[Variants in the TNFA, IL6 and IFNG genes are associated with the dengue severity in a sample from Colombian population].
The genetic makeup of the host contributes to the clinical profile of dengue. This could be due to the effect of variants in the genes encoding pro-inflammatory cytokines. To evaluate the association between the variants of three polymorphisms in TNFA, IL6 and IFNG candidate genes with dengue severity in a sample of Colombian population. We evaluated the rs1800750, rs2069843, and rs2069705 polymorphisms in TNFA, IL6 and IFNG candidate genes, respectively, in 226 patients with dengue infection. The genotypes were typed using both polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To determine the risk of different dengue phenotypes, we compared allele frequencies with chi-square and genotypes and haplotypes using logistic regression. Finally, these analyzes were adjusted with data from self-identification or the ancestral genetic component. The A allele in the rs2069843 polymorphism, adjusted by self-identification, was associated with dengue hemorrhagic fever cases in Afro-Colombians. In the entire sample, this polymorphism, adjusted by the ancestral genetic component, was reproducible. In addition, there were significant associations between GGT and GAC allelic combinations of rs1800750, rs2069843, and rs2069705 in dengue hemorrhagic fever patients, with and without adjustment by ancestral genetic component. Additionally, the AGC allelic combination produced 58.03 pg/ml of interleukin-6 more than the GGC combination, regardless of European, Amerindian and African genetic components. The variants of GGT and GAC polymorphisms of rs1800750, rs2069843, and rs2069705 in the TNFA, IL6 and IFNG genes, respectively, were correlated with the susceptibility to dengue severity in a sample of Colombian population.


Haptic study of three-dimensional objects activates extrastriate visual areas.
In humans and many other primates, the visual system plays the major role in object recognition. But objects can also be recognized through haptic exploration, which uses our sense of touch. Nonetheless, it has been argued that the haptic system makes use of 'visual' processing to construct a representation of the object. To investigate possible interactions between the visual and haptic systems, we used functional magnetic resonance imaging to measure the effects of cross-modal haptic-to-visual priming on brain activation. Subjects studied three-dimensional novel clay objects either visually or haptically before entering the scanner. During scanning, subjects viewed visually primed, haptically primed, and non-primed objects. They also haptically explored non-primed objects. Visual and haptic exploration of non-primed objects produced significant activation in several brain regions, and produced overlapping activation in the middle occipital area (MO). Viewing visually and haptically primed objects produced more activation than viewing non-primed objects in both area MO and the lateral occipital area (LO). In summary, haptic exploration of novel three-dimensional objects produced activation, not only in somatosensory cortex, but also in areas of the occipital cortex associated with visual processing. Furthermore, previous haptic experience with these objects enhanced activation in visual areas when these same objects were subsequently viewed. Taken together, these results suggest that the object-representation systems of the ventral visual pathway are exploited for haptic object perception.


Galeterone for the treatment of advanced prostate cancer: the evidence to date.
Major advances have been achieved recently in the treatment of metastatic castration-resistant prostate cancer, resulting in significant improvements in quality of life and survival with the use of several new agents, including the next-generation androgen receptor (AR)-targeted drugs abiraterone and enzalutamide. However, virtually all patients will eventually progress on these therapies and most will ultimately die of treatment-refractory metastatic disease. Recently, several mechanisms of resistance to AR-directed therapies have been uncovered, including the AR splice variant 7 (AR-V7), which is a ligand-independent constitutionally-active form of the AR that has been associated with poor outcomes to abiraterone and enzalutamide. Galeterone, a potent anti-androgen with three modes of action (CYP17 lyase inhibition, AR antagonism, and AR degradation), is a novel agent under clinical development that could potentially target both full-length AR and aberrant AR, including AR-V7. In this manuscript, we will first discuss the biological mechanisms of action of galeterone and then review the safety and efficacy data from Phase I and II clinical studies of galeterone in patients with metastatic castration-resistant prostate cancer. A Phase III study of galeterone (compared against enzalutamide) in AR-V7-positive patients is currently underway, and represents the first pivotal trial using a biomarker-selection design in this disease.


Involvement of dopamine in the differences in sexual behaviour between Roman high and low avoidance rats: an intracerebral microdialysis study.
Outbred Roman high- (RHA) and low-avoidance (RLA) rats are selected for respectively rapid vs. poor acquisition of the active avoidance response and display different copulatory patterns when exposed to a sexually receptive female, with RHA rats showing more robust sexual motivation and better performance than RLA rats also after repeated sexual activity. Here we show that the distinct patterns of sexual behaviour of the Roman lines are correlated with differences in the activity of the dopaminergic mesolimbic system, which plays a key role in sexual motivation and copulatory performance. Thus, differential increases in the concentrations of dopamine and its main metabolite 3,4-dihydroxyphenylacetic acid, occurred in dialysates obtained from the nucleus accumbens shell of naïve and sexually experienced Roman rats during the anticipatory and consummatory phases of sexual activity. These differences were particularly evident between sexually naïve RHA and RLA rats and tended to diminish but still persisted between sexually experienced rats, as did the differences in sexual behaviour. Analysis of the biochemical and behavioural findings showed that, while in RHA rats sexual experience caused a shift in the changes in both the dopaminergic activity and copulation towards the first period of the sexual test, in RLA rats sexual experience increased dopaminergic activity and copulation throughout the entire test. Therefore, this study adds experimental support to the view that the different sexual patterns of the Roman lines are due, at least in part, to a more robust functional tone of the mesolimbic dopaminergic system of RHA rats.


Sealed adult mice: new model for enterotoxin evaluation.
Outbred, inbred, and congenic strains of conventional mice which were ano-rectally occluded with cyanoacrylate ester glue and converted to sealed adult mice (SAM) were given, per os, crude cholera enterotoxin (CT) in 10% NaHCO3. At 6 h when the response was maximal, mice were killed, the small intestines were removed, and gut weight/body weight ratios were calculated. Experimental mice gave a linear response after receiving 1.5 to 60 micrograms of CT. Purified heat-stable enterotoxin from Escherichia coli and purified heat-labile enterotoxins from E. coli, Vibrio cholerae, and Clostridium difficile all elicited vigorous fluid outpouring as did culture filtrates from Vibrio fluvialis with cytotoxic activity. Active and passive immunization with crude CT completely or partially neutralized fluid secretion due to CT. Monospecific anti-CT incubated with CT before feeding also eliminated the response. Mice pretreated with penicillin, held in barrier cages, converted to SAM, and fed live vibrios, showed fluid responses similar to those seen with low doses of CT. Each of six different strains of inbred mice fed a half-maximal fluid accumulation response dose of CT gave fluid accumulation ratios which varied fourfold. There was no correlation of fluid accumulation with body weight, gut length, age, or sex. All poor responders were of H-2k haplotype and all good responders were H-2b. BALB congenic mice which differed only in H-2 haplotypes showed the same correlations, and body weights and gut lengths of all haplotypes were not significantly different.


Modeling naturalistic face processing in humans with deep convolutional neural networks.
Deep convolutional neural networks (DCNNs) trained for face identification can rival and even exceed human-level performance. The ways in which the internal face representations in DCNNs relate to human cognitive representations and brain activity are not well understood. Nearly all previous studies focused on static face image processing with rapid display times and ignored the processing of naturalistic, dynamic information. To address this gap, we developed the largest naturalistic dynamic face stimulus set in human neuroimaging research (700+ naturalistic video clips of unfamiliar faces). We used this naturalistic dataset to compare representational geometries estimated from DCNNs, behavioral responses, and brain responses. We found that DCNN representational geometries were consistent across architectures, cognitive representational geometries were consistent across raters in a behavioral arrangement task, and neural representational geometries in face areas were consistent across brains. Representational geometries in late, fully connected DCNN layers, which are optimized for individuation, were much more weakly correlated with cognitive and neural geometries than were geometries in late-intermediate layers. The late-intermediate face-DCNN layers successfully matched cognitive representational geometries, as measured with a behavioral arrangement task that primarily reflected categorical attributes, and correlated with neural representational geometries in known face-selective topographies. Our study suggests that current DCNNs successfully capture neural cognitive processes for categorical attributes of faces but less accurately capture individuation and dynamic features.


What can daily life assessment tell us about the bipolar spectrum?
Evidence suggests that bipolar psychopathology is better characterized as a spectrum than by categorical diagnoses. The examination of symptoms and impairment associated with bipolar spectrum psychopathology is important and can be enhanced by methods that examine affect, thoughts, and behavior in daily life. The present study extended findings that provide validation of a continuum of bipolar psychopathology in daily life. Young adults (n=294) completed the Hypomanic Personality Scale (HPS) and experience sampling using smartphones. Participants were signaled eight times daily for one week to complete surveys in their normal daily environment. Bipolar spectrum psychopathology was characterized by increased positive and negative affect, confidence, racing thoughts, energy, and impulsivity in daily life. The HPS moderated the association of stress with trouble concentrating, irritability with dysphoria and impulsivity, and confidence with feeling like one's emotions were out of control. This study demonstrated that bipolar spectrum psychopathology is associated with disruptions in affect, thoughts, and behaviors and provided further evidence for a continuum of bipolar psychopathology. ESM is a promising method for examining dynamic constructs such as bipolar spectrum psychopathology and has the potential to be a strong research and clinical tool.


