Characteristics associated with requested and required accelerometer wear in children.
To investigate characteristics associated with wearing an accelerometer for the required and requested time among 8-year-old to 10-year-old children. Cross-sectional. 60 Bristol and North Somerset primary schools taking part in the 'Active for Life Year 5' randomised controlled trial (RCT) in 2011. 2048 children, aged 8-10 years, invited to wear an accelerometer for 5 days of recording. Numbers meeting required wear-time for inclusion in main RCT analysis (≥8 h/day ≥3 days) and numbers meeting requested wear-time (≥8 h/day for all 5 days). 817 (40%) of the children wore the accelerometer for the requested time and 1629 (80%) for the required time. In adjusted multivariable analyses the odds of wearing the accelerometer for the required time were greater in females as compared with males (OR 1.76 (1.42-2.18)), those with higher scores for reporting their mother restricted time on sedentary behaviours (1.26 (1.04-1.52) per increase of 1 on a 1-4 scale) and in children from schools with larger year group sizes (1.01 (1.00-1.02) per additional child). Living in a neighbourhood with higher levels of deprivation (0.49 (0.33-0.72) comparing highest to lowest third of the deprivation score) or reporting higher levels of weekday outdoor play (0.97 (0.94, 1.00) per 30 min more) were associated with reduced odds of meeting required time. Results were essentially the same for requested wear-time. Other characteristics, including child body mass index, were not associated with required or requested wear-time. Only 40% of children wore the accelerometer for the requested time but 80% fulfilled the required criteria to be included in the main study analyses. Knowing which characteristics are associated with accelerometer wear could help target interventions to increase wear-time.


Consequence of the antioxidant activities and tyrosinase inhibitory effects of various extracts from the fruiting bodies of Pleurotus ferulae.
This study was initiated to screen the antioxidant activities, tyrosinase inhibitory effects on the fruiting bodies of Pleurotus ferulae extracted with acetone, methanol and hot water. The antioxidant activities were performed on β-carotene-linoleic acid, reducing power, DPPH, ferrous ions chelating abilities, and xanthine oxidase. In addition to this, phenolic compounds were also analyzed. The methanolic extract showed the strongest β-carotene-linoleic acid inhibition and high reducing power as compared to other extracts. The scavenging effects on DPPH radicals, the acetonic and methanolic extracts were more effective than hot water extracts. The strongest chelating effect was obtained from the methanolic extract as compared to the tested synthetic antioxidant. Gallic acid, protocatechuic acid, caffeic acid, vanillin, ferulic acid, naringin, resveratrol, naringenin, hesperetin, formononetin and biochanin-A were detected from acetonitrile and hydrochloric acid (5:1) solvent extract. Xanthine oxidase and tyrosinase inhibitory activities of acetonic, methanolic, and hot water extracts of P. ferulae increased with increasing concentration. The results suggested that consumption of P. ferulae might be beneficial to the antioxidant, xanthine oxidase, and tyrosinase protection system of the human body against oxidative damage and others complications.


A morphometric study of normal and abnormal fetal to childhood tongue size.
The weight, length, width and thickness of 83 normal tongues from patients aged 25 weeks of gestation to 10.5 years were compared statistically with several measures of body and head size and changes described by linear regression; the relationships between measures were examined by partial and least-squares correlation. Sex differences in tongue size were not evident. The tongue doubles in length, width and thickness between birth and adolescence and grows considerably beyond this period. That the major dimensions of the tongue correlated more with head size than body size implies that local factors affect lingual growth more than generalized somatic ones. The weights of 45 tongues thought to be abnormal in size were compared with those of controls. The volume of normal and abnormal tongues was identical to weight, indicating that density remains constant in a variety of conditions. The tongue was abnormally small in hypoglossia hypodactylia and in cleft lip and palate. Tongue weights were within 1 SD of control means in DiGeorge syndrome or oligohydramnios. The tongue was significantly enlarged when protuberant or in anencephaly, CHARGE association and Crouzon syndrome. Anasarca produced a variable degree of enlargement. Concomitant aberrations in the size of the tongue and mandible occurred frequently, but small tongues were not always associated with small mandibles and large tongues were not always observed with large mandibles. Thus, the association of lingual and craniofacial anomalies seems to develop from a number of diverse factors, in addition to biomechanical ones.


Handling traumatic experiences in facially disfigured female burn survivors.
This research deals with the impact of resilience, perceived stigmatization, social comfort and coping strategies on quality of life among female burn survivors with facial disfigurement, man many of which are found in Asian countries. Using cross-sectional research design, female burn survivors with severe facial disfigurement (N = 100) were drawn by using purposive sampling strategy from a public sector hospital and an organization working in Lahore, Pakistan. Perceived Stigmatization Questionnaire (PSQ) (Lawrence et al., 2006), Social Comfort Questionnaire (SCQ) (Lawrence et al., 2006), State-Trait Resilience Scale, Coping with Burns Questionnaire (CBQ) (Willebrand et al., 2001) and World Health Organization Quality of Life Brief Questionnaire (WHOQOL-BREF Questionnaire; World Health Organization, 2014) were used for assessment. The analyses showed a significant positive relationship among resilience, coping with burns and social comfort. A significant negative relationship was found between perceived stigmatization and coping with burns, resilience and social comfort. All these variables were tested for differentiation on the basis of survivor's age (less vs. more than 30 years), occupation (housewife vs. gainfully employed), education (less vs. more than matriculation), social status (low vs. middle class), family system (nuclear vs. joint), siblings (yes vs. no), residence (living in home vs. shelter home) and psychological help received or not after the burn injury. Results indicate a mixed type of phenomenon among variable's differentiation. Path analysis through AMOS resulted into a model showing no direct relationship of quality of life with coping with burns, perceived stigmatization and resilience; however, social comfort mediates the relationship between quality of life and coping with burns, perceived stigmatization and resilience. It is found that quality of life is dependent on coping with burns, perceived stigmatization and resilience through social comfort. The findings hold implications for the mental health professionals and rehabilitation service providers to emphasize on the restorative strategy for burn survivors to elevate their social comfort, to assist them in handling their injuries and develop a curative plan to support them in their coping skills.


Locations and dynamical perturbations for lipids of cationic forms of procaine, tetracaine, and dibucaine in small unilamellar phosphatidylcholine vesicles as studied by nuclear Overhauser effects in 1H nuclear magnetic resonance spectroscopy.
Locations and dynamical perturbations for lipids of local anesthetics (procaine . HCl, tetracaine . HCl, and dibucaine . HCl) in sonicated egg yolk phosphatidylcholine (PC) vesicles have been studied by 1H-1H nuclear Overhauser effect (NOE) measurements. It was found that tetracaine and dibucaine bind much strongly to the neutral lipids than does procaine and that their mobilities are lowered to such an extent that spin diffusion is transmitted (i.e., omega 2 tau c2 much greater than 1). The intermolecular NOEs between drugs and PC were more effective in the case of dibucaine than with tetracaine, indicating that dibucaine binds to the lipids more strongly than tetracaine; this order agrees well with that of anesthetic potency. However, it was only tetracaine that gave any appreciable dynamical perturbation to the PC vesicles when they were monitored by the extent of transfer of the negative NOE from alpha-methylene protons to choline methyls, olefinic methines, acyl methylenes and terminal methyl protons. This finding was interpreted as being due to the differences in the locations of these drugs in small unilamellar vesicles: (1) procaine interacts with lipids very weakly at the outer surface of the vesicles; (2) tetracaine binds to the lipids both at the outer and inner halves of the bilayer, inserting its rod-like molecule in a forest of acyl chains of PC; (3) dibucaine binds tightly to the polar head-group of PC, which resides only at the outer half of the bilayer vesicles. It was concluded that the relative order of anesthetic potency within these drugs can be correlated not with the ability to affect membrane fluidity but with the ability to bind to lipids at the polar head-group of the bilayer vesicles.


The Cognitive Evolution from "Plague" to "Infectious Disease".
According to the Grand Chinese Dictionary, plague is defined to be an acute infectious disease. The Chinese term "infectious disease" is not what it is commonly thought originated from Japanese. The medical nomenclature shift from the traditional "plague" to the modern "infectious disease" is completed by the medical missionaries, Chinese scholars, and the national authority, each utilising different strategies. It is a history of acceptance concerning the concept of "infectious disease" from academia to national level. The conscious use of infectious disease-related thought and terminology by Chinese officials and doctors when studying infectious disease is a scientific modernization towards the understanding of epidemics. In a sense, this evolution of medical knowledge embodies the modernization of infectious disease in China.


Contribution of stretch reflexes to locomotor control: a modeling study.
It is known that the springlike properties of muscles provide automatic load compensation during weight bearing. How crucial is sensory control of the motor output given these basic properties of the locomotor system? To address this question, a neuromuscular model was used to test two hypotheses. (1) Stretch reflexes are too weak and too delayed to contribute significantly to weight-bearing. (2) The important contributions of sensory input involve state-dependent processing. We constructed a two-legged planar locomotor model with 9 segments, driven by 12 musculotendon actuators with Hill-type force-velocity and monotonic force-length properties. Electromyographic (EMG) profiles of the simulated muscle groups during slow level walking served as actuator activation functions. Spindle Ia and tendon organ Ib sensory inputs were represented by transfer functions with a latency of 35 ms, contributing 30% to the net EMG profile and gated to be active only when the receptor-bearing muscles were contracting. Locomotor stability was assessed by parametric variations of actuator maximum forces during locomotion in open-loop ("deafferented") trials and in trials with feedback control based on either sensory-evoked stretch reflexes or finite-state rules. We arrived at the following conclusions. (1) In the absence of sensory control, the intrinsic stiffness of limb muscles driven by a stereotyped rhythmical pattern can produce surprisingly stable gait. (2) When the level of central activity is low, the contribution of stretch reflexes to load compensation can be crucial. However, when central activity provides adequate load compensation, the contribution of stretch reflexes is less significant. (3) Finite-state control can greatly extend the adaptive capability of the locomotor system.


