Clinical Integration of Digital Solutions in Health Care: An Overview of the Current Landscape of Digital Technologies in Cancer Care.
Digital health constitutes a merger of both software and hardware technology with health care delivery and management, and encompasses a number of domains, from wearable devices to artificial intelligence, each associated with widely disparate interaction and data collection models. In this review, we focus on the landscape of the current integration of digital health technology in cancer care by subdividing digital health technologies into the following sections: connected devices, digital patient information collection, telehealth, and digital assistants. In these sections, we give an overview of the potential clinical impact of such technologies as they pertain to key domains, including patient education, patient outcomes, quality of life, and health care value. We performed a search of PubMed ( www.ncbi.nlm.nih.gov/pubmed ) and www.ClinicalTrials.gov for numerous terms related to digital health technologies, including digital health, connected devices, smart devices, wearables, activity trackers, connected sensors, remote monitoring, electronic surveys, electronic patient-reported outcomes, telehealth, telemedicine, artificial intelligence, chatbot, and digital assistants. The terms health care and cancer were appended to the previously mentioned terms to filter results for cancer-specific applications. From these results, studies were included that exemplified use of the various domains of digital health technologies in oncologic care. Digital health encompasses the integration of a vast array of technologies with health care, each associated with varied methods of data collection and information flow. Integration of these technologies into clinical practice has seen applications throughout the spectrum of care, including cancer screening, on-treatment patient management, acute post-treatment follow-up, and survivorship. Implementation of these systems may serve to reduce costs and workflow inefficiencies, as well as to improve overall health care value, patient outcomes, and quality of life.


The incidental suggestive meningioma presenting as high 18F FP-CIT uptake on PET/CT study.
A 76-year-old woman with about a 13-month history of bradykinesia, gait disturbance and resting tremor of right upper extremity was referred to Nuclear Medicine Department. A PET-CT with 229 MBq of F FP-CIT was performed to diagnose suspected early Parkinson's disease (PD). The PET-CT showed a mass lesion with highly intense focal dopamine transporter uptake in the right frontal lobe. A subsequent brain magnetic resonance image also showed a mass in the right frontal lobe demonstrating homogeneous enhancement and extensive surrounding edema, highly suggestive of a brain tumor.


Predictors of acute complications in children with type 1 diabetes.
Diabetic ketoacidosis and severe hypoglycemia are acute complications of type 1 diabetes that are related, respectively, to insufficient or excessive insulin treatment. However, little is known about additional modifiable risk factors. To examine the incidence of ketoacidosis and severe hypoglycemia in children with diabetes and to determine the factors that predict these complications. A cohort of 1243 children from infancy to age 19 years with type 1 diabetes who resided in the Denver, Colo, metropolitan area were followed up prospectively for 3994 person-years from January 1, 1996, through December 31, 2000. Incidence of ketoacidosis leading to hospital admission or emergency department visit and severe hypoglycemia (loss of consciousness, seizure, or hospital admission or emergency department visit). The incidence of ketoacidosis was 8 per 100 person-years and increased with age in girls (4 per 100 person-years in < 7; 8 in 7-12; and 12 in > or =13 years; P<.001 for trend). In multivariate analyses, sex-adjusted and stratified by age (<13 vs > or =13 years), the risk of ketoacidosis in younger children increased with higher hemoglobin A(1c) (HbA(1c)) (relative risk [RR], 1.68 per 1% increase; 95% confidence interval [CI], 1.45-1.94) and higher reported insulin dose (RR, 1.40 per 0.2 U/kg per day; 95% CI, 1.20-1.64). In older children, the risk of ketoacidosis increased with higher HbA(1c) (RR, 1.43; 95% CI, 1.30-1.58), higher reported insulin dose (RR, 1.13; 95% CI, 1.02-1.25), underinsurance (RR, 2.18; 95% CI, 1.65-2.95), and presence of psychiatric disorders (for boys, RR, 1.59; 95% CI, 0.96-2.65; for girls, RR, 3.22; 95% CI, 2.25-4.61). The incidence of severe hypoglycemia was 19 per 100 person-years (P<.001 for trend) and decreased with age in girls (24 per 100 patient-years in < 7, 19 in 7-12, and 14 in > or =13 years). In younger children, the risk of severe hypoglycemia increased with diabetes duration (RR, 1.39 per 5 years; 95% CI, 1.16-1.69) and underinsurance (RR, 1.33; 95% CI, 1.08-1.65). In older children, the risk of severe hypoglycemia increased with duration (RR, 1.34; 95% CI, 1.25-1.51), underinsurance (RR, 1.42; 95% CI, 1.11-1.81), lower HbA(1c) (RR, 1.22; 95% CI, 1.12-1.32), and presence of psychiatric disorders (RR, 1.56; 95% CI, 1.23-1.98). Eighty percent of episodes occurred among the 20% of children who had recurrent events. Some children with diabetes remain at high risk for ketoacidosis and severe hypoglycemia. Age- and sex-specific incidence patterns suggest that ketoacidosis is a challenge in adolescent girls while severe hypoglycemia continues to affect disproportionally the youngest patients and boys of all ages. The pattern of modifiable risk factors indicates that underinsured children and those with psychiatric disorders or at the extremes of the HbA(1c) distribution should be targeted for specific interventions.


Neuroprotective Effects of Forced Exercise and Bupropion on Chronic Methamphetamine-induced Cognitive Impairment via Modulation of cAMP Response Element-binding Protein/Brain-derived Neurotrophic Factor Signaling Pathway, Oxidative Stress, and Inflammatory Biomarkers in Rats.
Forced exercise can act as non-pharmacologic neuroprotective agent. In current study, we tried the involved molecular mechanisms of protective effects of forced exercise against methamphetamine induced neurodegeneration. Forty adult male rats were divided to Group 1 and 2 which received normal saline and methamphetamine (10 mg/kg) respectively for 30 days. Groups 3, 4 and 5 were treated with methamphetamine for first 15 days and then were treated by forced exercise, bupropion (20 mg/kg/day) or combination of them for the following 15 days. Between 26th and 30th days, Morris Water Maze (MWM) was used to evaluate the cognition. On day 31, hippocampus was isolated from each rat and oxidative, antioxidant and inflammatory factors also the level of total and phosphorylated forms of cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) proteins were also evaluated. Chronic abuse of methamphetamine could decreases cognition and increase malondialdehyde (MDA), Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), while caused decreases in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities all these changes was significant (P < 0.001) in compared to control group while treatment with bupropion, forced exercise and bupropion in combination with forced exercise could prevent all these malicious effects of methamphetamine (P < 0.001). Bupropion, forced exercise and bupropion in combination with forced exercise could activate CREB (both forms) and activates BDNF proteins' expression with P < 0.001 in methamphetamine treated rats. P-CREB/BDNF signaling pathways might have critical role in forced exercise protective effects against methamphetamine induced neurodegeneration.


Do circulating OKT6-reactive cells belong to Langerhans cell lineage?
A few studies have been made in characterizing the phenotype, ontogeny, ultrastructure, and cytochemistry of circulating cord blood cells. Such studies have been hampered by the difficulty in obtaining pure populations of these cells. We therefore sought to obtain T6-positive cell-enriched populations from human cord blood using panning method. In cord blood, dendritic OKT6-labeled cells were classified in two types: some were similar to lymphocyte-like cells and some were consistent with monocyte-like cells. Both types lacked intracytoplasmic Birbeck granules. Homogeneous labeling of HLA-DR antigens were observed in both types. Heterogeneous labeling of T6 antigen was observed in both types. The monocyte-like cells have developed Birbek granule-like structures after exposure to OKT6 and immuno-adherence. The results suggest several different putative lineages of these OKT6-reactive cells: early precursors of dendritic cells, immature neonatal lymphoid subsets, and immature macrophagic leukocytes.


Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes.
The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death. Published data describing cell death in vitro as well as tumour oxygenation in vivo are used to inform parameters. Our model is validated by comparing simulations to in vivo data obtained from the radiation treatment of mice transplanted with human prostate tumours. We then predict the efficacy of untested hypofractionation protocols, hypothesizing that tumour control can be optimized by adjusting daily radiation dosage as a function of the degree of hypoxia in the tumour environment. Further biological refinement of this tool will permit the rapid development of more sophisticated strategies for radiotherapy.


Modulation of submucosal cholinergic neurons by 5-hydroxytryptamine and neuropeptides.
Release of [3H]acetylcholine ([3H]ACh) was examined in a submucous plexus preparation obtained from the guinea pig small intestine in vitro. Constant-current field stimulation evoked ACh output; this output was dependent on the stimulus frequency applied. Maximal release was observed at 10 Hz; this release was blocked by tetrodotoxin (1 x 10(-6) M) or in Ca2(+)-free buffer. Serotonin [5-hydroxytryptamine (5-HT)] stimulated the release of ACh dose dependently, with an ED50 of 5 x 10(-7) M. Substance P was ineffective, while vasoactive intestinal peptide weakly stimulated ACh secretion. Several neuropeptides were tested on their ability to modulate 5-HT-evoked ACh release. Dynorphin A inhibited 5-HT-stimulated ACh release, while Met-enkephalin was without any effect. Both somatostatin and galanin were effective modulators, with an inhibitory effect in the submicromolar range and an excitatory effect at higher concentrations. The response characteristics of the cholinergic neurons of submucosal plexus differ markedly from those of the myenteric plexus. These distinct features form an important framework for future functional studies on submucous plexus neurons.


Coping and participation in youth with spinal cord injury.
Coping and participation are important adjustment outcomes of youth with spinal cord injury (SCI). Research addressing how these outcomes are related is limited. This cross-sectional study examined relationships between coping and participation in youth with SCI. Youth ages 7 to 18 years were recruited from 3 hospitals specializing in rehabilitation of youth with SCI. The Kidcope assessed coping strategies, and the Children's Assessment of Participation and Enjoyment (CAPE) examined participation patterns. Point biserial and Pearson correlations assessed relationships among variables, and hierarchical multiple regression analyses examined whether coping significantly contributed to participation above and beyond significant demographic and injury-related factors. The sample included 294 participants: 45% female, 65% Caucasian, 67% with paraplegia. Mean age was 13.71 years (SD = 3.46), and mean duration of injury was 5.39 years (SD = 4.49). Results indicated that higher levels of social support and lower levels of self-criticism predicted higher participation in informal activities, lower levels of social withdrawal predicted participation in informal activities with a greater diversity of individuals, lower levels of blaming others predicted higher enjoyment of informal activities, and higher levels of cognitive restructuring predicted participation in formal activities with a greater diversity of individuals and in settings further from home. Results suggest higher levels of social support and cognitive restructuring and lower levels of self-criticism, social withdrawal, and blaming others predicted favorable participation outcomes. Interventions for youth with SCI that encourage higher levels of positive coping strategies and lower levels of negative and avoidant strategies may promote positive participation outcomes.


