Impact of endoscopic sinus surgery on otologic symptoms associated with chronic rhinosinusitis.
To evaluate improvements in otologic symptoms after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS), and identify differences in symptoms, if any, between CRS patients with (CRSwNP) and without (CRSsNP) nasal polyposis. Prospective multi-center observational cohort study. Academic tertiary medical centers. Adults with medically recalcitrant CRS who elected ESS were enrolled in a prospective, multi-center, observational cohort study between March, 2011 and October, 2014. Preoperative evaluation of subjects included assessment of clinical characteristics, measures of disease severity, and quality of life evaluation using the 22-item SinoNasal Outcome Test (SNOT-22). Postoperative improvement in otologic symptoms (ear fullness, dizziness, ear pain) scores were evaluated and compared between CRSwNP and CRSsNP subgroups. 395 study patients completed both preoperative and postoperative evaluations, with an average follow-up of 13.9 months after ESS. The prevalence of patients reporting at least one otologic symptom preoperatively (87%) significantly decreased after ESS (63%; p<0.001). Significant postoperative improvement across all otologic scores was also reported (p<0.001). Relative mean improvement in otologic symptom severity was similar for both CRSwNP and CRSsNP, except patients with CRSwNP reported significantly greater postoperative improvement in ear fullness compared to CRSsNP (54% vs. 41%; p=0.039). A total of 61%, 44%, and 43% of patients reported experiencing improvement in "ear fullness", "dizziness" and "ear pain", respectively. Sinus surgery significantly improves otologic symptoms associated with CRS. CRSwNP patients reported slightly greater relief of ear fullness than CRSsNP patients following ESS.


Development of Caco-2 cells expressing four CYPs via a mammalian artificial chromosome.
Oral administration is the most common way to deliver drugs to the systemic circulation or target organs. Orally administered drugs are absorbed in the intestine and metabolized in the intestine and liver. In the early stages of drug development, it is important to predict first-pass metabolism accurately to select candidate drugs with high bioavailability. The Caco-2 cell line derived from colorectal cancer is widely used as an intestinal model to assess drug membrane permeability. However, because the expression of major drug-metabolizing enzymes, such as cytochrome P450 (CYP), is extremely low in Caco-2 cells, it is difficult to predict intestinal metabolism, which is a significant factor in predicting oral drug bioavailability. Previously, we constructed a mouse artificial chromosome vector carrying the CYP (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and P450 oxidoreductase (POR) (4CYPs-MAC) genes and increased CYP expression and metabolic activity in HepG2 cells via transfer of this vector. In the current study, to improve the Caco-2 cell assay model by taking metabolism into account, we attempted to increase CYP expression by transferring the 4CYPs-MAC into Caco-2 cells. The Caco-2 cells carrying the 4CYPs-MAC showed higher CYP mRNA expression and activity. In addition, high metabolic activity, availability for permeation test, and the potential to assess drug-drug interactions were confirmed. The established Caco-2 cells with the 4CYPs-MAC are expected to enable more accurate prediction of the absorption and metabolism in the human intestine than parental Caco-2 cells. The mammalian artificial chromosome vector system would provide useful models for drug development.


Epidemiology of acute cholecystitis and its treatment in Bergamo District, Northern Italy.
Acute calcolous cholecystitis (ACC) is a very common pathology in western countries. The aim of our work was to assess the epidemiology of ACC and its treatment in Bergamo, a northern Italy province, during the last seventeen years. A restrospective analysis, covering 1997 to 2013, was performed based on the administrative register of the province Health System. Only patients admitted for ACC were selected. From 1997 to 2013 were collected 8959 cases of ACC, mean age was 61.28, 51.5% were male. The incidence of ACC was 48/100.000 per year; the operation rate was 66%. Overall mortality was 0.7%, mean hospitalization time was 9.7 days. The treatment of ACC in Bergamo Province seemed to be acceptable and comparable to literature results. Over the last years, laparoscopy has become the standard treatment. This study outlined some criticisms on the selection's methodology sourcing data from administrative registers, raising questions about truthfulness of results and usefulness for health policy issues.


Mapping Human Monoclonal IgE Epitopes on the Major Dust Mite Allergen Der p 2.
IgE Abs drive the symptoms of allergic disease upon cross-linking allergens on mast cells or basophils. If the IgE binding sites on the allergens could be identified, it may be useful for creating new forms of immunotherapy. However, direct knowledge of the human IgE (hIgE) epitopes is limited because of the very low frequency of IgE-producing B cells in blood. A new hybridoma technology using human B cells from house dust mite-allergic patients was used to identify four Der p 2-specific hIgE mAbs. Their relative binding sites were assessed and compared by immunoassays with three previously studied murine IgG mAbs. Immunoassays showed that the recognition of Der p 2 by the first three hIgE was inhibited by a single murine IgG, but the fourth hIgE recognized a different epitope from all the other mAbs. The functional ability of the hIgE that bind different epitopes to cross-link Der p 2 was demonstrated in a mouse model of passive systemic anaphylaxis. Nuclear magnetic resonance analyses of Der p 2 in complex with IgG and IgE Abs were used to identify specific residues in the epitopes. To our knowledge, the combination of immunoassays to distinguish overlapping epitopes and nuclear magnetic resonance analyses to identify specific residues involved in Ab binding provided the first epitope mapping of hIgE mAbs to an allergen. The technologies developed in this study will be useful in high-resolution mapping of human epitopes on other Ags and the design of improved therapeutics.


Determination of residual bromopropylate and coumaphos in honey and honeycomb by capillary gas chromatography.
This study describes a method for the quantitative determination of residual bromopropylate (BP) and coumaphos (Cph) in honey and honeycomb. It is based on a reversed phase extraction technique on sorbent octadecyl. Both phyto-pharmaceuticals are determined by electron-capture using a fused silica capillary column CP Sil 5 CB. The absolute detection limit for BP and Cph is 2.5 and 5 pg, respectively. Recoveries of 99.6% and 94.4% are obtained for samples fortified at levels of 400 micrograms BP/kg and 1,000 micrograms Cph/kg. Twelve samples of honey and 8 samples of honey-honeycomb have been analysed using this method. BP and Cph could not be detected in the honey samples. Samples of honey-honeycomb recently treated with Perizin (Cph) and Folbex VA (BP) contained different amounts of BP and Cph.


Physical properties of multifunctional TM-doped ZnO nanorods and their photocatalytic and anti-bacterial activities.
Dilute magnetic semiconductor Zn1-xCuxO (x = 0, 1.5, 3.0, and 4.5%) nanorods were prepared by hydrothermal method. The impact of dopant concentration on the physical properties was investigated along with the anti-bacterial and photocatalytic activities. Synthesis of ZnO nanorods was confirmed by the characteristic band at 380 nm in UV-Visible spectra of the synthesized samples. A red shift in absorbance spectra was observed from 380 to 465 nm with an increase in dopant concentration. The hexagonal wurtzite geometry and rod-like morphology of Cu-doped ZnO nanorods having an average size of 29 nm were confirmed by X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM), respectively. An increase in the crystallinity of the material was observed with an increase in the dopant (Cu) ratio without any alteration in geometry. EDX analysis was used to confirm the purity of samples. FTIR spectra were recorded to explore the functional group present in samples. The hysteresis loop drawn by a vibrating-sample magnetometer (VSM) was utilized to analyze the ferromagnetic behavior. As-synthesized pure and Cu-ZnO nanorods were evaluated for their photocatalytic behavior for the photodegradation of methyl orange (MO) dye. Zn1 - xCuxO with x = 4.5%, pH 3, and catalyst dosage of 0.5 g has shown the maximum efficiency. Results elucidated > 81% degradation of MO dye with a rate constant (k) value of - 1.930 × 10-2 min-1 in just 90 min of exposure to a visible light source. ZnO nanorods have also exhibited anti-bacterial potential against gram-positive and gram-negative strains of bacteria. However, smaller size nanorods were found more effective to suppress the growth of gram-negative bacteria. A slight decrease (11%) in catalytic potential was observed in the 5th cycle during recycling and reuse experiments.


Relevance of the capacity of phosphorylated fructose to scavenge the hydroxyl radical.
The hydroxyl radical (*OH) has detrimental biological activity due to its very high reactivity. Our experiments were designed to determine the effects of equimolar concentrations of glucose, fructose and mannitol and three phosphorylated forms of fructose (fructose-1-phosphate (F1P); fructose-6-phosphate (F6P); and fructose-1,6-bis(phosphate) (F16BP)) on *OH radical production via the Fenton reaction. EPR spectroscopy using spin-trap DEPMPO was applied to detect radical production. We found that the percentage inhibition of *OH radical formation decreased in the order F16BP>F1P>F6P>fructose>mannitol=glucose. As ketoses can sequester redox-active iron thus preventing the Fenton reaction, the Haber-Weiss-like system was also employed to generate *OH, so that the effect of iron sequestration could be distinguished from direct *OH radical scavenging. In the latter system, the rank order of *OH scavenging activity was F16BP>F1P>F6P>fructose=mannitol=glucose. Our results clearly demonstrate that intracellular phosphorylated forms of fructose have more scavenging properties than fructose or glucose, leading us to conclude that the acute administration of fructose could overcome the body's reaction to exogenous antioxidants during appropriate therapy in certain pathophysiological conditions related to oxidative stress, such as sepsis, neurodegenerative diseases, atherosclerosis, malignancy, and some complications of pregnancy.


Evaluation of Patients with Neurogenic Thoracic Outlet Syndrome.
Neurogenic thoracic outlet syndrome (NTOS) results from the compression or irritation of the brachial plexus within the thoracic outlet. The associated symptoms result in significant disability and negative effects on patient health-related quality of life. The diagnosis of NTOS, despite being the most common type of TOS, remains challenging for surgeons, in part due to the nonspecific symptoms and lack of definitive diagnostic testing. In this article, we present the essential components of the evaluation of patients with NTOS including a thorough history and physical examination, stress maneuvers, diagnostic and therapeutic imaging, and assessment of disability using standardized patient-centered instruments.