BYL719 reverses gefitinib-resistance induced by PI3K/AKT activation in non-small cell lung cancer cells.
Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation often obtain de novo resistance or develop secondary resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), which restricts the clinical benefit for the patients. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway is one of the most important mechanisms for the EGFR-TKIs resistance beyond T790M mutation. There are currently no drugs simultaneously targeting EGFR and PI3K signal pathways, and combination of these two pathway inhibitors may be a possible strategy to reverse theses resistances. To test whether this combinational strategy works, we investigated the therapeutic effects and mechanisms of combining BYL719, a PI3Kα inhibitor, with gefitinib, an EGFR-TKI inhibitor in EGFR-TKIs resistance NSCLC models induced by PI3K/AKT activation. Our results demonstrated that PIK3CA mutated cells showed increased growth rate and less sensitive or even resistant to gefitinib, associated with increased PI3K/AKT expression. The combination of BYL719 and gefitinib resulted in synergistic effect compared with the single agents alone in EGFR-mutated NSCLC cells with PI3K/AKT activation. The inhibition of AKT phosphorylation by BYL719 increased the antitumor efficacy of gefitinib in these cell lines. Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.


Medically unexplained physical symptoms: toward an alternative paradigm for diagnosis and treatment.
The treatment of patients with unexplained medical symptoms is difficult because there is neither a clear etiology for the symptoms, nor a useful paradigm with which to understand and treat them. Patients with such symptoms are often referred to psychiatry with vague diagnoses of "somatization" or "hypochondriasis." Rather than considering somatoform diagnoses based on the number or diversity of physical symptoms, evolving research suggests an emphasis on the type of physical symptom as an indicator of Axis I pathology. This article links specific symptomatic complaints, such as chronic pain, chest pain, and dizziness, to the respective Axis I disorders associated with them, such as depression, panic disorder, and anxiety disorders.


Zinc ions suppress mitogen-activated interleukin-2 production in Jurkat cells.
Calcineurin (CN) is thought to play an important role in the immune system by regulating cytokine production, for example, interleukin-2 (IL-2) in T-lymphocytes. We have previously shown that physiological concentrations of Zn2+ inhibit CN activity in vitro [K. Takahashi, E. Akaishi, Y. Abe, R. Ishikawa, S. Tanaka, K. Hosaka, Y. Kubohara, Zinc inhibits calcineurin activity in vitro by competing with nickel, Biochem. Biophys. Res. Commun. 307 (2003) 64-68], in spite of the fact that Zn2+ is an essential element of the CN catalytic domain. In this study, in order to assess whether Zn2+ regulates (suppresses) CN activity in vivo and whether Zn2+ can be used as an anti-inflammatory and/or immunosuppressive drug, we examined the effects of Zn2+ on IL-2 production induced by the mitogen, concanavalin A (ConA), in Jurkat T-cells. Zn2+ at 0.2 mM suppressed ConA-induced IL-2 accumulation in the medium of an in vitro culture of Jurkat cells. Zn2+ at 0.03-0.3 mM dose-dependently suppressed ConA-induced IL-2 mRNA expression in Jurkat cells. Zn2+ also suppressed IL-2 mRNA expression induced by phorbol ester (PMA) and ionomycin. Furthermore, Zn2+ and the immunosuppressant FK506 showed an additive inhibitory effect on ConA-induced IL-2 mRNA expression. These results suggest that exogenously added Zn2+ may disturb (increase) the intracellular Zn2+ concentration and inhibit CN activity, thereby suppressing IL-2 production in Jurkat cells. The present study further indicates that Zn2+ may have therapeutic potential in the treatment of T-cell related inflammation and also that Zn2+ may be utilized as a supplemental drug with FK506.


Obesity and Asthma: Key Clinical Questions.
Obesity is a common comorbidity of asthma that is associated not only with development of the disease, but also with poorer disease control and greater severity. Recent prospective evidence supports the idea that body weight gain precedes the development of asthma, although the debate is far from over. The objective of this document is to conduct a systematic review of 3 clinical questions related to asthma and obesity: (a) Obesity and asthma: the chicken or the egg? Clinical insights from epidemiological and phenotyping studies. (b) Is obesity a confounding factor in the diagnosis and management of asthma, especially in severe or difficult-to-control asthma? (c) How do obese asthma patients respond to pharmacological treatments and to biological drugs? Do we have effective specific interventions? Revised epidemiological, pathological, and mechanistic evidence combined with data from interventional clinical trials prevent us from clearly stating that obesity causes asthma. However, the complexity and heterogeneity of both illnesses make several clinical scenarios possible. Furthermore, asthma represents an additional clinical challenge in the obese patient. Physicians need to be aware of the confounding effects created by the more marked perception of symptoms, alterations in lung function, and the various comorbidities that obese persons present. Exhaustive phenotyping of the obese asthma patient should enable us to develop a rational therapeutic plan, including both the pharmacological approach and specific antiobesity therapies such as combining diet and exercise and, in extreme cases, bariatric surgery.


Unifying the field: developing an integrative paradigm for behavior therapy.
The limitations of early conditioning models and treatments have led many behavior therapists to abandon conditioning principles and replace them with loosely defined cognitive theories and treatments. Systematic theory extensions to human behavior, using new concepts and processes derived from and built upon the basic principles, could have prevented the divisive debates over whether psychological dysfunctions are the results of conditioning or cognition and whether they should be treated with conditioning or cognitive techniques. Behavior therapy could also benefit from recent advances in experimental cognitive psychology that provide objective behavioral methods of studying dysfunctional processes. We suggest a unifying paradigm for explaining abnormal behavior that links and integrates different fields of study and processes that are frequently believed to be incompatible or antithetical such as biological vulnerability variables, learned behavioral repertoires, and that also links historical and current antecedents of the problem. An integrative paradigmatic behavioral approach may serve a unifying function in behavior therapy (a) by promoting an understanding of the dysfunctional processes involved in different disorders and (b) by helping clinicians conduct functional analyses that lead to theory-based, individualized, and effective treatments.


The rate of MgADP binding to and dissociation from acto-S1.
The rate of binding and dissociation of MgADP from its ternary complex with actin and S1 was measured by following the extent to which fixed concentrations of MgADP slow down MgATP-induced dissociation of acto-S1. The solution of the equations describing this process shows that at any MgADP concentration the apparent rate of acto-S1 dissociation should be proportional to a square root of the equilibrium constant for MgADP dissociation and to MgATP concentration. By measuring the apparent rate of acto-S1 dissociation as a function of MgATP concentration, the rate of MgADP binding and dissociation were determined as 5 X 10(6) M-1 X s-1 and 1400 s-1, respectively. These rates were unchanged by modification of SH1 thiol of S1 by a variety of fluorescence and spin-labels, but dissociation rate was drastically reduced when SH1 was labelled with 5-iodoacetamidofluorescein.


Genomic and Transcriptomic Remodeling by Neoadjuvant Chemoradiotherapy (nCRT) and the Indicative Role of Acquired INDEL Percentage for nCRT Efficacy in Esophageal Squamous Cell Carcinoma.
The effect of genomic factors on the response of patients with esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT), as well as how nCRT influences the genome and transcriptome of ESCC, remain largely unknown. In total, 137 samples from 57 patients with ESCC undergoing nCRT were collected and subjected to whole-exome sequencing and RNA sequencing analysis. Genetic and clinicopathologic factors were compared between the patients achieving pathologic complete response and patients not achieving pathologic complete response. Genomic and transcriptomic profiles before and after nCRT were analyzed. Codeficiency of the DNA damage repair and HIPPO pathways synergistically sensitized ESCC to nCRT. nCRT induced small INDELs and focal chromosomal loss concurrently. Acquired INDEL% exhibited a decreasing trend with the increase of tumor regression grade (P = .06, Jonckheere's test). Multivariable Cox analysis indicated that higher acquired INDEL% was associated with better survival (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.86-1.01; P = .067 for recurrence-free survival [RFS]; aHR, 0.86; 95% CI, 0.76-0.98; P = .028 for overall survival [OS], with 1% of acquired INDEL% as unit). The prognostic value of acquired INDEL% was confirmed by the Glioma Longitudinal AnalySiS data set (aHR, 0.95; 95% CI, 0.902-0.997; P = .037 for RFS; aHR, 0.96; 95% CI, 0.917-1.004; P = .076 for OS). Additionally, clonal expansion degree was negatively associated with patient survival (aHR, 5.87; 95% CI, 1.10-31.39; P = .038 for RFS; aHR, 9.09; 95% CI, 1.10-75.36; P = .041 for OS, with low clonal expression group as reference) and also negatively correlated with acquired INDEL% (Spearman ρ = -0.45; P = .02). The expression profile was changed after nCRT. The DNA replication gene set was downregulated, while the cell adhesion gene set was upregulated after nCRT. Acquired INDEL% was negatively correlated with the enrichment of the DNA replication gene set (Spearman ρ = -0.56; P = .003) but was positively correlated with the enrichment of the cell adhesion gene set (Spearman ρ = 0.40; P = .05) in posttreatment samples. nCRT remodels the genome and transcriptome of ESCC. Acquired INDEL% is a potential biomarker to indicate the effectiveness of nCRT and radiation sensitivity.


Clinical aspects of 2541 patients with second stage human African trypanosomiasis.
The clinical symptoms and signs of patients with second stage HAT are described for a large cohort of patients treated in a prospective multicentre, multinational study. Special emphasis is given to the influence of disease stage (duration, number of WBC in CSF) and patient age to the clinical picture. Even though the frequencies of symptoms and signs are highly variable between centres, the clinical picture of the disease is similar for all countries. Headache (78.7%), sleeping disorder (74.4%) and lymphadenopathy (56.1%) are the most frequent symptoms and signs and they are similar for all stages of the disease. Lymphadenopathy tends to be highest in the advanced second stage (59.0%). The neurological and psychiatric symptoms increase significantly with the number of WBC in the CSF indicating the stage of progression of the disease. Pruritus is observed in all stages and increases with the number of WBC in CSF from 30 to 55%. In children younger than 7 years, lymphadenopathy is less frequently reported (11.8-37.3%) than in older children or adults (56.4-61.2%). Fever is most frequently reported in children between 2 and 14 years of age (26.1-28.7%) and malnutrition is significantly more frequently observed in children of all ages (43-56%) than in adults (23.5%).