Potential Application of Radiomics for Differentiating Solitary Pulmonary Nodules.
A solitary pulmonary nodule is defined as radiographic lesion with diameters no more than 3 cm and completely surrounded by normal lung tissue. It is commonly encountered in clinical practice and its diagnosis is a big challenge. Medical imaging, as a non-invasive approach, plays a crucial role in the diagnosis of solitary pulmonary nodules since the potential morbidity of surgery and the limits of biopsy. Advanced hardware, image acquisition and analysis technologies have led to the utilization of imaging towards quantitative imaging. With the aim of mining more useful information from image data, radiomics with high-throughput extraction can play a useful role. This article is to introduce the current state of radiomics studies and describe the general procedures. Another objective of this paper is to discover the feasibility and potential of radiomics methods on differentiating solitary pulmonary nodules and to look into the future direction of radiomics in this area.


Adequate dosing of micronutrients for different age groups in the life cycle.
Many studies of micronutrient supplementation in developing countries have used single-nutrient supplements with either vitamins or minerals. However, people in these countries often suffer from multiple, rather than single, micronutrient deficiencies. The objective of this paper is to discuss the factors that go into determining the adequate dosing of vitamins and/or minerals for people of different ages. To elaborate on the adequacy of micronutrient doses in supplements, a model described by the US FNB was used, which calculates the difference between the mean observed intake for an individual and the estimated average requirement for a life stage and gender group. This model allows estimating the degree of confidence that a certain nutrient intake (from supplements and diet) is adequate. The US/Canadian DRI values have been used as the basis for these calculations, from which it can be concluded that a daily supplement of one RDA of each micronutrient is adequate to cover the personal requirements of all individuals in each respective age and gender group of the population, provided that 20 to 40% of an RDA is supplied by the diet--likely a realistic value for developing countries. DRI values vary significantly between different age groups, reflecting changing needs over a life cycle. With the objective of a supplement to be adequate and safe, the design of a one-for-all supplement covering all age groups is not realistic. Such a supplement would either underscore or surpass the required intake of some of the age groups. Additionally the dosage of certain micronutrients might exceed the upper level of intake for lower age groups. Therefore, it is suggested that three different supplements following the one RDA concept for all micronutrients be developed for research use in developing countries for the following age groups; 1 to 3 years, 4 to 13 years, and females > 14 years (excluding during pregnancy).


[A case with a lower rectal gastrointestinal stromal tumor undergoing sphincter-preserving laparoscopic resection after neoadjuvant imatinib therapy].
A man in his 30s visited our hospital after a local doctor diagnosed him with a rectal submucosal tumor. Colonoscopy and fine needle biopsy revealed a lower rectal gastrointestinal tumor (GIST). Pelvic MRI examination revealed apparent tumor invasion of the left levator ani muscle. Curative abdominoperineal resection( APR) of the tumor was required. Our strategy involved the initiation of neoadjuvant imatinib therapy to facilitate subsequent sphincter-preserving resection. Neoadjuvant chemotherapy for 11 months reduced the tumor size and permitted the R0 laparoscopic sphincter-preserving resection. He was discharged without any postoperative complications. The pathological findings revealed semi-curative effects and pR0 resection. Thus, neoadjuvant chemotherapy for advanced rectal GIST was a useful strategy for this function- preserving operation.


Metaproteomic characterization of theVitis vinifera rhizosphere.
The rhizosphere is a hotspot of microbial activity where the release of root exudates stimulates bacterial density and diversity. The majority of the bacterial cells in soil are viable, unculturable, but active. Proteomic tools could be useful in gaining information about microbial community activity and to better understand the real interactions between roots and soil. The aim of this work was to characterize the bacterial community associated with Vitis vinifera cv. Pinot Noir roots using a metaproteome approach. Our results confirmed the large potential of proteomics in describing the environmental microbial communities and their activities: in particular, we showed that bacteria belonging to Streptomyces, Bacillus, Bradyrhizobium, Burkholderia and Pseudomonas genera are the most active in protein expression. Concerning the biological activity of these genera in the rhizosphere, we observed the exclusive presence of the phosphorus metabolic process and the regulation of primary metabolic processes. To our knowledge, this is the first study reporting the rhizosphere proteome of V. vinifera, describing the bacterial community structure and activity of an important ecosystem for the Italian landscape, agriculture and economy.


The Relationship between Positive Memory Phenomenology and Alcohol Use among Trauma-Exposed Individuals.
Evidence links positive memory characteristics and hazardous alcohol use (HAU). Relevant to the current study, evidence also indicates that trauma-exposed individuals, especially those with posttraumatic stress disorder (PTSD) symptoms, report difficulties retrieving/accessing positive memories and report HAU. Considering this literature, we uniquely examined if and which positive memory characteristics were associated with HAU, and the potential mediating role of PTSD symptom severity in the examined relations. A sample of 126 trauma-exposed community participants seeking mental health treatment (Mage=34.97 years) completed measures of HAU (Alcohol Use Disorders Identification Test), positive memory characteristics (Memory Experiences Questionnaire-Short Form [MEQ-SF]), and PTSD severity (PTSD Checklist for DSM-5). We conducted 8 hierarchical multiple regressions; Step 1 examined effects of gender and Step 2 added a single MEQ-SF dimension (specificity, valence, emotional intensity, sensory details, vividness, accessibility, coherence, sharing). In Steps 1 (β=.27) and 2 (βs from .27-.28), gender was associated with HAU. In Step 2, positive memory characteristics of specificity (β=.17), sensory details (β=.17), sharing (β=.23), and valence (β=-.19) were associated with greater HAU. PTSD severity mediated relations between sensory details (β=.09, p=.048), emotional intensity (β=.12, p=.011), and sharing (β=.09, p=.036), and the extent of HAU. Results that specificity, greater sharing, more sensory details, and higher negative valence of positive memories were associated with greater HAU offer potential points of intervention.


Solution-Processed Anatase Titania Nanowires: From Hyperbranched Design to Optoelectronic Applications.
The utilization of solar energy and the development of its related optoelectronic devices have become more important than ever. Solar cells or photoelectrochemical (PEC) cells that require the design of light harvesting assemblies for efficiently converting solar light into electricity or solar fuels are of particular interest. Semiconductor TiO2, serving as the photoelectrode for photovoltaic devices (e.g., dye- or quantum dot-sensitized solar cells (DSSCs/QDSSCs) or perovskite solar cells (PSCs)) and PEC cells, has aroused intense research interest owing to its inherent characteristics of wide band gap and promising optical and electrical properties. TiO2 nanowires (TNWs) have been widely used in optoelectronic devices due to their unique 1D geometry and salient optical and electrical properties. However, the insufficient surface area resulting from the relatively large diameter of NWs and considerable free space between adjacent NWs restricts their optoelectronic performance. Hence, it is desirable to explore every feasible aspect of TNWs in terms of structural design and optical management, aiming to further improve the performance of optoelectronic devices. In this Account, we present a brief survey of strategies for designing branched or hyperbranched TNW-based photoelectrodes and their applications in solar cells and PEC cells. The general strategies (e.g., alkaline/acid hydrothermal method, lift-off transfer, and self-assembly approach) are discussed to address the challenges associated with fabricating TNWs on transparent conducting oxide (TCO) substrates. A series of strategies to fabricate judiciously designed 3D branched array architectures, including length tuning and sequential surface branched or hyperbranched modification, are proposed. The versatile implantation of the TNWs onto other backbones (nanosheets, nanotubes, hollow spheres, or multilayered electrodes) and substrates (fiber-shaped metal wire or mesh, flexible metal foil, or plastic sheet) is demonstrated to construct a new class of the TNW-embedded composite electrode materials with desired morphological characteristics and optoelectronic properties, for example, favorable energy level alignment for cascade charge transfer and rational homogeneous/heterogeneous interfacial engineering. The functionalities of TNW-based electrodes include enlarged surface area and superior light scattering for maximized light harvesting, as well as facilitated charge transport and suppressed charge recombination for enhanced charge collection, which are promising in optoelectronic fields such as solar cells, photocatalysis, and PEC cells. Beyond TNWs, one can also integrate other types of semiconductor (e.g., Fe2O3 or WO3) NWs into rationally designed structures for preparing novel photocatalytic materials with panchromatic absorption, efficient charge transfer, and excellent catalytic properties. Finally, an insightful perspective for rational design of advanced NW-based materials is provided.


Microbiome-metabolome analysis reveals cervical lesion alterations.
Cervical cancer (CC) continues to be one of the most common cancers among females worldwide. It takes a few years or even decades for CC to arise in a minority of women with cervical precancers. An increasing corpus of studies today indicates that local microecology and carcinogenesis are intimately related. To investigate the changes in cericovaginal microecology with the development of cervical cancer, we performed 16S rDNA sequencing and metabolomic analysis in cericovaginal fluid from 10 LSIL patients, 10 HSIL patients, 10 CC patients and 10 healthy controls to reveal the differential flora and metabolites during cervical carcinogenesis. Carcinogenesis is associated with alterations in microbiome diversity, individual taxa, and functions with notable changes in Lactobacillus, Prevotella and Aquabacterium, as well as in cervicovaginal metabolites that correlate with cervicovaginal microbial patterns. Increased bacterial diversity and a decline in the relative abundance of Lactobacillus, the dominant species in the cericovaginal flora, are observed when cervical lesions advance. According to KEGG pathway enrichment analysis, lipids and organic acids change as cervical cancer progresses, and the phenylalanine, tyrosine, and tryptophan biosynthesis pathway is essential for the development of cervical cancer. Our results reveal that microbic and metabolomic profiling is capable of distinguishing CC from precancer and highlights potential biomarkers for the early detection of cervical dysplasia. These differential microorganisms and metabolites are expected to become a potential tool to assist in the diagnosis of cervical cancer.