[Diagnosis of Lawsonia intracellularis using the polymerase chain reaction (PCR) in pigs with and without diarrhea and other animal species].
Lawsonia (L.) intracellularis, an obligately intracellular bacterium, causes proliferative enteropathy (PE) in swine and, occasionally, in other animals. To determine the spread of the agent among German pig herds pooled fecal samples of five animals each of clinically normal Hessian pig herds collected between november 1998 and february 1999 as well as feces (n = 1684) from individual animals representing 648 herds, sent to our laboratory by veterinarians from all parts of Germany, were tested for L. intracellularis using the polymerase chain reaction (PCR). In addition, fecal samples from diarrhoic foals (n = 46), dogs (n = 57), cats (n = 50), calves (n = 37), hedge hogs (n = 9), seals (n = 8) and one giraffe were also studied. DNA was extracted from feces using high concentrations of chaotropic salt and diatomaceous earth. For PCR, primers flanking a 279 bp fragment of L. intracellularis DNA were used (JONES, G. F., WARD, G. E., MURTAUGH, M. P., LINN, G. (1993), J. Clin. Microbiol. 31, 2611-2615). Amplificates were separated by agarose gel electrophoresis and visualized under UV-light. L. intracellularis was found in 26 (12.8%) samples from 21 (30.0%) of the Hessian pig herds without symptoms of diarrhoea. In feces of pigs with diarrhoea (n = 1684) the agent was present in 431 (25.6%) samples originating from 224 (34.6%) herds. Of the other animal species studied, L. intracellularis was detected in feces of 4 (7.0%) dogs, 2 (5.4%) calves, 3 (33.3%) hedge hogs and in the sample of the giraffe. The remaining species were all tested negative.


TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity.
Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ). Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity.


Conflicting Morphological and Reproductive Species Boundaries in the Coral Genus Platygyra.
In mass-spawning corals, potential exists for gametes of a number of species to mix in the water column. The existence of morphologically distinct sympatric coral populations despite such an event implies the presence of isolating mechanisms to prevent hybridization and maintain species boundaries. Over 380 fertilization trials were conducted to determine the extent of reproductive isolation among the seven morphologically defined species (morphospecies) of the scleractinian coral genus Platygyra, on the Great Barrier Reef. Results from these experiments demonstrate that fertilization between-morphospecies can occur at rates equivalent to within-morphospecies fertilizations, indicating that no gametic-level barriers to fertilization exist among these morphological species. Observations of spawning times both in the field and in the laboratory have shown that all seven morphospecies spawn on the same night and that there is considerable overlap in the hour of spawning among them. These data indicate that few, if any, temporal barriers to fertilization exist among morphospecies of Platygyra on the Great Barrier Reef. In addition, larvae resulting from between-morphospecies crosses are capable of settlement and subsequent growth equivalent to that of within-morphospecies larvae. Our results reveal a discontinuity between reproductive and morphological species boundaries within the scleractinian genus Platygyra and challenge species definitions within the Scleractinia. It is not yet clear what mechanisms might maintain morphological boundaries in Platygyra in the face of the clear potential for gamete mixing. The disjunct distributions of certain morphospecies along latitudinal and habitat boundaries, and the small levels of variation in reproduction may be two such mechanisms.


Appropriately screened geriatric chest pain patients in an observation unit are not admitted at a higher rate than nongeriatric patients.
Observation units may exclude geriatric patients (defined as age >or=65) due to the high rate of observation failure (admission to an inpatient unit) among these patients. We evaluated whether geriatric patients on a chest pain protocol are admitted to an inpatient unit from an emergency department (ED) observation unit at a higher rate than nongeriatric patients. This was a retrospective chart review of all patients placed in the ED observation unit at the University of Utah Medical Center over a 14-month period from April 2006 to June 2007. The observation unit did not exclude geriatric patients nor did it exclude patients with a history of coronary disease; patients were admitted per the discretion of the attending ED physician. Patient information, including age, date of admission, history of coronary disease (defined as a previous myocardial infarction, stent, or coronary artery bypass graft), and admission to an inpatient unit from the observation unit, was recorded. Decision to admit to an inpatient unit was made by the consulting cardiologist. Results were analyzed using chi2 statistics. One hundred thirty-four geriatric patients were admitted to the observation unit under the chest pain protocol during the study period. Seventeen percent of these patients were admitted to an inpatient unit from the observation unit versus 10.7% of the 394 chest pain patients who were under age 65 (P = 0.048). Geriatric patients were more likely to have coronary disease (31.3%) than nongeriatric patients (20.8%; P = 0.013). We then performed a subanalysis on the 404 patients (92 geriatric, 312 nongeriatric) who had no history of coronary disease. Geriatric patients without a history of coronary disease had a 12% inpatient admission rate from the observation unit versus a 7.7% admission rate for nongeriatric patients without a history of coronary disease (P = 0.2). Geriatric patients without a history of coronary artery disease were admitted to an inpatient unit at a rate consistent with a generally accepted observation failure rate of 10%. When screened appropriately, these patients may be appropriate for chest pain evaluation in the ED observation unit.


Utility of Alternate, Noncentromeric Chromosome 17 Reference Probe for Human Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization Testing in Breast Cancer Cases.
Context PathVysion-a US Food and Drug Administration-approved dual-probe human epidermal growth factor receptor ( HER2) fluorescence in situ hybridization (FISH) assay-provides the HER2: CEP17 ratio, a centromeric enumeration probe ratio for determining HER2 status in breast cancers. However, pericentromeric amplifications might then skew the HER2: CEP17 ratio, underestimating the HER2 status, which calls into question the use of CEP17 as the reference probe. Objective To analyze the utility of a noncentromeric chromosome 17 reference locus ( D17S122) to assess HER2 gene status in cases showing "nonclassical" FISH patterns with the CEP17 probe. Design The HER2 status of breast cancers accessioned in the years 2015-2017, displaying "nonclassical" or "equivocal" results by the PathVysion (Abbott Molecular Inc, Des Plaines, Illinois) HER2 DNA Probe Kit were reflex tested using an alternate FISH probe (ZytoLight SPEC/D17S122, ZytoVision, Bremerhaven, Germany) and interpreted with American Society of Clinical Oncology/College of American Pathologists 2013 guidelines. Results Of 37 cases, 17 were FISH equivocal. With the alternate D17S122 probe, 13 (76.4%) were reclassified as amplified, 3 (17.6%) as nonamplified, and a single case retained an equivocal result. Of the 17 cases with a chromosome 17 polysomy pattern, disomy, polysomy, and monosomy patterns were seen with 14 cases, 2 cases, and 1 case, respectively. Within the 17 cases with polysomy pattern, 3 (17.6%) demonstrated an unusual colocalization pattern of HER2 and CEP17, which was not observed with the alternate probe. Conclusions The denominator-stable alternate probe is a useful adjunct in the diagnostic armamentarium to analyze HER2 status in cases with FISH equivocal and complex patterns.


Relationship between disease activity indices and their individual components and radiographic progression in RA: a systematic literature review.
The aim of this study was to investigate the relationship between different disease activity indices (DAIs) and their individual components and radiographic progression in patients with RA. A systematic literature review until July 2013 was performed by two independent reviewers using the Medline and Embase databases. Longitudinal studies assessing the relationship between DAIs and single instruments and radiographic progression were included. The results were grouped based on the means of measurement (baseline vs time integrated) and analysis (univariable or multivariable). Fifty-seven studies from 1232 hits were included. All published studies that assessed the relationship between any time-integrated DAI including joint count and radiographic progression reached a statistically significant association. Among the single instruments, only swollen joint count and ESR were associated with radiographic progression, while no significant association was found for tender joint count. Data with respect to CRP are conflicting. Data on patient's global health, pain assessment and evaluator's global assessment are limited and do not support a positive association with progression of joint damage. Published data indicate that all DAIs that include swollen joints are related to radiographic progression while, of the individual components, only swollen joints and acute phase reactants are associated. Therefore composite DAIs are the optimal tool to monitor disease activity in patients with RA.


U-SMILE: a brief version of the Short Multidimensional Inventory on Lifestyle Evaluation.
Lifestyle Medicine comprises six domains: diet, substance use, physical activity, stress management, social connection, and sleep. The comprehensive assessment of lifestyle is challenging, but the "Short Multidimensional Inventory on Lifestyle Evaluation" (SMILE) was developed to fill out this gap. In this paper, we describe the development and the psychometric properties (internal consistency, concurrent and convergent validity) of a shorter version of the SMILE among university students. Data from a cross-sectional study including 369 students from 10 Brazilian universities were used. Considering a theoretical nomological net, we performed exploratory factor analysis to obtain the most parsimonious, interpretable and good-fitting model. The final model was called U-SMILE, comprised 24 items, and presented acceptable internal consistency (Cronbach's α = 0.73, McDonald's ω = 0.79). To evaluate the concurrent validity of the U-SMILE, we compared it to the original SMILE and found a high correlation between the instruments (Spearman's r= 0.94). Furthermore, we evaluated convergent validity by examining the U-SMILE correlation with the PHQ-9 (Spearman's r= -0.517), and GAD-7 (Spearman's r= -0.356), two validated instruments to screen for depression and anxiety, respectively. Our findings suggest that the U-SMILE is a valid instrument for assessing lifestyle among university students. We recommend that the use of U-SMILE to evaluate overall lifestyle scores rather than individual domain scores. Finally, we discuss the importance of clarifying the definitions of lifestyle and related constructs in future research.


Mechanism for the regioselective asymmetric addition of grignard reagents to malimides: A computational exploration.
We present a systematic theoretical investigation on the addition reaction of Grignard reagents to malimides to understand its mechanism as well as the origin of its regio- and diastereo-selectivity. The computations carried out at a hybrid density functional B3LYP/6-31G* level of theory reveal that (i) the addition of Grignard reagents with N,O-dimethylmalimide (1-methyl-3-methoxypyrrolidine-2,5-dione) occurs regioselectively at the alpha-carbonyl (C1) by passing through a cis-alpha-chelated precursor and affords stereoselectively cis-addition product, in qualitative agreement with the previous experimental observations; (ii) such regioselectivity is ascribed to the preferential chelation of Grignard reagent to the alpha-carbonyl (C1) over the coordination to the alpha-carbonyl (C4); (iii) its unusual trans-addition, in sharp contrast to the Cram chelation-type stereoselectivity for the reaction of aliphatic alpha- or beta-alkoxy carbonyl compounds, is due primarily to the rigidity of the five-membered ring skeleton of the malimide that favors the formation of the cis-alpha-chelated precursor; and (iv) poor regioselectivity is predicted for the reaction of O-TBDMS-protected malimide (1-benzyl-3-(tert-butyldimethylsilyloxy)pyrrolidine-2,5-dione) with Grignard reagent and can be ascribed to the large steric repulsion of the bulky TBDMS group and the electronic effects of the silyl group that remarkably destabilizes the alpha-chelated precursors and the corresponding transition states.


