mice compared with young (4-week-old) mice. Our experimental approach also led to the identification of oxidatively modified proteins. Six proteins were found to be significantly oxidized in old R6/2 transgenic mice compared with either young transgenic mice or non-transgenic mice. These proteins are alpha-enolase, gamma-enolase (neuron-specific enolase), aconitase, the voltage-dependent anion channel 1, heat shock protein 90, and creatine kinase. Because oxidative damage has proved to play an important role in the pathogenesis and the progression of Huntington disease, our results for the first time identify specific oxidatively modified proteins that potentially contribute to the pathogenesis of Huntington disease.


Determinants to optimize response to clopidogrel in acute coronary syndrome.
The inhibition of platelet function by antiplatelet therapy determines the improvement of the survival of patients with clinically evident cardiovascular disease. Clopidogrel in combination with aspirin is the recommended standard of care for reducing the occurrence of cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. However, major adverse cardiovascular events including stent thrombosis occur in patients taking clopidogrel and aspirin. A growing body of evidence demonstrates that high post-treatment platelet reactivity on antiplatelet treatment is associated with increased risk of adverse clinical events. Clopidogrel requires conversion to active metabolite by cytochrome P450 isoenzymes. The active metabolite inhibits ADP-stimulated platelet activation by irreversibly binding to P2Y(12) receptors. Recently, the loss-of-function CYP2C19*2 allele has been associated with decreased metabolization of clopidogrel, poor antiaggregant effect, and increased cardiovascular events. In high risk vascular patients, the CYP2C19*2 polymorphism is a strong predictor of adverse cardiovascular events and particularly of stent thrombosis. Prospective studies evaluating if an antiplatelet treatment tailored on individual characteristics of patients, CYP2C19*2 genotypes, platelet phenotype, drug-drug interaction, as well as traditional and procedural risk factors, are now urgently needed for the identification of therapeutic strategies providing the best benefit for the single subject.


Intracellular pH regulation in trout urinary bladder epithelium: Na(+)-H+(NH4+) exchange.
We measured intracellular pH (pHi) of single epithelial cells in situ in the urinary bladder epithelium using microspectrofluorometry and the cytoplasmically trapped pH-sensitive fluorophore, 2',7'-bis(2-carboxyethyl)-5(6)- carboxyfluorescein (BCECF). The resting pHi was 7.21 +/- 0.03 (n = 40 bladders, 489 cells) in pH 7.8 bathing solutions, indicating that H+ is not passively distributed across the plasma membrane and is extruded against its electrochemical gradient. Whereas exposure to hypercapnia (5% CO2 saturation) reversibly decreased pHi, mucosally added 20 mM NH4+ reversibly increased pHi. Recovery from the NH4+ effect was slow and lacked an acid-load pHi undershoot; this is interpreted as suggesting significant NH4+ permeability. Recovery from hypercapnic acidosis was blocked by mucosally added amiloride, indicating that apical Na(+)-H+ exchange is involved in pHi regulation. Addition of 0.5 mM NH4+ to the basolateral side when the mucosal side was bathed in mock urine (2 mM NaCl) significantly increased undirectional mucosal-to-serosal Na+ flux, and the increase was blocked by mucosally added amiloride. We conclude that an apically located Na(+)-H+ exchange is important in pHi regulation and may also accept NH4+ as the counterion for Na+.