Assessment of chemical and physico-chemical properties of cyanobacterial lipids for biodiesel production.
Five non-toxin producing cyanobacterial isolates from the genera Synechococcus, Trichormus, Microcystis, Leptolyngbya and Chlorogloea were examined in terms of quantity and quality as lipid feedstock for biofuel production. Under the conditions used in this study, the biomass productivity ranged from 3.7 to 52.7 mg·L-1·day-1 in relation to dry biomass, while the lipid productivity varied between 0.8 and 14.2 mg·L-1·day-1. All cyanobacterial strains evaluated yielded lipids with similar fatty acid composition to those present in the seed oils successfully used for biodiesel synthesis. However, by combining biomass and lipid productivity parameters, the greatest potential was found for Synechococcus sp. PCC7942, M. aeruginosa NPCD-1 and Trichormus sp. CENA77. The chosen lipid samples were further characterized using Fourier Transform Infrared spectroscopy (FTIR), viscosity and thermogravimetry and used as lipid feedstock for biodiesel synthesis by heterogeneous catalysis.


Changes in Kinematic Coupling Among the Rearfoot, Midfoot, and Forefoot Segments During Running and Walking.
Understanding the concept of kinematic coupling is essential when selecting the appropriate therapeutic strategy and grasping mechanisms for the occurrence of injuries. A previous study reported that kinematic coupling between the rearfoot and shank during running and walking were different. However, because foot mobility involves not only the rearfoot but also the midfoot or forefoot, kinematic coupling is likely to occur among the rearfoot, midfoot, and forefoot segments. We investigated changes in kinematic coupling among the rearfoot, midfoot, and forefoot segments during running and walking. Ten healthy young men were instructed to run (2.5 ms-1) and walk (1.3 ms-1) on a treadmill at speeds set by the examiner. The three-dimensional joint angles of the rearfoot, midfoot, and forefoot were calculated based on the Leardini foot model Kinematic coupling was evaluated with the absolute value of the cross-correlation coefficients and coupling angles obtained by using a vector coding technique. The cross-correlation coefficient between rearfoot eversion/inversion and midfoot dorsiflexion/plantarflexion was significantly higher during running ( r = 0.79) than during walking ( r = 0.58), suggesting that running requires stronger kinematic coupling between rearfoot eversion/inversion and midfoot plantarflexion/dorsiflexion than walking. Furthermore, the coupling angle between midfoot eversion/inversion and forefoot eversion/inversion was significantly less during running (30.0°) than during walking (40.7°) ( P < .05). Hence, the magnitude of midfoot frontal plane excursion during running was greater than that during walking. Excessive rearfoot eversion during running is likely to lead to excessive midfoot dorsiflexion, and such abnormal kinematic coupling between the rearfoot and midfoot may be associated with mechanisms for the occurrence of injuries.


A comparative study of the inhibitory effects of purine nucleotides and carboxyatractylate on the uncoupling protein-3 and adenine nucleotide translocase.
Uncoupling proteins (UCPs) mediate fatty acid-induced proton cycling in mitochondria, which is stimulated by superoxide and inhibited by GDP. Fatty acid anions can also be transported by adenine nucleotide translocase (ANT), thus resulting in the uncoupling of oxidative phosphorylation. In the present work, an attempt was made to distinguish between the protonophoric activity of UCP3 and that of ANT using inhibition analysis. This study was carried out using mitochondria from skeletal muscles of hibernating Yakut ground squirrel, which have a significant level of UCP3 mRNA. We found that millimolar concentrations of GDP, which is considered to be a specific inhibitor of UCPs, slightly recoupled the mitochondrial respiration and restored the membrane potential. Addition of the specific ANT inhibitor CAT (carboxyatractylate), in micromolar concentration, prior to GDP prevented its recoupling effect. Moreover, GDP and ADP exhibited a competitive kinetic behavior with respect to ANT. In brown adipose tissue, CAT did not prevent the UCP1-iduced increase in chloride permeability and the inhibitory effect of GDP, thus confirming the inability of CAT to affect UCP1. These results allow us to conclude that the recoupling effect of purine nucleotides on skeletal muscle mitochondria of hibernating ground squirrels can be explained by interaction of the nucleotides with ANT, whereas UCP3 is not involved in the process.


[The effect of NGF on hematopoiesis of granulocyte-macrophage in normal and radiation, chemistry injury mice].
To explore the effect of nerve growth factor (NGF) on hematopoiesis of granulocyte-macrophage and to elucidate the underlying mechanism. Using flow cytometry, colony forming assay, blood cell count, fluorescent real-time quantitation PCR, and enzyme-linked immunosorbent assay (ELISA), changes in the bone marrow cells (BMCs) proliferation cycle, CFU-GM counts, the peripheral white blood cell (WBC)counts, BMC GM-CSF mRNA quantities, and serum GM-CSF, IL-3 concentrations were observed after NGF was injected intramuscularly into the thigh of normal and combined 60Co gamma ray irradiated and cyclophosphamide peritoneal cavity injected(combined radiation and chemistry injury mice, 60Co-Cy injury) mice. The effect of NGF on CFU-GM formation in vitro cooperation with exogenous GM-CSF or alone was also observed. An injection of NGF [7.5 microg/(kg x d) or 10 microg/(kg x d)] lasted 7 days, the S+G2/M proportions and the CFU-GM counts of BMCs rose greater than injection of physiological saline (PS) in normal and 60Co-Cy injury mice; the serum GM-CSF,IL-3 concentration in 60Co-Cy injury mice rose obviously. In vitro, NGF stimulated a dose-dependent increase of CFU-GM colonies formation in the semisolid culture system with exogenous rmGM-CSF. NGF cooperates with hematopoietic stimulating factors in culture system to promote the CFU-GM colonies in normal and 60Co-Cy injury mice in vitro. NGF accelerates the BMCs into mitosis, the hematopoietic stem cells differentiation into granulocyte-macrophage hematopoietic cells, the CFU-GM formation and promotes the white blood cells count in normal and 60Co-Cy injury mice in vivo, also NGF stimulates the secreting of GM-CSF and IL-3 in 60Co-Cy injury mice,this may be one of the reasons why NGF stimulate the granulocyte-macrophage hematopoiesis repair after combined radiation and chemistry injury.


A cross-sectional survey to evaluate the pet squirrel population and ownership profiles.
While the presence of squirrels in households is growing, little data is published on their status in captivity. A web-based questionnaire for owners was devised eliciting information about them, their squirrels and their squirrels' husbandry and health. One hundred owners answered the survey, with most respondents being located in Europe (n = 81). Only data from these respondents were analysed. Twenty-five percents of the owners housed an invasive non-native species of European Union concern (S. carolinensis and T. sibiricus), some of which were younger than three years of age and all but one were sexually intact. This is of particular concern, as the acquisition of these invasive species is illegal since 2015 (European Union Regulation 1143/2014), due to the severe threats they pose to biodiversity. Moreover, escapes derived from improper keeping of intact specimens may augment feral populations or establish new colonies. Among 81 cases, only 5% were neutered, mostly for health reasons. Sixty-three percents of the squirrels had health problems, particularly dermatologic (52%) and intestinal disorders (34%). Most owners reported to visit the veterinarian only if their pet was ill rather than for preventive care. This is the first survey on pet squirrel ownership reported to date. Information that emerges from this study will be useful in implementing rational veterinary strategies for managing pet squirrels properly and, in parallel, meeting the challenges arising from private keeping of alien species.


Olfactory Dysfunction in Healthcare Workers with COVID-19: Prevalence and Associated Factors.
The COVID-19 pandemic is a real global health crisis. Its clinical presentation has evolved over time with an increasing number of symptoms. Olfactory dysfunction (OD) has recently been recognized as a frequent symptom relevant to screening for COVID-19, especially in pauci-asymptomatic forms. However, the underlying mechanisms of OD are not yet fully understood. To determine the prevalence of OD in healthcare workers with SARS-CoV-2 and to identify its associated factors. This is a cross-sectional, analytical study, carried out during a period of six months and including all healthcare workers at Farhat Hached Academic Hospital (Tunisia) who were diagnosed with SARS-CoV-2 by PCR, RAT, or chest CT scan. A total of 474 healthcare workers were included, representing a participation rate of 85.4%. The mean age was 41.02±10.67 years with a sex ratio of 0.2. The distribution of this population by department noted that it was mainly maternity (13.9%). The most presented workstation was nursing (31.4%). OD represented 39.2% of the reasons for consultation. Hospitalization was indicated in 16 patients (3.4%). The average duration of hospitalization was 8.87 ± 7.8 days. The average time off work was 17.04 ± 11.6 days. OD persisted for more than 90 days in 35 patients (7.4%). After multiple binary logistic regression, OD was statistically associated with female gender (p =0.001; OR 95% CI: 2.46 [1.4-4.2]) and blue-collar occupational category (p =0.002; OR IC95%:3.1 [1.5-6.5]). A significant association was also noted between OD and professional seniority and absence from work duration (p =0.019; OR 95% CI: 0.97 [0.95-0.99] and p =0.03; OR 95% CI: 0.97 [0.95-0.99]) respectively. OD is common in COVID-19 patients. The identification of its associated factors may contribute to enhancing the understanding of its mechanism and drive therapeutic options.


Anal adenocarcinoma requires prophylactic inguinal nodal treatment: Results from a single Chinese institution.
Literature pertaining to prophylactic inguinal nodal treatment for anal adenocarcinoma in China is scarce. In this retrospective study, we analyzed 126 patients from 1965 to 2015. Among these, 67 patients received surgery only, 18 patients received chemoradiotherapy only, 27 patients received a combination of both, and the remaining 14 patients received palliative treatment. The median follow up period was 30 months. The 1-year, 3-year, and 5-year overall survival rates were 85.8%, 62.5%, and 43.4%, respectively. The 5-year overall survival was 46.9% for patients with negative inguinal lymph nodes and 19.1% for patients with positive inguinal lymph nodes (p=0.007). The overall 5-year inguinal node relapse-free survival was 83.0%. The 5-year inguinal node relapse-free survival was 87.5% for stage I, 86.9% for stage II, and 76.5% for stage III cancers. Among those with negative inguinal nodes, the 5-year inguinal node relapse-free survival was 85.7% for negative regional lymph nodes and 75.4% for positive regional lymph nodes (p=0.089). Inguinal lymph node is a high-risk subclinical area. Prophylactic inguinal nodal treatment is necessary for patients with anal adenocarcinoma irrespective of positive or negative inguinal lymph nodes.