Chiral PSiSi-Ligand Enabled Iridium-Catalyzed Atroposelective Intermolecular C-H Silylation.
Catalytic enantioselective intermolecular C-H silylation offers an efficient approach for the rapid construction of chiral organosilicon compounds, but remains a significant challenge. Herein, a new type of chiral silyl ligand is developed, which enables the first iridium-catalyzed atroposelective intermolecular C-H silylation reaction of 2-arylisoquinolines. This protocol features mild reaction conditions, high atom economy, and remarkable yield with excellent stereoselectivity (up to 99 % yield, 99 % ee), delivering enantioenriched axially chiral silane platform molecules with facile convertibility. Key to the success of this unprecedented transformation relies on a novel chiral PSiSi-ligand, which facilitates the intermolecular C-H silylation process with perfect chem-, regio- and stereo-control via a multi-coordinated silyl iridium complex.


Risk factors for and progression of myopia in young Taiwanese men.
Abstract Purpose: To investigate the association between potential risk factors for myopia and its progression in young adult Taiwanese men. A survey of male military conscripts (aged 18-24 years) was conducted from February 2010 to March 2011 in Taiwan. Participants underwent comprehensive eye examinations, including measurements of axial length and corneal radius by optical biometry and non-cycloplegic autorefraction. Participants also provided self-reported progression of myopia and information regarding potential risk factors, including age, parental myopia, educational level, close work, outdoor activities, and urbanization. Of 5145 eligible participants, 5048 (98.11%) provided refraction and questionnaire data; 2316 (45.88%) of the 5048 also had biometric measurements. The prevalence of myopia was 86.1% in this group, with a mean refractive error of -3.66 diopters (D). Of the 5048 participants, 1376 (27.3%) had experienced progression of their myopia during the past year. There were trends for a higher prevalence of myopia among older participants (p = 0.014), those with a history of parental myopia (p < 0.001), higher levels of education (p = 0.001), increased time spent reading (p < 0.001), less time outdoors (p = 0.003), and higher levels of urbanization (p = 0.010). However, only parental myopia, close work, and higher urbanization levels were significantly associated with self-reported progression of myopia. Older age, parental myopia, higher educational level, close work, fewer outdoor activities, and higher urbanization level were associated with the prevalence of myopia in Taiwanese men.


Inducible nitric oxide synthase and AMP-activated protein kinase in basal forebrain during prolonged waking.
Activation of inducible nitric oxide synthase (iNOS) and the subsequent production of adenosine in basal forebrain in the early phase of prolonged waking suggest that the wake-promoting basal forebrain is selectively sensitive to the metabolic demands of waking. In this study, iNOS protein, and activation of AMP-activated protein kinase - a marker of decreased cellular energy charge - were measured in the rat basal forebrain and cortex during prolonged waking (1.5-, 3- and 6 h). The site-specific increase in iNOS protein was accompanied with AMP-activated protein kinase activation in the basal forebrain. In contrast, no changes were found in the cortex. These results further support the hypothesis that basal forebrain, as compared to cortex, is selectively sensitive to the effects of prolonged waking.


Impact of short-term refeeding on appetite and meal experiences in new onset adolescent eating disorders.
Restrictive eating disorders (ED) are increasing and represent a serious risk to the health of adolescent females. Restrictive ED in youth are often treated through aggressive short-term refeeding. Although evidence supports that this intervention is the "gold standard" for improving ED outcomes in youth, little research has specifically probed appetite and meal-related responses to this type of intensive, short-term refeeding in newly diagnosed individuals. Information about appetite and meal-related dysfunction could provide valuable insights regarding treatment-interfering features of ED in both acute inpatient and longer-term outpatient treatment. The purpose of this study was to evaluate the hunger, fullness, olfactory, and gustatory responses of adolescents with newly-diagnosed restrictive ED and to probe how and when these responses are altered by refeeding. Using a quasi-experimental ecologically valid methodology, this study described and compared profiles of hunger, fullness, olfactory, and gustatory responses in adolescent females (n = 15) with newly diagnosed restrictive ED at hospital admission (i.e., severe malnutrition) and after medical refeeding, in comparison to healthy controls (n = 15). Results showed that newly diagnosed (i.e., malnourished) adolescents with ED showed significantly different meal-related experiences than controls. Refeeding improved some of these differences, but not all. Following refeeding, females with ED continued to show lower hunger, greater fullness, and lower pleasantness of smell ratings compared to controls. Unpleasantness of taste ratings maladaptively increased, such that females who were re-fed reported more aversive scents than pre-treatment. Profiles of meal-related responses were also identified and compared between groups. The applicability of these findings are discussed within the context of critical periods of change during refeeding treatment and potentially promising intervention targets that might enhance treatment outcomes for adolescents with newly onset, restrictive ED.


[Chapter 6. The law on the modernization of our health system: the provisions regarding health data].
The Law on the Modernization of our Health System passed in 2016 exteds the scope of the medical secrecy by creating the patients' shared health record. All health professionnals involved in the care pathway have an access to all recorded information. The patient can access to it via a dedicated Internet website. The implementing decrees of this facility determine the modalities to share the information and frame the creation of this automated processing of personal data. At last, this law creates an open and secure access to helath data in the interest of collectivity. This open data in health is placed under the governance of the Health Data National Institute.


Formulation optimization, skin irritation, and efficacy characterization of a novel skin-lightening agent.
Skin-lightening preparations are used by people all over the world for a diverse range of dermatologic indications. The gold standard treatment for skin lightening is with hydroquinone but has been controversial because of the presence of several side effects. Therefore, there has been a constant search for developing new treatment alternatives. Furthermore, the new amendments and bans on animal testing by ECVAM have made the three-dimensional models like EpiDerm(™) and MelanoDerm(™) increasingly popular. This work aims at the formulation development for a new skin-lightening agent, SMA-012, followed by testing for skin irritation and efficacy. Formulation parameters such as concentration of SMA-012, amount of ethanol, effect of permeation enhancers and pH were first optimized using Franz cell experiments. Tape stripping and underlying skin assays were performed to analyze the amounts of SMA-012 in different layers of skin. The irritation potential and efficacy of the screened formulation were evaluated using Epiderm(™) and Melanoderm(™) models. Skin permeation experiments suggested that concentrations of 0.1% SMA-012, 35% ethanol, and pH of 8.5 to be the best formulation characteristics. This particular formulation was found to be nonirritant for short-term exposure, when tested in Epiderm(™) model and also significantly effective in decreasing the amount of melanin in pigmented skin equivalent models. SMA-012 shows a good promise as a skin-lightening agent for cosmetic and therapeutic applications. Additionally, our study demonstrates the application of skin equivalent models as alternatives to animal testing in studying the regulation of skin pigmentation.


Endogenous psychoses and T and B lymphocytes.
By means of the rosette test an increase of active T lymphocytes (aE rosettes) in percent and a decrease of B lymphocytes (EA and EAC rosettes) could be proved in 42 psychotic patients. When dividing the tested patients into the group of depressions and the group of schizophrenics, the active T lymphocytes were more numerous in the former, T and also B lymphocytes were less frequent in the latter than in the sample of the population. An analysis of the entire group in response to medication indicates that administering of these drugs will probably influence these differences, too. Patients taking lithium and patients treated with phenothiazine neuroleptics more frequently showed an increased percentage of activated cells (aE rosettes) than those patients treated with other drugs (P < .05). These changes seemed to be especially significant in patients taking both these drugs simultaneously, moreover, a high frequency of aE rosettes also produced a decrease of B lymphocytes--EA and EAC rosettes--in these patients. In all three cases P < .001.


Epithelial mesenchymal transition and cancer stem cell-like phenotypes facilitate chemoresistance in recurrent ovarian cancer.
Overcoming intrinsic and acquired chemoresistance is the major challenge in treating ovarian cancer patients. Initially nearly 75% of ovarian cancer patients respond favourably to chemotherapy, but subsequently the majority gain acquired resistance resulting in recurrence, cancer dissemination and death. This review summarizes recent advances in our understanding of the cellular origin and the molecular mechanisms defining the basis of cancer initiation and malignant transformation with respect to epithelial-mesenchymal transition (EMT) of ovarian cancer cells. We discuss the critical role of EMT frequently encountered in different phases of ovarian cancer progression and its involvement in regulating cancer growth, survival, migration, invasion and drug resistance. Using a model ovarian cancer cell line we highlight the relationship between EMT and the 'migrating cancer stem (MCS) cell-like phenotype' in response to drug treatment, and relate how these processes can impact on chemoresistance and ultimately recurrence. We propose the molecular targeting of distinct 'EMT transformed cancer stem-like cells' and suggest ways that may improve the efficacy of current chemotherapeutic regimens much needed for the management of this disease.


Recurrent inactivation of the PRDM1 gene in primary central nervous system lymphoma.
Primary lymphomas of the CNS (PCNSLs) show molecular features of the late germinal center exit B-cell phenotype and are impaired in their terminal differentiation as indicated by a lack of immunoglobulin class switching. Because the positive regulatory domain I protein with ZNF domain (PRDM1/BLIMP1) is a master regulator of terminal B-cell differentiation into plasma cells, we investigated a series of 21 PCNSLs for the presence of mutations in the PRDM1 gene and alterations in the expression pattern of the PRDM1 protein. Direct sequencing of all coding exons of the PRDM1 gene identified deleterious mutations associated with abrogation of PRDM1 protein expression in 4 of 21 (19%) PCNSLs. Thus, similar to systemic diffuse large B-cell lymphomas, PRDM1 may be a tumor suppressor in some PCNSL and contribute to lymphomagenesis by impairing terminal differentiation.


A simple device for the collection of cells sorted by flow cytometry.
A simple device for the collection of cells sorted by flow cytometry under sterile and nonsterile conditions is described. Cells collected in this manner reflect a high recovery rate with superior preservation of viability and cytomorphology. Key terms: Cell sorting, cytomorphology, testing collection device.