5D-QSAR studies of 1H-pyrazole derivatives as EGFR inhibitors.
Epidermal growth factor receptor (EGFR) is highlighted as a target for anticancer treatment. Several EGFR inhibitors were approved in cancer treatment. Comparatively, 5D-QSAR is a new methodology which considers an ensemble of different induced-fit models. Based on 1H-pyrazole derivatives as EGFR inhibitors, a 5D-QSAR was studied in which the method of quasi-atomistic receptor surface modeling was used. The presented QSAR model showed contributions of the hydrogen bond acceptor, and hydrophobic and salt bridge fields to the activity. The QSAR model was statistically validated and also externally validated applying 19 compounds (test set) which were not included in the model generation process. The scramble tests were performed to further verify the robustness. Apart from exploration of the binding of 1H-pyrazole derivatives to the EGFR, the 5D-QSAR model can be helpful to design of new EGFR inhibitors. The five-dimensional quantitative structure-activity relationship (5D-QSAR) of 1H-pyrazole derivatives as EGFR inhibitors with quasi-atomistic receptor surface modeling approach is described.


Synthesis, evaluation and mechanism exploration of 2-(N-(3-nitrophenyl)-N-phenylsulfonyl)aminoacetohydroxamic acids as novel urease inhibitors.
Thirteen 2-(N-(3-nitrophenyl)-N-phenylsulfonyl)aminoacetohydroxamic acids which were reported for the first time were designed and synthesized as novel urease inhibitors. Most of them showed higher potency than the positive control acetohydroxamic acid, with 2-(N-(3-nitrophenyl)-N-(4-bromophenylsulfonyl)aminoacetohydroxamic acid (d7) being the most active (IC50 = 0.13 ± 0.01 μM). Compound d7 reversibly inhibits urease with mixed mechanism showing excellent binding affinity to urease active site (KD = 0.34 nM, Ki=0.065 ± 0.003 µM andKi' = 1.20 ± 0.09 µM) and very low cytotoxicity against mammalian cells (cell viability of 91.4 % against HepG2 at 250 μg/mL). These positive results indicated that d7 may be used as the lead for further research to develop urease inhibitors with promising properties.


Electricity consumption variation versus economic structure during COVID-19 on metropolitan statistical areas in the US.
The outbreak of novel coronavirus disease (COVID-19) has resulted in changes in productivity and daily life patterns, and as a result electricity consumption (EC) has also shifted. In this paper, we construct estimates of EC changes at the metropolitan level across the continental U.S., including total EC and residential EC during the initial two months of the pandemic. The total and residential data on the state level were broken down into the county level, and then metropolitan level EC estimates were aggregated from the counties included in each metropolitan statistical area (MSA). This work shows that the reduction in total EC is related to the shares of certain industries in an MSA, whereas regardless of the incidence level or economic structure, the residential sector shows a trend of increasing EC across the continental U.S. Since the MSAs account for 86% of the total population and 87% of the total EC of the continental U.S., the analytical result in this paper can provide important guidelines for future social-economic crises.


Associations between Neospora caninum specific antibodies in serum and milk in two dairy herds in Scotland.
The study evaluated the use of the Mastazyme ELISA for quantification of Neospora caninum (N. caninum) specific IgG in bovine milk and examined the relationship between serum and milk antibodies in two dairy herds. The serum and milk antibodies both had bimodal distributions in each herd. This was mainly due to between cow variation: in both herds, approximately two thirds of cows were either clearly and consistently seropositive or seronegative for N. caninum with one third consistently near the threshold. Milk and serum N. caninum IgG were strongly related. This relationship was modelled using a linear mixed model including a polynomial term for serum, the effect of herd, and between and within cow variance components. The latter gave a significantly better fit to the data than a model that allowed for a different relationship for the positive and negative (according to the serum test) groups of observations. The sensitivity and specificity (based on serum percentage positivity (pp)) of the milk antibody was determined for different milk pp thresholds. In spite of the differences between the relationship of milk to serum seen for the two herds, for those estimates with sufficient precision, sensitivity and specificity greater than 0.73 for both herds were obtained using single thresholds of 14 and 15.5 for milk pp in both herds based on, as our gold standard, serum antibody pp thresholds of 22.5 and 25, respectively. If milk antibody is to be used for detecting persistently infected cows, the higher threshold of 15.5 may be suitable while for epidemiological screening 14 would be preferable. Further validation in a greater number of herds is required, but our results suggest that this test may prove to be a useful adjunct to serum N. caninum IgG assays in the monitoring of N. caninum infection as part of herd health programmes and epidemiological studies.


A key to species of the genus Gastroserica Brenske of the China (Coleoptera, Scarabaeidae, Sericini), with the description of two new species and two new records for China.
Based on a revision of the material housed in Chinese collections and a key to species of Gastroserica of China is provided. Two new species are described, habitus photographs, and illustrations of the genitalia are given: Gastroserica nigrofasciatasp. n. (from China: Guangxi and Guizhou Prov.), Gastroserica yunnanensissp. n. (from China: Yunnan Prov.). Besides, illustrations of the genitalia of species mentioned in the key are provided. Additional distribution records of the Gastroserica species including an updated distribution map are given.


Corrigendum to "Ethanol Extract from Ampelopsis sinica Root Exerts Anti-Hepatitis B Virus Activity via Inhibition of p53 Pathway In Vitro".
[This corrects the article DOI: 10.1093/ecam/neq011.].


Increasing accessibility to the blind of virtual environments, using a virtual mobility aid based on the "EyeCane": feasibility study.
Virtual worlds and environments are becoming an increasingly central part of our lives, yet they are still far from accessible to the blind. This is especially unfortunate as such environments hold great potential for them for uses such as social interaction, online education and especially for use with familiarizing the visually impaired user with a real environment virtually from the comfort and safety of his own home before visiting it in the real world. We have implemented a simple algorithm to improve this situation using single-point depth information, enabling the blind to use a virtual cane, modeled on the "EyeCane" electronic travel aid, within any virtual environment with minimal pre-processing. Use of the Virtual-EyeCane, enables this experience to potentially be later used in real world environments with identical stimuli to those from the virtual environment. We show the fast-learned practical use of this algorithm for navigation in simple environments.


Stress reactions and fractures around the elbow in athletes.
Stress fractures of the upper limb affect athletes from a wide range of sports. Athletes involved in throwing sports are particularly susceptible along with athletes from sports involving high repetitive and compressive loads such as gymnastics. Diagnosis can be made from clinical history, examination and radiography in some cases however MRI imaging is often required for definitive diagnosis. The mainstay of management is rest and activity modification however advanced pathology often requires surgical management for successful resolution and return to play. In the elbow, the bones susceptible to excessive stress in sport are the distal humerus, the olecranon process of the ulna, the coronoid process of the ulna, the sublime tubercle and the radial head. In immature patients, medial epicondyle apophysis is the most common location. The article presents a narrative review of the literature.


Surgery for Metastatic Melanoma: an Evolving Concept.
This review describes the evolving role of surgery in stage III and IV melanoma. Surgery has been the first option to cure melanoma patients at initial diagnosis of metastatic spread: a complete surgical excision of the disease either in stage III or IV has been the gold standard for decades. A positive sentinel node biopsy (SNB) has been followed by a complete lymph node dissection (CLND) since the early stages of modern surgical oncology. However, since two randomized trials have indicated that a CLND does not improve survival in patients with a positive SNB, a CLND is no longer considered mandatory. A therapeutic lymph node dissection (TLND) is still offered to patients with macroscopic nodal disease and in highly selected cases, patients with distant melanoma metastases can be treated surgically as well. Also the availability of adjuvant, and in the future possibly neoadjuvant, systemic therapy have shifted the landscape to less extensive surgery in metastatic melanoma. With the development of new systemic options, surgery in metastatic melanoma has become more and more part of a multidisciplinary treatment: surgical indications are moving from previous standards to a new role.


Tuning the Strength of the Resonance-Assisted Hydrogen Bond in Acenes and Phenacenes with Two o-Hydroxyaldehyde Groups-The Importance of Topology.
The fact that intramolecular resonance-assisted hydrogen bonds (RAHBs) are stronger than conventional ones is attributed to the partial delocalization of the π-electrons within the hydrogen bond (HB) motif, the so-called quasi-ring. If an aromatic ring is involved in the formation of the RAHB, previous studies have shown that there is an interplay between aromaticity and HB strength. Moreover, in 1,3-dihydroxyaryl-2-aldehydes, some of us found that the position of the quasi-ring formed by the substituents interacting through RAHB influences the strength of the H bonding, the HBs being stronger when a kinked-like structure is generated by formation of the quasi-ring. In this work, we explore this concept further by considering a set of acenes and phenacenes of different sizes with two o-hydroxyaldehyde substituents. Calculations with the CAM-B3LYP/6-311++G(d,p) + GD3B method show that for long acenes or phenacenes, once the substituent effect loses importance because quasi-rings are pulled apart far from each other, the different topologies rule the HB distances. This fact can be explained in most cases using an extended Clar's aromatic π-sextet model. In some kinked systems, however, the justification from the Clar model has to be complemented by taking into account the repulsion between hydrogen atoms. Triphenylene-like compounds with different numbers of benzene rings have been studied, finding out a very good relationship between aromaticity of the ipso- and quasi-rings with the RAHB distances. This result confirms the importance of the communication of the π-systems of the ipso- and quasi-rings.


Prevalence and Factors Associated with Dyslipidemia Among People Living with HIV/AIDS on Follow-Up Care at a Tertiary Care Hospital in Ethiopia: A Cross-Sectional Study.
Despite its importance as a major risk factor for cardiovascular disease, dyslipidemia remains poorly characterized in the African population. To assess the prevalence and factors associated with dyslipidemia in people with HIV/AIDS in follow-up at Zewditu Memorial Hospital, Addis Ababa, Ethiopia. A hospital-based retrospective cross-sectional study evaluated the charts of 288 people living with HIV/AIDS who had received Highly Active Antiretroviral Treatment for at least six months at Zewditu Memorial Hospital from July to September 2021. Sociodemographic and clinical data were collected from the patient's charts. Statistical analysis was performed using the Statistical Package for Social Sciences software version 25. The overall prevalence of dyslipidemia was 55.2% in people living with HIV/AIDS. The prevalence of high-density lipoprotein cholesterol <40 mg/dl in men and <50 in women was 46.9%; total cholesterol ≥200 mg/dl was 22.6%; triglycerides ≥150 mg/dl was 18.8%, and low-density lipoprotein ≥130 mg/dl was 4.9%. Sex [Female adjusted odds ratio (AOR) = 0.595, 95% CI: 0.37-0.956], age greater than 40 years (AOR = 1.026, 95% CI: 1.005-1.048), body mass index >25 kg/m2 (AOR = 1.767, 95% CI: 1.099-2.84), viral load >50 (AOR = 0.477, 95% CI: 0.27-0.842), and CD4 <500 (AOR = 1.938, 95% CI: 1.18-3.183) were identified as determinants of dyslipidemia. There was a high prevalence of dyslipidemia among study participants compared to several studies published in a similar population. Being male, older age, higher BMI, low CD4 count, and viral load of < 50 copies/mL were associated with dyslipidemia in people living with HIV/AIDS. Therefore, lipid profile measurements at baseline must be part of routine care to prevent the devastating effects of dyslipidemia.