Reduced clot-stability during the first 6 hours after aneurysmal subarachnoid haemorrhage--a prospective case-control study.
Early rebleeding is an important cause of death and disability following aneurysmal subarachnoid haemorrhage (SAH). Recent studies have shown that 50-90% of the rebleedings occurred within the first 6 hours after the primary bleeding. The mechanism leading to rebleeding remains to be established. In the present prospective case-control study we hypothesize that patients with SAH develop a coagulopathy characterized by reduced clot stability during the early period after the initial bleeding. Patients with aneurysmal SAH was studied with a dynamic clot lysis assay and markers of fibrinolysis and clot stabilizers in blood samples taken within and after 6 hours after onset of bleeding. Results were compared with blood samples from age and gender matched healthy controls. 36 patients were enrolled, 26 patients had blood samples collected within 6 hours after the initial bleeding whereas 10 patients had blood samples taken later than 6 hours after the initial bleeding. Patients demonstrated significantly reduced clot stability during the first 6 hours after initial bleeding. Fibrinolytic activity was increased during the first 6 hours along with the inhibitors of fibrinolysis whereas the modulators of fibrinolysis were reduced or inactivated. During the first 6 hours after SAH patients exhibit reduced clot-stability. Probably a consequence of activated fibrinolysis in combination with reduced or inactivated factor XIII and thrombin-activable fibrinolysis inhibitor.


Aspergillus cyst of aortic valve bioprosthesis.
Aspergillus endocarditis (AE) is an ominous complication of cardiac surgery with a dismal prognosis. We present a 35-year-old female who developed AE 4 months after her aortic and mitral valve replacement. Transesophageal echocardiography revealed an aortic root abscess and a cystic mass attached to the aortic bioprosthesis. Intraoperatively, the cyst was filled with fungal material. The aortic bioprosthesis was replaced and the patient was treated with amphotericin B. Six weeks later her condition suddenly deteriorated and she died on the same day. Early performance of transesophageal echocardiography and extended blood culture is mandatory in suspected cases of AE.


Development of an efficient gene-targeting system in Aspergillus luchuensis by deletion of the non-homologous end joining system.
The industrial fungus Aspergillus luchuensis is used to produce a distilled spirit in Okinawa Island, Japan. Recently, the genome sequence of A. luchuensis RIB2604 (Aspergillus awamori NBRC 4314) was revealed and many functional genes are now expected to be analyzed. Gene targeting is necessary for analyzing the function of a gene; however, gene targeting frequencies in A. luchuensis are very low. To develop a highly efficient gene-targeting system for A. luchuensis, we disrupted A. luchuensis ligD (ALligD) encoding the human DNA ligase IV (ligIV) homologue using an Agrobacterium mediated gene transformation method. Deletion of ALligD dramatically improved homologous recombination efficiency (reached 100%) compared to that in the wild-type strain (0.8%), when 1000-bp homologous flanking regions were used. The ALligD disruptant showed no apparent defect in vegetative growth, and it exhibited increased sensitivity to phleomycin and high methyl methanesulphonate concentrations compared to the wild-type strain. Furthermore, using this ALligD disruptant, we disrupted ALpksP encoding an Aspergillus fumigatus polyketide synthase P (alb1/pksP) orthologue. The ALpksP disruptant displayed a decolourized conidial phenotype. This result indicated that ALpksP is a key factor for conidial black pigmentation in A. luchuensis. Our results indicate that the ALligD mutant is an efficient host for targeted gene disruption in A. luchuensis.


Compartmental models for trace metals in mammals.
Kinetic models for the distribution and elimination of certain trace metals in mammals allow evaluation of metal burdens in critical target organs under time-variables exposure patterns, and thus may assist in formulating exposure standards. The linear compartmental model is described and some of its implications for conceptual models of trace metal metabolism are developed. The model is then applied to data on multiple doses of cadmium in mice. Many trace metals do not follow simple linear kinetic models because exposure to more than one metal simultaneously often results in synergistic effects.


[Growth-stimulating effect of UF-irradiated blood. I. The radiation dose dependence of the initial growth potencies of blood and of the functional state of the target cells].
UV irradiation (UVI) of donor blood in the apparatus used in hospitals of the USSR with the therapeutic aim of autotransfusion of UV-irradiated blood (AUVIB), results in an increase of connective tissue cell growth potency: being added into culture media the supernatants of irradiated blood stimulate DNA-synthetic and proliferative activity of cultured human embryonic cells. The high activity of cells persists for about 2 days. The effect is great with low initial levels of cell proliferative activity. In this case the effect is maximum (about 125% of the control). It is suggested that the above effect may be involved in the mechanism of stimulation of regeneration processes in the organism after AUVIB.


Probing into the unique relationship between a soil bacterium, Pseudomonas putida AKMP7 and Arabidopsis thaliana: A case of "conditional pathogenesis".
Plant growth-promoting rhizobacteria (PGPR) are beneficial soil bacteria that colonise the rhizosphere and help plants in growth, development, and stress tolerance. While there is a significant body of research elucidating their benefits to plants, studies on the "abnormal" or "unexpected" behavior of these bacteria are almost non-existent. One such study from our laboratory has previously reported a unique situation in which a certain strain of drought and thermo-tolerant PGPR, namely, Pseudomonas putida AKMP7, becomes pathogenic towards Arabidopsis thaliana under drought conditions, but not under normal (well-watered) conditions. In this study, we have probed deeper into this phenomenon of "conditional pathogenesis". We found that, AKMP7 imparts an enhancement in plant growth under well-watered conditions, while, causing a deterioration in plant health under drought conditions. In an attempt to understand the underlying reasons for this phenomenon, we analysed the phytohormones released by Pseudomonas putida AKMP7 using LC-ESI-MS/MS technique. We identified that AKMP7 releases zeatin (a cytokinin), the auxin derivative -indole acetamide and amino acid-conjugates of auxin (indole-3-acetyl-L-alanine, indole-3-acetyl-L-phenylalanine and indole-3-acetyl-L-aspartate) in the growth medium. By treating the plants with commercially obtained forms of these phytohormones, individually or in combination with AKMP7, we identified that zeatin and auxin derivative indole acetamide can play a crucial role in the conditional pathogenesis exhibited by this bacterium on A. thaliana under drought conditions. Our work lays a foundation for further understanding the precise molecular mechanisms involved in this unique phenomenon of conditional/opportunistic pathogenesis.


Analyses of fugu hoxa2 genes provide evidence for subfunctionalization of neural crest cell and rhombomere cis-regulatory modules during vertebrate evolution.
Hoxa2 gene is a primary player in regulation of craniofacial programs of head development in vertebrates. Here we investigate the evolution of a Hoxa2 neural crest enhancer identified originally in mouse by comparing and contrasting the fugu hoxa2a and hoxa2b genes with their orthologous teleost and mammalian sequences. Using sequence analyses in combination with transgenic regulatory assays in zebrafish and mouse embryos we demonstrate subfunctionalization of regulatory activity for expression in hindbrain segments and neural crest cells between these two fugu co-orthologs. hoxa2a regulatory sequences have retained the ability to mediate expression in neural crest cells while those of hoxa2b include cis-elements that direct expression in rhombomeres. Functional dissection of the neural crest regulatory potential of the fugu hoxa2a and hoxa2b genes identify the previously unknown cis-element NC5, which is implicated in generating the differential activity of the enhancers from these genes. The NC5 region plays a similar role in the ability of this enhancer to mediate reporter expression in mice, suggesting it is a conserved component involved in control of neural crest expression of Hoxa2 in vertebrate craniofacial development.


Glucose dependent miR-451a expression contributes to parathyroid hormone mediated osteoblast differentiation.
Parathyroid hormone (PTH; amino acid 1-34, known as teriparatide) has reported promoting differentiation and glucose uptake in osteoblasts. However, how PTH regulates glucose metabolism to facilitate osteoblast differentiation is not understood. Here, we report that PTH promotes glucose dependent miR-451a expression which stimulates osteoblast differentiation. In addition to glucose uptake, PTH suppresses AMPK phosphorylation via PI3K-mTOR-AKT axis thereby preventing phosphorylation and inactivation of octamer-binding transcription factor 1 (OCT-1) which has been reported to act on the promoter region of miR-451a. Modulation of AMPK activity controls miR-451a levels in differentiating osteoblasts. Moreover, pharmacological inhibition of PI3K-mTOR-AKT axis suppressed miR-451a via increased AMPK activity. We report that this glucose regulated miRNA is an anabolic target and transfection of miR-451a mimic induces osteoblast differentiation and mineralization in vitro. These actions were mediated through the suppression of Odd-skipped related 1 (Osr1) and activation of Runx2 transcription. When injected in vivo, the miR-451a mimic significantly increased osteoblastogenesis, mineralization, reversed ovariectomy induced bone loss and improved bone strength. Together, these findings suggest that enhanced osteoblast differentiation associated with bone formation in case of PTH therapy is also a consequence of elevated miR-451a levels via glucose regulation. Consequently, this miRNA has the potential to be a therapeutic target for conditions of bone loss.


Acute renal failure in coronary artery bypass surgery: independent effect of cardiopulmonary bypass.
Acute renal failure after cardiac surgery is associated with a high morbidity and mortality, particularly when associated with hemodialysis. The aim of the study was to investigate whether the use of cardiopulmonary bypass increased the risk of developing acute renal failure. The 2199 consecutive patients undergoing isolated coronary artery bypass grafting between January 2000 and March 2002 were retrospectively analyzed. Patients with significant preoperative renal dysfunction (preoperative serum creatinine > 200 micromol/L) were excluded. A multivariate logistic regression model was constructed to identify independent risk factors for the development of acute renal failure. In the study, 53 patients (2.4%) developed acute renal failure before hospital discharge. The crude incidences of acute renal failure for isolated coronary artery bypass grafting in the on- and off- pump groups were 2.9% and 1.4%, respectively (p = 0.031). There were 1483 patients who underwent on-pump surgery whereas 716 patients were in the off-pump group. The two groups were broadly comparable on many variables. The off-pump group were slightly younger on average (63.6 versus 64.9 years old [p = 0.017]), but had more angina class IV patients (39.5% versus 28.9% [p < 0.001]) and a greater proportion of redo surgery (4.1% versus 1.6% [p < 0.001]). The on-pump group had more patients with three-vessel disease (82.8% versus 74.3% [p < 0.001]). The logistic regression model identified use of cardiopulmonary bypass as an independent risk factor for the development of acute renal failure (odds ratio 2.64 [95% confidence intervals 1.27 to 5.45]). Other independent predictors of acute renal failure were preoperative creatinine levels, diabetes, emergency operations, increasing age, increasing body mass index, and peripheral vascular disease. Cardiopulmonary bypass is associated with significantly increased risk of acute renal failure following isolated coronary artery bypass surgery.


