Evaluation of the deficiency status of 25-hydroxyvitamin D and associated factors in Southwest China: A hospital-based retrospective cross-sectional analysis of a low-latitude, high-altitude, multiracial region.
Vitamin D deficiency is widespread in different populations and regions worldwide and has become a global health issue. The vitamin D status of the population in the Yunnan Province of Southwest China has not been evaluated to date. Therefore, in this study, we evaluated the vitamin D status according to the serum concentrations of 25-hydroxyvitamin D (25(OH)D) in individuals of Yunnan Province, a low-latitude, high-altitude and multiracial region in China. The data on 25(OH)D concentrations from October 2012 to December 2017 were retrospectively collected and assessed using the laboratory information system from 52 950 hospital-based participants (age, 1 day-96 years; females, 73.74%). The serum concentration of 25(OH)D was evaluated using a chemiluminescent immunoassay. The analysis was stratified by sex, age, sampling season, testing year, minority, residential district, latitude, altitude and meteorological factors. Vitamin D status was classified as follows: severe deficiency: <10 ng/mL; deficiency: <20 ng/mL; insufficiency: <30 ng/mL; and sufficiency: ≥30 ng/mL. The results showed that vitamin D deficiency is highly prevalent in Yunnan Province in a hospital-based cohort, with a deficiency and severe deficiency rate of 65.1% and a sufficiency rate of 5.30%. Significantly lower vitamin D levels and sufficiency rates were observed in females than in males (20.13 ± 7.22 ng/mL vs. 17.56 ± 6.66 ng/mL and 8.20% vs. 4.20%; p < 0.01, respectively); in spring and winter (16.93 ± 6.24 ng/mL; 2.97% and 16.38 ± 6.43 ng/mL; 3.06%, respectively) than in summer and autumn (20.23 ± 7.14 ng/mL; 8.02% and 19.10 ± 6.97 ng/mL; 6.61% [p < 0.01], respectively); and in older individuals (0-6 years: 28.29 ± 13.13 ng/mL vs. >60 years: 14.88 ± 8.39 ng/mL; p < 0.01). Relatively higher vitamin D levels were observed in individuals of Yi, Zhuang, Hani, Dai, Miao and Lisu minorities and lower levels in individuals of Hui and Zang minorities compared with those of the Han nationality (p < 0.01). The mean sunlight duration, mean air temperature, maximum ultraviolet value and latitude were significantly correlated with vitamin D levels (r = -0.53, 0.60, 0.31, -0.68, respectively; p < 0.05). These results suggest that vitamin D status is influenced by sex, age, minority, latitude and some meteorological factors in areas with high and low altitudes. Hence, new public health policies, such as advice on sunshine exposure, food fortification and nutrition education, as well as the implementation of vitamin D supplementation programmes must be considered to alleviate vitamin D deficiency in Yunnan province, Southwest China.


[Echographic aspects of gynecomastia].
Gynecomastia is a size increase of man's breast, due to non neoplastic ductal and glandular stroma proliferation. Prevalent ductal proliferation defines the "florid" type, while prevalent stroma increase defines the "quiescent" type. Pseudo-gynecomastia is a non glandular volume increase. Sonography is able to recognize the different parts of normal male breast and to diagnose gynecomastia. Moreover by sonography we can distinguish three echo-patterns linked to the anatomopathologic pattern which can lead therapy.


A study of human epidermal growth factor receptor 2 overexpression by immunohistochemistry in patients with gastric adenocarcinoma.
Gastric cancer is one of the leading causes of cancer-related deaths across the world and in the Middle East. Human epidermal growth factor receptor 2 (HER2) overexpression has been observed in gastric cancers. Trastuzumab, a recombinant monoclonal antibody targeting HER2 protein, is being used for treatment of metastatic gastric cancer. To study the frequency and association of HER2 overexpression with age, gender, histopathological subtype and grade of differentiation in patients with gastric adenocarcinoma from Basra, Iraq. This cross-sectional single-center study collected demographic (age, gender), histopathological (histological subtype, grade of differentiation) and immunohistochemical (HER2 overexpression status) data from 100 consenting adult patients (male: 56) with histopathologically confirmed gastric adenocarcinoma from samples obtained through endoscopy or surgery. HER2 overexpression (ToGA score 3+) was observed in 6/100 (6%) of patients, with another 6 showing 'equivocal' HER2 expression (2+). Out of 20 patients with moderately differentiated gastric cancer, 4 (20%) showed HER2 overexpression (p=0.008). Other factors considered (age, gender, histological subtype) did not show statistically significant correlation with HER2 overexpression. More females showed HER2 overexpression than males (4 vs. 2), and more patients with intestinal type gastric cancer showed HER2 overexpression than diffuse gastric cancer (5 vs. 1), but the difference was not statistically significant in both variables. HER2 overexpression was 6% in this population; statistically significant correlation was found with histological grade. Statistically non-significant correlations were observed between HER2 overexpression and gender, age, and histological subtype.


Visceral Adiposity Measurements, Metabolic and Inflammatory Profi le in Obese Patients with and Without Type 2 Diabetes Mellitus: A Crosssectional Analysis.
Waist circumference does not distinguish subcutaneous from visceral adipose tissue, which is highly associated with impaired cardiometabolic profile and type-2 diabetes mellitus (T2DM). Because of the complexity of the assessment of visceral fat with imaging techniques, easy-to-apply and low-cost anthropometric measures have been proposed. The aim of the study was to show a possible association between Lipid Accumulation Product Index (LAP Index), Deep-abdominal adiposity tissue Index (DAAT) and Visceral Adiposity Index (VAI) with metabolic profile and adipokines in obese subjects with and without T2DM, and to compare the results with the use of waist circumference isolated. In this cross-sectional study, we enrolled 101 outpatients with obesity (BMI ≥ 30 kg/m2) of which 48% with diabetes and aged 48.9 ±13.3 years. Demographic, clinical and anthropometric data were collected. Plasma C-reactive protein, interleukin-6, vascular adhesion molecule type 1 and adiponectin levels, lipid profile and fasting glucose were assessed. LAP Index, DAAT and VAI were calculated and body composition was evaluated by bioelectric impedance analyses. Continuous variables were described as mean ±standard deviation, and categorical variables as absolute numbers and percentages. Nonparametric data were log-transformed and Student's t test, Wilcoxon-Mann-Whitney and chi-squared test, Pearson correlation and multiple linear regression were used for statistical analyses. In total, 31 men and 70 women were evaluated. Individuals with T2DM showed higher LAP values and percentage of body fat and lower waist circumference and BMI values. DAAT and LAP were positively correlated with BMI, waist circumference, percentage of body fat and free fat mass. After adjustment for age, sex and total body fat, both LAP Index and VAI were associated with plasma adiponectin, LDL-cholesterol, non-HDL cholesterol and VLDL-cholesterol in obese with and without T2DM (all P values ≤ 0.02); fasting glucose remained associated with LAP in obese patients without T2DM (P= 0.01). Waist circumference only correlated with adiponectin in obese subjects without T2DM (P= 0.048). Our data suggest that VAI and LAP Index are good predictors of an impaired cardiometabolic setting in obesity regardless of T2DM status. Besides, we were not able to find associations with waist circumference and biochemical markers in our sample.


α-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies-Part 1.
With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous radionuclides that decay by α-particle emission, only a few of these can reasonably be exploited for therapeutic purposes. Factors including radioisotope availability and physical characteristics (e.g., half-life) can limit their widespread dissemination. The first part of this review will explore the diversity, basic radiochemistry, restrictions, and hurdles of α-emitters.


Structural NMR and ab initio study of salicylhydroxamic and p-hydroxybenzohydroxamic acids: evidence for an extended aggregation.
The acid-base behavior and self-aggregation of salicylhydroxamic (SHA) and p-hydroxybenzohydroxamic acids (PHBHA)have been investigated by UV and 1HNMR spectroscopy, respectively. The acid-base parameters, measured in H2O at 25 degrees C and I=0.1 M, were pK1=7.56, pK2=9.85 for SHA and pK1=8.4, pK2=9.4 for PHBHA. The 1H NMR signals for salicylhydroxamic and p-hydroxybenzohydroxamic acids measured in acetone indicate that both acids self-aggregate according to a mechanism where two monomers produce planar E-E dimers stabilized by horizontal H-bonds. Further dimer aggregation yields sandwich-like tetramer structures stabilized by vertical H-bonds and pi-pi interactions. The p-hydroxybenzohydroxamic tetramers, less stable than those of salicylhydroxamic, contain two water molecules in their structures. The gas-phase structures of salicylhydroxamic acid and its anions were investigated by ab initio calculations using the density functional theory at the B3LYP/AUG-cc-pVDZ level. The SHA most stable gas-phase conformer is the A-Z amide, a structure with all three phenolate (OP), carboxylate (OC), and hydroxamate (OH) oxygen atoms in the cis position. The B-Z amide, with the OP oxygen trans to OC, lies 5.4 kcal above the A-Z amide. The most stable monoanion is the N-deprotonated A-Z amide.


Measuring teaching effectiveness--or not.
Faculty in the present-day academic medicine environment are expected to perform multiple functions, notably, the provision of high-quality teaching to the medical professionals of tomorrow. However, evaluating the effectiveness of this teaching is particularly difficult. Student evaluations of teaching, despite their many flaws, are widely used as a convenient tool to measure teaching effectiveness. Administrators continue to routinely use student evaluation of teaching surveys in faculty retention/promotion and merit pay decisions. This practice should be reevaluated since it may have unintended consequences, such as grade inflation and content debasement, and may contribute to faculty leaving the institution and even the profession. A more valid, reliable, and formative protocol for the evaluation of genuine teaching effectiveness needs to be developed as a matter of some urgency. In this review, alternatives to the student evaluation of teaching are explored to better measure true teaching effectiveness.