The diagnosis of colorectal cancer with cytologic brushings under direct vision at fiberoptic colonoscopy. A report of 59 cases.
Fifty nine cases of colorectal cancer confirmed postoperatively by histologic examination were correlated with the findings of biopsy specimens and cell brushings. Fifty one cases were positive for malignancy on biopsy (86.4 percent). Brush cytology was positive in 51 cases (86.4 percent). The total preoperative confirmed diagnostic rate of the series was 91.5 percent. Brushing cytology under direct vision at fiberoptic colonoscopy, is a safe, reliable, and quite accurate method for the diagnosis of colorectal cancer. The results from brush cytology did not relate to the configuration and appearance of the tumor. For cell brushing, the fluid in the colonic lumen should be aspirated off as thoroughly as possible. Cell brushings are often positive when colonic stricture and obstruction prevent the colonoscope from reaching the lesion; biopsy, obviously, cannot be done in such a case.


Energy sources for aquatic animals in the Orinoco River floodplain: evidence from stable isotopes.
Stable carbon and nitrogen isotope ratios in autotrophs, aquatic invertebrates and fishes from the Orinoco River floodplain of Venezuela reveal that microalgae, including both phytoplankton and epiphytic (attached) forms, are predominant energy sources for many aquatic animals, even though aquatic vascular plants are much more abundant. Floating mats of the grass Paspalum repens and the water hyacinth Eichhornia spp. harbor particularly high densities of aquatic animals, but isotopic evidence indicates that few species are dependent on organic carbon originating from these plants. The stable isotopic evidence for the trophic importance of algae contradicts traditional interpretations of food webs in freshwater wetlands, which are generally thought to be based largely on detritus originating from vascular plants.


Site-directed mutagenesis and homology modeling indicate an important role of cysteine 439 in the stability of betaine aldehyde dehydrogenase from Pseudomonas aeruginosa.
Betaine aldehyde dehydrogenase (BADH) from the human pathogen Pseudomonas aeruginosa is a tetrameric enzyme that contains a catalytic Cys286 and three additional cysteine residues, Cys353, 377, and 439, per subunit. In the present study, we have investigated the role of the three non-essentials in enzyme activity and stability by homology modeling and site-directed mutagenesis. Cys353 and Cys377 are located at the protein surface with their sulfur atoms buried, while Cys439 is at the subunit interface between the monomers forming a dimeric pair. All three residues were individually mutated to alanine and Cys439 also to serine and valine. The five mutant proteins were expressed in Escherichia coli and purified to homogeneity. Their steady-state kinetics was not significantly affected, neither was their structure as indicated by circular dicroism spectropolarimetry, protein intrinsic fluorescence, and size-exclusion chromatography. However, stability was severely reduced in the Cys439 mutants particularly in C439S and C439V, which were inactive when expressed at 37 degrees C. They also exhibited higher sensitivity to thermal and chemical inactivation, and higher propensity to dissociation by dilution or exposure to low ionic strength than the wild-type enzyme. Size-exclusion chromatography indicates that substitution of Cys439 lead to unstable dimers or to stable dimeric conformations not compatible with a stable tetrameric structure. To the best of our knowledge, this is the first study of an aldehyde dehydrogenase revealing a residue at the dimer interface involved in holding the dimer, and consequently the tetramer, together.


Deciphering the interaction of puerarin with cancer macromolecules: An in silico investigation.
The worldwide expanding increment in cancer pervasiveness is disturbing and this disease ranks among the main causes of mortality in both developing and developed countries. Unfortunately, available treatment options come with serious side effects and do not guarantee complete success. Although numerous models have been proposed for the development of better therapeutic agent, however the exact mechanism are still poorly understood. This then calls for continued research aimed at developing new drugs as an alternative or adjuvant anticancer agents. Here we have identified five vital proteins (CDK-2, Bcl-2, CDK-6, VEGFR, and IGF-1R) that aid tumor growth and we inhibited the activity of these proteins with Puerarin. Puerarin is an isoflavonoid C-glycosides used as a therapeutic agent against various human ailments. Our findings revealed that Puerarin fulfilled Veber's rule. Added to this, CDK-6 and Bcl-2 had better glide scores for puerarin than the control (doxorubicin) and molecular simulation showed the stability of the complexes. These findings suggest that inhibiting CDK-6 and Bcl-2 with Puerarin could prove more effective in the management of cancer than doxorubicin. Overall, this study provides a new direction that could facilitate rational drug design for cancer.Communicated by Ramaswamy H. Sarma.


Unravelling delayed therapy escape after thalamic deep brain stimulation for essential tremor? - Additional clinical and neuroimaging evidence.
Delayed therapy escape after thalamic deep brain stimulation (DBS) for essential tremor is a serious yet frequent condition. It is often difficult to detect this process at onset due to its gradual evolution. Here we aim to identify clinical and neuroimaging hallmarks of delayed therapy escape. We retrospectively studied operationalized and quantitative analyses of tremor and gait, as well as [18F]fluorodeoxyglucose (FDG) PET of 12 patients affected by therapy escape. All examinations were carried out with activated DBS (ON) and 72 h after deactivation (OFF72h); gait and tremor were also analyzed directly after deactivation (OFF0h). Changes of normalized glucose metabolism between stimulation conditions were assessed using within-subject analysis of variance and statistical parametric mapping. Additionally, a comparison to the [18F]FDG PET of an age-matched control group was performed. Exploratory correlation analyses were conducted with operationalized and parametric clinical data. Of the immediately accessible parametric tremor data (i.e. ON or OFF0h) only the rebound (i.e. OFF0h) frequency of postural tremor showed possible correlations with signs of ataxia at ON. Regional glucose metabolism was significantly increased bilaterally in the thalamus and dentate nucleus in ON compared to OFF72h. No differences in regional glucose metabolism were found in patients in ON and OFF72h compared with the healthy controls. Rebound frequency of postural tremor seems to be a good diagnostic marker for delayed therapy escape. Regional glucose metabolism suggests that this phenomenon may be associated with increased metabolic activity in the thalamus and dentate nucleus possibly due to antidromic stimulation effects. We see reasons to interpret the delayed therapy escape phenomenon as being related to long term and chronic DBS.


Effect of organic carbon on sorption of human adenovirus to soil particles and laboratory containers.
A key factor controlling the relationship between virus release and human exposure is how virus particles interact with soils, sediments and other solid particles in the environment and in engineered treatment systems. Finding no previous investigations of human adenovirus (HAdV) sorption, we performed a series of experiments to evaluate the role of soil organic carbon (SOC) and solution-phase dissolved organic carbon (DOC) on sorption capacity and reversibility. In preliminary methodological studies, we found that as much as 99% of HAdV was lost from inorganic buffer suspensions in polypropylene (PP) laboratory containers, but little loss occurred when using suspensions with substantial amounts of DOC or with glass containers from either type of suspension. It was confirmed that this loss was due to sorption rather than inactivation by using lysis-based recovery techniques and qPCR measurements that do not depend on virus viability. In isotherm experiments, soils with 2% OC had ≈ four-fold greater sorption capacity for HAdV than 8% OC soils; moreover, the sorption capacity of 2% OC soils was reduced ≈ seven-fold with an aqueous solution containing 150 mg/L of humic acid. After sequential extractions, higher fractions of sorbed HAdV were released from 8% OC soils. The amounts of HAdV and OC released remained relatively constant throughout each extraction step, indicating that desorbed HAdV could be caused primarily by the detachment of SOC from soils. Overall, results from this study suggest that OC plays a critical role in the sorption and desorption of HAdV, and as a result, on its environmental fate and transport.


Reverse serosal demucosalized gastrocystoplasty.
A novel technique of augmentation cystoplasty is suggested. The patch which is advocated is less likely to cause electrolyte imbalance, is autologous and easily available. It will avoid all the gut-mucosa-related early and late postoperative complications.


Yeast-template synthesized Fe-doped cerium oxide hollow microspheres for visible photodegradation of acid orange 7.
Fe-doped cerium oxide (CeO2) hollow microspheres were successfully synthesized by a simple co-precipitation route using yeast asa bio-template and nitrate as the oxide precursor. The products were characterized by scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, N2 adsorption-desorption isotherms and UV-Vis diffuse reflectance spectroscopy. It was found that the products had a well-defined ellipsoidal morphology and the size of the hollow microspheres was about 1.5-2.5μm. The formation mechanism of Fe-doped CeO2 hollow microspheres was proposed and discussed as well. The photocatalytic test results showed that the Fe-doped CeO2 hollow microspheres exhibited a higher photocatalytic activity in the degradation of acid orange 7 (AO7) aqueous solutions containing H2O2 under visible irradiation compared with CeO2 hollow microspheres and Fe-doped CeO2 nanoparticles, which was attributed to their more oxygen vacancies, higher specific surface area and lower band gap. The degradation rate of the Fe-doped CeO2 hollow microspheres was found to be 93% after 80min and the degradation reaction followed pseudo-first-order kinetics.


The Impact of Post-Procedural Asymmetry, Expansion, and Eccentricity of Bioresorbable Everolimus-Eluting Scaffold and Metallic Everolimus-Eluting Stent on Clinical Outcomes in the ABSORB II Trial.
The study sought to investigate the relationship between post-procedural asymmetry, expansion, and eccentricity indices of metallic everolimus-eluting stent (EES) and bioresorbable vascular scaffold (BVS) and their respective impact on clinical events at 1-year follow-up. Mechanical properties of a fully BVS are inherently different from those of permanent metallic stent. The ABSORB II (A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions) trial compared the BVS and metallic EES in the treatment of a de novo coronary artery stenosis. Protocol-mandated intravascular ultrasound imaging was performed pre- and post-procedure in 470 patients (162 metallic EES and 308 BVS). Asymmetry index (AI) was calculated per lesion as: (1 - minimum scaffold/stent diameter/maximum scaffold/stent diameter). Expansion index and optimal scaffold/stent expansion followed the definition of the MUSIC (Multicenter Ultrasound Stenting in Coronaries) study. Eccentricity index (EI) was calculated as the ratio of minimum and maximum scaffold/stent diameter per cross section. The incidence of device-oriented composite endpoint (DoCE) was collected. Post-procedure, the metallic EES group was more symmetric and concentric than the BVS group. Only 8.0% of the BVS arm and 20.0% of the metallic EES arm achieved optimal scaffold/stent expansion (p < 0.001). At 1 year, there was no difference in the DoCE between both devices (BVS 5.2% vs. EES 3.1%; p = 0.29). Post-procedural devices asymmetry and eccentricity were related to higher event rates while there was no relevance to the expansion status. Subsequent multivariate analysis identified that post-procedural AI >0.30 is an independent predictor of DoCE (hazard ratio: 3.43; 95% confidence interval: 1.08 to 10.92; p = 0.037). BVS implantation is more frequently associated with post-procedural asymmetric and eccentric morphology compared to metallic EES. Post-procedural devices asymmetry were independently associated with DoCE following percutaneous coronary intervention. However, this approach should be viewed as hypothesis generating due to low event rates. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281).