Promoting walking with pedometers in the community: the step-by-step trial.
Pedometers have been identified as a potential motivational aid for increasing physical activity, but their efficacy has not been demonstrated in a community-based, nonclinical sample. A randomized controlled trial was conducted from August to December 2005. Analysis was completed in June 2006. Inactive adults aged 30-65 years (n=369) recruited from the community. Comparison of a theoretically based self-help walking program (WP) and weekly diaries (sent by mail); the same walking program with a pedometer (WPP) (also by mail); and a no-treatment control group (C). Change in self-reported leisure time in any sports/recreation in the last 3 months, and all-purpose walking (APW) for exercise, recreation, and travel, and other moderate, vigorous physical activity in the last week. Proportions meeting physical activity recommendations (equal to or greater than 150 minutes and equal to or greater than five sessions/week(-1)) were determined. A 3-month follow-up interview was conducted with 314 (85%) participants. Intention-to-treat analyses indicated significance within-group increases of APW and leisure-time walking (LTW), but mean and median sessions and minutes changes were greatest in the WPP group. There were no significant between-group differences in regular LTW (walked equal to or greater than 5 sessions/week(-1) for at least 30 minutes/session), but the WPP group increased significantly participation in other sports/recreations and was more likely than the control group to meet physical activity recommendations by all leisure-time physical activity (adjusted odds ratio=2.40, 95% CI=1.17-4.93), by APW (adjusted odds ratio=1.75 95% CI=0.92-3.34) and all physical activity (adjusted odds ratio=1.59 95% CI=0.92-2.79) in the last week. Pedometers enhanced the effects of the self-help walking program. This low-cost intervention should be tested for sustainability.


Comparison of social cognition using an adapted Chinese version of the Reading the Mind in the Eyes Test in drug-naive and regularly medicated individuals with chronic schizophrenia and healthy controls in rural China.
Social cognition has not previously been assessed in treatment-naive patients with chronic schizophrenia, in patients over 60 years of age, or in patients with less than 5 years of schooling. We revised a commonly used measure of social cognition, the Reading the Mind in the Eyes Test (RMET), by expanding the instructions, using both self-completion and interviewer-completion versions (for illiterate respondents), and classifying each test administration as 'successfully completed' or 'incomplete'. The revised instrument (RMET-CV-R) was administered to 233 treatment-naive patients with chronic schizophrenia (UT), 154 treated controls with chronic schizophrenia (TC), and 259 healthy controls (HC) from rural communities in China. In bivariate and multivariate analyses, successful completion rates and RMET-CV-R scores (percent correct judgments about emotion exhibited in 70 presented slides) were highest in HC, intermediate in TC, and lowest in UT (adjusted completion rates, 97.0, 72.4, and 49.9%, respectively; adjusted RMET-CV-R scores, 45.4, 38.5, and 34.6%, respectively; all p < 0.02). Stratified analyses by the method of administration (self-completed v. interviewer-completed) and by education and age ('educated-younger' v. 'undereducated-older') show the same relationship between groups (i.e. NC>TC>UT), though not all differences remain statistically significant. We find poorer social cognition in treatment-naive than in treated patients with chronic schizophrenia. The discriminant validity of RMET-CV-R in undereducated, older patients demonstrates the feasibility of administering revised versions of RMET to patients who may otherwise be considered ineligible due to education or age by changing the method of test administration and carefully assessing respondents' ability to complete the task successfully.


The effects of kindling on GABA-mediated inhibition in the dentate gyrus of the rat. II. Receptor binding.
Receptor binding estimates of the number of GABA and associated benzodiazepine (Bz) receptors were made in several brain regions following kindling. While the number of GABA receptors, as measured by both [3H]GABA and [3H]muscimol binding, was unaltered by kindling, Bz receptors were significantly increased in kindled amygdala and hippocampus. As the Bz receptor apparently functions to enhance GABA transmission, this finding suggests a possible mechanism for the kindling-induced enhancement of inhibition observed in previous evoked potential experiments.


Stability of ascorbic acid in commercially available orange juices.
To compare the vitamin C content of reconstituted frozen orange juice concentrates at preparation to that of ready-to-drink orange juices purchased 4 to 5 weeks from expiration. Juices were unsealed and analyzed for reduced and oxidized vitamin C content at the time of purchase and reanalyzed 3 times weekly for 4 to 5 weeks. Same-lot samples of the ready-to-drink juices remained sealed after purchase and were opened for analyses at 3, 2, 1, or 0 weeks before expiration. SAMPLES/SETTING: Orange juices were reconstituted frozen concentrates, ready-to-drink juice packaged in resealable, screw-top containers, or ready-to-drink juice packaged in nonresealable containers. Juices were obtained from local retailers and stored at 4 degrees C in their original containers when appropriate. The reduced vitamin C content of juices analyzed repeatedly, 3 times weekly for 4 weeks, were compared using repeated measures analysis of variance. Linear regression lines were computed for reduced vitamin C in each juice over time, and differences between slopes were analyzed by oneway analysis of variance. The orange juices from frozen concentrates contained 86 mg reduced vitamin C per fluid cup at initial preparation and 39 to 46 mg/c after 4 weeks of storage. Ready-to-drink juices averaged significantly lower reduced vitamin C: 27 to 65 mg/c at opening and 0 to 25 mg/c at expiration 4 weeks later. Ready-to-drink orange juices had twofold to threefold higher concentrations of oxidized vitamin C vs the orange juices reconstituted from frozen, and the decomposition rate of reduced vitamin C was similar for all juices, about 2% per day once opened. Ready-to-drink orange juices should be purchased 3 to 4 weeks before expiration date and consumed within 1 week of opening.