Midline malignant reticulosis.
A combined histological, ultrastructural and cytological study was performed on biopsy materials from nasal lesions of 2 patients with midline granuloma. The histological and ultrastructural features of the tissues were necrosis, inflammation and infiltration of atypical histiocytic cells. The DNA-content of these histiocytes exceeded the limits of the 5c Exceeding-Rate and the 2c Deviation Index. The morphological characteristics and the results of the DNA-cytophotometry classify the midline granuloma as a local malignant histiocytosis. Clinical follow-up of the cases suggests that radiation therapy offers a good prospect of treatment success.


[Tuberculosis, today].
Tuberculosis is still a major health and social problem because, on the one hand, we have witnessed the dismantling of the sanatoriums, with a reduced level of diagnostic suspicion, knowledge and expertise on the management of the disease, while, the other side, are considered migratory flows, the lower socio-economic faced by immigrants, the states of immunosuppression associated with HIV prevalence of malnutrition and other diseases, and the phenomenon of multidrug-resistance, which often turns out to be iatrogenic. The success of the strategy of control/elimination of tuberculosis promoted by the World Health Organization requires a well coordinated multidisciplinary approach in which everyone does their part, the general practitioner, the pulmonologist, the infectious disease specialist, and the microbiologist.


Linear variant of chronic cutaneous lupus erythematosus: a clue for the pathogenesis of chronic cutaneous lupus erythematosus?
Lesions of chronic cutaneous lupus erythematosus usually occur in a discoid pattern as erythematous, well-defined, scaly patches affecting face and scalp. The linear variant of chronic cutaneous lupus erythematosus is an exceptional clinical variation with band-like arranged lesions along the lines of Blaschko which represent the developmental growth pattern of embryonic ectodermal cells. Therefore, this unusual clinical observation may provide additional clues for the pathogenesis of chronic cutaneous lupus erythematosus. It is intriguing to hypothesize that linear lesions of chronic cutaneous lupus erythematosus may be caused by increased susceptibility of resident skin cells due to mutations of genes in early embryogenesis.


Nitrification inhibitors can increase post-harvest nitrous oxide emissions in an intensive vegetable production system.
To investigate the effect of nitrification inhibitors (NIs) 3,4-dimethylpyrazole phosphate (DMPP) and 3-methylpyrazole 1,2,4-triazole (3MP + TZ), on N2O emissions and yield from a typical vegetable rotation in sub-tropical Australia we monitored soil N2O fluxes continuously over an entire year using an automated greenhouse gas measurement system. The temporal variation of N2O fluxes showed only low emissions over the vegetable cropping phases, but significantly higher emissions were observed post-harvest accounting for 50-70% of the annual emissions. NIs reduced N2O emissions by 20-60% over the vegetable cropping phases; however, this mitigation was offset by elevated N2O emissions from the NIs treatments over the post-harvest fallow period. Annual N2O emissions from the conventional fertiliser, the DMPP treatment, and the 3MP + TZ treatment were 1.3, 1.1 and 1.6 (sem = 0.2) kg-N ha-1 year-1, respectively. This study highlights that the use of NIs in vegetable systems can lead to elevated N2O emissions by storing N in the soil profile that is available to soil microbes during the decomposition of the vegetable residues. Hence the use of NIs in vegetable systems has to be treated carefully and fertiliser rates need to be adjusted to avoid an oversupply of N during the post-harvest phase.


Associated factors with constipation and health-related quality of life in lung cancer patients with platinum-based chemotherapy: A cross-sectional study.
The main purpose of this study was to investigate current state of constipation for lung cancer (LC) patients receiving platinum-based chemotherapy. The relationships between social demography, clinical variables, psychological status, and constipation were analyzed. In addition, quality of life (QoL) in LC patients with constipation was also analyzed. One hundred LC patients participated in this cross-sectional study. Under the guidance of the researchers, Functional Living Index-Emesis, Piper Fatigue Scale, Patient Health Questionnaire, Generalized Anxiety Disorder-7, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0), Pittsburgh Sleep Quality Index, General Well-being Scale, Social Support Rate Scale, General Self-Efficacy Scale, and other related questionnaires were completed. The result showed the symptom of constipation was observed in 41 (41%) LC patients. The occurrence and development of constipation were associated with gender, food intake, exercise, nausea, fatigue, anxiety, depression, sleep disorders, and happiness. The study also found patients with constipation had significant lower QoL scores, especially the score in the general state. Constipation was very common in LC patients undergoing platinum-based chemotherapy. Reduced food intake and fatigue were the independent factors. Constipation significantly affects the QoL of the patients. Therefore, more attention should be paid to the risk factors of constipation in LC patients undergoing platinum-based chemotherapy, the earlier intervention was done to these patients, the better to improve their QoL.


HbQ-India associated with microcytosis: An uncommon hemoglobin variant associated with a common hematologic condition.
HbQ-India is a rare alpha chain variant that usually presents in the heterozygous state. Normally, HbQ-India is clinically silent. It becomes symptomatic when present in association with other conditions. We report a case of HbQ-India with concomitant presence of iron deficiency anemia. A 16-year-old female presented with weakness and pallor intermittently for six years. Complete blood count showed severe microcytic hypochromic anemia. Hemoglobin electrophoresis showed a prominent band in the S,D,G region. Tests for sickling were negative. High performance liquid chromatography (HPLC) showed a peak in the unknown window (4.70-4.90 min) suggestive of HbQ-India. Serum iron profile was suggestive of iron deficiency anemia. Based on the above findings, a diagnosis of coexistent HbQ-India-iron deficiency anemia was made. A family study revealed the father as having moderate anemia with similar findings while the mother was normal. Abnormal hemoglobin in the patient was confirmed by molecular diagnosis. HbQ variants are the alpha globin chain variants due to structural mutations (α64 Asp→His) inherited in autosomal dominant fashion. Three molecular variant types have been documented, namely HbQ-India, HbQ-Thailand and HbQ-Iran. Normally, HbQ is clinically silent. Therefore, careful screening of the samples using routine techniques like Hb electrophoresis and HPLC are needed for identification of such abnormal hemoglobin variants like HbQ-India.


AAV-Mediated Artificial miRNA Reduces Pathogenic Polyglucosan Bodies and Neuroinflammation in Adult Polyglucosan Body and Lafora Disease Mouse Models.
Adult polyglucosan body disease (APBD) and Lafora disease (LD) are autosomal recessive glycogen storage neurological disorders. APBD is caused by mutations in the glycogen branching enzyme (GBE1) gene and is characterized by progressive upper and lower motor neuron dysfunction and premature death. LD is a fatal progressive myoclonus epilepsy caused by loss of function mutations in the EPM2A or EPM2B gene. These clinically distinct neurogenetic diseases share a common pathology. This consists of time-dependent formation, precipitation, and accumulation of an abnormal form of glycogen (polyglucosan) into gradually enlarging inclusions, polyglucosan bodies (PBs) in ever-increasing numbers of neurons and astrocytes. The growth and spread of PBs are followed by astrogliosis, microgliosis, and neurodegeneration. The key defect in polyglucosans is that their glucan branches are longer than those of normal glycogen, which prevents them from remaining in solution. Since the lengths of glycogen branches are determined by the enzyme glycogen synthase, we hypothesized that downregulating this enzyme could prevent or hinder the generation of the pathogenic PBs. Here, we pursued an adeno-associated virus vector (AAV) mediated RNA-interference (RNAi) strategy. This approach resulted in approximately 15% reduction of glycogen synthase mRNA and an approximately 40% reduction of PBs across the brain in the APBD and both LD mouse models. This was accompanied by improvements in early neuroinflammatory markers of disease. This work represents proof of principle toward developing a single lifetime dose therapy for two fatal neurological diseases: APBD and LD. The approach is likely applicable to other severe and common diseases of glycogen storage.


Identification of attention and cognitive control networks in a parametric auditory fMRI study.
In the competition for limited processing resources, top-down attention and cognitive control processes are needed to separate relevant from irrelevant sensory information and to interact with the environment in a meaningful way. The demands for the recruitment of top-down control processes depend on the relative salience of the competing stimuli. In the present event-related functional magnetic resonance imaging (fMRI) study we investigated the dynamics of neuronal networks during varying degrees of top-down control demands. We tested 20 participants with a dichotic auditory discrimination task in which the relative perceptual salience of two simultaneously presented syllables was parametrically varied by manipulating the inter-aural intensity differences (IIDs) and instructing the subjects to selectively attend to either the louder or weaker of the two stimuli. A significant interaction of IID manipulation and attentional instruction was detected bilaterally in the inferior parietal lobe and pre-supplementary motor area, and in the precentral gyrus, anterior cingulate cortex, and inferior frontal gyrus of the right hemisphere. The post hoc analysis of the interaction pattern allowed for an assignment of these regions to either of two sets of regions which can be interpreted to constitute two different brain networks: a fronto-parietal attention control network, involved in the integration of saliency-based and instruction-based processing preferences, and a medial-lateral frontal cognitive control network, involved in the processing of the conflicts arising in the attempt to follow the attentional instruction in face of the varying inter-aural stimulus salience.


[Nuclear matrix protein 22 and urinary cytology test in the diagnosis of bladder cancer: a meta-analysis].
Systematic reviews of diagnostic value of the nuclear matrix protein 22 (NMP22) and urine cytology for bladder cancer. Development of inclusion criteria, exclusion criteria and search strategy to retrieve relevant literature. Screening the literature according to inclusion criteria and exclusion criteria. Quality evaluation of the screening and data extraction, using MetaDiSc 1.4 software for Meta analysis. In total, 266 relevant studies were searched, excluded 256 studies, and then 10 studies were included, with 4895 patients involved. The pooled sensitivity and specificity of NMP22 to detect bladder cancer were 0.76 (95%CI: 0.74 - 0.77), 0.80 (95%CI: 0.79 - 0.82), respectively. The pooled sensitivity and specificity of urine cytology were 0.36 (95%CI: 0.34 - 0.38), 0.94 (95%CI: 0.93 - 0.95), respectively. The area under curve (AUC) for NMP22 and urine cytology were 0.8533 and 0.8628, and Q(*) index were 0.7863 and 0.7934, respectively. For the diagnosis of bladder cancer, the sensitivity of NMP22 was higher than urine cytology, but the specificity was lower than urine cytology. Overall diagnostic performance of NMP22 was medium, it was no significant difference with urine cytology. It can't replace urine cytology now.