Nuclear immunophilin FKBP39 from Drosophila melanogaster drives spontaneous liquid-liquid phase separation.
The FKBP39 from Drosophila melanogaster is a multifunctional regulatory immunophilin. It contains two globular domains linked by a highly charged disordered region. The N-terminal domain shows homology to the nucleoplasmin core domain, and the C-terminal domain is characteristic for the family of the FKBP immunophilin ligand binding domain. The specific partially disordered structure of the protein inspired us to investigate whether FKBP39 can drive spontaneous liquid-liquid phase separation (LLPS). Preliminary analyses using CatGranule and Pi-Pi contact predictors suggested a propensity for LLPS. Microscopy observations revealed that FKBP39 can self-concentrate to form liquid condensates. We also found that FKBP39 can lead to LLPS in the presence of RNA and peptides containing Arg-rich linear motifs derived from selected nuclear and nucleolar proteins. These heterotypic interactions have a stronger propensity for driving LLPS when compared to the interactions mediated by self-associating FKBP39 molecules. To investigate whether FKBP39 can drive LLPS in the cellular environment, we analysed it in fusion with YFP in COS-7 cells. The specific distribution and diffusion kinetics of FKBP39 examined by FRAP experiments provided evidence that immunophilin is an important driver of phase separation. The ability of FKBP39 to go into heterotypic interaction may be fundamental for ribosome subunits assembly.


MORC1 represses transposable elements in the mouse male germline.
The Microrchidia (Morc) family of GHKL ATPases are present in a wide variety of prokaryotic and eukaryotic organisms but are of largely unknown function. Genetic screens in Arabidopsis thaliana have identified Morc genes as important repressors of transposons and other DNA-methylated and silent genes. MORC1-deficient mice were previously found to display male-specific germ cell loss and infertility. Here we show that MORC1 is responsible for transposon repression in the male germline in a pattern that is similar to that observed for germ cells deficient for the DNA methyltransferase homologue DNMT3L. Morc1 mutants show highly localized defects in the establishment of DNA methylation at specific classes of transposons, and this is associated with failed transposon silencing at these sites. Our results identify MORC1 as an important new regulator of the epigenetic landscape of male germ cells during the period of global de novo methylation.


Recombinant human thyrotropin preparation for adjuvant radioiodine treatment in children and adolescents with differentiated thyroid cancer.
Although recombinant human thyrotropin (rhTSH) is widely used in treating differentiated thyroid cancer (DTC), almost all clinical investigation has been in adults. The aim of our retrospective study was to evaluate outcomes of adjuvant, rhTSH-aided radioiodine treatment in children/adolescents with DTC and to compare them to (131)I therapy during l-thyroxin withdrawal (THW). Patients with the diagnosis of DTC who were ≤18 years of age and had no signs of persistent disease at the time of (131)I treatment were included; 48 patients were treated after rhTSH (rhTSH group) and 82 after THW group. The median time of follow-up after therapy was 67 months and was longer in the THW group (99 vs 43 months, P<0.05). On the day of (131)I administration, all but one patient had TSH levels above 25 μIU/ml. Peak TSH concentration was significantly higher in the rhTSH group (152 μIU/ml vs 91 μIU/ml). Similarly, the thyroglobulin concentration was higher in the rhTSH group (9.7 ng/ml vs 1.8 ng/ml). No side effects requiring medical intervention were recorded after rhTSH administration. The evaluation of disease outcomes during TSH stimulation (6-18 months after (131)I treatment) revealed equal rates of thyroid ablation (71%) in both groups. During subsequent follow-up, five patients showed recurrence (P>0.05). In children/adolescents, rhTSH-aided adjuvant radioiodine treatment is associated with rates of remnant ablation and short-term recurrence similar to THW. As this preparation has several advantages over THW, rhTSH may become the preferred method of TSH stimulation once studies of long-term outcomes show non-inferiority to THW in this age group.


Mechanisms of mediator release from human skin mast cells upon stimulation by the bradykinin analog, [DArg0-Hyp3-DPhe7]bradykinin.
We have used the bradykinin analog, [DArg0-Hyp3-DPhe7]-bradykinin, as a model stimulus with which to examine peptide-induced mediator release from human skin mast cells (SMC) and to compare it with IgE-mediated release from the same cells. The bradykinin analog was an effective histamine secretagogue, inducing a comparable maximal level of release to that observed for anti-IgE. By contrast to anti-IgE, however, [DArg0-Hyp3-DPhe7]-bradykinin did not stimulate marked release of prostaglandin D2 (PGD2) from these cells. In experiments where cells were exposed to both stimuli simultaneously, histamine release was additive, while PGD2 release was the same as that observed for anti-IgE alone. The kinetics of [DArg0-Hyp3-DPhe7]-bradykinin-stimulated histamine release were rapid, with 50% of maximal release being achieved within 30 sec, compared to 2-3 min for anti-IgE. Interestingly, when both stimuli were applied simultaneously, the kinetics of release were intermediate between those of either stimulus alone. Studies of the signal transduction pathways that may be involved in [DArg0-Hyp3-DPhe7]-bradykinin-induced histamine release revealed striking differences to results obtained with anti-IgE. While agents that increase intracellular cyclic AMP have a pronounced inhibitory effect on IgE-mediated release, forskolin, isobutylmethylxanthine and isoproterenol were all totally ineffective at inhibiting histamine release induced by the bradykinin analog. Similarly, staurosporine, a relatively selective inhibitor of protein kinase C, and the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) an activator of this enzyme, both have pronounced effects on IgE-mediated histamine release from SMC but were completely inactive with regard to [DArg0-Hyp3-DPhe7]-bradykinin-stimulated release. SMC stimulated with this peptide showed characteristic changes in intracellular free calcium levels, as assessed by digital video microscopy. This response differs from that induced by anti-IgE in that it had a more rapd onset, achieved a lower peak, and decayed much more rapidly. Analysis at the single cell level showed that cells that responded in this fashion upon exposure to the bradykinin analog were capable of showing an additional response upon subsequent exposure to anti-IgE. We conclude that histamine release from SMC in response to [DArg0-Hyp3-DPhe7]-bradykinin occurs via a completely different mechanism from that in response to IgE-mediated stimuli. Peptide-induced release is rapid and is not susceptible to pharmacologic manipulation of intracellular cyclic AMP or protein kinase C but utilizes a rapid transient shift in intracellular calcium concentrations as part of its signal transduction pathway.


Diagnosis and successful treatment of a caudal lingual abscess in a geriatric dog.
A 13-year-old, intact male, golden retriever was presented for glossomegaly. A diagnosis of a caudal lingual abscess was made by fine needle aspiration under general anesthesia. The dog showed marked clinical improvement following abscess drainage. Lingual abscesses should be included as a differential diagnosis in any dog with an unexplained acute glossomegaly.


Drag forces in classical fields.
Inclusions, or defects, moving at constant velocity through free classical fields are shown to be subject to a drag force which depends on the field dynamics and the coupling of the inclusion to the field. The results are used to predict the drag exerted on inclusions, such as proteins, in lipid membranes due to their interaction with height and composition fluctuations. The force, measured in Monte Carlo simulations, on a pointlike magnetic field moving through an Ising ferromagnet is also well explained by these results.


Enhanced Serologically Based Detection of Liberibacters Associated with Citrus Huanglongbing.
'Candidatus Liberibacter spp.' are associated with the most devastating disease of citrus Huanglongbing (HLB). In previous work, we established an in situ tissue print method for the detection of 'Ca. L. asiaticus' (CLas) in sweet orange. We optimized the protocol by preincubation of the anti-Omp antibody with 5% (w/v) extract of healthy rough lemon. This simple process eliminated cross reactions between citrus and the antibody. The optimized protocol enhanced the application of the polyclonal antibody, and we demonstrate detection of CLas from all parts of the world, including isolates from Japan, Thailand, Vietnam, Pakistan, Saudi Arabia, Brazil, the United States, and a selection of strains from China representative of the diversity extant there. The assay also was used to detect four isolates of 'Ca. L. africanus' (CLaf) representative of the diversity present in South Africa. The corresponding outer membrane genes of representative isolates were cloned and sequenced. The coding sequences were highly conserved, and isolates of CLas and CLaf shared 53.8 to 55.9% identity between species at the amino acid level. The optimized protocol is efficient for recognition of both CLas and CLaf in phloem cells of different citrus tissues regardless of geographic origin of the HLB samples. The method is simple and scales well to match the urgent need for accurate, sensitive, and high-throughput screening of HLB bacteria, and may play an important role especially for plant inspection and quarantine programs.


Successful gastrointestinal cancer drug development.
A large number of new drugs have been approved over the past 10 years for the treatment of both common and rare gastrointestinal malignancies. Many other agents, however, have failed at a great cost of financial and patient resources. Drug development must identify potentially active compounds and reveal the most effective and least toxic manner and population in which to administer compounds. Pharmaceutical companies must show therapeutic efficacy and achieve regulatory approval as well as success in the marketplace to recoup their investment. It is worth examining successful examples of drug development such as imatinib, delayed but eventually successful agents such as oxaliplatin, as well as failures such as SU-5416, and applying those lessons to current and future drug development.


[Corticofugal projections to the periaqueductal gray matter in the cat midbrain].
Stereotaxic microinjections of horseradish peroxidase (HP) were made into different parts of the rostral and caudal periaqueductal gray (PAG) in cats to study corticofugal projections to the PAG. The method of retrograde axonal transport of HP demonstrated labeled neurons in the I and II somatosensory areas, frontal, cingular and insular cortex of the brain. It was shown that the II somatosensory cortex projects to all the areas of the rostral and caudal PAG. The frontal cortex projects to the dorsolateral quadrant of the PAG. The findings obtained enabled the detection of the morphological substrate of the corticofugal effects on one of the antinociceptive brain structures--the PAG.


Organ transplants in children and adolescents: social, emotional and psychopathological problems.
Organ transplantation has become the treatment of choice for a number of life-threatening childhood illnesses. Our review of the literature on the psychiatric aspects of organ transplantation in children and adolescents suggests that transplant programs routinely use psychosocial evaluations as a component of their assessment and to screen transplant recipients. This study explores 5 psychiatric issues raised by paediatric transplantation: 1) the role of family; 2) children's and adolescents' perception of illness; 3) pretransplant evaluation of a child's psychological state and environment; 4) the wait; 5) long-term effects. We conclude with recommendations for further research and the development of standardized assessment designed for the pediatric population.