Strength and bioactivity of PEEK composites containing multiwalled carbon nanotubes and bioactive glass.
Polyetheretherketone (PEEK) polymer is a widely accepted implantable biomaterial in the biomedical field. However, PEEK has a low elastic modulus (E-modulus) as well as a bio-inert nature which is not conductive to rapid bone cell attachment, hence, producing delayed or weak bone-implant integration. Multiwalled carbon nanotubes (MWCNTs) represent one of the strongest known materials that could be added to a polymer to improve its mechanical properties. Bioactive glasses (BGs) can form hydroxyapatite deposits on their surfaces and form a tight bond with the bone, thus, their incorporation into the PEEK matrix may improve its bioactivity. Eight groups were formulated according to the type and percentage of modification of PEEK by MWCNTs and BGs. Group 1: Pure PEEK (P), Group 2: P + 3% MWCNTs (PC3), Group 3: P + 5% MWCNTs (PC5), Group 4: P + 5% BGs (PG5), Group 5: P + 10% BGs (PG10), Group 6: P + 3% MWCNTs + 5% BGs (PC3G5), Group 7: P + 3% MWCNTs + 10% BGs (PC3G10), and Group 8: P + 5% MWCNTs + 5% BGs (PC5G5). Characterization of the vacuum-pressed PEEK and PEEK composite specimens was done using FE-SEM, EDS, FT-IR and TF-XRD. Three-point load test was done to obtain the flexural strength (F.S) and the E-modulus of the specimens. Wettability was determined by measuring the contact angle with distilled water. In-vitro bioactivity was determined after immersion of specimens in simulated body fluid (SBF). Moreover, the effect of the specimens on osteoblastic cell viability was evaluated. Three-point load test results have shown an improvement in both F.S. and E-modulus for groups PC5, PC3G5 and PC5G5. The lowest contact angle was obtained for group PC5G5 followed by the PC3G10 group. All specimens containing BGs showed the formation of hydroxyapatite-like deposits after their immersion in SBF, as well as an improvement in osteoblastic cell viability compared to PEEK. PC3G10, PC3G5 and PG10, groups are promising for the fabrication of patient-specific implants that can be used in low-stress-bearing areas.


Chimeric 3-hydroxy-3-methylglutaryl coenzyme A reductase-dihydrofolate reductase genes display bidirectional expression and unidirectional regulation in stably transfected cells.
We have constructed hybrid dihydrofolate reductase (DHFR) genes which are controlled by the sterol-responsive hamster 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase promoter. Stable transfection frequencies of these chimeric templates into a DHFR-deficient Chinese hamster cell line indicate that the HMG CoA reductase promoter fragment confers DHFR transformation irrespective of its orientation relative to a downstream murine DHFR cDNA. Sterol-regulated levels of DHFR RNA and protein are detected from hybrid genes which carry a properly oriented promoter fragment. Constructions which invert this HMG CoA reductase promoter, however, generate DHFR RNA levels which do not respond to sterols. In the context of these transfected fusion genes, we present evidence of divergent opposite-strand transcription initiating from the HMG CoA reductase 5' fragment. In contrast, the endogenous HMG CoA reductase promoter region shows no apparent evidence of such bidirectional activity.


Clinical application of arrhythmia analyzer in ICU.
A microcomputer system (NEC Sanei Ins. Company Ltd.) has been developed for the continuous monitoring and storage and retrieval of data from serial ECG tracings in each ICU patient. Eight hundred and forty patients were monitored using the system. Diagnosis of ventricular arrhythmias and ST-segment change was highly accurate. However, the false positive diagnosis was sometimes generated by artifact. Diagnosis of supraventricular arrhythmias or rhythmic abnormalities were less accurate compared with that of ventricular arrhythmias. Application of microcomputer system in the space limited ICU is of benefit to identify and evaluate ECG gracings in time saving way. However, further version-up is needed to promote the accuracy of the diagnosis.


Parallel factor analysis for multidimensional decomposition of functional near-infrared spectroscopy data.
Current techniques for data analysis in functional near-infrared spectroscopy (fNIRS), such as artifact correction, do not allow to integrate the information originating from both wavelengths, considering only temporal and spatial dimensions of the signal's structure. Parallel factor analysis (PARAFAC) has previously been validated as a multidimensional decomposition technique in other neuroimaging fields. We aimed to introduce and validate the use of PARAFAC for the analysis of fNIRS data, which is inherently multidimensional (time, space, and wavelength). We used data acquired in 17 healthy adults during a verbal fluency task to compare the efficacy of PARAFAC for motion artifact correction to traditional two-dimensional decomposition techniques, i.e., target principal (tPCA) and independent component analysis (ICA). Correction performance was further evaluated under controlled conditions with simulated artifacts and hemodynamic response functions. PARAFAC achieved significantly higher improvement in data quality as compared to tPCA and ICA. Correction in several simulated signals further validated its use and promoted it as a robust method independent of the artifact's characteristics. This study describes the first implementation of PARAFAC in fNIRS and provides validation for its use to correct artifacts. PARAFAC is a promising data-driven alternative for multidimensional data analyses in fNIRS and this study paves the way for further applications.


Cardiac transplantation after donor mitral valve commissurotomy.
Cardiac transplantation has become a relatively common procedure, with its limiting factor being the lack of donor hearts. The donor pool can potentially be increased by reevaluating donor criteria and performing innovative procedures on the donor heart, such as coronary bypass and valve repair. We present a recent case of donor heart mitral valve commissurotomy with successful transplantation.


Is the incidence of heparin-induced thrombocytopenia affected by the increased use of heparin for VTE prophylaxis?
The increased exposure to heparin products for thromboprophylaxis against VTE in hospitalized patients raises concerns for an increase in the incidence of heparin-induced thrombocytopenia(HIT). We analyzed, among 90,875 patients exposed to heparin products between 2005 and 2009, the number of hematologic consultations for thrombocytopenia, requests for heparin induced antibodies by enzyme-linked immunosorbent assay, and cases given a diagnosis of HIT by the hematology consult service. We observed that despite a doubling in the number of patients receiving pharmacoprophylaxis with heparin, there was no significant increase in the number of consultations for thrombocytopenia,the number of requests for HIT tests, the number of positive HIT test results, or the number of HIT diagnoses. The number of cases of HIT was low and represented < 0.1% of patients exposed to heparin. We conclude that concerns about HIT should not be a limiting factor for the systematic implementation of heparin-based VTE prophylaxis.


Shiga toxin 1 and 2 induce apoptosis in the amniotic cell line WISH.
The aim of this study was to evaluate the toxicity of Shiga toxin (Stx) 1 and 2 on amniotic cells in vitro. WISH cells, which were derived from human amniotic cells, and Vero cells were cultured with or without Stxs. After 24 hours of culture, cell viability was measured by Cell Counting Kit-8, and extracted DNA was electrophoresed on a 1% agarose gel. The morphologic changes were observed by Papanicolaou staining, and the apoptotic index (percentage of apoptotic nuclei per total nuclei) was calculated. Quantification of apoptotic cells was also measured by an enzyme-linked immunosorbent assay. The viability of WISH cells decreased in proportion to the concentrations of Stxs. Cellular ladder formation was observed by DNA electrophoresis of Stx-treated WISH cells, and the typical morphologic changes were observed by Papanicolaou staining. The proportion of apoptotic cells increased in response to Stxs. Stxs injured WISH cells directly and induced apoptosis in vitro. WISH cells were as sensitive as Vero cells to Stxs and cell death occurred by apoptosis.


Variation in ripe fruit volatiles across the tomato clade: An evolutionary framework for studying fruit scent diversity in a crop wild relative.
The scents of volatile organic compounds (VOCs) are an important component of ripe fleshy fruit attractiveness, yet their variation across closely related wild species is poorly understood. Phylogenetic patterns in these compounds and their biosynthetic pathways offer insight into the evolutionary drivers of fruit diversity, including whether scent can communicate an honest signal of nutrient content to animal dispersers. We assessed ripe fruit VOC content across the tomato clade (Solanum sect. Lycopersicon), with implications for crop improvement since these compounds are key components of tomato flavor. We analyzed ripe fruit volatiles from 13 species of wild tomato grown in a common garden. Interspecific variations in 66 compounds and their biosynthetic pathways were assessed in 32 accessions, and an accession-level phylogeny was constructed to account for relatedness. Wild tomato species can be differentiated by their VOCs, with Solanum pennellii notably distinct. Phylogenetic conservatism exists to a limited extent. Major cladewide patterns corresponded to divergence of the five brightly colored-fruited species from the nine green-fruited species, particularly for nitrogen-containing compounds (higher in colored-fruited) and esters (higher in green-fruited), the latter appearing to signal a sugar reward. We established a framework for fruit scent evolution studies in a crop wild relative system, showing that each species in the tomato clade has a unique VOC profile. Differences between color groups align with fruit syndromes that could be driven by selection from frugivores. The evolution of colored fruits was accompanied by changes in biosynthetic pathways for esters and nitrogen-containing compounds, volatiles important to tomato flavor.


The effect of Public Law 94--484 on pathology residency programs.
The Health Professions Educational Assistance Act of 1976 (Public Law 94--484) will affect graduate medical programs. The author surveyed directors of medical education in one major metropolitan area to study what the effects might be. With regard to pathology residency programs there are a number of important influences. For example, there will be fewer foreign medical graduates available to study in United States pathology programs. However, those who do come may be of higher quality. Also, owing to financial incentives to increase primary care, medical schools and hospitals may show less interest in the development of speciality programs such as pathology. The changing environment poses challenges to pathology directors to maintain or improve their programs.