Development of allergic sensitization and its relevance to paediatric asthma.
The purpose of this review is to summarize the recent evidence on the distinct atopic phenotypes and their relationship with childhood asthma. We start by considering definitions and phenotypic classification of atopy and then review evidence on its association with asthma in children. It is now well recognized that both asthma and atopy are complex entities encompassing various different sub-groups that also differ in the way they interconnect. The lack of gold standards for diagnostic markers of atopy and asthma further adds to the existing complexity over diagnostic accuracy and definitions. Although recent statistical phenotyping studies contributed significantly to our understanding of these heterogeneous disorders, translating these findings into meaningful information and effective therapies requires further work on understanding underpinning biological mechanisms. The disaggregation of allergic sensitization may help predict how the allergic disease is likely to progress. One of the important questions is how best to incorporate tests for the assessment of allergic sensitization into diagnostic algorithms for asthma, both in terms of confirming asthma diagnosis, and the assessment of future risk.


Effects of overlapping electric double layer on mass transport of a macro-solute across porous wall of a micro/nanochannel for power law fluid.
Effects of overlapping electric double layer and high wall potential on transport of a macrosolute for flow of a power law fluid through a microchannel with porous walls are studied in this work. The electric potential distribution is obtained by coupling the Poisson's equation without considering the Debye-Huckel approximation. The numerical solution shows that the center line potential can be 16% of wall potential at pH 8.5, at wall potential -73 mV and scaled Debye length 0.5. Transport phenomena involving mass transport of a neutral macrosolute is formulated by species advective equation. An analytical solution of Sherwood number is obtained for power law fluid. Effects of fluid rheology are studied in detail. Average Sherwood number is more for a pseudoplastic fluid compared to dilatant upto the ratio of Poiseuille to electroosmotic velocity of 5. Beyond that, the Sherwood number is independent of fluid rheology. Effects of fluid rheology and solute size on permeation flux and concentration of neutral solute are also quantified. More solute permeation occurs as the fluid changes from pseudoplastic to dilatant.


[Brief introduction to the development of ancient history of paediatric diagnosis of traditional Chinese medicine].
As an important part of paediatric science, paediatric diagnosis was in the initial stage of its development before the Song Dynasty. The main measures of diagnosing diseases were observation and pulse palpation, especially the latter. The rapid development of paediatrics in the Song Dynasty necessitated thepaediatric diagnosis to develop further, emphasizing the spiritual expressions of the eyes and fingerprint, with its special features gradually developed in the period of the Jin and Yuan Dynasties.During this period, the paediatrics diagnosis was developed on the basis of the previous generations, with equal importance paid to both observation and pulse feeling. In the period of the Ming and Qing Dynasties the four paediatric diagnostics were constantly enriched with attentions paid to the use of multiple approaches and thus the diagnostics was perfected day by day.


Potential Mechanisms Underlying the Deleterious Effects of Synthetic Cannabinoids Found in Spice/K2 Products.
The chief psychoactive constituent of many bioactive phytocannabinoids (Δ⁸-tetrahydrocannabinol, Δ⁸-THC) found in hemp, cannabis or marijuana plants are scientifically denoted by the Latin term, Cannabis sativa, acts on cell surface receptors. These receptors are ubiquitously expressed. To date, two cannabinoid receptors have been cloned and characterized. Cannabinoid receptor type 1 (CB1R) is found to serve as the archetype for cannabinoid action in the brain. They have attracted wide interest as the mediator of all psychoactive properties of exogenous and endogenous cannabinoids and they are abundantly expressed on most inhibitory and excitatory neurons. Recent evidence established that cannabinoid receptor type 2 (CB2R) is also expressed in the neurons at both presynaptic and postsynaptic terminals and are involved in neuropsychiatric effects. Distinct types of cells in many regions in the brain express CB2Rs and the cellular origin of CB2Rs that induce specific behavioral effects are emerging. To mimic the bliss effects of marijuana, synthetic cannabinoids (SCBs) have been sprayed onto plant material, and this plant material has been consequently packaged and sold under brand name "Spice" or "K2". These SCBs have been shown to maintain their affinity and functional activity for CB1R and CB2R and have been shown to cause severe harmful effects when compared to the effects of Δ⁸-THC. The present review discusses the potential brain mechanisms that are involved in the deleterious effects of SCBs.


The Effect of Training Sample Size on the Prediction of White Matter Hyperintensity Volume in a Healthy Population Using BIANCA.
Introduction: White matter hyperintensities of presumed vascular origin (WMH) are an important magnetic resonance imaging marker of cerebral small vessel disease and are associated with cognitive decline, stroke, and mortality. Their relevance in healthy individuals, however, is less clear. This is partly due to the methodological challenge of accurately measuring rare and small WMH with automated segmentation programs. In this study, we tested whether WMH volumetry with FMRIB software library v6.0 (FSL; https://fsl.fmrib.ox.ac.uk/fsl/fslwiki) Brain Intensity AbNormality Classification Algorithm (BIANCA), a customizable and trainable algorithm that quantifies WMH volume based on individual data training sets, can be optimized for a normal aging population. Methods: We evaluated the effect of varying training sample sizes on the accuracy and the robustness of the predicted white matter hyperintensity volume in a population (n = 201) with a low prevalence of confluent WMH and a substantial proportion of participants without WMH. BIANCA was trained with seven different sample sizes between 10 and 40 with increments of 5. For each sample size, 100 random samples of T1w and FLAIR images were drawn and trained with manually delineated masks. For validation, we defined an internal and external validation set and compared the mean absolute error, resulting from the difference between manually delineated and predicted WMH volumes for each set. For spatial overlap, we calculated the Dice similarity index (SI) for the external validation cohort. Results: The study population had a median WMH volume of 0.34 ml (IQR of 1.6 ml) and included n = 28 (18%) participants without any WMH. The mean absolute error of the difference between BIANCA prediction and manually delineated masks was minimized and became more robust with an increasing number of training participants. The lowest mean absolute error of 0.05 ml (SD of 0.24 ml) was identified in the external validation set with a training sample size of 35. Compared to the volumetric overlap, the spatial overlap was poor with an average Dice similarity index of 0.14 (SD 0.16) in the external cohort, driven by subjects with very low lesion volumes. Discussion: We found that the performance of BIANCA, particularly the robustness of predictions, could be optimized for use in populations with a low WMH load by enlargement of the training sample size. Further work is needed to evaluate and potentially improve the prediction accuracy for low lesion volumes. These findings are important for current and future population-based studies with the majority of participants being normal aging people.


Effects of MreB paralogs on poly-γ-glutamic acid synthesis and cell morphology in Bacillus amyloliquefaciens.
Actin-like MreB paralogs play important roles in cell shape maintenance, cell wall synthesis and the regulation of the D,L-endopeptidases, CwlO and LytE. The gram-positive bacteria, Bacillus amyloliquefaciens LL3, is a poly-γ-glutamic acid (γ-PGA) producing strain that contains three MreB paralogs: MreB, Mbl and MreBH. In B. amyloliquefaciens, CwlO and LytE can degrade γ-PGA. In this study, we aimed to test the hypothesis that modulating transcript levels of MreB paralogs would alter the synthesis and degradation of γ-PGA. The results showed that overexpression or inhibition of MreB, Mbl or MreBH had distinct effects on cell morphology and the molecular weight of the γ-PGA products. In fermentation medium, cells of mreB inhibition mutant were 50.2% longer than LL3, and the γ-PGA titer increased by 55.7%. However, changing the expression level of mbl showed only slight effects on the morphology, γ-PGA molecular weight and titer. In the mreBH inhibition mutant, γ-PGA production and its molecular weight increased by 56.7% and 19.4%, respectively. These results confirmed our hypothesis that suppressing the expression of MreB paralogs might reduce γ-PGA degradation, and that improving the cell size could strengthen γ-PGA synthesis. This is the first report of enhanced γ-PGA production via suppression of actin-like MreB paralogs.


[Outcome of pregnancy in patient with cloacal dysgenesis].
The cloacal dysgenesis or persistent cloaca is an anomaly included in urogenital tract malformations (UGM) and, in particular, in anomalies due to a missed development of the urogenital septum. The UGM occur during 6-11th weeks of gestation owing to a stop and/or alteration of the normal development and subdivision process of the cloaca, the embryonic structure from which gives origin to the ano-rectal segment of midgut, bladder, ureters, vagina and uterus. The case of a patient submitted to many surgical treatments for urogenital tract congenital malformations is described; when pregnant, she carried other pregnancy until the 34th week of gestation, giving birth a newborn by cesarean section. The patient was checked constantly for her general conditions and, in particular, her renal functions by an active collaboration between internist, nephrologist and gynecologist.


Haemophilia management: the application of DNA analysis for prenatal diagnosis.
The haemophilias are chronic debilitating disorders which cause significant morbidity for the patient and may affect the whole family. An important part of the management of these disorders is the provision of accurate carrier detection and prenatal diagnosis in conjunction with genetic counselling services. We report the results of carrier detection and prenatal diagnosis obtained over a two year period using recombinant DNA techniques. Eighty-seven individuals from 15 families with either haemophilia A or B have been evaluated using informative intragenic factor VIII or IX restriction fragment length polymorphisms. Chorionic villi biopsies for prenatal diagnosis have been performed in four subjects, revealing two female carriers, one normal male, one normal of unknown sex and one haemophiliac male. The use of genotypic diagnosis of haemophilia A and B, in conjunction with conventional assays, is now a routine part of the modern management of haemophilia and many other inherited disorders.