Aphasia and Dysarthria in Acute Stroke: Recovery and Functional Outcome.
Background Aphasia and dysarthria have major implications for activities of daily living and social participation following stroke. Few studies describe recovery in the acute stroke setting. We described the evolution of aphasia and dysarthria by three-months poststroke. Methods We conducted a retrospective analysis of pooled clinical trial data from the Virtual International Stroke Trials Archive. We defined aphasia and dysarthria at baseline as a score of ≥1 on the Best Language (Item 9) and Dysarthria (Item 10) domains of the National Institutes of Health Stroke Scale, respectively. We described recovery from these impairments by three-months. Covariate adjusted analyses described the associations between aphasia, dysarthria, and functional outcome using the modified Rankin Scale at three-months following stroke. Results At baseline, 4039/8904 (45·4%) people presented with aphasia and 6192 (69·5%) with dysarthria; 2639 (29·6%) had both impairments. By three-months, aphasia and dysarthria had resolved in 1292/7219 (17·9%) and 2892/7219 (40·1%) survivors, respectively, but persisted in 1713/7219 (23·7%) and 1940/7219 (27%), respectively. Age and severity of initial stroke were associated with poor recovery, whereas thrombolysis was associated with improved recovery. Aphasia at baseline [ P = 0·049, odds ratio = 0·89, 95% confidence interval (0·79,1·00)] and persistent aphasia at three-months [ P < 0·0001, odds ratio = 0·31, 95% confidence interval (0·27, 0·35)] were each associated with poorer modified Rankin Scale scores at three-months. Conclusion Aphasia or dysarthria persisted in at least a quarter of people in our dataset at three-months following stroke. The association between persistent aphasia at three-months and poor modified Rankin Scale renders this impairment a major therapeutic target for recovery and restitution.


Nevus lipomatosus cutaneous superficialis.
We report a case of nevus lipomatosus cutaneous superficialis of Hoffman-Zurhelle (NCLS), with multiple lesions, in a ten-year-old child. The NLCS is considered rare. The classical clinical presentation is characterized by multiple skin-colored or yellowish papules and nodules, which can have a linear distribution. Histologically, it is characterized by the presence of mature ectopic adipocytes in the dermis. The main therapeutic option is surgical excision. The classical Nevus lipomatosus cutaneous superficialis is reported in this case.


Inhibition of matrix metalloproteinases protects mice from ascending infection and chronic disease manifestations resulting from urogenital Chlamydia muridarum infection.
Matrix metalloproteinases (MMP) are a family of host-derived enzymes involved in the turnover of extracellular matrix molecules. We have previously reported enhanced expression of matrix metalloproteinases in Chlamydia muridarum urogenital tract infection of female mice. Kinetics and patterns of MMP expression as well as enhanced expression in susceptible strains of mice in the prior study implied a role for MMP in pathogenesis. To explore this further, we infected a susceptible strain of mice (C3H/HeN) with C. muridarum and treated two groups of mice with either one of two chemical inhibitors of MMP (MMPi; captopril and a chemically modified tetracycline) and reserved infected sham-treated mice as controls. Neither of the treatments affected shedding of viable chlamydiae from the lower urogenital tract, but the administration of either MMPi protected mice from the formation of hydrosalpinx-a surrogate marker of oviduct occlusion and infertility. Interestingly, the mechanism of protection for mice treated with chemically modified tetracycline 3, appeared to be related to prevention of ascending upper genital tract infection. These results imply that MMP are involved in pathogenesis of chlamydial infection in this model by mediating ascension of the infection into the upper genital tract.


Innovative technology shows impact of glycaemic control on peripheral retinal vessels in adolescents with type 1 diabetes.
Retinal imaging enables non-invasive microvasculature assessment; however, only central retinal vessels have been studied in type 1 diabetes. Peripheral smaller vessels have a major haemodynamic role and may differ from central vessels in their response to the diabetic milieu. We hypothesise that diabetes has a greater impact on peripheral retinal vessels vs central vessels. Retinal photographs from adolescents (n = 736; age 12-20 years) with type 1 diabetes were graded (Singapore I Vessel Assessment) with vessel calibres measured in the 'central zone' as central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively) and the 'extended zone' as mean width of arterioles and venules (MWa and MWv, respectively). Multivariable linear regression was used to explore associations between vessel calibres and HbA1c, diabetes duration, sex and BP. Mean ± SD age was 14.1 ± 1.5 years, HbA1c was 8.5 ± 1.3% (69.4 ± 14.1 mmol/mol) and median diabetes duration was 4.9 years (interquartile range 3.1-7.6 years). Wider MWa was associated with HbA1c (β 0.01 [95% CI 0.004, 0.03]), longer diabetes duration (0.07 [0.02, 0.13]) and higher systolic BP (0.04 [0.02, 0.05]). MWv was associated with HbA1c (0.02 [0.009, 0.03]) and higher systolic BP (0.04 [0.03, 0.06]). CRAE was associated with longer diabetes duration (0.93 [0.58, 1.28]) and higher systolic BP (-0.28 [-0.37, -0.19]). CRVE was associated with longer diabetes duration (0.91 [0.42, 1.41]) and higher systolic BP (-0.20 [-0.33, -0.07]). Girls had wider vessels (for all four calibre measurements). In adolescents with type 1 diabetes, higher HbA1c is associated with adverse changes to peripheral smaller retinal vessels but not central vessels. The predictive value of retinal vascular imaging should be evaluated using longitudinal data.


CT sinus and facial bones reporting by radiographers: findings of an accredited postgraduate programme.
The aim of this study was to compare the observer performance of a cohort of radiographers in reporting CT sinus and facial bone investigations against a reference standard and alternative comparator of summary data from peer-reviewed literature. The participants (n = 6) completed a 9-month part-time distance learning training programme prior to reporting an examination bank (n = 25 cases) from a retrospectively collected and anonymized digital imaging and communications in medicine archive of CT examinations with referral histories and clinical reports. A literature search was performed to identify an additional alternative comparison reference standard from studies reporting observer performance data in CT sinus and facial bone investigations of both trauma and sinus pathology (target conditions). The data analyses used to measure observer performance and determine differences between the cohort and the reference standards used statistical assessment models including accuracy, sensitivity, specificity, kappa (κ) and summary receiver-operating characteristic curves with estimated area under the curve (AUC). The cohort of radiographer sensitivity was 97.5%, specificity 93.6% and accuracy 95%, with p < 0.000, and a κ = 0.9121 score of agreement. The mean radiographer AUC was 0.9822. The summary reported data of the alternative literature reference standard comparator were AUC 0.9533 for sinus and 0.9374 for trauma. The results suggest that this cohort of radiographers at the end of a period training in CT sinus and facial bones are able to clinically report comparably high standards.


Sinomenine inhibits activation of rat retinal microglia induced by advanced glycation end products.
Diabetic retinopathy involves an inflammatory response in the retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of retina injury following an inflammatory stimulus. Cytokines, released by activated microglia, regulate the influx of inflammatory cells to the damaged area. Thus, therapeutic strategy to reduce cytokine expression in microglia would be neuroprotective. Sinomenine, an alkaloid isolated from the stem and root of Sinomenium acutum, has long been recognized as an anti-inflammatory drug for rheumatoid arthritis and also inhibits macrophage activation. In this study, we activated retinal microglia in culture with advanced glycation end products (AGEs) treatment and attempted to determine whether sinomenine could reduce the production of cytokines from the activated microglia at both gene and protein levels. Changes in inflammatory cytokines, TNF alpha, IL-1 beta and IL-6, were measured by semi-quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) both in the presence and absence of AGEs. The effect of sinomenine on levels of reactive oxygen species (ROS) and the nuclear translocation of NF-kB p65 were studied with a laser confocal scanning microscope. AGEs treatment induced a significant release of TNF alpha, IL-1 beta, and IL-6 from retinal microglia. Sinomenine could inhibit release of these cytokines. Sinomenine attenuated ROS production in a dose-dependent fashion and reduced the nuclear translocation of NF-kB p65 in AGEs-activated retinal microglia in culture.


Rice transgene flow: its patterns, model and risk management.
Progress has been made in a 12 year's systemic study on the rice transgene flow including (i) with experiments conducted at multiple locations and years using up to 21 pollen recipients, we have elucidated the patterns of transgene flow to different types of rice. The frequency to male sterile lines is 10(1) and 10(3) higher than that to O. rufipogon and rice cultivars. Wind speed and direction are the key meteorological factors affecting rice transgene flow. (ii) A regional applicable rice gene flow model is established and used to predict the maximum threshold distances (MTDs) of gene flow during 30 years in 993 major rice producing counties of southern China. The MTD0.1% for rice cultivars is basically ≤5 m in the whole region, despite climate differs significantly at diverse locations and years. This figure is particularly valuable for the commercialization and regulation of transgenic rice. (iii) The long-term fate of transgene integrated into common wild rice was investigated. Results demonstrated that the F1 hybrids of transgenic rice/O. rufipogon gradually disappeared within 3-5 years, and the Bt or bar gene was not detectable in the mixed population, suggesting the O. rufipogon may possess a strong mechanism of exclusiveness for self-protection. (iv) The flowering time isolation and a 2-m-high cloth-screen protection were proved to be effective in reducing transgene flow. We have proposed to use a principle of classification and threshold management for different types of rice.


Optimizing Intradermal Administration of Cryopreserved Plasmodium falciparum Sporozoites in Controlled Human Malaria Infection.
Controlled human malaria infection (CHMI) is a powerful tool to evaluate malaria vaccine and prophylactic drug efficacy. Until recently CHMI was only carried out by the bite of infected mosquitoes. A parenteral method of CHMI would standardize Plasmodium falciparum sporozoite (PfSPZ) administration, eliminate the need for expensive challenge facility infrastructure, and allow for use of many P. falciparum strains. Recently, intradermal (ID) injection of aseptic, purified, cryopreserved PfSPZ was shown to induce P. falciparum malaria; however, 100% infection rates were not achieved by ID injection. To optimize ID PfSPZ dosing so as to achieve 100% infection, 30 adults aged 18-45 years were randomized to one of six groups composed of five volunteers each. The parameters of dose (1 × 10(4) versus 5 × 10(4) PfSPZ total dose per volunteer), number of injections (two versus eight), and aliquot volume per ID injection (10 μL versus 50 μL) were studied. Three groups attained 100% infection: 1 × 10(4) PfSPZ in 50 μL/2 doses, 1 × 10(4) PfSPZ in 10 μL/2 doses, and 5 × 10(4) PfSPZ in 10 μL/8 doses. The group that received 5 × 10(4) PfSPZ total dose in eight 10 μL injections had a 100% infection rate and the shortest prepatent period (mean of 12.7 days), approaching the prepatent period for the current CHMI standard of five infected mosquitoes.