Developmental Pathway from Childhood Abuse to Adolescent Peer Victimization: The Role of Rejection Sensitivity and Aggression.
Despite the well-established relationship between early experiences of victimization and later re-victimization, little is known about the exact mechanism of this cycle of victimization. The present study examined whether the route from rejection sensitivity to aggression mediates the associations between different forms of childhood abuse and later peer victimization longitudinally. A total of 3525 adolescents (56.6% male; Mage = 13.21 ± 0.85) participated in this three-wave study, with a 6-month lag and a 9-month lag respectively. The results indicated that the association between childhood emotional abuse and peer victimization were independently mediated by aggression, and sequentially mediated by rejection sensitivity and aggression in both sexes. Sex differences existed regarding the association between childhood physical abuse and aggression, such that only in adolescent boys did physical abuse show significant effect on aggression, resulting in later peer victimization. In general, these findings suggest that maladaptive social-cognitive processes and behavioral patterns are crucial for understanding the mechanism of the vicious cycle of victimization, and sex differences must be considered when examining different types of childhood abuse.


Lightness, brightness and transparency: a quarter century of new ideas, captivating demonstrations and unrelenting controversy.
The past quarter century has witnessed considerable advances in our understanding of Lightness (perceived reflectance), Brightness (perceived luminance) and perceived Transparency (LBT). This review poses eight major conceptual questions that have engaged researchers during this period, and considers to what extent they have been answered. The questions concern 1. the relationship between lightness, brightness and perceived non-uniform illumination, 2. the brain site for lightness and brightness perception, 3 the effects of context on lightness and brightness, 4. the relationship between brightness and contrast for simple patch-background stimuli, 5. brightness "filling-in", 6. lightness anchoring, 7. the conditions for perceptual transparency, and 8. the perceptual representation of transparency. The discussion of progress on major conceptual questions inevitably requires an evaluation of which approaches to LBT are likely and which are unlikely to bear fruit in the long term, and which issues remain unresolved. It is concluded that the most promising developments in LBT are (a) models of brightness coding based on multi-scale filtering combined with contrast normalization, (b) the idea that the visual system decomposes the image into "layers" of reflectance, illumination and transparency, (c) that an understanding of image statistics is important to an understanding of lightness errors, (d) Whittle's logW metric for contrast-brightness, (e) the idea that "filling-in" is mediated by low spatial frequencies rather than neural spreading, and (f) that there exist multiple cues for identifying non-uniform illumination and transparency. Unresolved issues include how relative lightness values are anchored to produce absolute lightness values, and the perceptual representation of transparency. Bridging the gap between multi-scale filtering and layer decomposition approaches to LBT is a major task for future research.


Simple measurement of gluconeogenesis by direct 2H NMR analysis of menthol glucuronide enrichment from 2H2O.
The contribution of gluconeogenesis to fasting glucose production was determined by a simple measurement of urinary menthol glucuronide (MG) 2H enrichment from 2H2O. Following ingestion of 2H2O (0.5% body water) during an overnight fast and a pharmacological dose (400 mg) of a commercial peppermint oil preparation the next morning, 364 micromol MG was quantitatively recovered from a 2-h urine collection by ether extraction and a 125 micromol portion was directly analyzed by 2H NMR. The glucuronide 2H-signals were fully resolved and their relative intensities matched those of the monoacetone glucose derivative. The pharmacokinetics and yields of urinary MG after ingestion of 400 mg peppermint oil as either gelatin or enteric-coated capsules 1 h before breakfast were quantified in five healthy subjects. Gelatin capsules yielded 197 +/- 81 micromol of MG from the initial 2-h urine collection while enteric-coated capsules gave 238 +/- 84 micromol MG from the 2- to 4-h urine collection.


Assessing the risk of stroke development following retinal artery occlusion.
Retinal artery occlusion (RAO) can cause acute, painless, and irreversible loss of vision. Using a large sample population database, we investigated the possible impact of RAO and numerous other clinical and non-clinical factors on the risk of developing a subsequent cerebrovascular accident. Cases of RAO were obtained from the National Inpatient Sample (NIS) database between 2002 and 2013 using ICD-9 codes. Associated morbidities and procedures were assessed in these cases with a primary hospital admitting diagnosis of stroke. Univariate and multivariate logistic regression analyses were carried out in RAO cases to determine risk factors for stroke. The Bonferroni correction method was applied. The RAO group consisted of 19,809 cases that were separated into stroke (n=1,157, 55% male, mean age: 69±0.4 years) and non-stroke (n=18,652, 55% male, mean age: 68±0.1) cohorts. Age groups associated with reduced risk of stroke with respect to were 20-39 (OR: 0.391), 40-59 (OR: 0.842), and 60-79 (OR: 0.837). No cases of stroke were present for ages < 20. Other factors associated with a reduced stroke risk were carotid stenosis (OR: 0.187), transient ischemic attack (OR: 0.064), coronary artery disease (OR: 0.788), cardiac catheterization (OR: 0.481), and septicemia (OR: 0.333). Factors associated with an increased risk of stroke included hypertension (OR: 1.418), tobacco use (OR: 1.568), valvular disease (OR: 1.359), hyperlipidemia (OR: 1.298), and non-stroke cerebrovascular disease (OR: 2.985). A large patient population was used to determine that RAO patients with a history of hypertension, hyperlipidemia, tobacco usage, valvular disease, or non-stroke cerebrovascular disease had an increased risk of stroke. Patients below the age of 40 had significantly reduced the odds of stroke. Carotid stenosis, coronary artery disease, transient ischemic attacks, cardiac catheterization, and septicemia were all independently associated with a decreased risk of stroke development in RAO patients.


Analysis of human sweat proteins by two-dimensional electrophoresis and ultrasensitive silver staining.
The polypeptide components of human sweat have been detected with the methylamine-incorporating silver stain (T. Marshall, 1984, Anal. Biochem. 136, 340-346) following high resolution two-dimensional electrophoresis. This technique reveals over 400 polypeptide components in 65 microliters of unconcentrated human sweat.


Carbohydrate functionalization using cationic iron carbonyl complexes.
Cationic iron carbonyl cyclohexadiene complexes were employed in the derivatization of the 3-OH position of unprotected and protected methyl beta-D-galactopyranosides using two different approaches, giving access to galactopyranosides with an aromatic or cyclohexadienoic functionality in this position.


Differentiated ovine tracheal epithelial cells support the colonisation of pathogenic and non-pathogenic strains of Mannheimia haemolytica.
Mannheimia haemolytica is the primary bacterial species associated with respiratory disease of ruminants. A lack of cost-effective, reproducible models for the study of M. haemolytica pathogenesis has hampered efforts to better understand the molecular interactions governing disease progression. We employed a highly optimised ovine tracheal epithelial cell model to assess the colonisation of various pathogenic and non-pathogenic M. haemolytica isolates of bovine and ovine origin. Comparison of single representative pathogenic and non-pathogenic ovine isolates over ten time-points by enumeration of tissue-associated bacteria, histology, immunofluorescence microscopy and scanning electron microscopy revealed temporal differences in adhesion, proliferation, bacterial cell physiology and host cell responses. Comparison of eight isolates of bovine and ovine origin at three key time-points (2 h, 48 h and 72 h), revealed that colonisation was not strictly pathogen or serotype specific, with isolates of serotype A1, A2, A6 and A12 being capable of colonising the cell layer regardless of host species or disease status of the host. A trend towards increased proliferative capacity by pathogenic ovine isolates was observed. These results indicate that the host-specific nature of M. haemolytica infection may result at least partially from the colonisation-related processes of adhesion, invasion and proliferation at the epithelial interface.


Loss of G2 subunit of vacuolar-type proton transporting ATPase leads to G1 subunit upregulation in the brain.
Vacuolar-type ATPase (V-ATPase) is a primary proton pump with versatile functions in various tissues. In nerve cells, V-ATPase is required for accumulation of neurotransmitters into secretory vesicles and subsequent release at the synapse. Neurons express a specific isoform (G2) of the G subunit of V-ATPase constituting the catalytic sector of the enzyme complex. Using gene targeting, we generated a mouse lacking functional G2 (G2 null), which showed no apparent disorders in architecture and behavior. In the G2-null mouse brain, a G1 subunit isoform, which is ubiquitously expressed in neuronal and non-neuronal tissues, accumulated more abundantly than in wild-type animals. This G1 upregulation was not accompanied by an increase in mRNA. These results indicate that loss of function of neuron-specific G2 isoform was compensated by an increase in levels of the G1 isoform without apparent upregulation of the G1 mRNA.


Repair of transposition of the great arteries with total anomalous pulmonary venous return.
A 13-year-old Haitian girl presented with complex congenital heart disease consisting of transposition of the great arteries with total anomalous venous return. The patient exhibited clinical findings of long-standing congestive heart failure and cyanosis. She underwent complete repair with resolution of her symptoms.


Lex genetica: the law and ethics of programming biological code.
Recent advances in genetic engineering now allow the design of programmable biological artifacts. Such programming may include usage constraints that will alter the balance of ownership and control for biotechnology products. Similar changes have been analyzed in the context of digital content management systems, and while this previous work is useful in analyzing issues related to biological programming, the latter technology presents new conceptual problems that require more comprehensive evaluation of the interplay between law and technologically embedded values. In particular, the ability to embed contractual terms in technological artifacts now requires a re-examination of disclosure and consent in transactions involving such artifacts.