Dispensing errors in Lebanese community pharmacies: incidence, types, underlying causes, and associated factors.
To assess the incidence, types, the causes of as well as the factors associated with dispensing errors in community pharmacies in Lebanon. An observational cross-sectional study was conducted in 286 pharmacies located all over Lebanon. Data were collected by senior pharmacy students during their experiential learning placement. Collected data included information on the types of dispensing errors, the underlying causes of errors, handling approaches, and used strategies for dispensing error prevention. Data were analyzed using multiple logistic regression to determine factors that were associated with dispensing errors. In the twelve thousand eight hundred sixty dispensed medications, there were 376 dispensing errors, yielding an error rate of 2.92%. Of these errors, 67.1% (252) corresponded to dispensing near-miss errors. The most common types of dispensing errors were giving incomplete/incorrect use instructions (40.9% (154)), followed by the omission of warning(s) (23.6% (89)). Work overloads/time pressures, illegible handwriting, distractions/interruptions, and similar drug naming/packaging were reported as the underlying causes in 55% (206), 23.13% (87), 15.15 % (57), and 7% (26) of the errors respectively. Besides, high prescription turnover volume, having one pharmacist working at a time, and extended working hours, were found to be independent factors that were significantly associated with dispensing errors occurrence (p<0.05). This study sheds light on the need to establish national strategies for preventing dispensing errors in community pharmacies to maintain drug therapy safety, considering identified underlying causes and associated factors.


Vertigo syndromes associated with earthquake in Georgia.
Georgia experienced strong earthquake, after this event the amount of patients with vestibular symptoms increased. Study evaluates 60 outpatients (51 females, 9 males) aged from 18 to 85 years old who applied at outpatient clinics with vestibular complaints in the initial weeks following the earthquake. BPPV and PPV are the most common causes of vertigo. "Idiopathic" BPPV is the cause of BPPV in 50-70% of cases. Head trauma, vestibular neuritis, Meniere disease, migraine are the most common causes of "secondary" BPPV. (PPV) syndrome characterized by dizziness, subjective disturbance of balance and by perception of illusory body perturbations, usually triggered by perceptual stimulus. PPV frequently associated with anxiety symptoms in patients with obsessive-compulsive type personality. The study revealed "Idiopathic" BPPV in 49 cases and "secondary" types BPPV in 11 cases. 37 previously documented histories of BPPV patients had features typical for posterior semisercircular canal BPPV and 23 patients experienced subjective disturbance symptoms like BPPV, but there were no abnormal responses in their vestibular testing. It is assumed that earthquake could manifest psychogenic vertigo with panic attacks, anxiety, agoraphobia, PPV and could provoke a transition from organic vertigo to PPV. It is concluded that psychological stress play an important role in occurring "secondary" BPPV, earthquake may trigger exacerbation of "secondary" BPPV and could be provoked factor to developing psychogenic vertigo, mostly PPV.


Tb- and Eu-doped yttrium oxyselenides as novel absorber layers for superstrate thin-film photovoltaics: improved spectral optical absorption and green-red phosphor activation.
To generate and deliver alternative sustainable energy in the face of the current energy crisis, new materials that can capture solar energy and transform it into other useful energies are required. Rare-earth (RE) oxychalcogenides are now being used more frequently as up/down-conversion materials in established photovoltaic (PV) devices to boost their PV performance. Here, through an efficient microwave assisted synthesis procedure, novel nanoplate/sheet shaped nanomaterials of yttrium oxyselenide (YOSe) and its analogues doped with Tb and Eu (YOSe:Tb and YOSe:Eu) were successfully synthesized. Analyses of the structure, stability, morphology, light absorption, and electrochemistry were performed. This work showed that the parent YOSe exhibited green (543 nm) and red (615 nm) emission luminescence when doped with Tb and Eu with a luminescence quantum yield (LQY) of 0.56 and 0.53 for YOSe:Tb and YOSe:Eu nanomaterials, respectively. The surface and material conductivity of YOSe improved with the addition of the dopant elements, with the best outcome shown in YOSe:Eu, according to electrokinetic research evidenced by the enhanced current peaks, reduced charge-transfer resistance (Rct) and low impedance magnitude (Zmag) through electrochemical experiments. These improvements were induced by the distinctive properties of the dopant elements. PCEs of 0.25%, 0.67%, and 1.20% were obtained for YOSe, YOSe:Tb, and YOSe:Eu-based PV devices, respectively, using the nanomaterials as novel absorber layers in a superstrate device design. Our results can initiate further exploitation of the doped host structure for effective down-conversion NIR luminescence for applications in PV devices and to boost the PV performance of existing solar cells.


Effectiveness and Safety of Bivalirudin During Percutaneous Coronary Intervention in Acute Coronary Syndrome in the Real World: CARTAGOMAX Study.
The CARTAGOMAX study assessed the safety and efficacy of bivalirudin during real-world cardiac intervention. This was a single-center prospective study. Patients with acute coronary syndrome undergoing percutaneous coronary intervention were anticoagulated with bivalirudin alone or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor. Propensity score matching was performed to control for baseline imbalances and yielded 1168 patients. There was lower incidence of the composite outcome of death from any cause or major bleeding at 30 days (P = 0.005), 6 months (P = 0.005), and 12 months (P = 0.001) of follow-up in the bivalirudin group, compared with the heparin plus glycoprotein inhibitor group. The administration of bivalirudin was associated with lower rate of all-cause mortality at 1 year of follow-up (P = 0.009). The incidence of major bleeding was lower in the bivalirudin group at 1, 6, and 12 months of follow-up (P = 0.002, P = 0.013 and P = 0.017, respectively). The incidence of stroke and reinfarction were similar between groups during follow-up. The rate of stent thrombosis were slightly higher in the bivalirudin group, without reaching statistical significance at 1 and 12 months of follow-up (P = 0.06, P = 0.04, P = 0.07 at 1, 6, and 12 months, respectively). The CARTAGOMAX study found that the use of bivalirudin during percutaneous coronary intervention was associated with lower incidence of the composite outcome of death from any cause or major bleeding during follow-up. The use of bivalirudin was associated with similar rates of stroke, reinfarction, and stent thrombosis compared with heparin plus glycoprotein inhibitor. Bivalirudin proved to be a safe and effective anticoagulant during percutaneous coronary intervention.


Progress in the Understanding of Estrogen Receptor Alpha Signaling in Triple-Negative Breast Cancer: Reactivation of Silenced ER-α and Signaling through ER-α36.
Triple-negative breast cancer (TNBC) is an aggressive tumor that accounts for approximately 15% of total breast cancer cases. It is characterized by poor prognosis and high rate of recurrence compared to other types of breast cancer. TNBC has a limited range of treatment options that include chemotherapy, surgery, and radiation due to the absence of estrogen receptor alpha (ER-α) rendering hormonal therapy ineffective. However, possible targets for improving the clinical outcomes in TNBC exist, such as targeting estrogen signaling through membranous ER-α36 and reactivating silenced ER-α. It has been shown that epigenetic drugs such as DNA methyltransferase and histone deacetylase inhibitors can restore the expression of ER-α. This reactivation of ER-α, presents a potential strategy to re-sensitize TNBC to hormonal therapy. Also, this review provides up-to-date information related to the direct involvement of miRNA in regulating the translation of ER-α mRNA. Specific epi-miRNAs can regulate ER-α expression indirectly by post-transcriptional targeting of mRNAs of enzymes that are involved in DNA methylation and histone deacetylation. Furthermore, ER-α36, an alternative splice variant of ER-α66, is highly expressed in ER-negative breast tumors and activates MAPK/ERK pathway, promoting cell proliferation, escaping apoptosis, and enhancing metastasis. In the future, these recent advances may be helpful for researchers working in the field to obtain novel treatment options for TNBC, utilizing epigenetic drugs and epi-miRNAs that regulate ER-α expression. Also, there is some evidence to suggest that drugs that decrease the expression of ER-α36 may be effective in treating TNBC.


Transposition of the great trochanter in the treatment of congenital dysplasia of the hip and Perthes disease.
The authors report their results in 17 hips treated by distal transposition of the great trochanter in patients suffering from coxa vara resulting either from congenital dislocation of the hip or Perthes disease. The results, evaluated both clinically and radiologically, were excellent. We would emphasize that distal transposition inevitably implies lateralization, which restores the normal musculo-skeletal relationship. The "hyperlordosis" sign is described and its mechanism explained. This simple physical sign is a useful test in evaluating the indications for this type of operation.


An e-learning platform for aerospace medicine.
The appeal of online education and distance learning as an educational alternative is ever increasing. To support and accommodate the over-specialized knowledge available by different experts, information technology can be employed to develop virtual distributed pools of autonomous specialized educational modules and provide the mechanisms for retrieving and sharing them. New educational standards such as SCORM and Healthcare LOM enhance this process of sharing by offering qualities like interoperability, accessibility, and reusability, so that learning material remains credible, up-to-date and tracks changes and developments of medical techniques and standards through time. Given that only a few e-learning courses exist in aerospace medicine the material of which may be exchanged among teachers, the aim of this paper is to illustrate the procedure of creating a SCORM compliant course that incorporates notions of recent advances in social web technologies. The course is in accordance with main educational and technological details and is specific to pulmonary disorders in aerospace medicine. As new educational trends place much emphasis in continuing medical education, the expansion of a general practitioner's knowledge in topics such as aviation and aerospace pulmonary disorders for crew and passengers becomes a societal requirement.