Retinol enhances differentiation of the gastric parietal cell lineage in developing rabbits.
In the gastric glands, parietal cells are the targets for anti-ulcer drugs because they contain the proton pump or HK-ATPase responsible for acid secretion. Little is known about factors influencing developmental expression and activity of HK-ATPase. In this study, the parietal cell lineage was investigated in rabbits at post-natal days 0 (P0) to P60 by using morphological and biochemical methods. Immunohistochemical and ultrastructural studies show that the HK-ATPase-expressing cells that appear at P0 and P3 are pre-parietal cells. However, terminally differentiated, mature parietal cells make their appearance at P7. These data correlate with the activity of HK-ATPase, measured as K(+)-dependent hydrolysis of p-nitrophenyl phosphate. Three-day-retinol treatment of P3-P30 rabbits induced an increase in the (i) production of parietal cells, (ii) intensity of the HK-ATPase immunostaining per cell, (iii) activity of HK-ATPase and (iv) amount of HK-ATPase protein measured by Western blotting. In conclusion, retinol upregulates the development of HK-ATPase in rabbits, perhaps due to precocious acceleration of the differentiation program of parietal cell lineage.


Metabolic and circulatory limitations to VO2 max at the whole animal level.
The O2 path from environment to mitochondria can be viewed as a cascade of resistances in series, each being overcome by a specific pressure gradient (O2 conductance equation). To assess the relative importance of the different factors that can set a limit to VO2 max, three sets of resistances will be identified, RQ, Rc and Rm, inversely proportional to: O2 transport (Qmax X [Hb]), RQ; capillary cross section, Rc; and succinic dehydrogenase (SDH) activity, Rm. Published data show that changes of VO2 max can be induced by altering the blood O2 capacity, or by training, and that these changes are accompanied by measured changes of the above identified resistances. From these data, the ratio of each resistance to the overall resistance can be calculated by algebraic manipulation of the O2 conductance equation, expressed in relative form. It can thus be shown that: in two-legged exercise, about 75% of VO2 max is set by O2 transport, the remaining fraction being about equally partitioned between the two peripheral factors indicated above, and that in one-legged exercise, the limits to VO2 max are about equally set by central and peripheral factors.


Assessing safety and efficacy of microscopic and laparoscopic varicocoelectomy for varicocoele treatment: A comparative cohort study.
Surgical is appropriate for 35-40% of varicocoele-induced infertility. This comparative observational study presents a comparative assessment of microscopic or laparoscopic varicocoelectomy (grade II varicocoele; n = 132 cases). Sperm count, density, total motility, and forward motility rate (preoperative and postoperative 6 months), operation duration, pain at 1 month, testicular atrophy (by scrotal ultrasound at 3 months), recurrence (angiography at 6 months), and scrotal edema (at 12 months) were measured. The preoperative semen parameters were comparable between groups (P > 0.05), as were certain postoperative results (total sperm count [median 162 (range 100-242) compared with median 182 (range 84-253)]; sperm density [median 47 (range 38-83) compared with median 42 (range 27-88)]; forward motility (37.18 ± 4.14 compared with 34.13 ± 7.79); P > 0.05). However, sperm motility was higher in the microscope group (52.79 ± 8.21 compared with 46.64 ± 10.04; t = 2.304, P = 0.040). Within the microscope group, postoperative sperm density [median 47 (range 38-83)], total sperm motility (53.79 ± 8.25), and forward motility sperm rate (37.19 ± 4.14) demonstrated significant improvements compared with preoperative values (Z = -2.679, P = 0.005; t = -4.548, P < 0.001; t = -5.029, P < 0.001). In contrast, the postoperative forward motility sperm rate (34.13 ± 7.78) displayed substantial improvements compared with preoperative values (27.74 ± 14.42) within the laparoscopic group (t = -3.895, P = 0.001). Testicular atrophy occurred in neither group. Microscopic varicocoelectomy may be safer and more effective.