Patient-specific flow analysis of brain aneurysms at a single location: comparison of hemodynamic characteristics in small aneurysms.
The purpose of this study is to examine and compare the hemodynamic characteristics of small aneurysms at the same anatomical location. Six internal carotid artery-ophthalmic artery aneurysms smaller than 10 mm were selected. Image-based computational fluid dynamics (CFD) techniques were used to simulate aneurysm hemodynamics. Flow velocity and wall shear stress (WSS) were also quantitatively compared, both in absolute value and relative value using the parent artery as a baseline. We found that flow properties were similar in ruptured and unruptured small aneurysms. However, the WSS was lower at the aneurysm site in unruptured aneurysms and higher in ruptured aneurysms (P < 0.05). Hemodynamic analyses at a single location with similar size enabled us to directly compare the hemodynamics and clinical presentation of brain aneurysms. The results suggest that the WSS in an aneurysm sac can be an important hemodynamic parameter related to the mechanism of brain aneurysm growth and rupture.


Do participants' preferences for mode of delivery (text, video, or both) influence the effectiveness of a Web-based physical activity intervention?
In randomized controlled trials, participants cannot choose their preferred intervention delivery mode and thus might refuse to participate or not engage fully if assigned to a nonpreferred group. This might underestimate the true effectiveness of behavior-change interventions. To examine whether receiving interventions either matched or mismatched with participants' preferred delivery mode would influence effectiveness of a Web-based physical activity intervention. Adults (n = 863), recruited via email, were randomly assigned to one of three intervention delivery modes (text based, video based, or combined) and received fully automated, Internet-delivered personal advice about physical activity. Personalized intervention content, based on the theory of planned behavior and stages of change concept, was identical across groups. Online, self-assessed questionnaires measuring physical activity were completed at baseline, 1 week, and 1 month. Physical activity advice acceptability and website usability were assessed at 1 week. Before randomization, participants were asked which delivery mode they preferred, to categorize them as matched or mismatched. Time spent on the website was measured throughout the intervention. We applied intention-to-treat, repeated-measures analyses of covariance to assess group differences. Attrition was high (575/863, 66.6%), though equal between groups (t(86) (3) =1.31, P =.19). At 1-month follow-up, 93 participants were categorized as matched and 195 as mismatched. They preferred text mode (493/803, 61.4%) over combined (216/803, 26.9%) and video modes (94/803, 11.7%). After the intervention, 20% (26/132) of matched-group participants and 34% (96/282) in the mismatched group changed their delivery mode preference. Time effects were significant for all physical activity outcomes (total physical activity: F(2,801) = 5.07, P = .009; number of activity sessions: F(2,801) = 7.52, P < .001; walking: F(2,801) = 8.32, P < .001; moderate physical activity: F(2,801) = 9.53, P < .001; and vigorous physical activity: F(2,801) = 6.04, P = .002), indicating that physical activity increased over time for both matched and mismatched groups. Matched-group participants improved physical activity outcomes slightly more than those in the mismatched group, but interaction effects were not significant. Physical activity advice acceptability (content scale: t(368) = .10, P = .92; layout scale: t(368) = 1.53, P = .12) and website usability (layout scale: t(426) = .05, P = .96; ease of use scale: t(426) = .21, P = .83) were generally high and did not differ between the matched and mismatched groups. The only significant difference (t(621) = 2.16, P = .03) was in relation to total time spent on the website: the mismatched group spent significantly more time on the website (14.4 minutes) than the matched group (12.1 minutes). Participants' preference regarding delivery mode may not significantly influence intervention outcomes. Consequently, allowing participants to choose their preferred delivery mode may not increase effectiveness of Web-based interventions.


Dailysate calcium and plasma calcium fractions during and after haemodialysis.
Dialysate calcium and plasma calcium fractions during and after haemodialysis: The effect of differenct dialysate Ca concentrations on the plasma Ca fractions was examined in 28 patients. In 10 patients dialysed with a dialysate Ca concentration of 3.0 mEq/l the Ca fractions were determined at the start and end of dialysis. 8 patients were dialysed with dialysate with dialysate Ca of 3.5 mEq/l. In this group the Ca fractions were also estimated in the dialysis-free interval. The third group was dialysed with a dialysate Ca of 4.5 mEq/l. Total calcium and protein-bound calcium rose significantly in all groups. Ionised calcium in the first group was significantly reduced, in the second group it remained constant and in the third group it was significantly raised. Since parathyroid function depends on the plasma ionised calcium it is concluded that a dialysed concentration of 3.0 mEq/l is partly responsible for the pathogenesis of secondary hyperparathyroidism and of renal osteodystophy. In normocalcaemic patients a dialysate Ca concentration of 3.5 to 4.0 mEq/l is optimal. In patients entering long-term haemodialysis treatment with pronounced calcium deficiency symptoms a dialysate Ca of up to 4.5 mEq/l may be indicated for a short period after having normalized the inorganic phosphate levels in order to prevent extraosseous calcification.


Effect of amino acids on X-ray-induced hydrogen peroxide and hydroxyl radical formation in water and 8-oxoguanine in DNA.
Generation of hydrogen peroxide and hydroxyl radicals in L-amino acid solutions in phosphate buffer, pH 7.4, under X-ray irradiation was determined by enhanced chemiluminescence in the luminol-p-iodophenol-peroxidase system and using the fluorescent probe coumarin-3-carboxylic acid, respectively. Amino acids are divided into three groups according to their effect on the hydrogen peroxide formation under irradiation: those decreasing yield of H2O2, having no effect, and increasing its yield. All studied amino acids at 1 mM concentration decrease the yield of hydroxyl radicals in solution under X-ray irradiation. However, the highest effect is observed in the order: Cys > His > Phe = Met = Trp > Tyr. At Cys, Tyr, and His concentrations close to physiological, the yield of hydroxyl radicals decreases significantly. Immunoenzyme analysis using monoclonal antibodies to 8-oxoguanine (8-oxo-7,8-dihydroguanine) was applied to study the effect of amino acids with the most pronounced antioxidant properties (Cys, Met, Tyr, Trp, Phe, His, Lys, Arg, Pro) on 8-oxoguanine formation in vitro under X-ray irradiation. It is shown that amino acids decrease the content of 8-oxoguanine in DNA. These amino acids within DNA-binding proteins may protect intracellular DNA against oxidative damage caused by formation of reactive oxygen species in conditions of moderate oxidative stress.


Purification of glycocalicin from human plasma.
Glycocalicin (GC) is a large extracellular proteolytic fragment of glycoprotein Ib, a membrane platelet component playing an essential role in the physiological processes of platelet adhesion and aggregation. GC contains the binding sites for thrombin and von Willebrand factor. GC circulates normally in vivo in significant concentrations and the plasma level of this protein reflects a complex function of factors including platelet count or platelet turnover. It can therefore serve as a good indicator for many diseases like hypoplastic thrombocytopenia and idiopathic thrombocytopenic purpura. For this reason, several purification assays have been previously described. In this work, we describe a novel analytical method for GC purification from human platelets based on preparative HPLC gel filtration followed by immuno-affinity chromatography on NHS activated column conjugated with specific antibody. Pure GC was obtained from tiny amount of starting material. Our protocol of GC purification is simple, fast and provides a pure end product.


Structure of tumour necrosis factor by X-ray solution scattering and preliminary studies by single crystal X-ray diffraction.
The structure of tumour necrosis factor has been investigated by X-ray small-angle scattering and X-ray diffraction using synchrotron radiation. The overall radius of gyration is 25.5 A. A plausible model accounting for the scattering curves consists of an elongated trimer with an axial ratio of 3 to 4 and a maximal chord with a lower limit of 80 A. Tumour necrosis factor has been crystallized in a trigonal space group. Our results are in favour of a single trimer in the asymmetric unit. The diffraction extends to 3.5 A.


Nanoparticles-EPS corona increases the accumulation of heavy metals and biotoxicity of nanoparticles.
Microbial extracellular polymeric substances (EPS) coating nanoparticles (NPs) surface can form NPs-EPS corona, which significantly affect the adsorption of NPs to toxic substances and alter the ecotoxicological effect of NPs. In this work, the EPS coronas on TiO2 NPs (TNPs) and CeO2 NPs (CNPs) were characterized and the adsorption characteristics of NPs with and without EPS corona to five heavy metals were investigated in single-metal and multiple-metal systems. The results of spectral analysis showed that NPs-EPS corona exhibited new crystalline phases and abundant functional groups. Moreover, 42 and 13 proteins were identified in the TNPs-EPS and CNPs-EPS coronas, respectively. The rates of Cd2+, Pb2+, Cu2+, Ni2+ and Ag+ adsorption by NPs-EPS corona increased to values that were 6.7-7.6, 4.4-5.1, 4.2-5.5, 3.9-4.9 and 8.5-8.8 times those of NPs without EPS corona, respectively, in single-metal system. NPs-EPS coronas are effective in absorbing Ag+, Pb2+ and Cu2+ compared with Cd2+and Ni2+ in multiple metal adsorption. These results indicated that NPs-EPS corona effectively adsorb and remove heavy metals by forming NPs-EPS-metal complexes and inducing precipitation. However, NPs-EPS corona can enhance the toxicity of NPs by accumulating highly-toxic heavy metals in aquatic environments.


Therapeutic potential of peptides from Ole e 1 in olive-pollen allergy.
Olive-pollen allergy is one of the leading causes of respiratory allergy in Mediterranean countries and some areas of North America. Currently, allergen-specific immunotherapy is the only etiophatogenic treatment. However, this approach is not fully optimal, safe, or effective. Thus, efforts continue in the search for novel immunotherapy strategies, being one of the most promising the use of peptides derived from major allergens. This work tries to determine the therapeutic potential and safety of 5 dodecapeptides derived from the main allergen of olive-pollen allergy, Ole e 1. The immunomodulatory capacity of these peptides was studied using peripheral blood mononuclear cells (PBMCs) obtained from 19 olive-pollen-allergic patients and 10 healthy controls. We determined the capacity of these peptides to inhibit the proliferative response toward olive-pollen allergenic extract and to induce the regulatory cytokines, IL-10 and IL-35. To test the safety and absence of allergenicity of the peptides, the basophil activation was analyzed by flow-cytometry, using peripheral blood. The results showed that two of five peptides inhibited near to 30% the proliferative response against the total olive-pollen allergenic extract in olive-pollen-allergic patients. Inhibition increased to nearly 35% when the 5 peptides were used in combination. In both cases, a statistically significant induction of IL-10 and IL-35 secretion was observed in the supernatants of allergic patients PBMCs cultures. None of the 5 peptides induced basophil activation and cross-link inflammatory cell-bound IgE. In conclusion, these results open up new possibilities in the treatment of olive-pollen allergy, which could solve some of the problems facing current therapy approaches.