Functional connectivity of the sensorimotor area in naturally sleeping infants.
Patterns of cortical functional connectivity in normal infants were examined during natural sleep by observing the time course of very low frequency oscillations. Such oscillations represent fluctuations in blood oxygenation level and cortical blood flow thus allowing computation of neurophysiologic connectivity. Structural and resting-state information were acquired for 11 infants, with a mean age of 12.8 months, using a GE 1.5 T MR scanner. Resting-state data were processed and significant functional connectivity within the sensorimotor area was identified using independent component analysis. Unilateral functional connectivity in the developing sensory-motor cortices was observed. Power spectral analysis showed that slow frequency oscillations dominated the hemodynamic signal at this age, with, on average, a peak frequency for all subjects of 0.02 Hz. Our data suggest that there is more intrahemispheric than interhemispheric connectivity in the sensorimotor area of naturally sleeping infants. This non-invasive imaging technique, developed to allow reliable scanning of normal infants without sedation, enabled computation of neurophysiologic connectivity for the first time in naturally sleeping infants. Such techniques permit elucidation of the role of slow cortical oscillations during early brain development and may reveal critical information regarding the normative development and lateralization of brain networks across time.


Magnetic Resonance Imaging of Lung Perfusion.
"Lung perfusion" in the context of imaging conventionally refers to the delivery of blood to the pulmonary capillary bed through the pulmonary arteries originating from the right ventricle required for oxygenation. The most important physiological mechanism in the context of imaging is the so-called hypoxic pulmonary vasoconstriction (HPV, also known as "Euler-Liljestrand-Reflex"), which couples lung perfusion to lung ventilation. In obstructive airway diseases such as asthma, chronic-obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma, HPV downregulates pulmonary perfusion in order to redistribute blood flow to functional lung areas in order to conserve optimal oxygenation. Imaging of lung perfusion can be seen as a reflection of lung ventilation in obstructive airway diseases. Other conditions that primarily affect lung perfusion are pulmonary vascular diseases, pulmonary hypertension, or (chronic) pulmonary embolism, which also lead to inhomogeneity in pulmonary capillary blood distribution. Several magnetic resonance imaging (MRI) techniques either dependent on exogenous contrast materials, exploiting periodical lung signal variations with cardiac action, or relying on intrinsic lung voxel attributes have been demonstrated to visualize lung perfusion. Additional post-processing may add temporal information and provide quantitative information related to blood flow. The most widely used and robust technique, dynamic-contrast enhanced MRI, is available in clinical routine assessment of COPD, CF, and pulmonary vascular disease. Non-contrast techniques are important research tools currently requiring clinical validation and cross-correlation in the absence of a viable standard of reference. First data on many of these techniques in the context of observational studies assessing therapy effects have just become available. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 5.


Ship Detection in Gaofen-3 SAR Images Based on Sea Clutter Distribution Analysis and Deep Convolutional Neural Network.
Target detection is one of the important applications in the field of remote sensing. The Gaofen-3 (GF-3) Synthetic Aperture Radar (SAR) satellite launched by China is a powerful tool for maritime monitoring. This work aims at detecting ships in GF-3 SAR images using a new land masking strategy, the appropriate model for sea clutter and a neural network as the discrimination scheme. Firstly, the fully convolutional network (FCN) is applied to separate the sea from the land. Then, by analyzing the sea clutter distribution in GF-3 SAR images, we choose the probability distribution model of Constant False Alarm Rate (CFAR) detector from K-distribution, Gamma distribution and Rayleigh distribution based on a tradeoff between the sea clutter modeling accuracy and the computational complexity. Furthermore, in order to better implement CFAR detection, we also use truncated statistic (TS) as a preprocessing scheme and iterative censoring scheme (ICS) for boosting the performance of detector. Finally, we employ a neural network to re-examine the results as the discrimination stage. Experiment results on three GF-3 SAR images verify the effectiveness and efficiency of this approach.


Lower prepulse inhibition in clinical high-risk groups but not in familial risk groups for psychosis compared with healthy controls.
Although the lower level of prepulse inhibition (PPI) of the startle response is well known in schizophrenia, the onset of this difference is not clear. The aim of the present study was to compare PPI in individuals with clinical and familial high risk for psychosis, and healthy controls. We studied PPI in individuals within three groups: ultra-high risk for psychosis (UHR, n = 29), familial high risk for psychosis (FHR, n = 24) and healthy controls (HC, n = 28). The FHR group was chosen among siblings of patients with schizophrenia, whereas UHR was defined based on the Comprehensive Assessment of At-Risk Mental States (CAARMS). We collected clinical data using the BPRS-E, SANS and SAPS when individuals with UHR were antipsychotic-naïve. A cognitive battery that assessed attention, cognitive flexibility, working memory, verbal learning and memory domains was applied to all participants. PPI was lower in the UHR group compared with both the FHR and HC groups. Those with a positive family history for schizophrenia had lower PPI than others in the UHR group. There was no difference in PPI between the FHR and HC groups. We found no relationship between PPI and cognitive performance in the three groups. Startle reactivity was not different among the three groups. Positive and negative symptoms were not related to PPI and startle reactivity in the UHR group. Our findings suggest that clinical and familial high-risk groups for psychosis have different patterns of PPI.


[Gastroesophageal Reflux Disease Review (GERD)].
GERD is a highly prevalent disease in our country. It has a deep impact in patient´s quality of life, representing extremely high costs regarding health. The correct understanding of its pathophysiology is crucial for the rational use of diagnoses methods and the implementation of appropriate treatment adjusted to each individual case. In this review we evaluate this disorder based on the best available evidence, focusing in pathophysiological mechanisms, its epidemiology, modern diagnosis methods and current management standards.


Ferroelectric polarization in nanocrystalline hydroxyapatite thin films on silicon.
Hydroxyapatite nanocrystals in natural form are a major component of bone--a known piezoelectric material. Synthetic hydroxyapatite is widely used in bone grafts and prosthetic pyroelectric coatings as it binds strongly with natural bone. Nanocrystalline synthetic hydroxyapatite films have recently been found to exhibit strong piezoelectricity and pyroelectricity. While a spontaneous polarization in hydroxyapatite has been predicted since 2005, the reversibility of this polarization (i.e. ferroelectricity) requires experimental evidence. Here we use piezoresponse force microscopy to demonstrate that nanocrystalline hydroxyapatite indeed exhibits ferroelectricity: a reversal of polarization under an electrical field. This finding will strengthen investigations on the role of electrical polarization in biomineralization and bone-density related diseases. As hydroxyapatite is one of the most common biocompatible materials, our findings will also stimulate systematic exploration of lead and rare-metal free ferroelectric devices for potential applications in areas as diverse as in vivo and ex vivo energy harvesting, biosensing and electronics.


An examination of motives for tramadol and heroin use in an Egyptian sample.
Tramadol misuse is a significant problem in Egypt, yet little is known about tramadol users. The aim of this study is to examine the motivations for use of tramadol or heroin among patients in substance use disorder treatment in order to understand their unique treatment profiles. A cross-sectional observational study was conducted with 100 treatment-seeking men who reported either tramadol or heroin as their primary substance. Patients were recruited in 2014-2015 from inpatient and outpatient addiction treatment units in a public and private hospital in Cairo. A clinical assessment examined their motives for initiation and continuation of use of either substance based using the following categories: Negative reinforcement (Pain Avoidance), Positive reinforcement (Pleasure Seeking), Incentive salience (Craving), Stimulus-response learning (Habits), Impaired inhibitory control (Impulsivity), and Quasi-medical. Bivariate comparisons of mean scores on motive items and aggregate categories were conducted for tramadol vs. heroin groups; multivariate regression analyses controlled for demographic covariates and treatment site. A majority of the sample endorsed multiple motives for initiation and continuation of use of their primary substance. Primary heroin users were more likely to initiate use due to pain avoidance, whereas primary tramadol users were more likely to initiate use for pleasure seeking (p = 0.002). Pain avoidance was the strongest motive category for continuation of use for both groups. Craving was a stronger motivation for initiation and continuation of use among heroin patients. Patients in treatment for primary use of tramadol or heroin display unique profiles of motivations for initiation and continuation of use, which should be considered within treatment interventions.


Understanding knowledge, attitudes, and behaviors related to influenza and the influenza vaccine in US-Mexico border communities.
Hispanics are less likely to receive the influenza vaccine compared to other racial and ethnic groups in the US. Hispanic residents of the US-Mexico border region may have differing health beliefs and behaviors, and their cross-border mobility impacts disease control. To assess beliefs and behaviors regarding influenza prevention and control among border populations, surveys were conducted at border clinics. Of 197 respondents, 34 % reported conditions for which vaccination is indicated, and travel to Mexico was common. Few (35 %) believed influenza could make them 'very sick', and 76 % believed they should take antibiotics to treat influenza. Influenza vaccine awareness was high, and considered important, but only 36 % reported recent vaccination. The belief that influenza vaccination is 'very important' was strongly associated with recent vaccination; "Didn't think about it" was the most common reason for being un-vaccinated. Misconceptions about influenza risk, prevention and treatment were common in this Hispanic border population; improved educational efforts and reminder systems could impact vaccination behaviors.


Racial, ethnic and neighborhood socioeconomic differences in incidence of dementia: A regional retrospective cohort study.
Evidence on the effects of neighborhood socioeconomic disadvantage on dementia risk in racially and ethically diverse populations is limited. Our objective was to evaluate the relative extent to which neighborhood disadvantage accounts for racial/ethnic variation in dementia incidence rates. Secondarily, we evaluated the spatial relationship between neighborhood disadvantage and dementia risk. In this retrospective study using electronic health records (EHR) at two regional health systems in Northeast Ohio, participants included 253,421 patients aged >60 years who had an outpatient primary care visit between January 1, 2005 and December 31, 2015. The date of the first qualifying visit served as the study baseline. Cumulative incidence of composite dementia outcome, defined as EHR-documented dementia diagnosis or dementia-related death, stratified by neighborhood socioeconomic deprivation (as measured by Area Deprivation Index) was determined by competing-risk regression analysis, with non-dementia-related death as the competing risk. Fine-Gray sub-distribution hazard ratios were determined for neighborhood socioeconomic deprivation, race/ethnicity, and clinical risk factors. The degree to which neighborhood socioeconomic position accounted for racial/ethnic disparities in the incidence of composite dementia outcome was evaluated via mediation analysis with Poisson rate models. Increasing neighborhood disadvantage was associated with increased risk of EHR-documented dementia diagnosis or dementia-related death (most vs. least disadvantaged ADI quintile HR = 1.76, 95% confidence interval = 1.69-1.84) after adjusting for age and sex. The effect of neighborhood disadvantage on this composite dementia outcome remained after accounting for known medical risk factors of dementia. Mediation analysis indicated that neighborhood disadvantage accounted for 34% and 29% of the elevated risk for composite dementia outcome in Hispanic and Black patients compared to White patients, respectively. Neighborhood disadvantage is related to the risk of EHR-documented dementia diagnosis or dementia-related death and accounts for a portion of racial/ethnic differences in dementia burden, even after adjustment for clinically important confounders.