Enzyme immunoassay for identification of heat-killed mycobacteria belonging to the Mycobacterium tuberculosis and Mycobacterium avium complexes and derived from early cultures.
A simple enzyme-linked immunosorbent assay was developed for the identification of cultured mycobacteria belonging to the Mycobacterium tuberculosis complex, the Mycobacterium avium complex, and Mycobacterium kansasii. Six monoclonal antibodies were used: two (F23-49 and F24-2) were specific for the M. tuberculosis complex, two (F85-2 and F85-10) were specific for the identification of the M. avium complex, one (F126-22) was specific for M. kansasii, and one (F141-3) was broadly reactive and distinguished mycobacteria from other bacteria. In the enzyme-linked immunosorbent assay only 10(6) to 10(7) bacteria derived from early cultures (2 to 3 weeks) were needed for each monoclonal antibody. For the M. tuberculosis complex the sensitivity and specificity were both 100%. For the M. avium complex the specificity was 100% and the sensitivity was 70%. The three M. kansasii strains tested could all be identified as M. kansasii.


Mechanisms of endogenous nitrosation.
Endogenous formation of N-nitroso compounds has been demonstrated in both humans and experimental animals. The extent of this process has been estimated by measurement of urinary N-nitrosoproline and has been shown to be modulated by dietary precursors and inhibitors. It is now also recognized that other (non-gastric) pathways of endogenous nitrosation, including those catalysed by bacteria and mammalian cells, may exist. The mammalian cell catalysed pathway utilizes arginine as a precursor for the nitrosating agent and may occur in macrophages or endothelial cells. The estimated contribution of this pathway to normal basal endogenous nitrosation is approximately 20 nmol of N-nitrosoproline/day.


Normal numbers of retinotectal synapses during the activity-sensitive period of optic regeneration in goldfish: HRP-EM evidence implicating synapse rearrangement and collateral elimination during map refinement.
Optic and nonoptic fibers and synapses were counted in the primary optic innervation layer (S-SO-SFGS) in anteromedial tectum in normal goldfish and in fish 30, 60, and 240 d after the optic nerve was crushed. A newly developed "cold-fill" HRP-labeling protocol was used to label optic afferents for electron microscopy, and counts were then made on EM photomontages of columns through the HRP-labeled S-SO-SFGS. Normal numbers of retinotectal synapses were present at 30 d regeneration, at a time when activity-dependent refinement of the optic projection is incomplete. Normal numbers were also found at 60 and 240 d, when refinement is largely completed. In contrast to this constancy in optic synapse numbers, there was nearly 10 times the normal number of optic fibers in the SFGS at 30 d, and these were reduced by 50% at 60 d, remaining over 4 times normal at 240 d. These findings imply extensive rearrangement of optic synapses during map refinement. They also indicate that synapse rearrangement is associated with the elimination of optic collaterals.


Suppressive effects of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer on the adherence of Candida species and MRSA to acrylic denture resin.
The effects of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer on the adherence of microorganisms such as non-Candida albicans Candida (NCAC) and methicillin-resistant Staphylococcus aureus (MRSA), frequently detected in oral infections in immunocompromised and/or elderly people, to denture resin material, are still unclear. Here, we report the effects of MPC-polymer on the adherence of C. albicans, NCAC, and MRSA to acrylic denture resin. Sixteen strains of C. albicans, seven strains of C. glabrata, two strains of C. tropicalis, one strain of C. parapsilosis, and six strains of MRSA were used. We cultured the fungal/bacterial strains and examined the cell growth and adherence of fungi/bacteria to mucin-coated acrylic denture resin plates (ADRP) with or without MPC-polymer coating, by scanning electron microscopy. The cell surface hydrophobicity of the fungal/bacterial strains was measured by the adsorption to hydrocarbons. MPC-polymer did not affect the growth of all strains of Candida species and MRSA, but significantly suppressed adherence to ADRP in most strains of C. albicans and all strains of NCAC and MRSA. A significant positive correlation was found between cell hydrophobicity and the reduction rates of microbial adherence to ADRP treated with 5% of MPC-polymer. MPC-polymer treatment for acrylic resin material suppresses the adherence of C. albicans, NCAC and MRSA via their hydrophilicity interaction. The application of MPC-polymer for denture hygiene is potent to prevent oral candidiasis, denture stomatitis and opportunistic infection, caused by Candida species and MRSA, via suppressing the adherence of those fungus/bacteria.


PEG-tethered guanosine acetal conjugates for the enzymatic synthesis of modified RNA.
A short and efficient synthetic route to guanosine monophosphate conjugates connected to a protected aldehyde group via a flexible polydisperse polyethylene glycol linker is described. These conjugates are enzymatically incorporated into RNA transcripts with 52% yield. The resulting aldehyde-modified RNA gave full conversion in the reaction with biotin hydrazide, demonstrating the utility of the method.


Patterns of recurrence in patients undergoing curative treatment for maxillary alveolus squamous cell carcinoma.
The aim of this paper was to examine patterns of recurrence in patients undergoing curative treatment for maxillary alveolus squamous cell carcinoma (MASCC). Clinicopathological data on 41 patients undergoing curative resection for MASCC between February 2006 and May 2020 were retrospectively gathered. Outcomes included local, regional, or distant failure as first site of treatment recurrence. Univariate analysis identified significant clinicopathological variables for type of recurrence. Multivariate regression analysis generated predictive models. Ten of 41 patients developed regional recurrence, and nine manifested contralateral recurrence following ipsilateral neck dissection. In three patients the ipsilateral neck was pN0. Nodal metastasis was predictive of regional recurrence, particularly with extranodal tumour extension (ENE). Multivariate analysis with regional recurrence confirmed that ENE was independently predictive. Nodal disease and ENE in patients with MASCC was found to be predictive of contralateral regional recurrence. Management of the neck in MASCC that extends to the palatal aspect should therefore be considered as midline disease.


Paternal exposure to aluminum, acidity, and temperature affect fatty acid seminal profile, embryonic and larval development of Astyanax altiparanae.
We investigated the effects of water acidity, temperature, and aluminum (Al) on the fatty acid (FA) seminal profile, reproductive parameters (fertilization and hatching) and embryonic development of Astyanax altiparanae. We treated males with different experimental treatments, corresponding to the combination of water temperature (20 °C; 25 °C), pH (neutral - 7.0; acidic - 5.5), and the absence or presence of Al (0.5 mg L-1). After 96 h, we analyzed the FA profile of semen and performed artificial fertilization in activating medium with neutral pH or activating medium in the same experimental conditions of the males (neutral pH, acidic pH, and Al) to evaluate fertilization and hatching rates and to monitor embryonic development. Polyunsaturated FA percentage decreased in semen of fish from the neutral group, while monounsaturated FA increased in all groups maintained at 20 °C compared to 25 °C. Aluminum exposure decreased the percentage of C20:4n6 and increased the percentage of C22:5n3 at 20 °C. Males exposed to acidic pH and Al showed lower fertilization and hatching rates, as well as increased mortality of embryos and larvae. Moreover, Al favoured a higher percentage of abnormal larvae. Fertilization in Al activating medium harmed the embryos and larvae since fertilization and hatching rates decreased. Finally, temperature influenced fertilization time, hatching rate, and the morphology of embryos and larvae. Males exposed to Al had lower fertilizing capacity, which negatively affected the embryonic development of the species. Furthermore, Al activating medium reduced the number of fertilized oocytes, hatched embryos, and normal larvae. All events were temperature dependent.


Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.
Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability. Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE-/- mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE-/-Irf5-/- mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts. Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture.


β-2 spectrin is involved in hepatocyte proliferation through the interaction of TGFβ/Smad and PI3K/AKT signalling.
Transforming growth factor (TGF) β signalling pathway plays a crucial role in liver regeneration following partial hepatectomy in mice. Evidence demonstrated that β-2 Spectrin is involved in TGFβ/Smad signalling pathway as a Smad3/4 adaptor protein. The aim of this study was to explore the role of β-2 Spectrin in hepatocyte proliferation. β-2 Spectrin expression was evaluated in mice receiving partial hepatectomy. The effect of siRNA against β-2 Spectrin on hepatocyte proliferation was determined. The interaction between TGFβ/Smad and PI3K/Akt signalling was investigated. Hepatic β-2 Spectrin decreased dramatically 2 days after 70% hepatectomy in mice. In AML-12 cells, hepatocyte proliferation was inhibited after the stimulation of TGF β1 and a reduction in β-2 Spectrin mediated by siRNA resulted in increase in proliferative response. Confocal results revealed that β-2 Spectrin represented a key regulator in TGFβ/Smad signalling through controlling Smad3/4 subcellular localization. Moreover, Alternation of Akt phosphorylation led to the change in subcellular localization of Smad2, 3, 4 and β-2 Spectrin, A reduction in Smad2, 3 and 4 mediated by siRNA resulted in the induction of pAkt expression. These findings reveal that β-2 Spectrin plays a crucial role in hepatocyte proliferation, which contributes to liver regeneration following hepatectomy in mice. In addition, PI3K/Akt is involved in TGFβ/Smad signalling pathway through the interaction with Smad proteins and β-2 Spectrin.


Comparison of suppressive effects of demethoxycurcumin and bisdemethoxycurcumin on expressions of inflammatory mediators in vitro and in vivo.
Demethoxycurcumin and bisdemethoxycurcumin are the main active ingredients isolated from Curcumae Longae Radix. Recent studies demonstrated that both compounds exhibit antioxidative and anti-inflammatory effects as well as effects on cancer cell lines. In this study, we compared the activities of demethoxycurcumin and bisdemethoxycurcumin, and both compounds were evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), cycloxygenase-2 (COX-2) and nuclear factor-kappaB (NF-kappaB) activity in a RAW 264.7 macrophage cell line. The evaluation:results suggested that the anti-inflammatory properties of demethoxycurcumin and bisdemethoxycurcumin were attributed to the inhibition of iNOS and COX-2 expression, as initiated by the inhibition of NF-kappaB activity. Additionally, both of them significantly inhibited carrageenan-induced paw edema in mice. Taken together, all of the results showed that the suppressive effect of demethoxycurcumin was stronger than that of bisdemethoxycurcumin, indicating that the methoxy group had enhanced demethoxycurcumin's anti-inflammation effects.