Induction of endometrial adenocarcinomas by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine to aged Donryu rats showing spontaneously persistent estrus.
Induction of endometrial adenocarcinomas by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) to aged rats was examined. Donryu rats showing spontaneously persistent estrus were given a single intra-uterine administration of ENNG (20 mg/kg) at 10 months (44 weeks) of age. At the termination of the experiment (week 34 after the ENNG-treatment), 22% and 13% incidences of endometrial adenocarcinomas were observed in the experimental and control groups, respectively, the difference being without significance. No variation was found in the endocrine environment between experimental and non carcinogen-treated control animals throughout the experimental period. These results show that ENNG-treatment alone is not sufficient in aged rats for high induction of endometrial carcinomas. Comparison of the data with those from our previous studies, in which ENNG was given at a young age (10 weeks of age), indicates that young rats may be more sensitive than their old counterparts.


Serious overdoses involving buprenorphine in Helsinki.
Buprenorphine is used as maintenance therapy for opioid-dependent patients. In comparison with other opioids it is thought to be safer because it is less likely to cause serious respiratory depression. However, concomitant use of psychotropics, especially benzodiazepines, and intravenous injection of dissolved buprenorphine tablets increase the risk of a serious overdose. As part of a larger retrospective study of opioid overdoses in Helsinki, the emergency medical services (EMS) records from January 1995 to April 2002 were reviewed for overdoses involving buprenorphine. Hospital records were reviewed when available. We report 11 overdoses in which buprenorphine was involved. The classic symptoms and signs of an opioid overdose (respiratory depression, miosis and central nervous system depression) were present in most of the cases. At least eight of the patients had an overdose that was potentially fatal. One of the patients had a heroin overdose and was reportedly 'treated' by his friends with intravenously administered buprenorphine. The high-dosage formulation of buprenorphine used for opioid-dependent patients might have caused several dangerous and potentially fatal overdoses in Helsinki. However, it does cause considerably less serious overdoses than heroin. Drug abusers might be intravenously administering buprenorphine themselves to treat heroin overdoses.


Immunohistochemical demonstration of neuronal and astrocytic differentiation in retinoblastoma.
Sections of 51 surgically enucleated eyes from cases of retinoblastomas were examined immunohistochemically to delineate patterns of cellular differentiation. Employing the avidin-biotin immunoperoxidase technique, antibodies were used against glial fibrillary acidic protein (GFAP), S-100 protein and neuron specific enolase (NSE). Areas of uninvolved retina and/or optic nerve were used as built-in positive control. Most of the tumors showed GFAP and S-100 protein-positive perivascular glial cells that were interpreted as reactive astrocytes. In three well-differentiated retinoblastomas, glial cells were found to be interspersed randomly among tumor cells and not associated with blood vessels. These glial cells were interpreted as neoplastic based on their distribution pattern and cytologic features. In about half of the tumors, the retinoblastoma cells stained positively for NSE, indicating their neuronal tumor cells that stained positively for NSE but failed to show any evidence of photoreceptor differentiation. Based on these observations and similar differentiation patterns described in other primitive neuroectodermal tumors of the brain, it is suggested that retinoblastoma cells can differentiate not only into photoreceptor cells but also along other neuronal cell lines and rarely into glial cells.


Mitral valve replacement via right thoracotomy after coronary arterial grafting.
Mitral valve replacement was performed through a right thoracotomy using femorofemoral bypass under profound systemic hypothermia in a 62-year-old man who had undergone coronary artery bypass grafting using both internal thoracic arteries. The right thoracotomy approach minimizes the risk of injury to the arterial grafts, and deep hypothermia obviates the need to interrupt the grafts to administer cardioplegia. This technique provides excellent exposure of the mitral valve while minimizing the operative risk.


Endogenous opiates: 1988.
This paper is the eleventh installment in our annual review of the research during the past year involving the endogenous opiate system. It is concerned with nonanalgesic and behavioral studies of the opiate peptides that were published during 1988. The specific topics this year include stress; tolerance and dependence; eating; drinking; gastrointestinal, renal, and hepatic functions; mental illness; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurological disorders; electrical activity; locomotor activity; sex, pregnancy, and development; immunology and cancer; and other behavior.


Decellularization and In Vivo Recellularization of Abdominal Porcine Fascial Tissue.
Tissue decellularization has evolved as a promising approach for tissue engineering applications. In this study, we harvested fascial tissue from porcine anterior abdominal wall and the samples were decellularized with a combination of agents such as Triton X-100, trypsin and DNAase. Afterwards, we evaluated cell removal by histological analysis and DNA quantification. Mechanical functionality was evaluated by applying a range of hydrostatic pressures. A sample of decellularized fascia was transplanted into a rabbit and after 15 days a biopsy of this tissue was examined; the animal was observed during 6 months after surgery. The extracellular matrix was retained with a complete decellularization as evidenced by histologic examination. The DNA content was significantly reduced. The scaffold preserved its tensile mechanical properties. The graft was incorporated into a full thickness defect made in the rabbit abdominal wall. This tissue was infiltrated by granulation and inflammatory cells and the histologic structure was preserved 15 days after surgery. The animal did not develop hernias, infections or other complications, after a 6-months of follow up. The protocol of decellularization of fascial tissue employed in this study proved to be efficient. The mechanical test demonstrated that the samples were not damaged and maintained its physical characteristics; clinical evolution of the rabbit, recipient of the decellularized fascia, demonstrated that the graft was effective as a replacement of native tissue.In conclusion, a biological scaffold derived from porcine fascial tissue may be a suitable candidate for tissue engineering applications.


Non-functional malignant paraganglioma of the stomach.
We report the second case of a malignant paraganglioma of the stomach in a 56-year-old female patient. However, our case is the first investigated by immunohistochemistry and electron-microscopy. The tumour was characterized immunohistochemically by the presence of neurofilament protein, glial fibrillary acidic protein, S-100 protein, neuron-specific enolase, chromogranin A, ACTH, leu-enkephalin and vasoactive intestinal polypeptide, and ultrastructurally by demonstration of neurosecretory granules and paranuclear intermediate filament whorls. Despite massive metastatic spread in the abdominal cavity, the patient is still alive 4 years after initial diagnosis.


Indications and techniques for midline approach to aortic coarctation in infants and children.
A variety of techniques have been described for the repair of aortic coarctation. Most of these use operative exposure through a left thoracotomy. There are, however, instances when a median sternotomy provides a more versatile approach and allows for equally acceptable repair. Twelve patients (age, 2 days to 16 years) with coarctation of the aorta serve to illustrate the value of the technique. All but 3 patients were under 3 years old. Five patients had repair of coarctation combined with repair of other congenital cardiac anomalies (atrial and ventricular septal defects, 2 patients; atrial septal defects, 2 patients; and valvular aortic stenosis, 1 patient). Six patients had complicated recurrences of previously repaired coarctations and 1 patient had a primary coarctation that involved the aortic arch. All repairs were accomplished through a median sternotomy with the use of cardiopulmonary bypass and periods of (1) total circulatory arrest (6 patients); (2) reduced flow (4 patients); or (3) normal flow with multiple sites of arterial inflow (2 patients). All patients did well with no operative mortalities and no sequelae to date (8 weeks to 4 years). Examples of various techniques are provided to demonstrate the flexibility obtainable with this method. Median sternotomy can provide a viable approach to difficult problems involving coarctation of the aorta.


Management of non-healing lesion from surgical treatment of necrotizing fasciitis through Ayurveda- a case report.
Necrotizing fasciitis is a soft-tissue infection that is rare but life-threatening. The early clinical presentation of necrotizing fasciitis is local erythema, pain, and fever. It occurs in any part of the body, but it is mainly found in the extremities, abdominal wall, and perineum. It needs intensive care with appropriate antibiotics and extensive surgical debridement. This Case of necrotizing fasciitis was initially treated with surgical debridement and splint skin grafting. After two months of failed medical-surgical interventions and dressing, the 17-year old female in an irritable but oriented state approached the outpatient department of kayachikitsa with the unhealed wound. The Ayurvedic diagnosis of Vidradhi was deliberated after considering PittaDosha and Rakta, Mamsa, and MedaDhatu. She was treated with medicines, including external applications, for one month. It resulted in complete wound healing and minimal scarring, and a satisfied patient. This Case can be the basis for future research studies.


Localization of the human HF.10 finger gene on a chromosome region (3p21-22) frequently deleted in human cancers.
The finger motif is a tandemly repeated DNA-binding domain recently identified in the primary structure of several eukaryotic transcriptional regulatory proteins. It has been proposed that some members of the finger-gene family are implicated in both normal cell proliferation and differentiation. We isolated several human finger genes by means of hybridization with a finger motif-containing DNA probe. One of these finger genes, HF.10, is expressed at low levels in a variety of human tissues and is down-regulated during the in vitro terminal differentiation of human leukemic myeloid cell lines. By in situ hybridization experiments and analysis of interspecific somatic cell hybrids we mapped the HF.10 gene to 3p21-22, a chromosome region frequently involved in karyotypic rearrangements associated with lung and renal cancer.


A case of severe Pierre Robin sequence with failure to thrive and tachycardia resolved after redo-fundoplication and hiatoplasty.
We report an infant suffering from Pierre Robin sequence complicated by gastro-oesophageal reflux and failure to thrive, which were resistant to conservative therapy and a hemifundoplication. Gastro-oesophageal reflux was accompanied by supraventricular tachycardia, treated with propafenone. Tachycardia may be present in Pierre Robin sequence as a consequence of cardiac parasympathetic imbalance. The patient recovered completely from the gastro-oesophageal reflux and tachycardia after redo-fundoplication (Nissen) and a hiatoplasty were performed. This case shows that a thorough search for gastro-oesophageal reflux is indicated in each case of Pierre Robin sequence with failure to thrive.