R4/4 (30) rectangular rings in 2,5-dioxopiperazine-1,4-diacetic acid.
Molecules of the title 2,5-dioxopiperazinedione derivative, C(8)H(10)N(2)O(6), occupy centres of symmetry in the crystal structure. The six-membered ring has an almost planar conformation, with the substituent on nitrogen nearly perpendicular to the ring. The ideal geometry of the isolated molecule, as determined by ab initio HF-LCAO quantum-mechanical calculations, is slightly more puckered than that observed in the solid state. In the crystal structure, a strong hydrogen bond joins neighbouring molecules, thus forming a network of rectangular R(4)(4)(30) rings.


Algoriphagus marinus sp. nov., isolated from marine sediment and emended description of the genus Algoriphagus.
A Gram-stain-negative, facultatively anaerobic coccobacilli approximately 0.4-0.5×0.5-1.1 µm, non-motile, orange-pigmented bacterial strain, designated am2T, was isolated from the coastal area of Weihai, PR China (121° 57' E, 37° 29' N). The temperature, pH and NaCl ranges for growth were 4-40 °C, pH 6.5-8.5 and 0.0-6.0 % (w/v) NaCl. The results of phylogenetic analyses based on 16S rRNA gene sequences revealed that am2T was phylogenetically related to members of the genus Algoriphagus and was closely related to Algoriphagus boritolerans, Algoriphagus namhaensis and Algoriphagus antarcticus with 96.4, 96.2 and 95.8 % sequence similarities, respectively. The quinone system contained menaquinone MK-7 as the predominant component. The dominant fatty acids were iso-C17 : 1ω9c,iso-C16 : 1H and iso-C15 : 0. The major polar lipids consisted of one phospholipid, phosphatidylethanolamine and six unknown lipids. The DNA G+C content was 40.6 mol%. On the basis of morphological, physiological and molecular properties as well as on phylogenetic distinctiveness, am2T should be placed into the genus Algoriphagus as a novel species, for which the name Algoriphagus marinus sp. nov. is proposed. The type strain is am2T (=KCTC 52549T=MCCC 1H00178T).


Simian foamy virus isolated from an accidentally infected human individual.
Evidence for natural foamy virus (FV) infections in humans is still lacking. However, accidental infections of humans with simian FV have been demonstrated by serology and PCR, but all previous attempts to recover infectious virus in such cases have failed. Here we describe the isolation of a simian FV from peripheral blood mononuclear cells (PBMC) of a healthy animal caretaker, who acquired the virus 20 years ago from an African green monkey (AGM) bite. Properties of the human isolate such as host range in cell cultures including human PBMC and ability to induce neutralizing antibodies in the primate host proved to be similar to those of FV obtained from AGM. The genomic sequence of the isolate was found to be virtually identical to the proviral sequence present in the host lymphocytes and related to AGM isolates but distinct from those of all FV isolates handled in the laboratory. For successful virus isolation, it was essential to stimulate the host lymphocytes by phytohemagglutinin and interleukin-2 for 2 weeks prior to cocultivation with permissive cells. In contrast to the situation found in FV-infected monkeys, virus isolation from the saliva of the animal caretaker was not possible, and no evidence for FV transmission to family contacts was obtained. We conclude that, in contrast to active infection in monkeys, FV persists in a state of latency following accidental infection of humans.


Relationship between the Incidence of Dengue Virus Transmission in Traditional Market and Climatic Conditions in Kaohsiung City.
In 2014 and 2015, Southern Taiwan experienced two unprecedented outbreaks, with more than 10,000 laboratory-confirmed dengue cases in each outbreak. The present study was aimed to investigate the influence of meteorological and spatial factors on dengue outbreaks in Southern Taiwan and was conducted in Kaohsiung City, which is the most affected area in Taiwan. The distributed lag nonlinear model was used to investigate the role of climatic factors in the 2014 and 2015 dengue outbreaks. Spatial statistics in the Geographic Information System was applied to study the relationship between the dengue spreading pattern and locations of traditional markets (human motility) in the 2015 dengue outbreak. Meteorological analysis results suggested that the relative risk of dengue fever increased when the weekly average temperature was more than 15°C at lagged weeks 5 to 18. Elevated relative risk of dengue was observed when the weekly average rainfall was more than 150 mm at lagged weeks 12 to 20. The spatial analysis revealed that approximately 83% of dengue cases were located in the 1000 m buffer zone of traditional market, with statistical significance. These findings support the influence of climatic factors and human motility on dengue outbreaks. Furthermore, the study analysis may help authorities to identify hotspots and decide the timing for implementation of dengue control programs.


APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide-based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial.
APF530, a novel extended-release granisetron injection, was superior to ondansetron in a guideline-recommended three-drug regimen in preventing delayed-phase chemotherapy-induced nausea and vomiting (CINV) among patients receiving highly emetogenic chemotherapy (HEC) in the double-blind Phase III Modified Absorption of Granisetron In the prevention of CINV (MAGIC) trial. This MAGIC post hoc analysis evaluated CINV prevention efficacy and safety of APF530 versus ondansetron, each with fosaprepitant and dexamethasone, in patient subgroup receiving an anthracycline plus cyclophosphamide (AC) regimen. Patients were randomized 1:1 to APF530 500 mg subcutaneously (granisetron 10 mg) or ondansetron 0.15 mg/kg intravenously (IV) (≤16 mg); stratification was by planned cisplatin ≥50 mg/m2 (yes/no). Patients were to receive fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1, then dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3 and 4. Patients were mostly younger females (APF530 arm, mean age 54.1 years, female, 99.3%; ondansetron arm, 53.8 years, female 98.3%). The primary end point was delayed-phase (>24-120 hours) complete response (CR). APF530 versus ondansetron regimens achieved numerically better CINV control in delayed and overall (0-120 hours) phases for CR, complete control, total response, rescue medication use, and proportion with no nausea. APF530 trends are consistent with the overall population, although not statistically superior given the underpowered AC subgroup analysis. The APF530 regimen in this population was generally well tolerated, with safety comparable to that of the overall population. APF530 plus fosaprepitant and dexamethasone effectively prevented CINV among patients receiving AC-based HEC, a large subgroup in whom CINV control has traditionally been challenging.


Recurrent pericarditis as the initial manifestation of Familial Mediterranean fever.
Familial Mediterranean fever is an autosomal recessive disease largely restricted to certain ethnic groups and presenting with recurrent febrile serositis attacks. Peritonitis, pleuritis, and synovitis are common manifestations; however, the pericardium is rarely affected. In this case report, we describe a 25-year-old Turkish woman who presented with recurrent pericarditis of no obvious cause, which eventually responded to colchicine therapy. Using gene mutation analysis to detect the MEFV gene, the patient's condition was finally diagnosed as Familial Mediterranean fever. Familial Mediterranean fever should be considered in patients with idiopathic recurrent pericarditis unresponsive to nonsteroidal anti-inflammatory medications and corticosteroids. Mutation analyses should be done.


Genome-wide identification and expression analysis of dirigent-jacalin genes from plant chimeric lectins in Moso bamboo (Phyllostachys edulis).
Dirigent-jacalin (D-J) genes belong to the plant chimeric lectin family, and play vital roles in plant growth and resistance to abiotic and biotic stresses. To explore the functions of the D-J family in the growth and development of Moso bamboo (Phyllostachys edulis), their physicochemical properties, phylogenetic relationships, gene and protein structures, and expression patterns were analyzed in detail. Four putative PeD-J genes were identified in the Moso bamboo genome, and microsynteny and phylogenetic analyses indicated that they represent a new branch in the evolution of plant lectins. PeD-J proteins were found to be composed of a dirigent domain and a jacalin-related lectin domain, each of which contained two different motifs. Multiple sequence alignment and homologous modeling analysis indicated that the three-dimensional structure of the PeD-J proteins was significantly different compared to other plant lectins, primarily due to the tandem dirigent and jacalin domains. We surveyed the upstream putative promoter regions of the PeD-Js and found that they mainly contained cis-acting elements related to hormone and abiotic stress response. An analysis of the expression patterns of root, leaf, rhizome and panicle revealed that four PeD-J genes were highly expressed in the panicle, indicating that they may be required during the formation and development of several different tissue types in Moso bamboo. Moreover, PeD-J genes were shown to be involved in the rapid growth and development of bamboo shoots. Quantitative Real-time PCR (qRT PCR) assays further verified that D-J family genes were responsive to hormones and stresses. The results of this study will help to elucidate the biological functions of PeD-Js during bamboo growth, development and stress response.


[Prostaglandin E (PGE) and gastric carcinoma].
Since 1984, an experimental and clinical study on the relation between PGE and gastric carcinoma has been performed by determining PGE content in the bioptic gastric mucosa and plasma. It is found the PGE content in the gastric mucosa and plasma is increased in all patients with gastric cancer, especially with signet ring cell carcinoma. It is higher in the regional lymph node metastasis than in the early cancer, extensive metastases and normal subjects. The PGE content in the plasma is reduced obviously 7-10 days after operation but is increased markedly in recurrent patients. There is no significant difference in extensive metastases, relapse free and normal subjects. The PGE content in the plasma is significantly higher in gastric carcinoma than in chronic atrophic gastritis, but no difference is present between chronic atrophic gastritis and normal subjects.


The Influence of Boron on the Structure and Properties of Hybrid Compounds Containing Zirconium and Phosphorus.
In the present work, novel organic-inorganic hybrid materials containing boron, zirconium, and phosphorus were synthesized at different molar ratios, using the sol-gel method, starting from zirconyl chloride hexa-hydrate, triethyl borate, and phenyl phosphonic acid as the precursors. The sol-gel process is used for the first time in the present work in order to obtain organic-inorganic hybrids (or the so-called inorganic polymers) containing together boron, zirconium, and phosphorus. The sol-gel syntheses were performed at room temperature in ethanol. Zirconium containing compounds are already well known for their applications in medicine in restorative or prosthetic devices, including dental implants, knee and hip replacements, middle-ear ossicular chain reconstruction, and so on. Zirconium is a strong transition metal, which started to replace hafnium and titanium in the last decade in important applications. On the other hand, boron has the capability (similar to carbon) to form stable covalently bonded molecular networks. In addition to this capability, boron also offers mixed metallic and nonmetallic properties, because of its place on the periodic table, at the border between metals and nonmetals. Boron is responsible for the higher thermal stability of synthesized hybrid compounds. In the structure of those hybrid compounds, zirconium, boron, and phosphorus atoms are always connected via an oxygen atom, by P-O-Zr, Zr-O-Zr, or Zr-O-B bridges.