Regulation of collagen synthesis in fetal rat calvaria by 1,25-dihydroxyvitamin D3.
1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) inhibited type I collagen synthesis in the central bone but not the periosteum of fetal rat calvaria maintained in organ culture. The central bone synthesized primarily type I collagen, whereas the periosteum synthesized both types I and III collagen. Enhanced degradation of newly synthesized collagen seemed an unlikely mechanism for the observed decrease in collagen synthesis since 1,25-(OH)2D3 reduced both the labeling of intracellular procollagen and total [3H]hydroxyproline formation in fetal rat calvaria. As measured by cell-free translation of RNA extracted from calvaria, 1,25-(OH)2D3 decreased the level of functional procollagen mRNA and collagen synthesis to the same extent. Both collagen synthesis and procollagen mRNA levels were decreased as early as 3 h after exposure to 1,25-(OH)2D3 and were 50% of the control level by 24 hr. Upon removal of 1,25-(OH)2D3 from the cultures, collagen synthesis and procollagen mRNA remained depressed for 24 h but returned to control levels by 48 h. A reduction in collagen synthesis and procollagen mRNA was also observed in calvaria excised from 6-day-old rat pups given a single subcutaneous injection of 1,25-(OH)2D3 (1.6 ng/g body weight). We conclude that 1,25-(OH)2D3 inhibits the synthesis of type I collagen in the differentiated osteoblast by reducing the level of functional procollagen mRNA.


Micropropagation of Ficus religiosa L. via leaf explants and comparative evaluation of acetylcholinesterase inhibitory activity in the micropropagated and conventionally grown plants.
A high-frequency, season-independent, in vitro regeneration of Ficusreligiosa was developed, followed by comparative acetylcholinesterase inhibitory (AChEI) activity assay of the in vitro raised and conventionally grown plants. The use of AChEI activity is the most accepted strategy for the treatment of Alzheimer disease. Fully expanded, mature leaves were cut into different segments to initiate the cultures. The middle section of the leaf in vertical orientation with cut portion inserted inside the medium was found most suitable for direct shoot regeneration. Leaf explants responded with nearly consistent frequency (60-66.67 %) throughout the year. To obtain high frequency response with enhanced shoot multiplication rate, 32 plant growth regulator regimes were screened amongst which benzylaminopurine at 5.0 mg/l was found most suitable, yielding 100 % response and maximum number of shoots per explant (7.93); same concentration was also most supportive for repeated multiplication (6.53 shoots). The quality of the shoots and multiplication rate could be significantly enhanced (24.35 shoots) when adenine sulphate, glutamine and phloroglucinol, in an optimised concentration, were additionally supplemented. The clonal nature of the micropropagated plants was confirmed by random amplified polymorphic DNA analysis. A comparative analysis of AChEI activity was carried out amongst the methanolic extracts of stem segments of the mother plant, randomly selected seedlings of different age (4 and 6 months old) of the same mother plant and randomly selected micropropagated plants of different age (3 and 6 months age). The mother plant sample showed effective AChEI activity, with IC50 of 66.46 μg/ml while seedlings, of different age groups, performed poorly (6-month-old seedlings, Se-16M, yielded IC50 of 20,538.46 μg/ml, while two randomly selected 4 months' aged seedlings, Se-24M and Se-34M exhibited IC50 of 19,341.03 and 24,281.70 μg/ml). On the other hand, various micropropagated plants, 2 of 3 months (MiP-13M, MiP-23M) and 2 of 6 months (MiP-36M and MiP-46M) age behaved like the mother plant, exhibiting IC50 values of 71.87, 72.91, 67.65 and 69.65 μg/ml, respectively.


Infectious complications of neoplastic disease.
Progress has been made in the diagnosis and treatment of infection in patients with neoplastic disease. Among the advances is the appreciation that certain opportunistic infections occur in association with particular host immune defects and epidemiologic factors. Such immune defects are seen secondary to or as a consequence of treatment for the patient's basic disease. Improved methods such as serology, open lung biopsy, and fiberoptic bronchoscopy have allowed for earlier diagnosis and treatment of opportunistic infections. The development of empiric antibiotic regimens, particularly aminoglycosides and the antipseudomonal penicillins, have improved the outcome in the febrile neutropenic patient. The benefits of protective environments have been challenged; prophylactic antibiotics and various forms of immunotherapy are of interest but remain investigational.


Integrating equity frameworks into surgical quality improvement and health administrative databases: A narrative review.
Ensuring safe, timely, and effective surgery is critical for high-quality healthcare and is the goal of surgical quality monitoring systems. At the heart of these systems are health administrative databases which house patient clinico-demographic information, healthcare processes and outcomes. Through analysis of monitoring systems outputs, we can identify gaps within healthcare delivery, patient experience, and surgical outcomes. However, gaps in our healthcare can only be measured by the variables we collect. Equity stratifiers are sociodemographic descriptors that can identify patient populations who experience differences in health and healthcare that may be considered unjust or unfair. They include age, education, gender, geographic location, income, Indigenous identity, racialized group, and sex at birth. These equity stratifiers represent measurable components of the social determinants of health housed within health administrative databases and allow for standardized analysis and reporting of health inequity. However, not all databases collect these stratifiers - making granular analysis of patient subgroups who may experience health inequity impossible to measure. Moreover, in databases that do collect this information, a wide range in the classification systems used makes for comparisons across jurisdictions challenging. The focus of this narrative review will be to apply the principles of the equity stratifier framework to examine what measures are collected in surgical quality improvement databases, cancer monitoring systems and provincial/state health administrative databases in the United States of America and Canada. The goal of this narrative review is to 1) inform researchers, surgeons, and policymakers of the current landscape of social variables collected within common health administrative databases. 2) Outline the pros and cons of the current collection system. 3) Issue a call to action for policymakers to incorporate health equity frameworks into the collection and reporting of data.


Cesarean delivery and its impact on the anomalous infant.
Although cesarean deliveries frequently are performed for anomalous fetal conditions, available data do not always support a fetal benefit from this delivery management. The literature on cesarean delivery for anomalous infants reports insufficient information on comorbid neonatal conditions, so these complications are unknown in this population of newborns. In a minority of cases, a cesarean delivery is reasonable to prevent dystocia or optimize outcome. Areas for future investigation include prospective, randomized, controlled trials of prelabor cesarean compared with vaginal deliveries for myelomeningocele and anterior abdominal wall defects. The rarity of other lesions likely precludes randomized controlled trials.


Use of psychiatric drugs in Slovenia in comparison to Scandinavian countries.
To find out the consumption of psychotropic drugs in Slovenia and the extent to which Slovenian consumption correlates to Scandinavian countries. Data of ambulatory prescribing of psychiatric drugs in Slovenia for the years 1999 and 2000 and data for Norway, Sweden and Denmark are shown. All data are expressed in defined daily doses per thousand inhabitants per day (DDD's). The use of all neuroleptics in Slovenia is lower (5.3 vs 6.1-7.6 DDD's), however the share of atypicals (34%) is comparable to Scandinavian countries. Use of anticholinergics is up to five times greater (1.6 vs 0.3-0.5 DDD's). The use of lithium is five time lower (0.2 vs 1.1-1.4). Regarding the use of antidepressants, Slovenia is behind Scandinavia (12.2 vs 30-47 DDD's), whereas the share of SSRI's (73%) is at the same level. The use of anxiolytics is higher (25.4 vs 16-22.4 DDD's) and ratio with antidepressants is also unfavourable. The use of hypnotics and sedatives is favourably low (10.7 vs 31.8-44.6 DDD's). Low use of hypnotics and sedatives is favourable. The share of new neuroleptics and antidepressants is comparable. The use of antidepressants is probably too low. However, prescribing guidelines for anxiolytics, anticholinergics (too high use of both group) and lithium (too low use) should be introduced in Slovenia.


Patch Testing in Patients with Suspected Footwear Dermatitis: A Retrospective Study.
Footwear dermatitis represents a common but often undiagnosed or misdiagnosed condition. Patch testing aids in its confirmation and identification of the offending allergen. This study aimed to find the frequency of positive patch test reactions in cases with suspected allergic contact dermatitis (ACD) to footwear, as well as the common responsible allergens. This is a retrospective record based study of 37 patients, with suspected ACD to footwear, who underwent patch testing with Indian standard series and Indian footwear series from July 2012 to July 2015. The majority of patients (45.94%) belonged to the age group of 20-40 years. Dorsal aspects of feet (81.08%) and soles (18.92%) were the common sites involved. Patch test was positive in 18.92% patients. The most common causative allergens were hydroquinone monobenzylether (8.11%) and 4-aminoazobenzene (5.41%). Common chemicals implicated in ACD were rubber, rubber additives, and dyes. The principal culprit allergens were hydroquinone monobenzylether and 4-aminoazobenzene.


Difficulties In Emotion Regulation During Rehabilitation For Alcohol Addiction: Correlations With Metacognitive Beliefs About Alcohol Use And Relapse Risk.
Understanding how difficulties in emotion regulation can be related to metacognitive beliefs during early abstinence, identifying which factors are associated with craving and relapse risk may be useful in residential rehabilitation treatment of alcohol addiction. Sixty-five patients underwent a 28-day rehabilitation program for alcohol addiction. They underwent a brief semi-structured interview at admission and completed a battery of five self-report questionnaires between days 7 and 10 of alcohol abstinence (T0) and 3 days prior to discharge (T1). After rehabilitation program, all symptoms of psychological distress decreased. We found a significant improvement in all emotional, cognitive and metacognitive scales except for "Cognitive harm" (NAM), "Awareness" (DERS) and a small effect size (low statistical power) for "Emotional clarity" (DERS). Compared to those still abstinent at 1 month from discharge, we found more difficulties in "Emotional clarity" in those who had an early relapse. Difficulties in "Emotional clarity" were observed also in patients with a high level of craving at discharge. Significant differences were observed between the groups "abstinence vs non-abstinence" at 1 month from discharge concerning difficulties in emotion regulation. In particular, we found difficulty in the awareness and understanding of emotion, precisely to identify correctly the emotions. The "Emotional Clarity" seems to be the emotional difficulty that characterized also the group with a high level of craving at discharge and the individuals with early relapse, suggesting the importance of this function as a preliminary factor in emotion regulation.