Lactobacillus gasseri LGV03 isolated from the cervico-vagina of HPV-cleared women modulates epithelial innate immune responses and suppresses the growth of HPV-positive human cervical cancer cells.
Persistent human papillomavirus (HPV) infections is necessary for the development of cervical cancers. An increasing number of retrospective studies have found the depletion of Lactobacillus microbiota in the cervico-vagina facilitate HPV infection and might be involved in viral persistence and cancer development. However, there have been no reports confirming the immunomodulatory effects of Lactobacillus microbiota isolated from cervico-vaginal samples of HPV clearance in women. Using cervico-vaginal samples from HPV persistent infection and clearance in women, this study investigated the local immune properties in cervical mucosa. As expected, type I interferons, such as IFN-α and IFN-β, and TLR3 globally downregulated in HPV+ persistence group. Luminex cytokine/chemokine panel analysis revealed that L. jannaschii LJV03, L. vaginalis LVV03, L. reuteri LRV03, and L. gasseri LGV03 isolated from cervicovaginal samples of HPV clearance in women altered the host's epithelial immune response, particularly L. gasseri LGV03. Furthermore, L. gasseri LGV03 enhanced the poly (I:C)-induced production of IFN by modulating the IRF3 pathway and attenuating poly (I:C)-induced production of proinflammatory mediators by regulating the NF-κB pathway in Ect1/E6E7 cells, indicating that L. gasseri LGV03 keeps the innate system alert to potential pathogens and reduces the inflammatory effects during persistent pathogen infection. L. gasseri LGV03 also markedly inhibited the proliferation of Ect1/E6E7 cells in a zebrafish xenograft model, which may be attributed to an increased immune response mediated by L. gasseri LGV03.


Study of dosimetry and clinical factors for assessment of xerostomia in head and neck squamous cell carcinoma treated by intensity-modulated radiotherapy: A prospective study.
Clinical and dosimetric factors related to toxicity in terms of xerostomia in patients with head and neck squamous cell cancer (HNSCC) treated with intensity-modulated radiotherapy (IMRT). Patients older than 18 years, with the WHO Performance Status Score <2 with primary diagnosis of HNSCC Stage II, III, and IV who had undergone primary or postoperative radiotherapy (RT) treated by IMRT at the center, from November 2015 to November 2016 were included in the study. Patients were assessed by physical examination and questioned to score their quality of life for dryness (HNDR) and stickiness (HNSS) by EORTC-HN-35 (Hindi or English version) at baseline (before treatment), at 3, 6, and 12 months following treatment. The validation of EORTC-HN-35 for HNDR and HNSS in patients was handed. Thirty patients were included in the study. The mean symptom score values for HNSS at baseline, 3, 6, and 12 months' post-RT treatment were 17.8, 62.2, 64.4, and 20.8, respectively. Dryness and stickiness also increased over 3-6 months in follow-up but slightly relieved at 12 months, but it could not reach to baseline. In subgroup analysis, at baseline mean score of dryness of mouth in elderly patients (≥60 years) (P = 0.248), poor performance status (Eastern Cooperative Oncology Group 2) (P = 0.80) and patients with advanced stage (Stage III and IVA) (P = 0.185) was higher. Correlation of normal tissue complication probability for xerostomia with contralateral mean parotid gland showed insignificant linearity with shallow curve. Patients remained symptomatic for xerostomia chiefly till 6 months' postirradiation, but it was slightly relieved in 12 months but could not reach the baseline. Dosimetric sparing ofcontralateral parotid resulted in decreased probability of developing xerostomia.


Purification and characterization of recombinant porcine prorelaxin expressed in Escherichia coli.
In this report we describe the purification and characterization of recombinant porcine prorelaxin expressed in Escherichia coli. Nucleotide sequence encoding porcine prorelaxin was inserted into an E. coli expression vector, pOTS, and the recombinant plasmid was transformed into the E. coli host (AR120). Upon induction with nalidixic acid, the 19-kDa recombinant porcine prorelaxin was produced at a level of approximately 8% of the total accumulated cell protein. The recombinant prorelaxin was purified to homogeneity by CM-cellulose chromatography and reversed-phase HPLC, after refolding in the presence of reduced and oxidized glutathione and a low concentration of guanidine-HCl. The identity of the recombinant prorelaxin was confirmed by the correct size, immunoreactivity with antibodies against native porcine relaxin, and direct amino-terminal sequence analysis. Furthermore, the purified recombinant prorelaxin could be converted to the 6-kDa relaxin by limited digestion with trypsin. Trypsin was shown to cleave at the carboxyl side of Arg29 and Arg137 residues of the recombinant prorelaxin, producing the des-ArgA1-B29-relaxin, and degrade the 13-kDa connecting peptide into small peptides. Both the recombinant prorelaxin and converted relaxin were found to be biologically active in an in vitro bioassay for relaxin.


Blood levels, tissue distribution and the duration of action in rats of ciprofibrate, a new hypolipidemic agent.
The blood levels, distribution and duration of action of ciprofibrate, an orally active hypolipidemic agent, was investigated in rats. Serum concentrations of 30 micrograms of ciprofibrate/ml are associated with significant reductions in both serum cholesterol and triglycerides in rats on a hyperlipidemic diet. Increasing the plasma concentrations of ciprofibrate to 69 micrograms/ml resulted in only a modest incremental reduction in serum lipids. The distribution of radioactivity from [14C]ciprofibrate within rat tissues was not affected by prior treatment for 14 days with ciprofibrate at either 1.5 or 3.0 mg/kg/day. Varying the dosage regimen of ciprofibrate at 30 mg/kg, with medication at intervals of one, 2 or 3 days resulted in similar peak plasma levels of about 300 micrograms/ml, 4 h after medication. The half-life of ciprofibrate, during the terminal disposition phase, was about 82 h. Levels of serum cholesterol remained suppressed up to 3 days after medication with ciprofibrate was discontinued; triglyceride levels returned to control values more slowly.


Outcome measures for oral health based on clinical assessments and claims data: feasibility evaluation in practice.
It is well known that treatment variation exists in oral healthcare, but the consequences for oral health are unknown as the development of outcome measures is still in its infancy. The aim of this study was to identify and develop outcome measures for oral health and explore their performance using health insurance claims records and clinical data from general dental practices. The Dutch healthcare insurance company Achmea collaborated with researchers, oral health experts, and general dental practitioners (GDPs) in a proof of practice study to test the feasibility of measures in general dental practices. A literature search identified previously described outcome measures for oral healthcare. Using a structured approach, identified measures were (i) prioritized, adjusted and added to after discussion and then (ii) tested for feasibility of data collection, their face validity and discriminative validity. Data sources were claims records from Achmea, clinical records from dental practices, and prospective, pre-determined clinical assessment data obtained during routine consultations. In total eight measures (four on dental caries, one on tooth wear, two on periodontal health, one on retreatment) were identified, prioritized and tested. The retreatment measure and three measures for dental caries were found promising as data collection was feasible, they had face validity and discriminative validity. Deployment of these measures demonstrated variation in clinical practices of GDPs. Feedback of this data to GDPs led to vivid discussions on best practices and quality of care. The measure 'tooth wear' was not considered sufficiently responsive; 'changes in periodontal health score' was considered a controversial measure. The available data for the measures 'percentage of 18-year-olds with no tooth decay' and 'improvement in gingival bleeding index at reassessment' was too limited to provide accurate estimates per dental practice. The evaluated measures 'time to first restoration', 'distribution of risk categories for dental caries', 'filled-and-missing score' and 'retreatment after restoration', were considered valid and relevant measures and a proxy for oral health status. As such, they improve the transparency of oral health services delivery that can be related to oral health outcomes, and with time may serve to improve these oral health outcomes.


Urinary MHPG and HVA excretion in boys with attention deficit disorder and hyperactivity treated with d-amphetamine.
The authors examined the excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in nine hyperactive and nine control boys admitted to a clinical research center. The hyperactives excreted lower 24 hr MHPG and HVA levels than controls. d-Amphetamine 0.5 mg/kg body weight daily for 2 weeks decreased MHPG and increased HVA. These data replicate the authors' previous findings on MHPG and HVA and on the effect of d-amphetamine in hyperactive children. The data suggest the involvement of norepinephrine and dopamine in the etiology of hyperactivity. It further suggests d-amphetamine may achieve its clinical effects in hyperactivity by inhibiting NE and potentiating DA activity.


Adaptive control reduces trip-induced forward gait instability among young adults.
A vital functional plasticity of humans is their ability to adapt to threats to posture stability. The purpose of this study was to investigate adaptation to repeated trips in walking. Sixteen young adults were recruited and exposed to the sudden (electronic-mechanical) release of an obstacle, 11-cm in height, in the path of over ground walking during the mid-to-late left swing phase. Although none of the subjects fell on the first of eight unannounced, consecutive trips, all of them had to rely on compensatory step with a step length significantly longer than their regular to reduce their instability. In the subsequent trials, they were able to rapidly make adaptive adjustments in the control of their center-of-mass (COM) stability both proactively and reactively (i.e., before and after hitting or crossing the obstacle), such that the need for taking compensatory step was substantially diminished. The proactive adaptations included a reduced forward COM velocity that lessened forward instability in mid-to-late stance and an elevated toe clearance that reduced the likelihood of obstacle contact. The reactive adjustments were characterized by improved trunk control (by reducing its forward rotation) and limb support (by increasing hip height), and reduced forward instability (by both the posterior COM shift and the reduction in its forward velocity). These findings suggest that young adults can adapt appropriately to repeated trip perturbations and to reduce trip-induced excessive instability in both proactive and reactive manners.


[Life style and occupational factors and prevention of second primary cancers after childhood and adolescent cancer: Current state of knowledge].
Survival of children, adolescents and young adults treated for cancer increased with improved treatments. But there is still an increased risk of second primary cancer (SPC) in the long term compared to the population of the same age, especially related to treatments. A reflection on the follow-up of this population and the prevention of SPC is an important issue. To perform a synthesis of the available literature on SCP risk factors, related risk behaviors, occupational exposures and prevention strategies. Literature search on PubMed from the following equation: "cancer [Tiab] AND young adult [Tiab] or teen [Tiab] or childhood [Tiab] AND prevention [Tiab] AND survivors [Mesh term]". Twenty-seven articles were included in this synthesis. Children, adolescents and young adults have similar risk behaviors than those of their peers regarding tobacco, diet and sun exposure; however, they have lower physical activity. There are few studies on prevention strategies focused on this population. Results of available studies remain inconclusive. No publication was found in relation to occupational exposure and risk of second cancer. Children, adolescents and young adults treated for cancer are a population at risk and require long-term follow-up and the implementation of effective prevention strategies tailored to this population.