Occurrence survey and spatial distribution of perfluoroalkyl and polyfluoroalkyl surfactants in groundwater, surface water, and sediments from tropical environments.
The occurrence and spatial distribution of 22 selected perfluoroalkyl and polyfluoroalkyl substances (PFASs) in surface water (n=75), groundwater (n=80) and surficial sediment (n=15) were investigated for the first time in the tropical areas constituted by the French Overseas Territories (French Guiana, Guadeloupe, Martinique, Mayotte and Reunion). Descriptive statistics and correlations between PFASs were evaluated through the use of specific statistical treatments to handle left-censored data ("non-detects"). PFASs were ubiquitous in these samples and detection frequencies as high as 79% for perfluorooctane sulfonate (PFOS) and 65% for perfluorooctanoate (PFOA) were reported in surface waters. ∑PFASs was in the range<LOD-77ngL-1 (median=1.8ngL-1) in surface waters and <LOD-638ngL-1 (median=0.56ngL-1) in groundwater. PFOS and PFOA dominated PFAS composition profiles in surface water, while shorter-chain compounds prevailed in groundwater, highlighting their higher transfer potential through infiltration processes and the possible influence of precursors. Elevated levels of 6:2 fluorotelomer sulfonate (6:2 FTSA) and short-chain perfluoroalkyl carboxylates were found in groundwater near several industrial facilities such as oil refineries or electricity power plants. This may be related to the existence of firefighting operations involving the use of aqueous film forming foams (AFFFs) that contain precursors to such compounds. These findings would also tend to confirm recent trends regarding the increasing proportion of C4- or C6-based perfluoroalkyl acids, their precursors, or even shorter-chain congeners at PFAS hot spots.


The Ethics of Taxing Sugar-Sweetened Beverages to Improve Public Health.
The World Health Organization highlights fiscal policies as priority interventions for the promotion of healthy eating in its Action Plan for the Prevention and Control of Non-communicable Diseases. The taxation of sugar sweetened beverages (SSBs) in particular is noted to be an effective measure, and SSBs taxes have already been implemented in several countries worldwide. However, although the evidence base suggests that this will be effective in helping to combat rising obesity rates, opponents of SSBs taxation argue that it is illiberal and paternalistic, and therefore should be avoided. Bioethical analysis may play an essential role in clarifying whether policymakers should adopt SSBs taxes as part of wider obesity strategy. In this article we argue that no single ethical theory can account for the complexities inherent in obesity prevention strategy, especially the liberal theories relied upon by opponents of SSBs taxation. We contend that a pluralist approach to the ethics of SSBs taxation must be adopted as the only suitable way of accounting for the multiple overlapping, and sometimes, conflicting factors that are relevant to determining the moral acceptability of such an intervention.


Fetal growth in twin pregnancies.
In 65 consecutive twin pregnancies, 722 measurement of fetal abdominal circumference have been obtained with ultrasound. Zygosity was established after delivery in 85% of the pregnancies. There was no difference in mean abdominal circumference measurements between monozygotic and dizygotic pregnancies. In both groups, the pattern of growth was linear throughout pregnancy in contrast to that predicted by birthweight for gestational age charts. It is suggested that increasing trunk flexion, in later twin pregnancy, may distort accurate abdominal circumference measurement.


Magnetically-driven implantable pump for on-demand bolus infusion of short-acting glucagon-like peptide-1 receptor agonist.
For type 2 diabetic patients, short acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) is often prescribed with frequent needled injections. Long-acting GLP-1 RA for less frequent injections do not mimic physiologic secretion of GLP-1. Therefore, an implantable pump is proposed in this work, which can deliver a short-acting GLP-1 RA, exenatide, without needles and batteries. The implanted pump can infuse an accurate amount of exenatide bolus only when a noninvasive magnetic force is applied from outside the body. The pump includes a safety feature of patterned magnets for actuation to prevent accidental infusion possibly caused by a general household magnet. The reservoir for exenatide is made of a flexible biomaterial and thus, a negative pressure build-up in the reservoir can be prevented even after multiple actuations and almost all drug consumption (~ 94%). This allows a reproducible drug dose for a longer period after implantation, hence less frequent replenishment procedures. The pump is also equipped with an intermediate container with two distinct check-valves and thus, the reservoir of exenatide can be further separated and better prevented from infiltration of the bodily fluid surrounding the implanted pump. When tested in Goto-Kakizaki rats, the pump demonstrates the efficacy of exenatide similar to conventional subcutaneous injections. Therefore, the pump can be promising for patient-friendly, optimal delivery of short-acting GLP-1 RA that better follows the physiologic secretion profile of GLP-1.


Update: prevalence of Salmonella in pork sausage.
One hundred seventy-five samples of fresh pork sausage representing thirty-five different commercial brands from six different retail stores were examined for the presence of salmonellae by standard enrichment, plating, biochemical and serological techniques. Contamination levels varied from 0 to 50% among stores and from 0 to 28% among brands. Prior research implied reduced prevalence of salmonellae in fresh pork sausage; however, these results indicate no variation in prevalence since 1969.


The ICSH reference method for serum iron assay: recommendation for a viable automated alternative.
A viable alternative to the ICSH reference method for serum iron assay is proposed where automated batch analysis is required. The introduction of Ferrozene into contemporary automated methodology makes this possible. The Donnan effect on membrane dialysis has been resolved by observing the fate of aqueous and protein matrices inoculated with 59FeCl3 as they leave the system.


Layer-by-layer assembly for biomedical applications in the last decade.
In the past two decades, the design and manufacture of nanostructured materials has been of tremendous interest to the scientific community for their application in the biomedical field. Among the available techniques, layer-by-layer (LBL) assembly has attracted considerable attention as a convenient method to fabricate functional coatings. Nowadays, more than 1000 scientific papers are published every year, tens of patents have been deposited and some commercial products based on LBL technology have become commercially available. LBL presents several advantages, such as (1): a precise control of the coating properties; (2) environmentally friendly, mild conditions and low-cost manufacturing; (3) versatility for coating all available surfaces; (4) obtainment of homogeneous film with controlled thickness; and (5) incorporation and controlled release of biomolecules/drugs. This paper critically reviews the scientific challenge of the last 10 years--functionalizing biomaterials by LBL to obtain appropriate properties for biomedical applications, in particular in tissue engineering (TE). The analysis of the state-of-the-art highlights the current techniques and the innovative materials for scaffold and medical device preparation that are opening the way for the preparation of LBL-functionalized substrates capable of modifying their surface properties for modulating cell interaction to improve substitution, repair or enhancement of tissue function.


Heredopathia atactica polyneuritiformis (Refsum's disease): 1. Clinical features and dietary management.
In a patient with Refsum's disease successful dietary control of the disease has been shown to depend on adequate energy and protein intake from phytanic acid-free sources and restriction of dietary phytanic acid to a maximum of 10 mg per day, with the provision of a generous amount of the essential fatty acid, linoleic acid. The present work gives data on the phytanic-acid content of various foodstuffs and suggests dietary manipulation of the patient. Although the role that chlorophyll-bound phytol plays in Refsum's disease is uncertain, it is advisable that this is eliminated until its role is more clearly identified.


Combination of a peroxisome proliferator-activated receptor-gamma agonist and an angiotensin II receptor blocker attenuates myocardial fibrosis and dysfunction in type 2 diabetic rats.
We aimed to examine the effect of an angiotensin II receptor blocker (ARB), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, and their combination on myocardial fibrosis and function in type 2 diabetic rats. Five male Long-Evans Tokushima Otsuka (LETO) rats and 20 male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used. OLETF rats were assigned to four groups (n = 5 per group) at 28 weeks-of-age: untreated, losartan-treated, rosiglitazone-treated and combination-treated. The ARB, losartan, was administered at a dose of 5 mg/kg/day, and the PPAR-gamma agonist, rosiglitazone, was administered at a dose of 3 mg/kg/day by oral gavage for 12 weeks. Urine and blood samples were collected, and two-dimensional echocardiograms and strain rate imaging were obtained at 28 and 40 weeks. Cytokines were evaluated by reverse transcriptase polymerase chain reaction, and histological analysis was carried out at 40 weeks. At 40 weeks, the global radial strains of the losartan-treated (55.7 ± 4.5%, P = 0.021) and combination-treated groups (59.3 ± 6.7%, P = 0.001) were significantly higher compared with the untreated OLETFs (44.3 ± 10.5%). No difference was observed when compared with LETO rats. Although the rosiglitazone-treated group showed a better metabolic profile than the untreated OLETF group, there was no difference in the global radial strain (49.8 ± 6.0 vs 44.3 ± 10.5, P = 0.402). The expression of pro-inflammatory cytokines, and collagen type I and III were consistently attenuated in the losartan-treated and combination-treated OLETF groups, but not in the rosiglitazone-treated group. A combination of rosiglitazone and losartan attenuates myocardial fibrosis and dysfunction in type 2 diabetic rats.


Enhanced dye wastewater degradation efficiency using a flowing aqueous film photoelectrocatalytic reactor.
A TiO(2)/Ti flowing aqueous film photoelectrocatalytic (PEC) reactor was developed and successfully applied to degrade Reactive Brilliant Blue X-BR (RBB) and textile effluent. The high treatment efficiency achieved by flowing aqueous film PEC process was attributed to the enhanced light utilization resulting from the significantly reduced path length (down to average approximately 78 micro m level). The dye wastewater was kept circulating (7.7 L h(-1)) during the experiments to continuously refresh the aqueous film on the TiO(2)/Ti photoanode and promote the mass transfer of the target pollutants and the degradation products in the bulk solution. Using a 20-150 mg L(-1)RBB solution as the model system, flowing aqueous film PEC removed color by 83-44% in one hour, much higher than the 75-12% by conventional PEC. Results also suggested that flowing aqueous film PEC was particularly superior to conventional PEC for treatment of a high concentration solution. The feasibility of the TiO(2)/Ti flowing aqueous film PEC reactor was investigated by treating industrial textile effluent. A color and total organic carbon (TOC) removal of 75% and 50% respectively, were achieved in two hours. Thus, in the present study, we propose a new concept for the design of a PEC reactor applicable to industrial wastewater treatment.