Endogenous benzodiazepine activity in the peripheral and portal blood of dogs with congenital portosystemic shunts.
The purpose of this study was to determine whether an endogenous benzodiazepine receptor ligand (EBZ) was present in the arterial and portal blood of dogs with congenital portosystemic shunts (CPSS). The presence or absence of an EBZ was determined by the collection of systemic and portal blood from dogs with CPSS. Fifteen client-owned dogs with a confirmed CPSS. All dogs had historical signs compatible with hepatic encephalopathy. Eight healthy dogs were used as controls. In all dogs, systemic blood samples were collected after they were anesthetized. Portal blood samples were collected intraoperatively. EBZ was measured by radioreceptor assay. In 10 of 15 dogs, the portal blood concentration of EBZ was significantly elevated compared with normal dogs (mean, 13.2 +/- 18.55 ng/mL). Five dogs had elevated systemic blood EBZ levels (mean, 8.2 +/- 16.08 ng/mL). Eleven of 15 dogs had a higher portal than systemic blood concentration of EBZ. In contrast, control dogs had extremely low EBZ concentrations detected in their portal blood (mean, 0.16 +/- 0.3 ng/mL) and systemic blood (0 ng/mL). The mean portal and systemic blood concentrations in dogs with CPSS were significantly greater than in control dogs (P < .05). Elevated blood levels of EBZ were found in dogs with CPSS. The portosystemic gradient noted in 11 dogs suggests the gastrointestinal tract as a possible source for the endogenous ligand. Generalized motor seizures have been reported in dogs after surgical correction of CPSS. If the presence of a CPSS results in stimulation of brain receptors for benzodiazepines, post-CPSS ligation seizures may result from a withdrawal of EBZ after ligation of the portosystemic shunt.


Breast milk and infant iodine status during the first 12 weeks of lactation in Tianjin City, China.
The present study investigated the iodine status of breast milk and breast-fed infants during the first 12 weeks postpartum in Tianjin, China. A total of 175 pregnant women were recruited before delivery. Their breastmilk and 24-h urine samples were collected at 4, 8, and 12 weeks postpartum; spot urine samples were simultaneously collected from their infants. The iodine content of the samples was measured. The mean breast milk iodine concentrations (BMICs) at 4, 8, and 12 weeks were 221.7±103.5 μg/L, 175.2±76.2 μg/L, and 148.1±66.2 μg/L, respectively. Significant differences existed between the mean BMICs of the three sampling times (F=12.449, p<0.001). The BMIC showed a decreasing trend during the first 12 weeks postpartum. The median urinary iodine concentrations (UICs) of the mothers were 152, 112, and 109 μg/L at the different sampling times. The BMIC and UIC were not correlated in the mothers. The median UICs in the infants were 251, 183, and 164 μg/L. The infant UICs were statistically different at the three sampling times (p=0.001). Moreover, the infant UICs correlated with the BMICs (Rs=0.205, p=0.010) but not with the maternal UICs (Rs=0.131, p=0.067). The BMIC in and infant iodine intake from breast milk decreased in the first 12 weeks. Breastfed infants could receive adequate iodine from breast milk in Tianjin City.


[Treatment compliance in asthma: a Tunisian transversal study].
As a chronic disease, asthma requires a continued treatment and poses the problem of compliance with medication. To study in a Tunisian population of asthmatics, the level of compliance and the factors affecting it, we included 190 adults with persistent asthma in a transversal study using a self-questionnaire. The mean age was 38.56 years. 2/3 of patients had medium or poor socioeconomic status. 1/3 had severe persistent asthma, progressing for 5 years in 68 % of case. All patients received inhaled corticosteroids; only 44 had high dosed corticosteroids. 29.5 % of patients were compliant with medication in our study. Omission and intentional negligence were the two main reasons for non-compliance. Level of compliance was positively related to socioeconomic status, urban way of life, hystory of hospitalization, high dosed corticosteroids and knowledge of their indication. We conclude that treatment compliance in asthma is very low. Further efforts should be made to improve compliance: by increasing the accessibility of medication and by the educational programs which should be a priority in the management of asthma.


Carbon monoxide treatments to impart and retain muscle color in tilapia fillets.
Carbon monoxide (CO) has been used for improving the color of muscle foods. In the current study, we compared the postmortem treatment of tilapia fillets with 100% CO and euthanasia of live tilapia with CO for their ability to stabilize the color of white and red muscle of tilapia fillets. Both postmortem CO treatment and CO euthanasia were effective in increasing the redness (a* value) and lightness (L* value) of tilapia white and red muscle. Fillets obtained from CO-euthanized tilapia showed significantly higher a* and L* values during 1 mo of frozen storage at -20 degrees C and subsequent thawing and storage at 4 degrees C for 18 d. The amount of CO present in the red and white muscles decreased during the 18 d of storage at 4 degrees C. There was no significant difference in the pH, drip, or thaw loss of CO-treated tilapia fillets compared to the untreated fillets.


Low-fiber intake as an etiologic factor in cancer of the colon.
A case-control dietary study of 198 patients with cancer of the colon and two matched control groups demonstrated a significantly lower fiber consumption frequency among the cancer patients. This difference was not confined to a few items. Of the 73 items on the fiber list, 61 were eaten less often by the cancer patient than by a neighborhood control, and 57 were consumed less frequently than by a surgical control. These findings support the hypothesis that low-residue foods play an etiologic role in colon carcinogenesis. A mechanism related to the possible potential carcinogenic properties of degraded biliary compounds may be implicated.


The effect of aspirin on Gomori-positive glia in mouse brain.
Aspirin (acetylsalicylic acid, ASA) treatment resulted in a significant decrease in the amount of the sulfur-rich Gomori-positive material present in the cytoplasm of periventricular glia. It also caused the accumulation of the Gomori-positive neurosecretory material in the supraoptic and paraventricular nuclei and, most pronounced, in the neurosecretory axons of the paraventricular- and supraoptic-neurophypophysial tract.


How effective is lithium in the prevention of relapse in bipolar disorder? A prospective naturalistic follow-up study.
The effectiveness of lithium in preventing recurrences of bipolar disorder was examined prospectively for 2 years in two representative samples of bipolar I patients being treated in a comprehensive program following recommended guidelines. One hundred and twenty patients were recruited from consecutive admissions to two catchment area psychiatric services (one in the United Kingdom, the other in New Zealand). They were seen at 3-monthly intervals by a member of the research team. Treatment was adjusted according to clinical needs. Overall, two-thirds of the patients had a recurrence. Of the 57 on lithium as sole treatment, 39 (68%) had a further episode; 17 after stopping lithium. The 42 on other mood stabilisers and/or an antipsychotic, with or without lithium, did no better. By contrast, only eight (38%) of the 21 who were taking no prophylactic medication had a recurrence. Lithium is much less effective in clinical practice than would be expected from clinical trial results. A major reason for this is poor compliance. Alternative treatment strategies are needed to improve the outcome for bipolar disorder patients.


Salmonella meningitis in a paediatric patient caused by Salmonella enterica serotype Houtenae.
The authors report a case of a 6-week-old baby girl who was admitted to the paediatric ward due to a high fever for 2 days. The patient experienced three fits which took place while in the ward. A brain sonogram showed subdural heterogeneous collection consistent with focal empyema; however, no hydrocephalus or infarction was detected. An urgent Burr hole procedure was performed to remove the collected pus. Both blood and cerebrospinal fluid (CSF) culture grew Salmonella species which remain sensitive to some antibiotics. This strain was sent to the institute of medical research (IMR) for serotyping. The patient was treated with intravenous combination of ceftriaxone and ciprofloxacin for 3 weeks. One week later, IMR sent results that identified the strain as Salmonella enterica serotype Houtenae. Following antibiotic treatment, repeat ultrasound illustrated an improvement of the subdural empyema, and the gram stain of the CSF specimen failed to isolate bacteria.


BioMercator V3: an upgrade of genetic map compilation and quantitative trait loci meta-analysis algorithms.
Compilation of genetic maps combined to quantitative trait loci (QTL) meta-analysis has proven to be a powerful approach contributing to the identification of candidate genes underlying quantitative traits. BioMercator was the first software offering a complete set of algorithms and visualization tool covering all steps required to perform QTL meta-analysis. Despite several limitations, the software is still widely used. We developed a new version proposing additional up to date methods and improving graphical representation and exploration of large datasets. BioMercator V3 is implemented in JAVA and freely available (http://moulon.inra.fr/biomercator) email@example.com.


The TICAS-RTCIP real time cell identification processor.
A preliminary model of a real time processing system, the TICAS-RTCIP (for Taxonomic Intra-Cellular Analytic System--Real Time Cell Identification Processor) has been disigned and is being tested under operational conditions, proving the substantial advantages of employing a network of microprocessors operating in parallel. The system is designed only to demonstrate the feasibility, while more extensive development and biologic testing will be required to assess general applicability to automated uterine cytology.


Meta-Analysis of Maternal and Neonatal Outcomes Associated with the Use of Insulin Glargine versus NPH Insulin during Pregnancy.
As glargine, an analog of human insulin, is increasingly used during pregnancy, a meta-analysis assessed its safety in this population. A systematic literature search identified studies of gestational or pregestational diabetes comparing use of insulin glargine with human NPH insulin, with at least 15 women in both arms. Data was extracted for maternal outcomes (weight at delivery, weight gain, 1st/3rd trimester HbA(1c), severe hypoglycemia, gestation/new-onset hypertension, preeclampsia, and cesarean section) and neonatal outcomes (congenital malformations, gestational age at delivery, birth weight, macrosomia, LGA, 5 minute Apgar score >7, NICU admissions, respiratory distress syndrome, neonatal hypoglycemia, and hyperbilirubinemia). Relative risk ratios and weighted mean differences were determined using a random effect model. Eight studies of women using glargine (331) or NPH (371) were analyzed. No significant differences in the efficacy and safety-related outcomes were found between glargine and NPH use during pregnancy.