Public long-term care insurance and consumption of elderly households: Evidence from China.
This study investigates the impact of long-term care insurance (LTCI) on the non-health consumption of elderly households. By exploiting a quasi-experiment on the public LTCI pilot program in China, we identify the effect of LTCI using a triple-difference approach. Using longitudinal data from the China Health and Retirement Longitudinal Study, we find that LTCI has led to an increase in the non-health consumption of elderly households by 15.7%, mostly observed in households having no older members with need for long-term care (LTC). Further evidence suggests that the effects are stronger for households with higher expected LTC risks, less wealth or family insurance, and covered by more generous schemes. Finally, LTCI increases the expectation of using formal LTC when disabled and subjective longevity expectations for older adults having no need for LTC. Overall, these findings offer empirical support for the role of LTCI in mitigating precautionary savings against LTC risks.


Pyrethroid induced behavioral responses of Anopheles dirus, a vector of malaria in Thailand.
Contact and noncontact behavioral actions of wild-caught Anopheles dirus in response to the operational field dose of three synthetic pyrethroids (bifenthrin, α-cypermethrin and λ-cyhalothrin) were evaluated using an exito-repellency test chamber. DEET was used as the repellency standard for comparison with the other three synthetic pyrethroids. Results showed that test specimens rapidly escaped from the test chamber when exposed to direct contact with a surface treated with each of the three synthetic pyrethroids and DEET. Alpha-cypermethrin demonstrated the strongest irritant action (84.9% escape), followed by DEET (77.0%), λ-cyhalothrin (68.6%) and bifenthrin (68.3%). In the noncontact configuration, fewer mosquitoes escaped from the test chambers as compared to contact trials, although a significant escape response was still observed as compared to the controls (P<0.05). We conclude that An. dirus exhibits both irritant and repellent actions in response the three pyrethroids testing in this study. The information obtained will allow us to better understand the behavioral responses of vectors to various chemicals and provide guidance when designing control strategies for targeting specific disease vectors.


Correlation of Immunomodulatory Cytokine Expression with Histopathological Changes and Viral Antigen in a Hamster Model of Equine Herpesvirus-9 Encephalitis.
A group of hamsters (n = 25) was intranasally infected with equine herpesvirus-9 (EHV-9) and mRNA transcription levels of several proinflammatory (IFN-γ, TNF-α and IL-6) and anti-inflammatory (IL-4, IL-10 and TGF-β) cytokines were investigated in brain tissue using RT-qPCR. These levels were correlated with the severity of sequential histopathological changes and intensity of immunohistochemical labelling of virus antigen in brain. Early and progressive upregulation of all the proinflammatory and anti-inflammatory cytokines investigated (P < 0.05) was correlated with increasing severity of encephalitis and viral antigen expression from 2 days post infection (dpi) with a peak at 4-5 dpi (P <0.05).


Psychopathological features in referred adolescents with psychogenic nonepileptic seizures with or without epilepsy.
Psychogenic nonepileptic seizures (PNES) are episodic manifestations that mimic epileptic seizures (ES) although not associated with electroencephalogram (EEG) abnormalities. Psychogenic nonepileptic seizures and ES, however, can often cooccur. Emotional distress in adolescents can trigger PNES, but the psychopathological and personality features are still unknown. The aim of this study was to explore psychopathological features in a sample of referred youth with PNES, with or without ES, compared with a control group with ES. Thirty-four patients aged 12 to 21 years, 19 females and 15 males, were included in the study, 15 patients with PNES, 7 with PNES and ES, and 12 with ES. The three groups were compared according to psychiatric categorical diagnoses, psychopathological dimensions, life stressors, and personality traits, including alexithymia, interpersonal reactivity, and resilience, all assessed with structured measures. Patients with PNES, with or without ES, were more severely impaired, had a higher incidence of mood disorders, more frequent lifetime traumatic experiences, and lower resilience. All the three groups presented alexythimic traits and emotional dysregulation. Major limitations are the small sample size and the lack of a control group of healthy subjects. Disentagling psychopathological characteristics in PNES can help clinicians to focus diagnostic approaches and therapeutic interventions.


Semantic priming of Kanji words in the cerebral hemispheres.
Two experiments were conducted to investigate how the spreading activation arose in hemispheres using single and 2-letter Kanji words. Results suggested that single- and 2-letter Kanji words were processed differentially and the semantic activation mechanisms seemed to be different from that of English words.


Evaluation of survival in patients after pancreatic head resection for ductal adenocarcinoma.
Surgery remains the only curative option for the treatment of pancreatic adenocarcinoma (PDAC). The goal of this study was to investigate the clinical outcome and prognostic factors in patients after resection for ductal adenocarcinoma of the pancreatic head. The data from 195 patients who underwent pancreatic head resection for PDAC between 1993 and 2011 in our center were retrospectively analyzed. The prognostic factors for survival after operation were evaluated using multivariate analysis. The head resection surgeries included 69.7% pylorus-preserving pancreatoduodenectomies (PPPD) and 30.3% standard Kausch-Whipple pancreatoduodenectomies (Whipple). The overall mortality after pancreatoduodenectomy (PD) was 4.1%, and the overall morbidity was 42%. The actuarial 3- and 5-year survival rates were 31.5% (95% CI, 25.04%-39.6%) and 11.86% (95% CI, 7.38%-19.0%), respectively. Univariate analyses demonstrated that elevated CEA (p = 0.002) and elevated CA 19-9 (p = 0.026) levels, tumor grade (p = 0.001) and hard texture of the pancreatic gland (p = 0.017) were significant predictors of a poor survival. However, only CEA >3 ng/ml (p < 0.005) and tumor grade 3 (p = 0.027) were validated as significant predictors of survival in multivariate analysis. Our results suggest that tumor marker levels and tumor grade are significant predictors of poor survival for patients with pancreatic head cancer. Furthermore, hard texture of the pancreatic gland appears to be associated with poor survival.


Social disparities in parental smoking and young children's exposure to secondhand smoke at home: a time-trend analysis of repeated cross-sectional data from the German KiGGS study between 2003-2006 and 2009-2012.
Children who are exposed to secondhand smoke (SHS) have an increased risk of a wide range of health problems and illnesses. Smoke-free legislation aims to improve indoor air quality and in this way protect the health of people who do not smoke. This paper examines trends in SHS exposure at home among children in Germany since the introduction of smoking bans in public places. Special focus is placed on the importance of the family of origin's socioeconomic status (SES) and on parental smoking behaviour. The analyses are based on two waves of the "German Health Interview and Examination Survey for Children and Adolescents" (KiGGS)-one of which was conducted immediately before the introduction of central smoke-free legislation in the 2003-2006 period, the other approximately 6 years later from 2009 to 2012. A comparison is made between the answers given by the parents of children aged between 0 to 6 (KiGGS baseline study, n = 6680; KiGGS Wave 1, n = 4455). Domestic SHS exposure is covered in the parent interviews by asking whether anyone is allowed to smoke at home in the presence of their child. Parental smoking behaviour is determined separately for mothers and fathers. SES is determined on the basis of the parents' education, occupational status and income. The percentage of 0- to 6-year-old children exposed to SHS in the parental home fell from 23.9 to 6.6 % in the period from 2003-2006 to 2009-2012. At the same time, the percentage of children with at least one parent who smokes decreased from 49.8 to 41.8 %. While relative social inequalities in parental smoking behaviour have tended to increase over time, inequalities in domestic SHS exposure have persisted. Children whose parents smoke and children from low-SES families are still most likely to be exposed to tobacco smoke. In both study periods and after statistical adjustment for parental smoking behaviour, children with a low SES had a 6.6-fold higher risk for SHS exposure in the parental home than children from high-SES households. The results of the KiGGS study show that the proportion of children in Germany who are exposed to SHS at home has declined significantly over the last few years. There is much to suggest that the smoke-free legislation that has been introduced in Germany has led to a heightened awareness of the health risks of SHS both in public and in the private sphere, as well as to a denormalization of smoking. Children whose parents smoke, and among them particularly children from socially disadvantaged families, should be recognised as key target groups when implementing future tobacco-control measures.


Terrestrial Vegetation Drives Methane Production in the Sediments of two German Reservoirs.
Inland waters and reservoirs in particular are significant sources of methane to the atmosphere. However, little information is available on the extent to which organic carbon from terrestrial vegetation or from internal photosynthesis fuels the methane production. This limits our ability to constrain methane emissions efficiently. We studied the isotopic composition (13C, 14C) of pelagic and sedimentary carbon sources in two small German reservoirs. The methane was enriched by radiocarbon with isotopic ranges (∆14C 5‰ to 31‰) near to fresh terrestrial organic carbon (OC, 17‰ to 26‰). In contrast, potential source OC produced by internal photosynthesis was characterized by negative ∆14C values (-30‰ and -25‰) as derived from signatures of inorganic carbon in the reservoirs. The particulate OC in stream supplies (terrestrial OC) was also 14C depleted in almost all cases, but highly variable in ∆14C (-131‰ to 42‰). Although the import of terrestrial OC was lower than the amount of OC produced by reservoir-internal photosynthesis, we conclude that the methane production was predominantly fuelled by catchment vegetation. The utilized terrestrial OC was of contemporary origin, fixed within years to decades before sampling and supplemented with reservoir-internal or aged terrestrial OC. Our results indicate that terrestrial biomass is an important driver of methane production in reservoirs receiving significant imports of terrestrial OC.


Measurement of the conductance of single conjugated molecules.
Electrical conduction through molecules depends critically on the delocalization of the molecular electronic orbitals and their connection to the metallic contacts. Thiolated (- SH) conjugated organic molecules are therefore considered good candidates for molecular conductors: in such molecules, the orbitals are delocalized throughout the molecular backbone, with substantial weight on the sulphur-metal bonds. However, their relatively small size, typically approximately 1 nm, calls for innovative approaches to realize a functioning single-molecule device. Here we report an approach for contacting a single molecule, and use it to study the effect of localizing groups within a conjugated molecule on the electrical conduction. Our method is based on synthesizing a dimer structure, consisting of two colloidal gold particles connected by a dithiolated short organic molecule, and electrostatically trapping it between two metal electrodes. We study the electrical conduction through three short organic molecules: 4,4'-biphenyldithiol (BPD), a fully conjugated molecule; bis-(4-mercaptophenyl)-ether (BPE), in which the conjugation is broken at the centre by an oxygen atom; and 1,4-benzenedimethanethiol (BDMT), in which the conjugation is broken near the contacts by a methylene group. We find that the oxygen in BPE and the methylene groups in BDMT both suppress the electrical conduction relative to that in BPD.