Stocks and cryptocurrencies: Antifragile or robust? A novel antifragility measure of the stock and cryptocurrency markets.
In contrast with robust systems that resist noise or fragile systems that break with noise, antifragility is defined as a property of complex systems that benefit from noise or disorder. Here we define and test a simple measure of antifragility for complex dynamical systems. In this work we use our antifragility measure to analyze real data from return prices in the stock and cryptocurrency markets. Our definition of antifragility is the product of the return price and a perturbation. We explore different types of perturbations that typically arise from within the system. Our results suggest that for both the stock market and the cryptocurrency market, the tendency among the 'top performers' is to be robust rather than antifragile. It would be important to explore other possible definitions of antifragility to understand its role in financial markets and in complex dynamical systems in general.


Neonatal colonic inflammation sensitizes voltage-gated Na(+) channels via upregulation of cystathionine β-synthetase expression in rat primary sensory neurons.
The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood, and treatment remains difficult. We have previously reported that colon-specific dorsal root ganglion (DRG) neurons were hyperactive in a rat model of IBS induced by neonatal colonic inflammation (NCI). This study was designed to examine plasticity of voltage-gated Na(+) channel activities and roles for the endogenous hydrogen sulfide-producing enzyme cystathionine β-synthetase (CBS) in chronic visceral hyperalgesia. Abdominal withdrawal reflex (AWR) scores were recorded in response to graded colorectal distention in adult male rats as a measure of visceral hypersensitivity. Colon-specific DRG neurons were labeled with 1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate and acutely dissociated for measuring Na(+) channel currents. Western blot analysis was employed to detect changes in expressions of voltage-gated Na(+) (Na(V)) channel subtype 1.7, Na(V)1.8, and CBS. NCI significantly increased AWR scores when compared with age-matched controls. NCI also led to an ~2.5-fold increase in Na(+) current density in colon-specific DRG neurons. Furthermore, NCI dramatically enhanced expression of Na(V)1.7, Na(V)1.8, and CBS in colon-related DRGs. CBS was colocalized with Na(V)1.7 or -1.8 in colon-specific DRG neurons. Administration of O-(carboxymethyl)hydroxylamine hemihydrochloride (AOAA), an inhibitor for CBS, remarkably suppressed Na(+) current density and reduced expression of Na(V)1.7 and Na(V)1.8. More importantly, intraperitoneal or intrathecal application of AOAA attenuated AWR scores in NCI rats in a dose-dependent manner. These data suggest that NCI enhances Na(+) channel activity of colon DRG neurons, which is most likely mediated by upregulation of CBS expression, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.


A new species of Heteromyoxyuris (Nematoda: Oxyuridae), parasite of Perognathus flavus (Rodentia: Heteromyidae) from Mexico.
Heteromyoxyuris otomii n. sp., which inhabits the intestinal caecum of Perognathus flavus (Heteromyidae), in Zaragoza, Hidalgo, Mexico, is described. This new species differs from the 2 other congeneric species in the morphology and length of lateral alae in males. Heteromyoxyuris deserti has simple lateral alae located at both sides of the body, whereas in the new species, these structures are double at both sides; in contrast, lateral alae of Heteromyoxyuris longejector begin at the posterior half of the body, whereas they arise in the first third in the new species. Heteromyoxyuris longejector was found in 2 new host species, i.e., Perognathus amplus and Chaetodipus hispidus. This record represents the first record for the species in Mexico, increasing its geographic distribution.


Pediatric Invasive Candidiasis: Epidemiology and Diagnosis in Children.
Pediatric patients present with differing underlying conditions and cytotoxic therapeutic protocols, so the differing epidemiology of invasive candidiasis in children versus adults is not surprising. Understanding the Candida species epidemiology is critical, as we often begin empiric therapy or therapy before antifungal susceptibilities are known. Reports with newer molecular diagnostic assays for invasive candidiasis are rare and require more study to develop firm pediatric-specific guidance. Antifungal treatment of pediatric candidiasis is reviewed in the context of larger epidemiologic studies and the few trials completed to date.


Real-time ultrasonography in the neonate: a systematic study of a high-risk infants population.
During a 12-month period a prospective and systematic study was carried out by means of portable real-time ultrasound (US) scanner in order to detect cerebral lesions in a population of high-risk neonates. Newborn infants were allocated into two groups: group A: all premature infants (n = 83) of less than or equal to 34 weeks' gestation or less and group B: neonates (n = 36) of more than 34 weeks' gestation presenting with abnormal neurological signs. Group A: the overall incidence of periventricular haemorrhage (PVH) was 47% (15 grade I, 16 grade II, 3 grade III, 1 Plexus choroid haemorrhage, 1 isolated intraventricular haemorrhage). Infants of 30 weeks or less were at highest risk to develop a PVH. The degree of severity did not depend on gestational age. Repeated scans accurately timed the onset of PVH; 67% developed a PVH within the first 24 hours of life and 31% within the first 6 hours. A post-haemorrhagic ventricular dilatation was noted in 50% of the 28 infants who survived more than 28 days (4 transient, 7 arrested and 3 rapidly progressive). Group B: 15 of 36 infants had US abnormalities. Cerebral lesions were miscellaneous. Diagnosis of PVH, leukomalacia, agenesis of corpus callosum, calcifications in the basal ganglia, hydranencephaly were made and confirmed at autopsy in 9 fatal cases. US has proved useful for the detection of cerebral lesions among high-risk newborn infants in a Neonatal Unit.


Pulsatile release of LH and oestradiol during the periovulatory period in women.
Blood was collected every 8 h in five women from Day 10 of the menstrual cycle for 5-7 d for the measurement of LH, oestradiol and progesterone. In all women the LH surge started between 2400 and 0800 h before there was any significant decline in the concentration of oestradiol. In order to investigate the pulsatile secretion of LH and estradiol during the mid-cycle surge, blood samples were collected every 5 min for up to 5 h. Immediately before and during the LH surge there were numerous episodic pulses of LH with an interpulse interval (44 +/- 7 min) very similar to that observed in two women with hypergonadotrophic hypogonadism (48 min). The concentration of oestradiol fluctuated in a similar manner although it was not always possible to relate each pulse of oestradiol to a corresponding pulse of LH. The mid-cycle surge of LH is characterized by frequent pulses of high amplitude. These results are compatible with the view that the positive feedback effect of oestradiol is due not only to enhanced sensitivity of the anterior pituitary to LHRH but also to the high frequency of LHRH pulses released from the hypothalamus.


Intravascular coronary lithotripsy for the treatment of iatrogenic calcium embolization: The "block and crack" technique.
Intracoronary calcium embolization during percutaneous procedure is a very rare and unpredictable event, that can lead to serious complications and even expert operators could face some technical issues to solve it. This case report presents a technique called "block and crack" used to manage iatrogenic intracoronary calcium embolization of left anterior descending coronary artery. The technique involves implanting a drug eluting stent (DES) to block the embolus against the vessel wall, followed by the use of lithotripsy balloon inflated inside the DES to crack the calcium and achieve a better stent expansion. This technique allowed to avoid further distal calcium embolization as well as to minimize residual stenosis degree after stent implantation.


Agricultural Green Revolution as a driver of increasing atmospheric CO2 seasonal amplitude.
The atmospheric carbon dioxide (CO2) record displays a prominent seasonal cycle that arises mainly from changes in vegetation growth and the corresponding CO2 uptake during the boreal spring and summer growing seasons and CO2 release during the autumn and winter seasons. The CO2 seasonal amplitude has increased over the past five decades, suggesting an increase in Northern Hemisphere biospheric activity. It has been proposed that vegetation growth may have been stimulated by higher concentrations of CO2 as well as by warming in recent decades, but such mechanisms have been unable to explain the full range and magnitude of the observed increase in CO2 seasonal amplitude. Here we suggest that the intensification of agriculture (the Green Revolution, in which much greater crop yield per unit area was achieved by hybridization, irrigation and fertilization) during the past five decades is a driver of changes in the seasonal characteristics of the global carbon cycle. Our analysis of CO2 data and atmospheric inversions shows a robust 15 per cent long-term increase in CO2 seasonal amplitude from 1961 to 2010, punctuated by large decadal and interannual variations. Using a terrestrial carbon cycle model that takes into account high-yield cultivars, fertilizer use and irrigation, we find that the long-term increase in CO2 seasonal amplitude arises from two major regions: the mid-latitude cropland between 25° N and 60° N and the high-latitude natural vegetation between 50° N and 70° N. The long-term trend of seasonal amplitude increase is 0.311 ± 0.027 per cent per year, of which sensitivity experiments attribute 45, 29 and 26 per cent to land-use change, climate variability and change, and increased productivity due to CO2 fertilization, respectively. Vegetation growth was earlier by one to two weeks, as measured by the mid-point of vegetation carbon uptake, and took up 0.5 petagrams more carbon in July, the height of the growing season, during 2001-2010 than in 1961-1970, suggesting that human land use and management contribute to seasonal changes in the CO2 exchange between the biosphere and the atmosphere.


Safety and tolerability of sorafenib in clear-cell renal cell carcinoma: a Phase III overview.
This review summarizes the safety of sorafenib, an oral multikinase inhibitor, focusing on the randomized, placebo-controlled, Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) in renal cell carcinoma, which formed the basis of the approval of sorafenib. Similar to other targeted agents, sorafenib acts primarily to induce disease stabilization, rather than tumor regression, suggesting that long-term administration is necessary. The tolerability of an agent is important in long-term treatment, and a predictable and manageable side-effect profile is advantageous. Although IL-2 and interferon have been standard care treatments for advanced renal cell carcinoma for over a decade, they are poorly tolerated. Targeted agents offer an alternative for patients with advanced renal cell carcinoma, as initial therapy or after failure of cytokine treatment.


Sensitized Photochemical CO2 Reduction by Hetero-Pacman Compounds Linking a ReI Tricarbonyl with a Porphyrin Unit.
The hetero-Pacman architecture places two different metal coordination sites in close proximity, which can support efficient energy and/or electron transfer and allow for cooperative activation of small molecules. Here, the synthesis of dyads consisting of a porphyrin unit as photosensitizer and a rhenium unit as catalytically active site, which are held together by the rigid xanthene backbone, is presented. Mononuclear [(NN)Re(CO)3 (Cl)] complexes for CO2 reduction in which NN represents a bidentate diimine ligand (e.g., bipyridine or phenanthroline) lack light absorption in the visible region, resulting in poor photocatalysis upon illumination with visible light. To improve their visible-light absorption, we have focused on the incorporation of a strongly absorbing free base or zinc porphyrin unit. Resulting photocatalytic experiments showed a strong dependence of the catalytic performance on both the type of photosensitizer and the excitation wavelengths. Most notably, the intramolecular hetero-Pacman system containing a zinc porphyrin unit showed much better catalytic activity in the visible region (excitation wavelengths >450 nm) than the free base porphyrin version or the corresponding mononuclear rhenium compound or an intermolecular system comprised of a 1:1 mixture of the mononuclear analogues.