[Temperature compensation in homeothermic animals].
Low temperature optimum of the glutaminase activity in synaptosomal fraction of the brain occurs in deep hypothermia, similar phenomenon occurring in hibernation. The optimum depends on the animal body temperature. The data obtained suggest a manifestation of the temperature compensation.


Insights in Developmental Coordination Disorder.
Developmental Coordination Disorder (DCD) is a neurological impairment occurring in nearly 6% of general population, and sometimes mimics other developmental disorders like Attention Deficit Hyperactivity Disorder (ADHD) or, in the most severe cases, intellectual deficiency. To review the general portrait of DCD, the physiology, the clinical assessments, and to provide an overview of functional studies on the subject. We finally report some proposed DCD managements which vary depending on the manifestation of the disorder and on the goals of the therapy. DCD can be stated as a sum of fine motor, perceptual visual and executive difficulties, emerging during childhood brain development and lasting throughout adulthood. Even if DCD can be isolated from other co-morbidities in certain individuals, it is still difficult to categorize it in delimited subclasses of characteristics, e.g. problems of vision or language. The findings in functional imaging also diverge in locating the cerebral deficit for a given motor task. Finding a single explanation seems difficult as many cerebral regions are associated with DCD and many clinical aspects are involved, but, further studies could explore genetic (or epigenetic) explanation for the prevalence of DCD in population.


Design guidelines for the development of digital nutrigenomics learning material for heterogeneous target groups.
Nutritional genomics, or nutrigenomics, can be considered as the combination of molecular nutrition and genomics. Students who attend courses in nutrigenomics differ with respect to their prior knowledge. This study describes digital nutrigenomics learning material suitable for students from various backgrounds and provides design guidelines for the development of the learning material. These design guidelines, derived from theories on cognitive science and instructional design, describe the selection of interaction types for learning tasks and the timing of information presentation. The learning material supports two learning goals: 1) the formulation of meaningful research questions in the field of nutrigenomics and 2) the development of feasible experiments to answer these questions. The learning material consists of two cases built around important nutrigenomics topics: 1) personalized diets and 2) the role of free fatty acids in the regulation of hepatic gene transcription. Each case consists of several activities to promote active learning by the student. Evaluation of the cases in a realistic academic educational setting indicates that the cases were useful.


Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia.
To describe long-term outcomes of anti-CD19 chimeric antigen receptor T (CART) cells in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Between January 2013 and June 2016, 42 patients with relapsed or refractory CLL were enrolled in this study and 38 were infused with anti-CD19 CART cells (CART-19). Of these, 28 patients were initially randomly assigned to receive a low (5 × 107) or high (5 × 108) dose of CART-19, and 24 were evaluable for response assessment. After an interim analysis, 10 additional patients received the selected (high) dose and of these, eight were evaluable for response. Patients were followed for a median 31.5 months (range, 2 to 75 months). At 4 weeks, the complete and overall responses for the 32 evaluable patients were 28% (90% CI, 16% to 44%) and 44% (90% CI, 29% to 60%), respectively. The median overall survival (OS) for all patients was 64 months; there was no statistically significant difference between low- and high-dose groups (P = .84). Regardless of dose, prolonged survival was observed in patients who achieved a CR versus those who did not (P = .035), with median OS not reached in patients with CR versus 64 months in those without CR. The median progression-free survival was 40.2 months in patients with CR and 1 month in those without a CR (P < .0001). Toxicity was comparable in both dose groups. In patients with advanced CLL, a 5 × 108 dose of CART-19 may be more effective than 5 × 107 CART-19 at inducing CR without excessive toxicity. Attainment of a CR after CART-19 infusion, regardless of cell dose, is associated with longer OS and progression-free survival in patients with relapsed CLL.