Childhood somatic complaints predict generalized anxiety and depressive disorders during young adulthood in a community sample.
Children with somatic complaints are at increased risk for emotional disorders during childhood. Whether this elevated risk extends into young adulthood - and to which specific disorders - has rarely been tested with long-term prospective-longitudinal community samples. Here we test whether frequent and recurring stomach aches, headaches, and muscle aches during childhood predict emotional disorders in adulthood after accounting for childhood psychiatric and physical health status and psychosocial adversity. The Great Smoky Mountains Study is a community representative sample with 1420 participants. Children/adolescents were assessed 4-7 times between ages 9-16 years. They were assessed again up to three times between ages 19-26 years. Childhood somatic complaints were coded when subjects or their parents reported frequent and recurrent headaches, stomach aches, or muscular/joint aches at some point when children were aged 9-16 years. Psychiatric disorders were assessed with the Child and Adolescent Psychiatric Assessment and the Young Adult Psychiatric Assessment. Frequent and recurrent somatic complaints in childhood predicted adulthood emotional disorders. After controlling for potential confounders, predictions from childhood somatic complaints were specific to later depression and generalized anxiety disorder. Long-term predictions did not differ by sex. Somatic complaints that persisted across developmental periods were associated with the highest risk for young adult emotional distress disorders. Children from the community with frequent and recurrent physical distress are at substantially increased risk for emotional distress disorders during young adulthood. Preventions and interventions for somatic complaints could help alleviate this risk.


Non-anaplastic peripheral T cell lymphoma in children and adolescents-an international review of 143 cases.
Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified was the largest subgroup, followed by extranodal NK/T cell lymphoma, hepatosplenic T cell lymphoma (HS TCL), and subcutaneous panniculitis-like T cell lymphoma (SP TCL). Probability of overall survival (pOS) at 5 years for the whole group was 0.56 ± 0.05, and probability of event-free survival was (pEFS) 0.45 ± 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 ± 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 ± 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 ± 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype-based treatment recommendations for children and adolescents with PTCL.


Rhodium-catalyzed intermolecular oxidative cross-coupling of (hetero)arenes with chalcogenophenes.
A straightforward and efficient method for the rhodium-catalyzed intermolecular oxidative cross-coupling of arenes and heteroarenes with thio- and selenophene derivatives (chalcogenophenes) via double C-H bond cleavage has been developed by using Cu(OAc)2/AgSbF6 as an oxidant. The reaction is applicable to a wide range of (hetero)arenes carrying a directing group and chalcogenophenes to yield substituted biaryl heterocyclic derivatives and oligothiophene derivatives in moderate to high yields.


Prevalence of resistance to antituberculosis drugs in Riyadh and a review of previous reports.
Resistance to antituberculosis drugs is an important cause of treatment failure. We evaluated the prevalence and pattern of antituberculosis drug resistance in the central region of Saudi Arabia, and reviewed previous reports from Saudi Arabia. We retrospectively examined the records of sputum smear and culture-positive pulmonary tuberculosis patients admitted consecutively from 1998 through 1999 in a main referral hospital in Riyadh, and analyzed drug sensitivity reports. We also reviewed previous reports on antituberculosis drug resistance in Saudi Arabia. Of 515 patients with pulmonary tuberculosis, 80 (15.5%) had resistance to at least one antituberculosis drug. Resistance to streptomycin was most frequent (9.7% ), followed by rifampicin (9.5%), isoniazid (4.3%), and ethambutol (0.2%). Resistance to one antituberculosis drug was found in 8.9%, resistance to two drugs in 5.2%, resistance to three drugs in 1.2%, and resistance to four drugs in 0.2%. Multidrug resistance (defined as resistance to at least isoniazid and rifampicin) was found in 1.9% of patients. A literature review including 6114 patients in Saudi Arabia showed that resistance against streptomycin was most common (8.8%), followed by rifampicin (8%), and isoniazid (7.2%). Of the 6114 patients, 6.8% patients were resistant to only one drug, 3.6% were resistant to two drugs, and 3.7% to three drugs. The high prevalence of rifampicin resistance and resistance to multiple drugs in the Riyadh region and in other parts of Saudi Arabia is a major challenge to the control of tuberculosis in this country. Efforts should be made to prevent the emergence of further antituberculosis drug resistance.


Applying and comparing empirical and full Bayesian models in study of evaluating relative risk of suicide among counties of Ilam province.
Disease mapping includes a set of statistical techniques that provides maps based on estimates of diseases rates. Bayesian ones are the most important models in this field. They consider prior information on changes in the disease rates in overall map and spatial pattern of the disease. These include a broad range of models with their own formulation, characteristics, strengths, and weaknesses. In the present study, we explain and compare three important and widely-used Bayesian models in the study of evaluating relative risk of suicide in Ilam province. In this applied-ecological research, suicide incidence in Ilam province in 2008 and 2009 was analyzed by use of Gamma-Poisson, Log-normal, and BYM Bayesian models. Models were fitted to data using WinBUGS software. Fitting the three models showed that Darehshahr and Shirvan-Chrdavol had the highest and the lowest relative risk of suicide, respectively (relative risks based on Gamma-Poisson, Log-normal, and BYM models were 2.243, 2.275, and 2.279 for Dareshahr and 0.321, 0.321, and 0.319 for Shirvan-Chrdavol, respectively). Despite some differences in estimates, the ranks of relative risks in counties in all three models are the same. The counties based on the relative risks of suicide from the most to the least are: Darehshahr, Ilam, Dehloran, Eyvan, Abdanan, Mehran, Malekshahi, and Shirvan-Chrdavol.


High prevalence of exocrine pancreatic insufficiency in diabetes mellitus. A multicenter study screening fecal elastase 1 concentrations in 1,021 diabetic patients.
There have been numerous reports on pancreatic exocrine dysfunction in diabetes mellitus using either direct or indirect function tests. The measurement of fecal elastase 1 concentrations (FEC) has been used as a screening tool for exocrine pancreatic disease in different patient groups indicating a high prevalence of exocrine dysfunction in diabetic populations. In this study we had the opportunity to study more than 1,000 diabetic patients to confirm recent observations in smaller populations. FEC were measured by ELISA in 323 patients with type 1 and 697 type 2 diabetes mellitus. Subjects with a history of alcohol abuse, gastrointestinal surgery, cancer or inflammatory diseases were not included. Diabetes history and clinical data were recorded using a standard case report form. 1,021 patients (334 female, 687 male; mean age 50 years; mean diabetes duration 11 years; mean age at onset of diabetes 39 years) were studied. FEC was normal (>200 microg/g) in 59.3% and severely reduced (<100 microg/g) in 22.9%. There were significant differences between type 1 and type 2 patients as well as between insulin-treated and non-insulin-treated patients. Furthermore, there were weak associations between FEC and diabetes duration, age at onset of diabetes and body mass index, respectively. We could confirm that both type 1 and type 2 diabetic patients show pathological exocrine function in high prevalence. Exocrine insufficiency seems to be correlated to early onset of endocrine failure, long-lasting diabetes mellitus and low body mass index levels.


Melanocytic matricoma. Report of a further case with clinicopathological and immunohistochemical findings, differential diagnosis and review of the literature.
Melanocytic matricoma is a rare recently described lesion. It usually presents as a pigmented, dark-papular, crusted lesion on sun-damaged skin of adult patients. Histopathologically, these lesions are characterized by well-circumscribed nodules composed of matrical and supramatrical cells with clustered shadow cells, and admixed pigmented dendritic melanocytes. It differs from matricomas and pilomatricomas by its lack of calcification, cyst formation, granulomas, and connections to the epidermis and other adnexal structures. The clinical differential diagnosis includes hemangioma, pigmented basal cell carcinoma, and melanoma. Melanocytic matricoma presumably is the representation of an epithelial-melanocytic interaction in the anagen phase of the hair cycle. An extensive search of the medical literature revealed 11 reports of benign melanocytic matricomas and 5 malignant counterparts. We report an additional case of melanocytic matricoma with discussion of clinicopathologic features and differential diagnosis.


Maternal exposure to aircraft emitted ultrafine particles during pregnancy and likelihood of ASD in children.
There is increasing evidence for adverse health effects associated with aircraft-emitted particulate matter (PM) exposures, which are largely in the ultrafine (PM0.1) size fraction, but no previous study has examined neurodevelopmental outcomes. To assess associations between maternal exposure to aircraft ultrafine particles (UFP) during pregnancy and offspring autism spectrum disorder (ASD) diagnosis. This large, representative cohort study included 370,723 singletons born in a single healthcare system. Demographic data, maternal health information, and child's ASD diagnosis by age 5 were extracted from electronic medical records. Aircraft exposure estimates for PM0.1 were generated by the University of California Davis/California Institute of Technology Source Oriented Chemical Transport model. Cox proportional hazard models were used to assess associations between maternal exposure to aircraft PM0·1 in pregnancy and ASD diagnosis, controlling for covariates. Over the course of follow-up, 4,554 children (1.4 %) were diagnosed with ASD. Increased risk of ASD was associated with maternal exposure to aircraft PM0.1 [hazard ratio, HR: 1.02, (95 % confidence interval (CI): 1.01-1.03) per IQR = 0.02 µg/m3 increase during pregnancy. Associations were robust to adjustment for total PM0.1 and fine particulate matter (PM2.5), near-roadway air pollution, and other covariates. Noise adjustment modestly attenuated estimates of UFP effects, which remained statistically significant. The results strengthen the emerging evidence that maternal particulate matter exposure during pregnancy is associated with offspring ASD diagnosis and identify aircraft-derived PM0.1 as novel targets for further study and potential regulation.


The therapeutic impact of abdominal ultrasound in patients with acute abdominal symptoms.
The technical performance of abdominal ultrasound in the investigation of acute abdominal pain has been thoroughly investigated but its therapeutic effects are less well understood. We aimed to determine the therapeutic effect of abdominal ultrasound in the investigation of acute abdominal pain. A pre- and post-intervention observational study design was used to determine the diagnostic and therapeutic effects of abdominal ultrasound for acute abdominal pain. Referring clinicians completed a pre-ultrasound questionnaire that detailed their leading diagnosis, confidence in this and intended management in 100 consecutive adult patients. Following ultrasound a second questionnaire was completed. This again detailed the leading diagnosis, confidence in this and their intended management. Clinicians quantified the management contribution of ultrasound both for the individual case in question and in their clinical experience generally. The leading diagnosis was either confirmed or rejected in 72 patients and a new diagnosis provided where no prior differential diagnosis existed in 10. Diagnostic confidence increased significantly following ultrasound (mean score 6.5 pre-ultrasound vs 7.6 post-ultrasound, P < 0.001). Intended management changed following ultrasound in 22 patients; 15 intended laparotomies were halted and a further seven patients underwent surgery where this was not originally intended. Ultrasound was rated either 'very' or 'moderately' helpful in 87% of patients, with 99% of clinicians finding it either 'very' or 'moderately' helpful generally. Abdominal ultrasound has considerable diagnostic and therapeutic effect in the setting of acute abdominal pain.