Evaluation of pituitary function after infectious meningitis in childhood.
A number of studies of adults have shown that pituitary deficiencies can develop in a considerable proportion of subjects during the acute phase of meningitis or years after the infection has disappeared. The results of the very few studies of the impact of pediatric meningitis on hypothalamic-pituitary function are conflicting. In order to determine the incidence of pituitary dysfunction in children with central nervous system infection, we evaluated pituitary function and anthropometric parameters in 19 children with meningitis of different etiologies (15 males; mean age ± standard deviation [SD] at pituitary evaluation, 5.9 ± 4.0 years; mean time from the acute event ± SD, 18 ± 10 months). All of the subjects had a normal stature and growth velocity for their age and gender, and none of them was obese. On the basis of Tanner's reference charts, 17 subjects (13 boys and all four girls) were pre-pubertal; two boys were in Tanner stage 2. None of the subjects had central hypothyroidism. All of the patients had normal serum of insulin growth factor (IGF)-I and prolactin. Their sex steroid and gonadotropin levels were concordant with their age and pubertal status. Early morning urine osmolality and serum electrolyte levels showed no signs of diabetes insipidus. All of the patients had normal plasma adrenocorticotropic hormone (ACTH) levels. Peak cortisol responses to the standard dose Synacthen test (SDST) were normal in all cases. The results showed that hypopituitarism following infectious meningitis appears to be infrequent in childhood and children's pituitary glands seem to be less vulnerable to damage than those of adults.


Effectiveness of Oral Antiseptics on Tooth Biofilm: A Study in vivo.
To evaluate the effectiveness of five different mouthwashes through measurement of the plaque index. Fifty subjects took part in this blind study, randomized into blocks of five groups according to the active ingredient of the mouthwash: CHX group (0.12% chlorhexidine gluconate), essential oils (EO) group, cetylpyridinium chloride (CPC) group, Tri group (triclosan) and Hamamelis virginiana (HV) group. All subjects were evaluated for a reduction in the bacterial plaque index at 7, 14 and 21 days. There was a significant reduction in the mean plaque index during the period of evaluation (p < 0.01), and the reduction during the period of evaluation was different between mouthwashes (p < 0.01). The reduction in the plaque index at the end of 21 days was, in decreasing order, CHX > EO > CPC > Tri > HV. The reduction in the plaque index during the period of evaluation was different between the types of mouth-wash. The mouthwash containing the active ingredient chlorhexidine was the most effective, followed by the essential oil, cetylpyridinium chloride, triclosan and H. virginiana.


Leiomyosarcoma of the ovarian vein: a case report with radiological findings.
Leiomyosarcomas of the ovarian vein are very rare. Four cases have been reported in the English language clinical literature. We present a case of leiomyosarcomas where the use of multi-detector CT had a substantial role in the establishment of the preoperative diagnosis. The radiological images as well as intraoperative features are illustrated. We also discuss the radiological findings of the ovarian vein leiomyosarcoma in comparison with those of other venous or retroperitoneal leiomyosarcomas. We expect that the use of multi-detector CT will be the choice for the diagnostic work-up of vascular leiomyosarcomas.


PD-1 blockade induces responses by inhibiting adaptive immune resistance.
Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance). Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next-generation sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8(+) T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance.


Th17 and IL-17 Cause Acceleration of Inflammation and Fat Loss by Inducing α2-Glycoprotein 1 (AZGP1) in Rheumatoid Arthritis with High-Fat Diet.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints. High-fat diet (HFD) is a risk factor for RA and is related to inflammation but responds minimally to medication. Given the association between HFD and inflammation, it is important to understand the function of inflammation-related T cells in RA with HFD. Collagen-induced arthritis (CIA), a model of RA, was induced in HFD mice by injection of collagen II, and metabolic markers and T cells were analyzed. The metabolic index and IgG assay results were higher in HFD-CIA mice than in nonfat diet-CIA mice. Numbers of inflammation-related T cells and macrophages, such as Th1 and Th17 cells and M1 macrophages, were higher in spleens of HFD-CIA mice. HFD-CIA mice had a high level of α2-glycoprotein 1 (Azgp1), a soluble protein that stimulates lipolysis. To examine the association between Azgp1 and Th17 cells, the reciprocal effects of Azgp1 and IL-17 on Th17 differentiation and lipid metabolism were measured. Interestingly, Azgp1 increased the Th17 population of splenocytes. Taken together, our data suggest that the acceleration of fat loss caused by Azgp1 in RA with metabolic syndrome is related to the increase of IL-17. Mice injected with the Azgp1-overexpression vector exhibited more severe CIA compared with the mock vector-injected mice.


Relationship between Proinflammatory Cytokines/Chemokines and Adipokines in Serum of Young Adults with Obesity.
The adipose tissue has been recognized as an important endocrine organ, which is metabolically active and expresses and secretes various inflammatory cytokines. Inflammation is involved in obesity-related complications. As such, the present study investigated the correlation between biochemical parameters, serum proinflammatory cytokines and adipokines in individuals with obesity. Based on the body mass index (BMI), 30 subjects were divided into 3 groups: eutrophic (GC, n = 10), overweight (GOW, n = 10) and obese (GOB, n = 10). Serum glucose, cholesterol (total-C, HDLC and LDL-C), triglycerides, total proteins, uric acid and insulin were determined, as well as cytokines IL-8, TNF-α, IL-1β, and IL-6, leptin and adiponectin. GOB showed the highest glucose, total and LDL-C, triglycerides, uric acid, insulin, leptin, IL- 8, IL-1β, IL-6, TNF-α and lowest adiponectin levels. In general, adiponectin exhibited an inverse correlation with BMI, abdominal circumference, LDL-C, IL-6, TNF-α, leptin and leptin-adiponectin ratio (LAR) and a positive correlation with HDL-C. Leptin was positively correlated with BMI, abdominal circumference, insulin, IL-6, TNF-α and LAR and negatively correlated with HDL-C and adiponectin. The LAR was positively correlated with BMI, waist circumference, insulin, TNF-α and negatively associated with HDL-C. The results confirm that obesity changes the lipid and glycemic profiles of individuals, increases the proinflammatory adipokine levels and reduces those of anti-inflammatory adipokines, promoting a state of chronic inflammation.


Detection of Ophidiomyces, the Causative Agent of Snake Fungal Disease, in the Eastern Massasauga ( Sistrurus catenatus ) in Michigan, USA, 2014.
Snake fungal disease (SFD), caused by Ophidiomyces ophiodiicola, threatens free-ranging snake populations across the US. We assayed 112 swabs from 102 individual eastern massasaugas ( Sistrurus catenatus ) at three locations in Michigan in 2014 for Ophidiomyces using quantitative PCR (qPCR). We observed a 12.7% qPCR prevalence of skin lesions. Individuals at each site had lesions, and occurrence of skin lesions was not significantly different between sites. We detected Ophidiomyces DNA at each of the three sites in five individuals (4.9%). We found no difference in detection probabilities between sites; however, snakes with dermatitis had higher Ophidiomyces DNA detection probabilities (P=0.15±0.08 SE) than snakes without dermatitis (P=0.02±0.01 SE, P=0.026). The emergence of SFD mortalities has potentially serious consequences for the viability of the eastern massasauga in Michigan. Future work should track temporal patterns in vital rates and health parameters, link health data to body condition indices for individual snakes, and conduct a "hotspot" analysis to examine health on a landscape scale.


Malignant histiocytic lymphoma with large lacunar cells.
A case of lymph node biopsy with a peculiar histological aspect is described. The clinical data suggest a malignant lymphoid disease. The histological picture is that of a malignant histiocytosis but, among the majority of small histiocytes, there are some large cells like the large lacunar cells from Hodgkin's disease. These large cells (and some small cells) contain the CD 30 antigen of Reed-Sternberg cells. It is discussed whether the appropriate diagnosis is Hodgkin's disease, malignant histiocytosis, or non-Hodgkin's malignant lymphoma. Our diagnosis is Hodgkin's disease, the nodular sclerosing form.


End-of-life management protocol offered within emergency room (EMPOWER): study protocol for a multicentre study.
Patients at their end-of-life (EOL) phase frequently visit the emergency department (ED) due to their symptoms, yet the environment and physicians in ED are not traditionally equipped or trained to provide palliative care. This multicentre study aims to measure the current quality of EOL care in ED to identify gaps, formulate improvements and implement the improved EOL care protocol. We shall also evaluate healthcare resource utilisation and its associated costs. This study employs a quasiexperimental interrupted time series design using both qualitative and quantitative methods, involving the EDs of three tertiary hospitals in Singapore, over a period of 3 years. There are five phases in this study: (1) retrospective chart reviews of patients who died within 5 days of ED attendance; (2) pilot phase to validate the CODE questionnaire in the local context; (3) preimplementation phase; (4) focus group discussions (FGDs); and (5) postimplementation phase. In the prospective cohort, patients who are actively dying or have high likelihood of mortality this admission, and whose goal of care is palliation, will be eligible for inclusion. At least 140 patients will be recruited for each preimplementation and postimplementation phase. There will be face-to-face interviews with patients' family members, review of medical records and self-administered staff survey to evaluate existing knowledge and confidence. The FGDs will involve hospital and community healthcare providers. Data obtained from the retrospective cohort, preimplementation phase and FGDs will be used to guide prospective improvement and protocol changes. Patient, family and staff relevant outcomes from these changes will be measured using time series regression. The study protocol has been reviewed and ethics approval obtained from the National Healthcare Group Domain Specific Review Board, Singapore. The results from this study will be actively disseminated through manuscript publications and conference presentations. NCT03906747.