The impact of co-location employment partnerships within the Australian mental health service and policy context: A systematic review.
Adults with a serious persistent mental illness (SPMI) express a strong desire to work. However, they continue to experience higher levels of unemployment, barriers, and occupational exclusion that impact their vocational outcomes and choice of work. The aim of this study was to investigate the impact of co-location partnerships between adult mental health and disability employment services (DES) on employment outcomes and consumer choice of work for adults with a SPMI. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, a systematic literature review was conducted by searching four databases. The relationship between mental health, employment, and DES was examined. Inclusion criteria were adults with a SPMI; employment services and outcomes; and job retention and sustainability. Twelve studies met inclusion criteria. All studies were peer-reviewed, Australian-based, and published between 01 January 2017 and 30 August 2021. Individual placement and support (IPS); DES practice, funding, policy, and reform within the Australian mental health system; and barriers to participation in DES were the three main themes that emerged. Findings highlight the importance of joint, co-location partnerships between mental health and employment services, including a collaborative approach to policy reform between both services, to assist adults with a SPMI to gain and sustain competitive employment. Vocational, non-vocational, systemic, and structural barriers still exist; hence, adults with a SPMI continue to face challenges with gaining and sustaining long-term employment. Hence, it is important for these partnerships to be systematically set up to support the complexity of the employment journey for adults with a SPMI.


Polyolefins Formed by Chain Walking Catalysis-A Matter of Branching Density Only?
Recently developed chain walking (CW) catalysis is an elegant approach to produce materials with controllable structure and properties. However, there is still a lack in understanding of how the reaction mechanism influences the macromolecular structures. In this study, a series of dendritic polyethylenes (PE) synthesized by Pd-α-diimine-complex through CW catalysis (CWPE) is investigated by means of theory and experiment. Thereby, the exceptional ability of in situ tailoring polymer structure by varying synthesis parameters was exploited to tune the branching architecture, which allowed us to establish a precise relationship between synthesis, structure, and solution properties. The systematically produced polymers were characterized by state-of-the-art multidetector separation and neutron scattering experiments as well as atomic force microscopy to access molecular properties of CWPE. On a global scale, the CWPE appear in a worm-like conformation independently on the synthesis conditions. However, severe differences in their contraction factors suggested that CWPE differ substantially in topology. These observations were verified by NMR studies that showed that CWPE possess a constant total number of branches but varying branching distribution. Small angle neutron scattering experiments gave access to structural characteristics from global to segmental scale and revealed the unique heterogeneity of CWPE, which is predominantly based on differences in their dendritic side chains. The experimental data were compared to theoretical CW structures modeled with different reaction-to-walking probabilities. Simple theoretical arguments predict a crossover from dendritic to linear topologies yielding a structural range from purely linear to dendritic chain growth. Yet, comparison of theoretical and empirical scattering curves gave the first evidence that a transition state to worm-like topologies is actually experimentally accessible. This crossover regime is characterized by linear global features and dendritic local substructures contrary to randomly hyperbranched systems. Instead, the obtained CWPE systems have characteristics of disordered dendritic bottle brushes and can be adjusted by the walking rate/reaction probability of the catalyst.


Factors predicting perceived improved health after emergency room visits.
This study examines the key factors contributing to perceived improved health after emergency room (ER) visits. Perceived health is a subjective measure of health status. It is an important and useful concept in nursing and assessment of health services because it reflects the clients' own assessment of his/her health, which may have led to their subsequent health-seeking behaviour. Secondary analysis of a main study which aimed at examining the effects of nurse follow-up on ER revisits using randomized-controlled trial. In this study, binary logistic regressions were conducted to identify factors associated with the dependent variable, perceived improved health 30 days after the index ER visit. Data were collected from 795 subjects and the sources of data were from medical records and telephone interviews. Gender, income, usual practice in managing minor illness, what to do other than attending the ER, nurse follow-up, general self-rated health, triage, considered other doctors on the day of index ER visit, times of attending general outpatient clinic and times of attending general practitioner were found to be significantly associated with perceived improved health 30 days after the index ER visit. Many of the variables identified in this study that predicted perceived improved health concurred with previous findings. What is of interest is that nurse follow-up but not multiple medical consultations helped enhance perceived improved health. We speculate that there was no continuity of care in the multiple medical consultations. Where as in the nurse follow-up, the nurse was able to follow through the care of individuals, monitor their progress and make appropriate referrals. This study shows that the nurse is an appropriate person to mediate the health needs of individuals and the healthcare system and to enhance health maintenance for individuals in the community without excessively using medical services. The nurses providing care during the transitional phase should not only include the traditional clinical or hospital system variables, but should also take into account the general health perception of patients, because these are the predictors of health services utilization and morbidity.