Innate immunity: the missing link in neuroprotection and neurodegeneration?
Innate immunity was previously thought to be a nonspecific immunological programme that was engaged by peripheral organs to maintain homeostasis after stress and injury. Emerging evidence indicates that this highly organized response also takes place in the central nervous system. Through the recognition of neuronal fingerprints, the long-term induction of the innate immune response and its transition to an adaptive form might be central to the pathophysiology and aetiology of neurodegenerative disorders. Paradoxically, this response also protects neurons by favouring remyelination and trophic support afforded by glial cells.


Update on the Pathophysiology and Risk Factors for the Development of Malignant Testicular Germ Cell Tumors in Complete Androgen Insensitivity Syndrome.
Prophylactic gonadectomy in young adult women with complete androgen insensitivity syndrome (CAIS) to avoid development of an invasive testicular germ cell tumor (TGCT) is currently advised in most centers. However, women with CAIS increasingly question the need of this procedure. In order to provide optimal counseling and follow-up of these women, insight in the mechanisms underlying TGCT development in androgen insensitivity syndrome (AIS), data regarding the incidence of TGCT in AIS adults specifically, and an overview of existing and novel screening tools for in situ and invasive neoplastic lesions are crucial. The current knowledge regarding these topics is revised in this paper.


Treatment of retinal vein occlusion in rabbits with traditional Chinese medicine Fufang XueShuan Tong.
Retinal vein occlusion (RVO) is one of the most common causes of visual loss. Many approaches have been tried to treat central retinal vein occlusion (CRVO), and branch retinal vein occlusion (BRVO) with various results. However, there is no defined protocol and limited evidence to support the interventions currently used. The aim of this study was to assess the efficacy of the traditional Chinese medicine Fufang XueShuan Tong (FXST) in treating experimentally created RVO. RVO model was first induced in forty-four pigmented rabbits through photocoagulation following injection of rose Bengal. The rabbits were divided into four groups based on the dose of FXST administered (212 mg/kg, 424 mg/kg, 848 mg/kg and control group). The rabbits were observed for four weeks after the procedure, using color fundus photography, fundus fluorescein angiography and electroretinogram examination. Vascular endothelial growth factor (VEGF), interleukin-6 and nitric oxide (NO) levels in the vitreous and histopathologic evaluation were monitored. The obstructed vessels in the treatment groups reopened or anastomosed faster than those in the control group (P < 0.05). The amplitude of maximum b wave and the oscillatory potential were significantly higher in the treatment groups than in the control group (P < 0.01). At both two weeks and four weeks, VEGF and IL-6 levels in the vitreous were significantly decreased in the treatment groups (P < 0.01), while NO levels were significantly elevated (P < 0.01). At the same time, histopathologic evaluation showed different retinal neuroepithelium structures in the different groups. Immunoreactivity of VEGF was greater in the control group than in the treatment groups. FXST was helpful in reconstructing retinal vessels in the RVO model, protecting retinal structures and improving visual function, and could inhibit the neovascular factor.


Gender differences in diagnostic procedures.
This review examines the contribution of the literature to the controversial issue of diagnostic procedures in women affected by coronary artery disease (CAD), on which a large number of papers have been published. It has been reported that cerebro- and cardiovascular diseases represent the first cause of death in the New as well as in the Old World, Italy included. Some studies are conditioned by bias; one of these is the Framingham study, in which angina was reported and defined only clinically and for a relatively young age range, as a benign condition in women. Angiographic studies, such as the CASS, considered a super elected group of women referred to the hemodynamic laboratory for chest pain, which in the female gender often has atypical characteristics. In our opinion, it is mandatory to take into account: 1) what chest pain really means in women; 2) the fact that there are gender differences: women have a different biological and hormonal status, lifestyle, and perception of the disease; 3) that there is a different approach of the physicians to a woman with possible or suspected CAD. We suggest, therefore, a more peculiar and individualized diagnostic approach to women suspected as having CAD. This approach should also take the pre-test probability of disease into consideration. The first investigational step we recommend is the exercise ECG test; should this be unfeasible or not interpretable, an imaging and/or pharmacological stress test is advisable. In case of positive first test results, coronary angiography should be performed.


Hereditary cancer risk notification and testing: how interested is the general population?
Great interest in predictive testing for hereditary cancer syndromes has been reported. Prior research has focused on testing for specific hereditary syndromes and/or among individuals at high risk for positive carrier status. Given anticipated expansion of both the range of hereditary syndromes for which testing will be available, as well as the clinical settings in which testing will occur, assessment of interest in hereditary cancer risk testing and notification in the general public is warranted. As part of an annual statewide telephone survey, adults' (N = 654) interest in hereditary cancer risk testing and notification was assessed. Interest in both risk testing (82%) and risk notification (87%) was high. Logistic regression analyses indicated that disinterest in risk notification was associated with female sex, performance of fewer health protective behaviors, and better perceptions of personal health. Disinterest in risk testing was associated with these same variables as well as older age, less concern over developing cancer, and a more extensive history of cancer in first degree relatives. In the absence of risk-reducing behaviors with demonstrable efficacy, hereditary risk testing programs may have difficulty attracting the interest of those at greatest risk for carrier status. In contrast, many individuals at low risk for positive carrier status might seek testing, perhaps as a means of seeking reassurance regarding their low hereditary risk.


RNA binding motif protein 3 (RBM3) drives radioresistance in nasopharyngeal carcinoma by reducing apoptosis via the PI3K/AKT/Bcl-2 signaling pathway.
Radioresistance is an important obstacle to nasopharyngeal carcinoma (NPC) therapy. In this study, we explored the role of RNA-binding motif protein 3 (RBM3) in the radioresistance of NPC and its underlying mechanism. We measured the expression of RBM3 in 20 clinical NPC tissues and in NPC cell lines. We found that RBM3 was upregulated in radioresistant NPC tissues and cells. Radioresistant NPC cells (CNE1/IR) and parental NPC cells (CNE1) were subjected to RBM3-shRNA knockdown and RBM3 overexpression, respectively. RBM3 depletion in CNE1/IR cells sensitized cells to radiotherapy, increased DNA damage, and accelerated the rate of apoptosis. In contrast, RBM3 overexpression in CNE1 cells significantly enhanced radioresistance and reduced the rate of apoptosis. Additionally, radioresistance conferred by RBM3 was attributed to the activation of the AKT/Bcl-2 signaling pathway and reduction of caspase 3. Inhibition of AKT signaling attenuated RBM3-mediated radioresistance. Furthermore, RBM3 directly interacted with PI3K subunit p85 in NPC cell lines. Altogether, our data demonstrate that RBM3 enhances radioresistance by inhibiting the apoptotic response to radiotherapy through the PI3K/AKT/Bcl-2 signaling pathway. RBM3 may serve as a novel factor for predicting radioresistance and as a molecular target in the treatment of NPC.


[Willingness to pay for Japanese cedar pollinosis: comparison between pollination and non-pollination seasons].
Allergic rhinitis is not fatal illness, but its high prevalence and several symptoms result in substantial medical cost. There is increasing interest in the use of economic evaluations in healthcare; therefore, we investigated patients' willingness to pay (WTP) for prevention and cure from Japanese cedar pollinosis (JCP), and compared WTP values assessed in non-pollination season (June 1998) and pollination season (February-March 2003). Japanese economic woes got worse in 2003 than in 1998. Patients were randomly selected from ENT clinical sites in Osaka, 175 and 645 patients completed WTP questionnaire in 1998 and 2003, respectively. WTP value was lower in 2003 than in 1998, which related to part-time employees and housewives' reducing WTP. Declining WTP value did not associated with the differences in patient characteristics between 1998 and 2003 including age, duration of disease, nasal symptom severity and comorbid condition. These results show that we have to take employment status into account in economic evaluations. Decline in WTP for JCP in 2003 was strongly affected by Japanese sluggish economy, and the WTP seemed to be stable value in individual patients.


Moderators and mediators of symptoms and quality of life outcomes in an open-label study of adults treated for attention-deficit/hyperactivity disorder.
The Quality of Life, Effectiveness, Safety, and Tolerability (QU.E.S.T.) study was designed to evaluate effectiveness of long-acting amphetamines in adults with attention-deficit/hyperactivity disorder (ADHD) in community practice settings. This article reports moderators and mediators of symptoms and quality of life outcomes. This was an open-label study of 725 adults with DSM-IV-diagnosed ADHD, treated with mixed amphetamine salts extended release and followed for up to 8 months. Multiple regressions were used to determine if patient moderators impact response in ADHD symptoms and how ADHD symptoms and medication satisfaction mediate quality of life. The study was conducted from December 2003 to December 2004. Amphetamine treatment of ADHD resulted in a robust and enduring symptom response. Patient characteristics such as age, female gender, severity of illness, and treatment-naive status moderate improved symptom outcome. Symptom change and satisfaction with medication independently mediate change in mental but not physical quality of life outcomes. There is no time lag between changes in symptoms and improved quality of life. Attention is a stronger mediator of ADHD-specific quality of life outcomes than disruptive behavior. If symptoms and quality of life improve simultaneously, improvement in quality of life can be understood as more than just a downstream, secondary effect of symptom remission. Satisfaction with medication is a direct measure of the complex interplay of symptom change, tolerability, and patient perception of treatment that predicts self-report of quality of life benefits. Although the disruptive symptoms of ADHD are more obvious, adults self-report that attention has greater impact.


[Small cell carcinoma of the prostate. Complete remission after chemoradiotherapy: apropos of a case].
The authors report a case of pure small cell carcinoma of the prostate expressing neuroendocrine markers on immunohistochemistry. Treatment consisted of chemotherapy with cisplatin and etoposide combined with regional external beam radiotherapy. The result is encouraging with complete remission 15 months after the diagnosis.