Association between Awareness of Nutrition Labels and Menstrual Cycle Irregularity in Korean Women: The Fifth Korea National Health and Nutrition Examination Survey (2010~2012).
The aim of this study was to identify the relationship between awareness of nutrition labeling and menstrual cycle irregularity in women from a nationally representative sample of the Korean population. A cross-sectional analysis was performed using hierarchical multivariable logistic regression analysis models. A total of 4,324 women aged 19~54 years from the 2010~2012 Korean National Health and Nutrition Examination Survey participated in the study. The participants were classified into three groups based on self-report responses to a questionnaire about their awareness of nutrition labels: Reading, Not-Reading, and Not-Knowing Groups. The Reading, Not-Reading, and Not-Knowing Groups comprised 46.4%, 44.9%, and 8.7% of the participants, respectively, and 53.6% of the participants had never used nutrition labels. In the Not-Knowing Group, irregular menstrual cycles for more than 3 months were significantly more common than women with irregular menstrual cycles for up to 3 months and women with regular menstrual cycles. Women in the Not-Knowing Group were more likely to exhibit menstrual cycle irregularity (adjusted odds ratio: 1.63, 95% confidence interval: 1.10~2.41) compared to women in the Reading Group after adjusting for age, body mass index, smoking status, alcohol intake, exercise regularity, stress, depression, suicidal ideation, metabolic syndrome, age at menarche, parity, and use of oral contraceptives. No awareness of nutrition labeling appears to be associated with a higher prevalence of menstrual cycle irregularity in a nationally representative group of Korean women.


[Organ-protective effect of continuous renal replacement therapy in a patient with severe polymyositis and dermatomyositis].
A patient with skin rash, skin denudation, anuria, general dropsy and dyspnea for unknown etiology underwent continuous renal replacement therapy (CRRT) for 3 consecutive days. The biochemical indexes were monitored during the therapy and biopsy was performed on the right thigh. Pathological examination of the biopsy sample established the diagnosis of polymyositis(PM) and dermatomyositis(DM). After the start of CRRT, the patient's heart, liver, kidney and lung injuries showed obvious improvement, and the urine volume (UV) increased and serum creatinine (Cr), urea, total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) levels all decreased promptly. The patient showed progressive improvement of the physiological condition even after CRRT, and was discharged 10 days later. This case suggests the efficacy of CRRT in the management of severe PM/DM and its value as a good option for treatment of severe autoimmune disease, especially systemic inflammatory response syndrome.


Seasonal fluctuation in the incidence of intracranial aneurysm rupture and its relationship to changing climatic conditions.
Seasonal and climatic variations have been linked to the occurrence of some types of cerebrovascular disease; however, the conditions that lead to intracranial aneurysm rupture are not known. The purpose of the present study was to determine whether seasonal and climatic conditions are related to intracranial aneurysm rupture. Data provided by the Connecticut Health Information Management and Exchange were analyzed for all patients with a primary diagnosis of aneurysmal subarachnoid hemorrhage (SAH) for the fiscal years 1981, 1983, 1985, 1987, 1988, and 1989. Patient records were correlated with climatic conditions for the years 1981 to 1989 obtained from the National Climatic Data Center, National Oceanic and Atmospheric Administration, National Environmental Satellite Data, and Information Service. During the time periods studied, 1487 patients with a primary diagnosis of aneurysmal SAH were treated by reporting hospitals. Seasonal variation in the incidence of aneurysmal SAH and admission clustering were observed but differed significantly between men and women. Men showed a single large peak in late fall (Roger's r = 11.5, p < 0.005), whereas women had an annual peak occurring in late spring (Roger's r = 10.3, p < 0.01). Substantial climatic change occurred during the 72 hours prior to 10 of the 14 clusters of men who were admitted (p < 0.01, Yates' corrected chi-square 7.33, df = 1). In contrast, clusters of women admitted were not related to preceding climatic change (p > 0.25, Yates' corrected chi-square 0.06, df = 1). Hospital admissions for aneurysmal SAH display seasonal fluctuation, with women showing a different seasonal pattern from men. Changing climatic conditions precede aneurysm rupture in men but not in women, which suggests that weather is causally related to aneurysm rupture in men, and that factors that lead to aneurysm rupture in women may be different from those in men. These data do not explain why weather fronts or gradients are associated with aneurysm rupture in men.


Gradually-Deteriorating Liver Function due to Iron Overload Over Four Years after Allogeneic Stem Cell Transplantation.
In allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients with liver dysfunction, it is often difficult to determine the cause. Several cases of liver dysfunction may be interpreted as chronic graft versus host disease without a definitive diagnosis, resulting in continued immunosuppressive therapy for longer periods. Allo-SCT recipients commonly require frequent red blood cell transfusions during the course of treatment and transplantation, leading to significant iron overload, which could be one of causes of liver dysfunction. Here we report an allo-SCT recipient with chronic deteriorating liver dysfunction due to iron overload, despite maintaining transfusion independence for more than four years. Using magnetic resonance-based liver iron concentration (MR-LIC), iron overload-related liver dysfunction was diagnosed. It drastically improved with monthly phlebotomy and has not recurred following its termination. The observations from our case suggested that iron overload should be recognized as a cause of chronic liver dysfunction even in patients who remain transfusion-independent for several years and that MR-LIC analysis is a useful and reliable method for detecting iron overload and monitoring the effect of iron-reduction therapy.


Invasive diagnostic procedures for pulmonary infiltrates in pediatric hematopoietic stem cell transplant recipients.
To evaluate the role of BAL, CTB, and OLB in the management of pulmonary infiltrates in pediatric HSCT recipients, we conducted a retrospective review of clinical records of pediatric HSCT recipients. Data were analyzed using Chi-square for dichotomous and anova for continuous variables. Logistic regression was used to adjust confounding variables for diagnostic yield. Forty patients underwent 44 separate procedures. Infections were the prevailing cause of infiltrates with a positive diagnostic yield (96%). CTB and OLB were performed more often in patients with focal infiltrates compared with BAL (100%, 71% vs. 22%; p < 0.01). Adverse events were not significantly different across the three procedures. OLB more often yielded information that led to change in medical management (71% vs. 0%, 34%; p < 0.05) compared with CTB and BAL. Patients who had a positive diagnostic yield had no apparent survival advantage when compared with those in whom a procedure yielded no information. Logistic regression demonstrated that focal infiltrate was the only independently predictive variable for identifying a cause of pulmonary infiltrate. In conclusion, all three invasive diagnostic procedures were safe. Having a focal infiltrate was independently and significantly associated with having a positive diagnostic yield.


Epidemiology of HIV, programmatic progress and gaps in last 10 years in Nepal.
Nepal has made progress with the control of HIV infection in recent years. There have been changes in epidemiology, programme interventions in different population groups, and changes in policies over the last 10 years, particularly in diagnosis and treatment. Therefore, this review was conducted to identify the effectiveness of different interventions/policies in different sub-populations at risk, targeted towards epidemiology and treatment outcomes for those with HIV infection in Nepal. This review was prepared based on a review of published and unpublished documents from the Nepalese HIV infection control programme, published articles in different journals, different survey reports including integrated bio-behavioural surveillance (IBBS) survey reports. The prevalence of HIV infection among adults in 2014 was 0.20% with a progressive decreasing trend from 2005. The prevalence of HIV infection among injecting drug users (51.7% in 2005 and 6.4% in 2015 in Kathmandu valley) was relatively high in all years as compared to other risk groups. HIV infection prevalence among women attending antenatal clinics was higher in the year 2006 (0.25%) but there was a decreasing trend in the following years to 2015, when prevalence was 0.077%. Although different interventions were conducted to cover key populations at risk, the coverage in some risk population was very low. HIV testing status among the general population was very low (7.5% among males and 2.9% among females) in 2011. Only one-third of HIV-infected individuals were on ART in 2015, although this proportion has increased since 2005. The share of domestic budget among the total expenditure on HIV control program is below 15%. There is the need for implementation of control programmes more efficiently and effectively with expanding geographical and population coverage. Surveillance systems should be strengthened to get up-to-date information for evidence-based planning and developing strategies. The domestic budget for HIV control programme should be increased to improve their sustainability.


Male pelvic floor: history and update.
Our understanding of the male pelvic floor has evolved over more than 2,000 years. Gradually medical science has sought to dispel ancient myths and untruths. The male pelvic floor has many diverse functions. Importantly, it helps to support the abdominal contents, maintains urinary and fecal continence, and plays a major role in gaining and maintaining penile erection. Weakness of the male pelvic floor muscles may cause urinary and fecal incontinence and erectile dysfunction. Function may be restored in each of these areas by a comprehensive pelvic floor muscle training program. Spasm of the pelvic floor muscles may produce pain and require relaxation techniques. Additional research is needed to add further evidence to our knowledge base.


Morphometric analysis of gold particles in low-label cell compartments.
Quantitative estimation of the binding of gold-conjugated ligands to various cell organelles has become a commonly used method to quantify the amount of ligand-binding sites associated with those organelles. However, often a small percentage of organelles is labeled or the density of gold labeling is low. We have defined the "gold-labeled region" as a zone that has a boundary defined by the localization of the outermost gold particles. Such a phenomenon was recently observed in a study of the internalization of gold-labeled native surfactant into lamellar bodies of cultured pulmonary type II cells. We estimated the size and density of gold-labeled regions in lamelar bodies using a simple stereological approach and demonstrated that the low percentage of gold-labeled organelles can be explained as a result of the probability of random selecting through the labeled areas. Our method, which permits use of transmission electron microscopy to calculate the true parameters of gold-labeled regions, can significantly facilitate analyses of ligand binding to various cell compartments.


Simulating the activation, contraction and movement of skeletal muscles using the bidomain model.
A simulation of the muscle activation, contraction and movement is here presented. This system was developed based on the Bidomain mathematical model of the electrical propagation in muscles. This study shows an electrical stimuli input to a muscle and how this behave. The comparison between healthy subject and patient with muscle activation impairment is depicted, depending on whether the signal reaches a threshold. A 3D model of a bicep muscle and a forearm bone connected was constructed using OpenGL. This platform could be used for development of controllers for biomechatronic systems in future works. This kind of bioinspired model could be used for a better understanding of the neuromotor system.


Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK).
Midkine (MDK) expression is associated with the proliferation of many cancers, including glioma. However, the upstream signaling that leads to MDK accumulation remains elusive. This study investigates the molecular mechanism that induces MDK overexpression in human glioma. The Repository for Molecular Brain Neoplasia Data was analyzed to identify potential MDK regulators. Expression of MDK and specificity protein 1 (SP1) was compared in glioma specimens. Chromatin immunoprecipitation assay was used to confirm the transcriptional regulation. MDK-force-expressed, SP1-silenced glioma cells were used to test rescue effects in vitro and in vivo. MDK and SP1 expression in gliomas was significantly higher than in adjacent tissues and was positively correlated in glioma clinical samples and cell lines. The promoter of the human MDK gene has a putative SP1 binding site. SP1 binds to the promoter of the MDK gene and directly regulates MDK expression. MDK or SP1 gene silencing inhibited the proliferation of glioma cells and reduced the tumor volume in nude mice. Overexpression of MDK in SP1-silenced cells could partially rescue the SP1 inhibition effects in vivo and in vitro. SP1 directly up-regulated the expression of MDK, and the SP1-MDK axis cooperated in glioma tumorigenesis.


Automatic sleep stage classification using ear-EEG.
Sleep assessment is of great importance in the diagnosis and treatment of sleep disorders. In clinical practice this is typically performed based on polysomnography recordings and manual sleep staging by experts. This procedure has the disadvantages that the measurements are cumbersome, may have a negative influence on the sleep, and the clinical assessment is labor intensive. Addressing the latter, there has recently been encouraging progress in the field of automatic sleep staging [1]. Furthermore, a minimally obtrusive method for recording EEG from electrodes in the ear (ear-EEG) has recently been proposed [2]. The objective of this study was to investigate the feasibility of automatic sleep stage classification based on ear-EEG. This paper presents a preliminary study based on recordings from a total of 18 subjects. Sleep scoring was performed by a clinical expert based on frontal, central and occipital region EEG, as well as EOG and EMG. 5 subjects were excluded from the study because of alpha wave contamination. In one subject the standard polysomnography was supplemented by ear-EEG. A single EEG channel sleep stage classifier was implemented using the same features and the same classifier as proposed in [1]. The performance of the single channel sleep classifier based on the scalp recordings showed an 85.7 % agreement with the manual expert scoring through 10-fold inter-subject cross validation, while the performance of the ear-EEG recordings was based on a 10-fold intra-subject cross validation and showed an 82 % agreement with the manual scoring. These results suggest that automatic sleep stage classification based on ear-EEG recordings may provide similar performance as compared to single channel scalp EEG sleep stage classification. Thereby ear-EEG may be a feasible technology for future minimal intrusive sleep stage classification.


Evaluation of the Clinical and Laboratory Characteristics of Previously Followed-up Thalassemia Intermedia Patients to Provide Them Better Care in the Future.
The increased awareness about the severity of complications in thalassemia intermedia patients led authorities to develop strategies for better management and follow-up of these patients. In this study, we aimed to define the clinical and laboratory characteristics in previously followed-up β-thalassemia intermedia patients and wanted to gain an insight about the follow-up of this patient population in a developing country to provide them better care in the future. The mean age at diagnosis was 4 years, and the mean hemoglobin was 7.13 g/dL. The mean age at the beginning of regular transfusion was 4.8 years. An overall 74% of patients were on a regular transfusion program. The mean ferritin values at diagnosis and the last follow-up were 487 and 1225 ng/mL, respectively. The most common mutations detected in patients were IVS-I-110, IVS-I-6, IVS-II-1, and FCS 8/9 in order of frequency. Complications were seen in 48% of patients. The most common complications were osteopenia/osteoporosis (34%), growth retardation (24%), hypogonadism (18%), and cardiomyopathy (13%). In conclusion, the relatively higher complication rate in our patients who were previously treated highlights once again the need for an increased effort for optimal management and follow-up of this specific group of patients.


IMPACT OF SULPHUR DIOXIDE ON THE RESPIRATORY SYSTEM OF TBILISI POPULATION.
The possible relationship between levels of sulphur dioxide (SO2) in the air and the rate of respiratory diseases has been studied. Results of monitoring of main contaminants of outdoor air were analyzed and they are reflected in Environmental Report 2015. Information on morbidity by respiratory system diseases of Tbilisi population is has been taken from 2011-2015 reports of the National Center of Disease Control. Identified that there is no consistent correlation between sulphur dioxide concentration in the air and respiratory system disease rates in the population, including children. Obtained data demonstrated that during the study period maximum SO2 concentration was registered in 2015 - 0,14 mg/m3 (exceeding almost 3 times maximum permissible concentration - 0,5 mg/m3) and in the same year high morbidity rates are registered (incidence -18106,08), though the lowest rates are registered in 2011 (0,09 mg/m3), when incidence of respiratory system diseases in this period (13103.2) exceeds the rates registered in 2012, 2013 and 2014 (12736.4, 11336.3, 13009.0 accordingly). There is no direct correlation between the morbidity rates of 0-15 year old children and SO2 concentration. Maximum incidence rate is registered in 2015 (48487.0) and in the same year is also registered maximum concentration of SO2 (0,14 mg/m3), whereas the lowest rate is registered in 2013 (35538,70), when SO2 concentration in 2013 is lower only by 0.02 mg/m3 compared to the concentration in 2015. Direct correlation between morbidity with asthma in children and concentration of SO2 was not identified. Prevalence of asthma is minimal in 2014 (65,4), maximal in 2012 (207,1), whereas SO2 concentration in 2014 (0,13 mg/m3) exceeds the concentration in 2012 (0,12 mg/m3). It has to be considered, that besides SO2 there are many small intensity adverse factors, which are also risk factors for development of respiratory diseases. Isolated action of these factors with certain concentrations may not demonstrate any adverse effects on human health, but the combined effect of their action is stronger and obviously will affect general health and specifically - respiratory system. Implementation of urgent measures for further improvement of their ambient air quality has been recommended, which will be the basis for minimizing of many chronic diseases.


Craniofacial morphology in children with van der Woude syndrome and isolated cleft palate.
To compare cephalometrically 6-year-old children with van der Woude syndrome and cleft palate (VWS) to children with isolated cleft palate alone (CP). A retrospective case-control study. Forty-four children with VWS were compared to 73 children with CP using lateral cephalograms. The mean age of the children with VWS was 6.6 years (range = 5.9-8.2) and that of the children with CP, 6.2 years (range = 5.7-6.7). Palatal closure had been done at a mean age of 1.4 years (range = 0.8-2.2), mostly with the Veau-Wardill-Killner or the Cronin pushback surgical techniques. The data was collected over a 30-year period. Linear and angular measurements were obtained from lateral cephalograms. A Student's t-test was used in the statistical analysis. The craniofacial morphology in children with VWS and CP was similar, but those with VWS had slightly smaller diameters of the lower pharyngeal airway. The maxilla and mandible were well related to each other, although a little retrusive in relation to the cranial base. The soft tissue profile reflected the skeletal relationships, no significant protrusion of the lower lip was noted. Six-year-old children with VWS and CP have similar craniofacial morphology.


The potential value of serial cerebral SPECT scanning in the evaluation of psychiatric illness.
Cerebral SPECT imaging has the potential to make an important contribution to clinical psychiatry. Cerebral SPECT scanning, stimulated by the work with PET, is readily available and much less expensive than PET. This paper reports a case demonstrating the potential value of cerebral SPECT scanning with I-123 IMP, specifically in the serial evaluation of a schizophrenic patient with auditory hallucinations. The initial scan revealed focal areas of increased uptake in the caudate nuclei of the basal ganglia, and in the right temporal lobe. After pharmacological treatment with clinical improvement, the follow-up SPECT scan demonstrated significant improvement in the distribution of the radiopharmaceutical.


Drinking Non-nutritive Sweetness Solution of Sodium Saccharin or Rebaudioside a for Guinea Pigs: Influence on Histologic Change and Expression of Sweet Taste Receptors in Testis and Epididymis.
Saccharin sodium and rebaudioside A are extensively used as non-nutritive sweeteners (NNSs) in daily life. NNSs elicit a multitude of endocrine influences on animals, differing across species and chemically distinct sweeteners, whose exposure induce activation of sweet taste receptors in oral and extra-oral tissues with consequences of metabolic changes. To evaluate the influence of NNSs on histologic change and expression of sweet taste receptors in testis and epididymis of young male guinea pigs, thirty 4-week-old male guinea pigs with body weight 245.73 ± 6.02 g were randomly divided into five groups (n = 6) and received normal water (control group) and equivalent sweetness low dose or high dose of sodium saccharin (L-SS, 1.5 mM or H-SS, 7.5 mM) or rebaudioside A (L-RA, 0.5 mM or H-RA, 2.5 mM) solution for 28 consecutive days. The results showed that the relative testis weight in male guinea pig with age of 56 days represented no significant difference among all groups; in spite of heavier body weight in L-SS and H-RA, NNS contributes no significant influence on serum testosterone and estradiol level. Low-dose 0.5 mM rebaudioside A enhanced testicular and epididymal functions by elevating the expressions of taste receptor 1 subunit 2 (T1R2) and gustducin α-subunit (GNAT3), and high-dose 7.5 mM sodium saccharin exerted adverse morphologic influences on testis and epididymis with no effect on the expression of T1R2, taste receptor 1 subunit 2 (T1R3), and GNAT3. In conclusion, these findings suggest that a high dose of sodium saccharin has potential adverse biologic effects on the testes and epididymis, while rebaudioside A is a potential steroidogenic sweetener for enhancing reproductive functions.


Electroconvulsive seizures regulates the Brd1 gene in the frontal cortex and hippocampus of the adult rat.
Depressive disorders represent a significant health concern as they are associated with high social and physical dysfunction and increased risk for suicide. Electroconvulsive therapy (ECT) is the most effective treatment for patients with drug-resistant severe depressive disorders. However, the underlying biological mechanisms of ECT are not well characterized. In particular, the regulation of transcription factors upon ECT has only just started to be unveiled. The schizophrenia and bipolar disorder associated bromodomain containing 1 (BRD1) gene is important for the acetylation of histone H3K14 and holds a key role in normal embryonic development and survival. In this study, we have measured Brd1 mRNA in the hippocampus and the frontal cortex of male Sprague-Dawley rats upon acute and repeated electroconvulsive seizures (ECS) over a period of 10 days. We found an increase in the general expression of Brd1 mRNA in the hippocampus after repeated ECS compared to sham (F = 8.108, P = 0.003). Furthermore, we provide evidence suggesting a decrease in the expression of the Brd1 mRNA variant comprising an extended version of exon 7 (Brd1-L) in the frontal cortex after repeated ECS compared to sham (F = 6.225, P = 0.023). These findings indicate that regulation of the Brd1 gene is part of the biological response to ECS and that splice variants are induced differentially in different brain regions.