The emerging outcome of postoperative radiotherapy for stage IIIA(N2) non-small cell lung cancer patients: based on the three-dimensional conformal radiotherapy technique and institutional standard clinical target volume.
The aim of this study was to evaluate the clinical efficacy of postoperative radiotherapy (PORT), administered using three-dimensional conformal radiotherapy (3D-CRT) and our institutional standard clinical target volume (CTV) delineation, for completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC). From 2005 to 2012, consecutive patients with pT1-3N2 NSCLC who were treated with PORT employing our institutional CTV delineation after complete surgery or who underwent complete resection in our hospital but without PORT were identified. We excluded patients who had received neoadjuvant chemotherapy or radiation therapy (RT). Kaplan-Meier estimates for locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were performed. In the OS estimation, patients who received epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) during follow-up were censored at the time of TKI initiation. Data from 70 patients in the PORT group and 287 in the non-PORT group were analysed. All 70 cases received 3D-CRT following our institutional CTV guideline, with a median total dose of 50.4 Gy at 1.8 Gy/fraction. At a median follow-up of 34.3 months for the PORT group and 31.2 months for the non-PORT group, PORT significantly improved local control (5-yr LRFS 91.9% for PORT vs 66.4% for non-PORT, P < 0.001) and OS (5-yr OS 57.5% for PORT vs 35.1% for non-PORT, P = 0.003), whereas no differences in DMFS were noted (P = 0.18). In multivariable analyses, PORT was independently associated with an improved LRFS (HR 0.2, P = 0.001) and OS (HR 0.4, P = 0.001). All patients completed the planned RT dose without interruption of RT due to treatment-related complications. Our data suggested that PORT administered using the 3D-CRT technique following our institutional CTV delineation guideline resulted in a promising outcome with favourable survival for completely resected IIIA(N2) NSCLC, after controlling for subsequent EGFR-TKI confounding in the OS analysis. Prospective trials are needed to further corroborate these results.


Efficient inspired concentration of sevoflurane for vital capacity rapid inhalation induction (VCRII) technique.
To evaluate the efficient inspired concentration of sevoflurane for a vital capacity rapid inhalation induction (VCRII) technique with respect to induction time, characteristics, and acceptability. Prospective study. Medical college hospital. 68 unpremedicated healthy adult volunteers were assigned to one of four groups in order of sequential entry of informed consent. 3%, 4.5%, 6%, or 7.5% concentrations of sevoflurane were administered for 5 minutes (3% and 4.5%) or 3 minutes (6% and 7.5%) using a single breath technique. The mean induction time required with 3%, 4.5%, 6%, or 7.5% sevoflurane was 120 +/- 26 sec, 79 +/- 18 sec, 52 +/- 15 sec, or 47 +/- 17 seconds, respectively. Each induction time was significantly different from the others (p < 0.05) except for that between 6% and 7.5%. There appeared to be a direct inverse relationship between the mean induction time and the logarithm of inspired concentration of sevoflurane, but this relationship did not extend beyond concentrations above 6%. Blood pressure decreased by approximately 18% from baseline at the end of inhalation of the drug, and heart rate remained constant in all groups. Except of one subject in the 7.5% group, no coughing was observed and laryngospasm, breath-holding, and secretions were not seen in any subjects. Slight limb movement was observed in a few subjects in each group. All subjects except one in the 3% group would accept undergoing a similar procedure again. Sevoflurane 6% can be recommended for VCRII, but increasing the concentration higher than this does not markedly shorten the induction time and thus seems to add little benefit.


Cough-variant asthma in children and adults: case reports and review.
Two cases of cough-variant asthma are presented, one in an adult and one in a child. We discuss the diagnosis, treatment, and course of this common, yet often unrecognized entity. The keys to diagnosis are a typical history, clinical suspicion, and subsequent response to bronchodilator therapy. Treatment of cough-variant asthma is no different from that of classic asthma.


Biothiol modulated growth and aggregation of gold nanoparticles and their determination in biological fluids using digital photometry.
This work describes a novel and easy to use method for the determination of biologically important thiols that relies on their ability to inhibit the catalytic enlargement of AuNP seeds in the presence of ACl4- ions and trigger their aggregation. UV-vis spectroscopic monitoring of the plasmon resonance bands of the formed AuNPs showed that the spectral and color transitions depend both on the concentration and the structure of biothiols. The colorimetric changes induced by biothiols were quantified in the concentration range from 5 to 300 μM in the RGB color system with digital photometry using a commercially available flatbed scanner as detector. On the basis of these results, the applicability of the method was tested to the determination of glutathione in red blood cells and cysteine in blood plasma with satisfactory recoveries (88.7-96.5%), low detection limits (1.0 μM), good selectivity against major biomolecules under physiologically relevant conditions and satisfactory reproducibility (<8%). The method requires minimum technical expertise, is easy to use and is performed without scientific equipment, holding promise as a simple assay of biothiol testing even by non-experts.


Pediatric cardiac surgery in the 1990s.
Future developments in the repair of these complex anomalies will rely heavily on a complete understanding of present results, which can be achieved only with attention to detail and rigorous standards. Results must be continually updated and management changes carefully planned and then critically examined for significant differences. Thus, the day-to-day care of patients with congenital heart disease must withstand careful scrutiny, both for consistency and for end results.


Analytical calculations of counting losses in internal gas proportional counting.
In internal gas proportional counting, the evaluation of counting losses is important in order to obtain high accuracy measurement results. In this paper, counting losses due to the wall effect and not counted beta particles with very low energy are evaluated by analytical calculations. The calculated and experimental results are compared and a very good agreement is found.


Factors influencing readmission to hospital: II. Paraplegia.
This study of 200 paraplegics shows that occupational status at the time of becoming paralysed exerts as great an influence upon readmission to hospital as does the level or the extent of the lesion and that the effect of the level of the lesion on readmission to hospital increases with lower occupational status.


A smart multisyringe flow injection system for analysis of sample batches with high variability in sulfide concentration.
A fully automated smart multisyringe flow injection analysis (MSFIA) system for the monitoring of sulfide in a wide concentration range is proposed. It allows the determination of sulfide in samples containing suspended solids without requiring any preliminary batch sample treatment. The smart system is able to choose by itself the best approach to quantify the analyte, selecting either a spectrophotometric or a reflectometric detection. The method, carried out in a multi-commuted system, is based on the analyte release as hydrogen sulfide from the donor channel of the gas-diffusion module into an alkaline acceptor channel solution, which is merged with N,N-dimethyl-p-phenylenediamine (DMPD) and Fe(III). The in-line generated methylene blue (MB) dye can be delivered to an optical fiber diffuse reflectance sensor or to a flow-cell spectrophotometer according to the analyte concentration. The detection limit (3s(b)/S) was 4.6 microg l(-1). Two linear calibration graphs between 50-1000 and 500-10000 microg l(-1) sulfide for reflectometry and spectrophotometry, respectively, were obtained. The potentialities of this method were assessed via the determination of sulfide at a wide range of concentrations (4.6 microg l(-1) to 100 mg l(-1)). The high selectivity and sensitivity, the low reagent consumption and the miniaturization of the proposed automated method should be highlighted.


Self-inflicted oral penetration injury: An intravenous drip pole advanced from the mouth to the retroperitoneum.
Patients with oral penetration injuries require a systematic physical examination. These patients should be managed by a multidisciplinary medical team. Airway management, operative procedures, and transfusion needs of the patient with an oral penetration injury should be discussed before surgery. A 63-year-old man with a history of recurrent hepatic duct cancer attempted suicide by advancing an intravenous pole through his mouth, neck, and thorax, ultimately penetrating into the right retroperitoneal space. A multidisciplinary team assembled by code blue emergently treated the patient, initially with fiberoptic intubation. The injured right lower lung was resected under one lung ventilation via a double lumen tube after tracheostomy. Fortunately, the pole did not injure any other organs or major vessels. Despite successful removal of the pole after lung resection, the patient died 14 days postoperatively due to his primary hepatic duct cancer. We highlight the need for a multidisciplinary approach to this patient's management and discuss particular aspects of airway and transfusion management. A systematic and multidisciplinary approach allowed successful removal of the drip pole and stabilization of the patient's respiratory and hemodynamic status.


Different early effets of tyrphostin AG957 and geldanamycins on mitogen-activated protein kinase and p120cbl phosphorylation in anti CD-3-stimulated T-lymphoblasts.
AG957, a tyrphostin tyrosine kinase inhibitor, has been shown previously to inhibit p210(bcr-abl) phosphorylation with concurrent inhibition of p210(bcr-abl)-expressing K562 cell growth (Kaur G and Sausville EA, Anticancer Drugs 7: 815-824, 1996). To assess the specificity of the action of AG957, we have examined its effect in another tyrosine kinase-mediated system, anti CD-3-stimulated Jurkat T Acute Lymphoblastic Leukemia cells. We also compared the effects of AG957 with those of geldanamycin, which can disrupt tyrosine kinase signaling through binding to heat shock protein (hsp90), and two geldanamycin analogs, 17-amino-17-demethoxygeldanamycin (17AG) and 17-allylamino-17-demethoxygeldanamycin (17AAG). At concentrations found to produce 90% inhibition of Jurkat T-cell growth, AG957 within 4 hr of addition inhibited mitogen-activated protein (MAP) kinase activation and activity, as shown by a decreased anti CD-3-stimulated erk-2 mobility shift in lysates of treated cells and a decrease in the stimulated myelin basic protein peptide kinase activity in erk-2 immunoprecipitates, respectively. AG957 did not inhibit this activity when added directly to immunoprecipitates. Effects in cells were found to be accompanied by a decrease in the anti CD-3-stimulated phosphorylation of p120cbl. Under conditions of a similar degree of growth inhibition, geldanamycin initially did not inhibit MAP kinase activation. Geldanamycin analogs did not decrease anti CD-3-induced cbl phosphorylation, but did reduce basal p120cbl tyrosine phosphorylation. The action of AG957 occurred with an apparent shift of several tyrosine-phosphorylated proteins to apparent higher molecular weights, which also did not occur with the geldanamycins. These results suggest that growth inhibition by AG957 can alter tyrosine kinase signaling systems unrelated to p210(bcr-abl) with a prominent early effect on MAP kinase activation in T-lymphoblasts. AG957 and geldanamycin affect tyrosine kinase signaling by distinct mechanisms.