Clinical expression of cystic fibrosis in a large cohort of Italian siblings.
A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF. We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis. Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the "whole" CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency. Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain.


Distinct roles of the last transmembrane domain in controlling Arabidopsis K+ channel activity.
The family of voltage-gated potassium channels in plants presumably evolved from a common ancestor and includes both inward-rectifying (K(in)) channels that allow plant cells to accumulate K(+) and outward-rectifying (K(out)) channels that mediate K(+) efflux. Despite their close structural similarities, the activity of K(in) channels is largely independent of K(+) and depends only on the transmembrane voltage, whereas that of K(out) channels responds to the membrane voltage and the prevailing extracellular K(+) concentration. Gating of potassium channels is achieved by structural rearrangements within the last transmembrane domain (S6). Here we investigated the functional equivalence of the S6 helices of the K(in) channel KAT1 and the K(out) channel SKOR by domain-swapping and site-directed mutagenesis. Channel mutants and chimeras were analyzed after expression in Xenopus oocytes. We identified two discrete regions that influence gating differently in both channels, demonstrating a lack of functional complementarity between KAT1 and SKOR. Our findings are supported by molecular models of KAT1 and SKOR in the open and closed states. The role of the S6 segment in gating evolved differently during specialization of the two channel subclasses, posing an obstacle for the transfer of the K(+)-sensor from K(out) to K(in) channels.


Allicin enhances antimicrobial activity of macrophages during Mycobacterium tuberculosis infection.
The emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains has severely hampered global efforts towards tuberculosis (TB) eradication. The internationally accepted therapy "Directly Observed Treatment Short-course (DOTS)" is lengthy, and incorporates risks for the generation of drug-resistant M.tb variants. Multiple and extremely drug-resistant (MDR and XDR) variants of TB are now widespread throughout the globe, and totally drug-resistant (TDR) strains have appeared. Therefore, new classes of antibiotics are urgently needed to combat these deadly organisms. Historically, garlic is known to kill mycobacterial strains, and its active compound, allicin, kills various microorganisms. Here we have shown that allicin not only reduced the bacterial burden in the lungs of mice infected with Mycobacterium tuberculosis (M.tb), but also induces strong anti-tubercular immunity. In the present study, the anti-mycobacterial and immunomodulatory activity of garlic extract and its pure constituent allicin were demonstrated based on several in vitro and in vivo experiments in murine model of tuberculosis. Furthermore, the validation of study was done by immunoblots showing the modulation of MAPK and SAPK/JNK signaling by allicin in macrophages. Here, we report that allicin/garlic extract exhibits strong anti-mycobacterial responses in vitro and in vivo against drug-sensitive, MDR and XDR strains of TB. In addition to direct killing, allicin also induced pro-inflammatory cytokines in macrophages. Moreover, allicin/garlic extract treatment in murine models of infection resulted in induction of strong protective Th1 response, leading to drastic reduction in mycobacterial burden. These results indicated that allicin/garlic extract has both antibacterial and immunomodulatory activity. Furthermore, garlic extract reversed the immune dampening effects of frontline anti-TB drugs. Allicin/garlic extract alone or as an adjunct to classical antibiotics holds great promise for treatment of drug-sensitive as well as drug-resistant TB. These results warrant further study and validation of allicin for treatment of TB.