Self-Medicating for Pain: A Public Health Perspective.
Pain is one of the symptoms for which any man is willing not only to go to the doctor but also to resort to any means, including self-medication, to "get rid" of it. Self-medication is not only a current practice but also a public health problem, under the circumstances that it can influence the way in which a disease is diagnosed and/or treated in a timely manner, and, consequently, repercussions may occur on the cost of treatment, in the case of severe forms. Pain is a vital symptom, and the diminution until the disappearance of pain is a fundamental right of each individual; the analysis of ethical issues in the case of self-administration of analgesic medication has not been a major concern. Understanding the problem is important to realize whether self-medicating for pain is a necessity or an abuse, and in this respect, we review scientific articles from international databases: PubMed and ProQuest. The study is based on the consultation of scientific articles from international databases-PubMed and ProQuest, the main keywords in the search being pain and self-medication, to which a stigma or public health is sequentially added. Pain is becoming more and more a global problem and the extent of its spread can substantiate our assertion about pathology with pandemic impact. Under the pressure of patient associations, of the media, and of nonmedical authorities, the opinion about the need for a stoic approach to pain has long become an outdated theory, and chronic pain, beyond a multidimensional approach, is increasingly considered not only a useless element but also even a destructive one. Pain and self-medication must be addressed, including in medical practice, starting from their multidimensionality from the following perspectives: medicobiological, sociocultural, instructive-educational, legal-political, and especially ethical. They are not only individual health problems but also become, when connected with a stigma, a public health problem.


Cardiorespiratory Responses of Adults and Children during Normoxic and Hypoxic Exercise.
We aimed to elucidate potential differential effects of hypoxia on cardiorespiratory responses during submaximal cycling and simulated skiing exercise between adults and pre-pubertal children. Healthy, low-altitude residents (adults, N=13, Age=40±4yrs.; children, N=13, age=8±2yrs.) were tested in normoxia (Nor: PiO2=134±0.4 mmHg; 940 m) and normobaric hypoxia (Hyp: PiO2=105±0.6 mmHg; ~3 000 m) following an overnight hypoxic acclimation (≥12-hrs). On both days, the participants underwent a graded cycling test and a simulated skiing protocol. Minute ventilation (VE), oxygen uptake (VO2), heart rate (HR) and capillary-oxygen saturation (SpO2) were measured throughout both tests. The cycling data were interpolated for 2 relative workload levels (1 W·kg-1 & 2 W·kg-1). Higher resting HR in hypoxia, compared to normoxia was only noted in children (Nor:78±17; Hyp:89±17 beats·min-1; p<0.05), while SpO2 was significantly lower in hypoxia (Nor:97±1%; Hyp:91±2%; p<0.01) with no between-group differences. The VE, VO2 and HR responses were higher during hypoxic compared to normoxic cycling test in both groups (p<0.05). Except for greater HR during hypoxic compared to normoxic skiing in children (Nor:155±19; Hyp:167±13 (beats·min-1); p<0.05), no other significant between-group differences were noted during the cycling and skiing protocols. In summary, these data suggest similar cardiorespiratory responses to submaximal hypoxic cycling and simulated skiing in adults and children.


Cellular location of heat-labile enterotoxin in Escherichia coli.
We demonstrated that both the A and B subunits of heat-labile enterotoxin from Escherichia coli are located in the periplasm. The toxin was shown to form aggregates in Tris-EDTA buffers which are routinely used for isolating membranes. The aggregates pellet upon centrifugation, and this may explain why several previous investigators have concluded that enterotoxin is associated with membranes.


Intermediate scale for assessment of Parkinson's disease. Characteristics and structure.
The present study is devoted to the verification of the basic metrical characteristics of the ISAPD. One hundred and sixty-seven Parkinson's disease (PD) patients were included. Group A (n = 40) was simultaneously assessed by five raters who applied the ISAPD and other PD rating scales (PDRS). A set of timed tests, the MiniMental State Examination (MMSE) and the Hamilton Scale for Depression (HSD) were administered by an independent examiner. Group B (n = 127) was individually assessed through the UPDRS and the other PDRSs by separate neurologists in four different hospitals. The ISAPD was administered in 7.0 +/- 3.7 min. The internal consistency of this scale was high (Cronbach's alpha = 0.97). The inter-rater reliability of their items was very satisfactory (for all items, kappa > 0.70). There was a high correlation with the Hoehn and Yahr classification (r(s) = 0.71; p < 0.001) and some timed tests. The convergent validity with the other PDRS (UPDRS and Schwab and England Scale) was also very high (r(s) = 0.83-0.92; p < 0.001). The ISAPD also correlated with the MMSE and the HSD. Factor analysis identified three factors (activities of daily living; gait and mobility; speech and eating) that explained 76% of the variance. The ISAPD is an easy to apply, reliable, and valid scale that fulfills the aim for which it was designed.


A Developmental Lexical Bias in the Interpretation of Discrepant Messages.
Children's interpretations of lexical and vocal cues to speaker affect, independently and in combination, were examined in four studies. In Experiments 1 and 2, 7- to 11 -year-olds'judgments of lexical and paralinguistic cues were evaluated. In Experiment 3, these cues were combined to produce consistent and discrepant messages. The affective interpretations of 7- to 10-year-olds reflected a weighted-averaging strategy favoring the affect conveyed lexically. In Experiment 4, the developmental trajectory of children's interpretations of discrepancy from 4 to 10 years of age was investigated. Both 4- and 7-year-olds appeared to use a weighted-averaging strategy favoring lexical content, whereas 10-year-olds utilized a strategy favoring paralanguage.


Assessment of myocardial perfusion by harmonic power doppler imaging at rest and during adenosine triphosphate stress: comparison with coronary flow velocity reserve in the left anterior descending coronary arter.
To clarify whether the myocardial perfusion abnormalities observed on harmonic power Doppler imaging (HPDI) during hyperemia are related to a decrease in coronary flow velocity reserve (CFVR), HPDI and CFVR were measured in the left anterior descending coronary artery (LAD) territory of 75 patients. During continuous infusion of Levovist, dual-frame triggered apical 4-chamber views were obtained at rest and during adenosine triphosphate (ATP) infusion. The persistence of perfusion defects during ATP infusion or stress-induced defects in the LAD territory was defined as abnormal. Both HPDI and coronary flow velocity recordings of adequate quality were successfully obtained in 73 patients, and 37 patients showed abnormal myocardial perfusion. CFVR was significantly lower in patients with abnormal perfusion than in patients who had normal findings (1.38+/-0.38 vs 2.60+/-0.76, p<0.001). A CFVR less than 1.9 had a sensitivity of 89% (33/37) and a specificity of 89% (32/36) for predicting the presence of abnormal myocardial perfusion. This study demonstrates that myocardial perfusion abnormalities observed during HPDI using ATP stress are closely correlated to a decrease in CFVR and may reflect significant stenosis or microvascular damage in the LAD territory.


Three-year follow-up of changes of cortical bone thickness after implantation of Endo-Exo-Prosthesis (EEP) for transfemoral amputees.
Transcutaneous Osseointegrated Prosthetic Systems (TOPS) offer a good alternative for patients who cannot be satisfactorily rehabilitated by conventional suspension sockets. The Endo-Exo-Prothesis (EEP, ESKA Orthopaedic Handels GmbH®, Deutschland) is the most implanted TOPS in Germany. Previous studies have shown that cortical thickness increases after implantation of TOPS. The aim of this study is to determine changes of cortical thickness in relation to the time after implantation of the Endo-Fix-Stem. All transfemoral amputees treated by EEP from 2007 to 2013 were operated by the last author of this study. X-ray images of 4 follow-up intervals (postoperative, 3 months, 12 months, 3 years) were analyzed retrospectively. The femoral residuum was divided into 3 sections (proximal, middle, distal) with 2 measuring points in each section: medial and lateral. Cortical thickness was measured at these 6 points and compared at regular intervals using the Friedman test for non-parametric dependent variables. Thirty-seven patients with 40 implants were included. The average age was 52.2 years (30-79 years). 83.7% of the patients were male. No statistical significance could be shown for any of the measuring points of the femoral residual (proximal medial, proximal lateral, middle medial, middle lateral, distal medial, distal lateral) among the mean values of the cortical thickness at the different follow-up times (p > 0.05 for all measuring points). Cortical remodeling processes (> 1 millimeter (mm)) occurred in all implants despite a missing statistical significance. Hypertrophy could be confirmed for 42.5% and atrophy for 37.5%. Twenty percent of the cases showed a parallel occurrence of both entities. Cortical changes greater than 5 mm were only observed at the distal end of the femur. Even if our results did not show any significant difference, it can be deduced that the osseointegration process leads to a remodeling of the bone structure, both in terms of increased bone formation and bone resorption. However, it has not yet been conclusively clarified which processes lead to hyper- or atrophy. The force transmission between prosthesis and bone and the facultative bacterial colonization of the stoma are still the main factors which may be responsible for the bone remodeling processes.


Characterization of two minor saponins from Cordia piauhiensis by 1H and 13C NMR spectroscopy.
A careful NMR analysis with full assignment of the 1H and 13C spectral data for two minor saponins isolated from stems of Cordia piauhiensis is reported. These saponins were isolated by high-performance liquid chromatography and characterized as 3beta-O-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl]pomolic acid 28-O-[beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl] ester (1) and 3beta-O-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl]oleanolic acid 28-O-[beta-D-xylopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl] ester (2). Their structures were established using a combination of 1D and 2D (1H, 1H-COSY, TOCSY, NOESY, gs-HMQC and gs-HMBC) NMR techniques, electrospray ionization mass spectrometry and chemical evidence.


Spatial distribution and losses by grain destroying insects in transgenic corn expressing the toxin Cry1Ab.
Insect pests are one of the factors that most impact plant yield. The magnitude of the losses and the spatiotemporal pest distribution in crops is a result of their interactions with the environment. Therefore, the understanding of the causes of production losses and the pest spatial patterns is important for the development of suitable sampling plans and pest management programs. Thus, this study aimed to quantify grain losses caused by insects and to determine the spatial distribution pattern of arthropod pest species in Bt and non-Bt corn. The prevailing insect pests in the corn ears were the earworm and fall armyworm caterpillars (Helicoverpa spp. and Spodoptera frugiperda), the cornsilk fly (Euxesta spp.), the maize weevil (Sitophilus zeamais), and the square-necked grain beetle (Cathartus quadricollis). The non-Bt corn was more attacked by the caterpillars and the weevil, while Bt corn was more affected by the cornsilk fly Euxesta spp. Spatial dependence was significant for the damage caused by the caterpillars, the grain beetle and the maize weevil in both the Bt and non-Bt corn genotypes. The range of the damage caused by the insects was between 9.0-9.7 m for the caterpillars, 6.9-12.20 m for the cornsilk fly, 10.7-80.4 m for the square-necked grain beetle, and 51.9-170.7 m for the maize weevil. The pattern of the spatial distribution of pest damage in both corn genotypes (i.e., Bt and non-Bt corn) was similar with a prevalence of moderate to strong spatial dependence and aggregate damage distribution. The plants near to the sampling points exhibited injury and infestation levels similar to those of the sampled plants.