A study of functional outcomes following implantation of a total distal radioulnar joint prosthesis.
This paper reports a long-term follow-up measuring pain, range of motion and weight-bearing ability, following implantation of a total distal radioulnar joint prosthesis. This prosthesis differs from excision arthroplasties and ulnar head replacements by replacing all three components of the distal radioulnar joint, viz. the sigmoid notch, the ulnar head and the triangular fibrocartilage. The design allows longitudinal migration of the radius throughout pronation and supination, as well as load bearing of the wrist. Thirty-one patients receiving the prosthesis returned or were interviewed by telephone at a mean of 5.9 (range 4-9) years. Pronation increased from a mean of 65.5 degrees (range 5-90 degrees ) to 74 degrees (range 20-90 degrees ) and supination from 53 degrees (range 5-90 degrees ) to 70 degrees (range 20-90 degrees ) while greatly diminishing and/or eliminating pain. Grip increased from a mean of 10 kg (22 lbs) to 24 kg (52 lbs). Weight bearing was restored or increased in 29 of 31 patients.


Exploring the Effects of Item-Specific Factors in Sequential and IRTree Models.
Test items for which the item score reflects a sequential or IRTree modeling outcome are considered. For such items, we argue that item-specific factors, although not empirically measurable, will often be present across stages of the same item. In this paper, we present a conceptual model that incorporates such factors. We use the model to demonstrate how the varying conditional distributions of item-specific factors across stages become absorbed into the stage-specific item discrimination and difficulty parameters, creating ambiguity in the interpretations of item and person parameters beyond the first stage. We discuss implications in relation to various applications considered in the literature, including methodological studies of (1) repeated attempt items; (2) answer change/review, (3) on-demand item hints; (4) item skipping behavior; and (5) Likert scale items. Our own empirical applications, as well as several examples published in the literature, show patterns of violations of item parameter invariance across stages that are highly suggestive of item-specific factors. For applications using sequential or IRTree models as analytical models, or for which the resulting item score might be viewed as outcomes of such a process, we recommend (1) regular inspection of data or analytic results for empirical evidence (or theoretical expectations) of item-specific factors; and (2) sensitivity analyses to evaluate the implications of item-specific factors for the intended inferences or applications.


Serial serum determination on alpha-fetoprotein as a marker of the effect of postoperative chemotherapy in ovarian endodermal sinus tumor.
Serial serum determinations of alpha-fetoprotein (alpha FP) as a tumor marker were carried out in the management of six patients with endodermal sinus tumor (EST). Histological examinations in all six patients revealed a typical EST pattern, and in one of them another germ cell tumor, a malignant teratoma, was also found. All patients were treated postoperatively with combination chemotherapy. The serum alpha FP concentrations before treatment, using radioimmunoassay, were abnormally high and ranged from 2500 to 100,000 ng/ml. One patient having Stage Ia neoplasm is living at 50 months after diagnosis with a normal alpha FP concentration and without clinical evidence of recurrence. The other five patients with Stage III disease died from 4 to 9 months after surgery, respectively, although the serum alpha FP in all these cases during chemotherapy decreased markedly but temporarily to a normal level (less than 20 ng/ml) or to 3000 ng/ml and was paralleled by a certain improvement in the conditions of the disease. These results suggest that serial serum determination of alpha FP may be useful as a marker and prognostic indicator of endodermal sinus tumor.


Mutational and gene dosage analysis of calcium-activated potassium channels in Drosophila: correlation of micro- and macroscopic currents.
In Drosophila, two Ca2(+)-activated K+ currents, ICF and ICS, have previously been distinguished in conventional voltage clamp experiments. The slowpoke (slo) mutation eliminates ICF specifically. We report that in patch clamp recordings a single-channel Ca2(+)-activated K+ current is readily distinguished from other channel activities in normal larval muscle membrane, whereas no such current is observed in slo muscles. This single-channel current thus correlates with the macroscopic ICF. No obvious differences in amplitude or properties were detected between normal (+/+) and heterozygous (slo/+) ICF channels in whole-cell voltage clamp recordings or single-channel patch clamp recordings. These results are consistent with the hypothesis that slo is a structural gene for the ICF channels only under certain conditions. The selective effect of the slo mutation may reflect a defect in a regulatory mechanism that is specific for the functioning of the ICF channel protein.


Toward a better understanding of transition from paediatric to adult care in type 1 diabetes: A qualitative study of adolescents.
Type 1 diabetes is associated with significant morbidity, with an increasing risk of acute diabetes-related complications in adolescence and emerging adulthood. Purposeful transition from paediatric to adult-oriented care could mitigate this risk but is often lacking. Detailed understanding of the perspectives of adolescents in their final year of paediatric care is essential to inform delivery of transition care programs. We conducted semi-structured interviews with adolescents (aged 17 years) with type 1 diabetes at an academic institution from April 2017 to May 2018. Participants were recruited through convenience sampling. Sixty-one interviews were transcribed for analysis. Coding followed the principles of thematic analysis. Thirty-six percent of participants were male, and participants were from diverse socioeconomic backgrounds. We found three overarching themes in our analysis: first, difficulties navigating changing relationships with parents and healthcare teams; second, the need to increase type 1 diabetes self-management and differing comfort levels based on age of diagnosis; and third, perceived responsibilities for transition care preparation (for both the paediatric team and adolescents themselves) focused not only on type 1 diabetes-specific skills but also on healthcare system structures. Our findings suggest that novel transition programs addressing changing inter-personal relationships, disease-specific self-management (adapted for age of diagnosis), and healthcare system navigation, supported by parents and peers, may be needed to improve transition care for adolescents with type 1 diabetes.


T1-deficient and T1-Fc-transgenic mice develop a normal protective Th2-type immune response following infection with Nippostrongylus brasiliensis.
The IL-1 receptor-related protein T1 is expressed on the surface of Th2, but not Th1 cells. Studies with anti-T1 monoclonal antibodies have suggested that T1 is critical for development of normal Th2-type responses. To elucidate the role of T1 in vivo, we generated T1-deficient mice and a T1-transgenic strain which secretes soluble T1-Fc fusion protein into the serum. These were analyzed for the Th2 immune response induced by infection with the parasitic nematode Nippostrongylus brasiliensis. Although Th2 cytokine production by lymph node cells was similar in all groups of N. brasiliensis-infected mice, a decrease in IL-5 production by lung lymphocytes was detected in both T1-deficient and T1-Fc-transgenic mice compared to control littermates. This difference in IL-5 production did not influence blood eosinophilia, but recruitment of eosinophils into lung tissue, especially in T1-Fc-transgenic mice was slightly decreased. However, induction of all other immune parameters was normal and both T1-deficient and T1-Fc-transgenic mice were able to clear the parasite infection within 12 days with kinetics similar to those in control mice. Therefore, in contrast to previous suggestions, we conclude that the T1 protein is not obligatory for normal development of Th2 immune responses.


Motion and Sash Height (MASH) alarms for efficient fume hood use.
Ventilation, including fume hoods, consumes 40-70% of the total energy used by modern laboratories. Energy-conscious fume hood usage-for example, closing the sash when a hood is unused-can significantly reduce energy expenditures due to ventilation. Prior approaches to promote such behaviors among lab users have primarily relied on passive feedback methods. In this work, we developed a low-cost fume hood monitoring device with active feedback to alert lab users when a fume hood is left open and unused. Using data collected by the building management system, we observed a 75.6% decrease in the average sash height after installation of these "Motion and Sash Height" (MASH) alarms, which would result in a reduction roughly equal to 43% of the annual carbon emissions of a typical American vehicle, for each fume hood. The MASH alarm presented here reduced energy costs by approximately $1,159 per year, per hood, at MIT.


[Prevention and treatment of MODS in severely burned patients: an institute based retrospective study].
To determine if the preventive and treatment measures developed from basic and clinical research work have any effects on the incidence and outcome of MODS in severely burned patients. 657 extensively burned patients (burn size exceeding 30% TBSA) admitted to the clinical department from January 1970 through October 1999 were studied. The morbidity and mortality rates were compared in patient groups hospitalized before and after January 1990 when major preventive and treatment measures began to be extensively executed. These measures consisted of prompt, rapid and adequate fluid resuscitation, restoration of bowel blood supply with anisodamine (654 - 2), use of oxygen free radical scavengers (e.g. mannitol, vitamin C and E), extensive escharectomy during shock stage, early tube feeding, support of organ function, etc. Before 1990 when very few preventive and treatment measures were applied, the incidence of MODS, 17.3% (64 out of 369), and the death rate 87.5% (56 out of 64). After 1990, with the application of various preventive measures and treatment, the morbidity and mortality rates were reduced to 6.9% (20/288) and 40.0% (8/20), respectively. Our results suggest that measures which mitigate or eliminate the predisposing and causative factors of MODS may be salutary in the prevention and treatment of MODS after extensive burn injury.


Effects of PmDOME and PmSTAT knockdown on white spot syndrome virus infection in Penaeus monodon.
Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway plays an important role in antiviral immunity. This research reports the full-length DOME receptor gene in Penaeus monodon (PmDOME) and examines the effects of PmDOME and PmSTAT silencing on immune-related gene expressions in shrimp hemocytes during white spot syndrome virus (WSSV) infection. PmDOME and PmSTAT were up-regulated in shrimp hemocytes upon WSSV infection. Suppression of PmDOME and PmSTAT showed significant impacts on the expression levels of ProPO2 (melanization), Vago5 (interferon-like protein) and several antimicrobial peptides, including ALFPm3, Penaeidin3, CrustinPm1 and CrustinPm7. Silencing of PmDOME and PmSTAT reduced WSSV copy numbers and delayed the cumulative mortality caused by WSSV. We postulated that suppression of the JAK/STAT signaling pathway may activate the proPO, IFN-like antiviral cytokine and AMP production, resulting in a delay of WSSV-related mortality.