Clinical predictors of quality of life in patients with head and neck cancer.
To identify clinical predictors of quality of life (QoL) in a head and neck cancer patient population. A convenience sample of 570 patients with upper aerodigestive tract cancers were surveyed at a tertiary care oncology clinic and Veterans Affairs otolaryngology clinic. A self-administered health survey was constructed to collect demographic, health, smoking, alcohol, depression symptom, and QoL information. Tumor site and tumor stage, clinical, and treatment data were abstracted from the patient medical records. Quality of life was assessed using the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) and the Head and Neck QoL (HNQoL) instrument. Of the 570 eligible respondents, the presence of a feeding tube had the most negative impact on QoL, with significant decrements in 6 of the 8 SF-36 scales and all 4 HNQoL scales (P<.01). In descending order of severity, medical comorbid conditions, presence of a tracheotomy tube, chemotherapy, and neck dissection were also associated with significant (P<.05) decrements in QoL domains. Patients who took the survey more than 1 year after diagnosis had improved QoL in 7 of 12 domains. Hospital site, age, education level, sex, race, and marital status were also significant predictors of QoL. There are at least 13 demographic and clinical characteristics that are significant predictors of QoL in patients with head and neck cancer, which should be considered when treating patients and conducting QoL studies in the future.


[Placenta--a source of biologically active substances].
In the review there are some data displaying the scientific and patent literature presenting placenta as a rich source of some biologically active substances (BAS): proteins, lipids, enzymes, glycolipids and glycolipoproteins, hormones. This information is capable to be used while developing the techniques of BAS producing from placenta in order of creating the organospecific complex preparations with medically-preventive properties.


[Effects of Chinese herbal medicines for regulating liver qi on expression of 5-hydroxytryptamine 3B receptor in hypothalamic tissues of rats with anger emotion].
To explore the central mechanisms of anger emotion and the effects of Chinese herbal medicines for regulating liver qi on the anger emotion and the expression level of 5-hydroxytryptamine 3B receptor (5-HT3BR) in rat hypothalamus. Rat models of anger-in or anger-out emotions were prepared by the methods of resident intruder paradigm. There were five groups in this study: control, anger-in model, Jingqianshu Granule-treated anger-in, anger-out model and Jingqianping Granule-treated anger-out groups. The treatment groups were orally given Jingqianshu granules and Jingqianping granules respectively, and the model groups and the normal control group were given sterile water. Open-field test and sucrose preference test were used to evaluate behavioristics of the rats. Semi-quantitative reverse transcription-polymerase chain reaction and Western blot methods were used to detect the expression levels of 5-HT3BR mRNA and protein in the rat hypothalamus. The expression of 5-HT3BR in hypothalamus of anger-in model rats increased obviously (P<0.01) and that of anger-out model rats decreased obviously (P<0.01) compared with the normal control group. Compared with the model group, the expressions of 5-HT3BR in the treatment groups were significantly improved (P<0.01) after treatment, and recovered to normal level. The anger-in stimulation obviously increases hypothalamic 5-HT3BR expression and the anger-out emotion can obviously reduce its expression. Chinese herbal medicines for regulating liver qi may treat anger emotion in rats by improving the hypothalamic 5-HT3BR protein and gene expression levels.


Predicting psychiatric emergency admissions and hospital outcome.
A decision support tool for psychiatric hospital admissions was developed and validated to provide reliable, clinically relevant information to providers and case managers. Using the Severity of Psychiatric Illness rating system, an empirical model of psychiatric emergency decision-making was constructed and validated on a spilt sample of 254 crisis cases. Three dimensions of the Severity of Psychiatric Illness system-Suicide Potential, Danger to Others, and Severity of Symptoms-were used to construct a model that successfully predicted 73% of decisions about level of care (inpatient or outpatient). Clear misses, patients with a 0.20 probability of being hospitalized who were admitted, and patients with an 0.80 probability or greater of being hospitalized who were not admitted were reviewed to allow for utilization review. This decision support tool then was validated by predicting hospital outcomes in two additional samples. First, a random sample of consecutive admissions to a not-for-profit psychiatric hospital were studied. Second, a panel of admissions from a large managed care firm were evaluated. Results demonstrate that the decision to hospitalize patients in psychiatric hospitals is rational and that models predicting admission also can predict in-hospital outcomes.