Monoclonal antibodies against different epitopes of a 40 Kd capsid protein of infectious bursal disease viruses.
Nine monoclonal antibodies (Mab) against a 40 Kd capsid protein of infectious bursal disease virus (IBDV) strain P3009 were isolated. They were characterized by enzyme-linked immunosorbent assay, indirect fluorescent antibody staining and virus neutralization. They were divided into two groups concerning virus neutralization. Group I Mabs were able to neutralize virus infectivity; however, group II Mabs were not. Competitive binding assays using these Mabs demonstrated the existence of two distinct antigenic regions (A and B) on the 40 Kd protein. Region A was recognized by group I Mabs and region B was by group II Mabs. The binding reaction with group I Mabs was affected by denaturing of the viral proteins, indicating that the antigenic region involving neutralization was conformation-dependent. The results of enzyme-linked immunosorbent assays and virus neutralization tests suggested that group I Mabs might react with one epitope within region A and group II Mabs with 2 or 3 epitopes within region B.


[Recurrent hypersomnia].
Recurring hypersomnias are described according to 3 etiological groups: 1) idiopathic - the Kleine Levin syndrome and its clinical variants - 2) organic and 3) psychiatric. The typical form of the Kleine Levin syndrome is remarkable for the association of recurring episodes of sleep, overeating and temporary mental disturbances lasting from a few hours to several days. Its diagnosis is mainly based on clinical data Laboratory investigations have so far failed to document specific features. Emphasis is laid on circumstances at onset and pathological studies which could be in favour of a viral origin. Some clinical aspects and polysomnographic features are reminiscent of endogenous depression. The treatments of hypersomniac episodes based on stimulants are often disappointing. On the other hand, the prevention of the hypersomniac episodes of the Kleine Levin syndrome with lithium carbonate has been successful in several well-documented cases as well as the prevention of the hypersomniac episodes of the menstruation related hypersomnia with ovulatory inhibitors. Organic and psychiatric forms of recurring hypersomnias are not well known. Their clinical features are described and their various possible etiologies indicated.


[A case of hemangiopericytoma with multiple extracranial metastasis: a case report].
A case of a patient with hemangiopericytoma with multiple extracranial metastasis, who has survived for more than twenty years is reported. A fifty-five-year-old male presented brain tumor twenty years ago. He underwent total removal of the tumors, but recurrences occurred each time. Liver metastasis was found seven years ago. After that multiple metastases extended to the lung, vertebra and pancreas and operations and irradiations were performed. At present, there is no progression of the tumors and he enjoyed a high quality of life. We concluded that, to ensure long time survival, a patient with hemangiopericytoma must be monitored carefully for local recurrence and systemic metastases.


Mechanism underlying defective interferon gamma-induced IDO expression in non-obese diabetic mouse fibroblasts.
Indoleamine 2,3-dioxygenase (IDO) can locally suppress T cell-mediated immune responses. It has been shown that defective self-tolerance in early prediabetic female non-obese diabetic (NOD) mice can be attributed to the impaired interferon-gamma (IFN-γ)- induced IDO expression in dendritic cells of these animals. As IFN-γ can induce IDO in both dendritic cells and fibroblasts, we asked the question of whether there exists a similar defect in IFN-γ-induced IDO expression in NOD mice dermal fibroblasts. To this end, we examined the effect of IFN-γ on expression of IDO and its enzymatic activity in NOD dermal fibroblasts. The results showed that fibroblasts from either prediabetic (8 wks of age) female or male, and diabetic female or male (12 and 24 wks of age respectively) NOD mice failed to express IDO in response to IFN-γ treatment. To find underlying mechanisms, we scrutinized the IFN- γ signaling pathway and investigated expression of other IFN-γ-modulated factors including major histocompatibility complex class I (MHC-I) and type I collagen (COL-I). The findings revealed a defect of signal transducer and activator of transcription 1 (STAT1) phosphorylation in NOD cells relative to that of controls. Furthermore, we found an increase in MHC-I and suppression of COL-I expression in fibroblasts from both NOD and control mice following IFN-γ treatment; indicating that the impaired response to IFN-γ in NOD fibroblasts is specific to IDO gene. Finally, we showed that an IFN-γ-independent IDO expression pathway i.e. lipopolysaccharide (LPS)-mediated-c-Jun kinase is operative in NOD mice fibroblast. In conclusion, the findings of this study for the first time indicate that IFN-γ fails to induce IDO expression in NOD dermal fibroblasts; this may partially be due to defective STAT1 phosphorylation in IFN-γ-induced-IDO signaling pathway.


The case of babesiosis in farmed wolf (Canis lupus L).
There was recognised the case of canine babesiosis in farmed wolf (Canis lupus) in Białowieza, northeastern Poland. The typical symptoms were observed in animal--depression, asitia, and haematocyturia. The treatment with antibiotics gave positive results. It was the first observation of babesiosis in wolf in Poland.


Legal capacity of the elderly in Greece.
Legal capacity of the elderly people in Greece is of great legal, medical and social importance, but has received little attention till now from medical literature. This paper aims to study whether elderly people with dementia are able to participate in legal contracts like sales, purchases, loans, leases, donations and testaments. We tried to introduce a new test for the above legal-financial contracts and show some preliminary findings. The test consists of six examined relevant domains concerning basic monetary skills, cash transactions, bank statement management, financial conceptual knowledge, knowledge of potential heirs (beneficiaries) and assets/estate and finally the decision making process for different dilemmas on sales, purchases, loans, leases, donations and testaments. We studied 203 people. Eighty three people were healthy, 64 with Alzheimer's disease (AD) (10 with severe AD, 22 with moderate, and 32 with mild AD), 10 with Parkinson's disease (PD), and 46 with amnestic Mild Cognitive Impairment (aMCI). Individuals were included in the study only if they were aged 60 and over and only if they had a partner or a guardian who could give information on the individual's daily living. The exclusion criteria were predefined as follows: history of any other mental health disease and/or any other serious somatic health disease except for their official diagnosis of dementia. Results showed statistically significant differences with all three groups of patients characterized as incapable for legal-financial actions. Patients with severe AD (P<0.001), patients with moderate AD (P<0.001), patients with mild AD (P<0.001), patients with PD (P<0.001) and aMCI patients (P<0.001) differed significantly from healthy controls. Further research should include more extensive sampling of elderly patients with varying demographic characteristics in Greece, to confirm and expand our initial findings. In conclusion, our new test which is based on Marson's theoretical model of financial capacity seems to be highly correlated with the so far use of MMSE/HMSE scores, but it gives more specific information that is of interest in the field of civil forensics for characterizing someone as legally (in) capable for large and/or small scale financial acts. Our preliminary results show for the first time in Greece that: a) four groups of elderly people (suffering from Alzheimer's disease at different stages, Parkinson's disease and amnestic Mild Cognitive Impairment and healthy elders) show a significantly different profile on all examined domains of this new test according to their diagnosis, b) people with MCI from Greece do face problems in the domains outlined above (mainly financial decision making problems), and that c) subsequent changes in the Greek law should be made.


Central nervous system and spinal tuberculosis in children at a tertiary care center in Saudi Arabia.
Tuberculosis (TB) remains a global health problem. There is limited data on pediatric central nervous system tuberculosis (CNSTB) in Saudi Arabia on diagnosis and therapy. Retrospective review of health record of pediatric patients < 14 years old who were diagnosed as having CNSTB or spinal TB and admitted to a tertiary care center. Health records and microbiology data of pediatric patients diagnosed with CNSTB were over 20-year period were reviewed. Data on demographics, clinical presentation, surgical interventions, neuroimaging, mycobacterial cultures and susceptibility and treatment were collected. Thirteen children were diagnosed with CNSTB or spinal TB. Tuberculoma was the most frequent in 8 cases (62%), followed by TB of the spine in 4 cases (31%), and one case of meningitis. Six patients had a history of TB contact (46%) and 8 (62%) patients had a positive tuberculin skin test (TST). Seizure and weakness was the most frequent symptoms (38% each), while fever was less frequently encountered (23%). Tissue cultures (brain tissues/spinal tissues) showed a high yield (92%) of Mycobacterium tuberculosis with positive cultures for 11 surgical specimens out of 12 for whom cultures were done. There were no surgical complications from biopsies. All of MTB isolates were sensitive to first-line agents. Brain or spinal biopsy is safe and has a high culture yield for MTB so it is advisable to perform a biopsy for any child in whom CNSTB is suspected and when there is no other less risky involved site for biopsy. All MTB isolates in this series were sensitive to first-line anti-tubercular agents.


Lymphoplasmacytoid lymphoma presenting as severe osteoporosis.
We report four cases presenting with severe osteoporosis which on further investigation were found to have an underlying lymphoplasmacytoid lymphoma (LPL). Common secondary causes of osteoporosis were excluded in each case. Three of the cases responded to treatment with a biphosphonate. As these lymphomas share some common pathological and clinical features with multiple myeloma (MM) an association with osteoporosis is likely to represent more than a coincidental finding. The incidence of osteoporosis occurring with LPL will become clearer if routine imaging is carried out in patients at presentation. Issues relating to the treatment of the osteoporosis as well as the lymphoma arise in patients that present in this way. Based on the model of bone disease in MM, correlating serum levels of osteoclast activating cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumour necrosis factor (TNF) with the actual finding of bone disease provides a basis for future research into the pathogenesis and management of bone disease in these rare forms of low grade non-Hodgkin's lymphoma.