Synthesis of chromium containing pigments from chromium galvanic sludges.
In this work the screening results of the scientific activity conducted on laboratory scale to valorise chromium(III) contained in the galvanic sludge as chromium precursor for ceramic pigments are reported. The valorisation of this waste as a secondary raw material (SRM) is obtained by achievement of thermal and chemical stable crystal structures able to color ceramic material. Two different pigments pink CaCr(0.04)Sn(0.97)SiO(5) and green Ca(3)Cr(2)(SiO(4))(3) were synthesized by solid-state reactions using dried Cr sludge as chromium oxide precursor. The obtained pigments were characterized by X-ray diffraction and SEM analysis. Furthermore the color developed in a suitable ceramic glaze was investigated in comparison with the color developed by the pigments prepared from pure Cr(2)O(3). The characterization carried out corroborates the thermal and chemical stability of the synthesized pigments and, especially for the Cr-Sn pink pigment, the powders develop an intense color that is very similar to the color developed by the pigments obtained starting from pure Cr(2)O(3).


Sensory Processing Difficulties Correlate With Disease Severity and Quality of Life Among Children With Migraine.
Introduction: Headaches are common among children and about 80% of children reporting them. Migraine and tension type headaches are the most common primary headaches in children and the prevalence of migraine is about 8%. Accompanying sensory symptoms are common before, during and after migraine attacks. They may be a part of a wider symptom constellation called sensory processing disorder or difficulties (SPD). This includes both hyper or hypo sensitivity to sensations. However, the literature regarding sensory processing symptoms of children and youth with headaches as well as its interaction with child's emotional aspects and quality of life is scarce. Materials and Methods: One hundred and thirty-four children between the ages of 8 and 12 participated in this study. Fifty-four children (22 boys and 32 girls) with episodic migraine were prospectively recruited from pediatric neurological clinics during the years 2014-2017. The control group included 80 healthy children. Both groups completed a health and demographic questionnaire, headache assessment including Ped-MIDAS, Short Sensory Profile, State-Trait Anxiety Inventory (STAI) for children, and the Pediatric Quality of Life Inventory. Results: Children with migraine showed significantly higher prevalence of sensory processing difficulties and lower quality of life compared to healthy controls. Among children with migraine, sensory processing difficulties significantly correlated with lower quality of life. Headache-related disability and sensory processing difficulties predicted quality of life. Conclusion: The possible relationship between migraine and sensory processing disorder or difficulties stresses the need to screen for sensory processing difficulties among children with migraine and when found-refer to their impacts on children's daily function and quality of life.


[Monitoring of pregnancy complicated by maternal-fetal isoimmunization. A comparison between two clinical protocols].
Invasive techniques such as amniocentesis and cordocentesis are used for the diagnosis and treatment of fetus at risk for anemia due to maternal red-cell alloimmunization. The purpose of this study was to determine the value of non invasive measurements of the peak velocity middle cerebral artery in the fetus (PVMCA) for the diagnosis of fetal anemia. From 1996 to September 2002, we studied 23 pregnancies with anti D title >1:32. In the 1(st) group of 11 women (from 1996 to 1999) fetal anemia was detected by invasive techniques (amniocentesis and cordocentesis). In the 2(nd) group of 12 women (from 1999 to 2002) fetal anemia was suspected on the basis of PVMCA. When PVMCA was significantly increased, cordocentesis was performed in order to rule out fetal anemia and to provide in utero transfusions. In the 1(st) period we performed 23 invasive techniques (7 amniocentesis and 16 cordocentesis) in 11 women, but we identified fetal anemia only in 4 cases. In the 2(nd) period we performed only 2 cordocentesis in women in which PVMCA was increased; the blood sampling confirmed fetal anemia in both cases. PVMCA and fetal hematocrit are highly significantly correlated: high values of PVMCA are associated with fetal anemia. Doppler velocity of PVMCA is related to fetal anemia with positive predictive value 100% and negative predictive value 100%. The middle cerebral artery blood velocity is a non invasive technique for detecting anemia in pregnancies complicated by alloimmunization.