Triaging Primary Care Patients Referred for Chest Pain to Specialist Cardiology Centres: Efficacy of an Optimised Protocol.
Patients referred for chest pain from primary care have increased, along with demand for outpatient cardiology consultations. We evaluated 'Triage Protocol' that implements standardised diagnostic testing prior to patients' first cardiology consultation. Under the 'Triage Protocol', patients referred for chest pain were pretriaged using a standardised algorithm and subsequently referred for relevant functional diagnostic cardiology tests before their initial cardiology consultation. At the initial cardiology consultation scheduled by the primary care provider, test results were reviewed. A total of 522 triage patients (mean age 55 ± 13, male 53%) were frequency-matched by age, gender and risk cohort to 289 control patients (mean age: 56 ± 11, male: 52%). Pretest risk of coronary artery disease was defined according to a Modified Duke Clinical Score (MDCS) as low (<10), intermediate (10-20) and high (>20). The primary outcome was time from referral to diagnosis (days). Secondary outcomes were total visits, discharge rate at first consultation, patient cost and adverse cardiac outcomes. The 'Triage Protocol' resulted in shorter times from referral to diagnosis (46 vs 131 days; P <0.0001) and fewer total visits (2.4 vs 3.0; P <0.0001). However, triage patients in low-risk groups experienced higher costs due to increased testing (S$421 vs S$357, P = 0.003). Adverse cardiac event rates under the 'Triage Protocol' indicated no compromise to patient safety (triage vs control: 0.57% vs 0.35%; P = 1.000). By implementing diagnostic cardiac testing prior to patients' first specialist consultation, the 'Triage Protocol' expedited diagnosis and reduced subsequent visits across all risk groups in ambulatory chest pain patients.


[Differential diagnosis of specific gastric lesions in early syphilis patients with helicobacter infection].
To evaluate differential-diagnostic significance of different clinical signs, endoscopic and serological studies in making diagnosis of early gastric syphilis (EGS) in patients with helicobacter infection. Thirty patients were hospitalized with diagnosis of gastric and/or duodenal ulcer. Helicobacter pylori was identified morphologically or with a rapid urease test. Syphilis was rejected when microprecipitation reaction was negative and confirmed with Wassermann reaction. The patients received standard treatment including a course of eradication therapy. Endoscopic examination discovered single and multiple ulcers in 25 and 5 patients, respectively, located in the stomach and duodenum. A rapid test for syphilis produced negative and positive results in 28 and 2 patients, respectively. Twenty two patients tolerated eradication therapy well. Positive results were achieved in 19 (84.6%) patients. Six patients had side effects (pruritus, urticaria, dyspepsia) on eradication treatment day 2-3. Jarisch-Herxheimer reaction (elevated body temperature 38-38.6 degrees C) and roseola eruption were observed in 2 (6.7%) patients with positive serological reactions for syphilis on the first day of eradication therapy. Diagnostic criteria of EGS are the following: serologically confirmed manifest or latent syphilis, poor effect of standard antiulcer treatment, rapid elimination of the disease symptoms in antisyphilis therapy and positive changes in pathological alterations in gastric mucosa.


Simple and rapid block face alignment methods for the ultramicrotome.
Light from the fluorescent lamp on an ultramicrotome can be reflected from a mirror located beneath the knife face so that the knife and edge can be imaged on the block face. It is well known that this image can be used to accurately align the block face to the knife edge and cutting direction. A method is described of pre-aligning the lamp, stereomicroscope, knife, and the mirror, which is fixed with respect to the knife face, so that a bright reflection of the knife face on the block face is obtained only when the block face is brought close to alignment. This initial alignment is an extremely rapid procedure, and is followed by slower, more accurate manipulation of the block and knife for precise alignment. The mirror, easily mounted to a Porter-Blum MT-2 ultramicrotome knife holder, is very simple in design and readily adaptable to any ultramicrotome. Methods to permit small movements of the block for the MT-1 and MT-2 ultramicrotomes are also described.


A new generation of sensors based on extraordinary optical transmission.
[Reaction: see text]. Plasmonic-based chemical sensing technologies play a key role in chemical, biochemical, and biomedical research, but basic research in this area is still attracting interest. Researchers would like to develop new types of plasmonic nanostructures that can improve the analytical figures of merit, such as detection limits, sensitivity, selectivity, and dynamic range, relative to the commercial systems. They are also tackling issues such as cost, reproducibility, and multiplexing with the goal of providing the best plasmonic-based platform for chemical analysis. In this Account, we will describe recent advances in the optical and spectroscopic properties of nanohole arrays in thin gold films and their applications for chemical sensing. These nanostructures support the unusual phenomenon of "extraordinary optical transmission" (EOT), that is, they are more transparent at certain wavelengths than expected by the classical aperture theory. The EOT is a consequence of surface plasmon (SP) excitations; hence, the resonance should respond to the adsorption of organic molecules. We explored this effect and implemented the integration of the arrays of nanoholes as sensing elements in a microfluidic architecture. We then demonstrated how these devices could be applied in biochemical affinity tests. Arrays of nanoholes offer a small sensing footprint and operate at normal transmission mode, which make them more suitable for miniaturization. This new approach for SPR sensing is more compatible with the lab-on-chip concept and offers the possibility of high-throughput analysis from a single sensing chip. We explored the field localization properties of EOT for surface-enhanced spectroscopy. We could control the enhancement factors for SERS and SEFS by adjusting the geometry of the arrays. The shape of the individual nanoholes offers another handle to tune the enhancement factor for surface-enhanced spectroscopy and SPR sensitivity. Apexes in shaped nanostructures function as optical antennas, focusing the light at extremely small regions at the tips. We observed additional surface enhancement by tuning the apexes' properties. The extra enhancement in these cases originated only from the small number of molecules in the apex regions. The arrays of nanoholes are an exciting new substrate for chemical sensing and enhanced spectroscopy. This class of nanomaterials has the potential to provide a viable alternative to the commercial SPR-based sensors. Further research could exploit this platform to develop nanostructures that support high field localization for single-molecule spectroscopy.


Dietary modulation of circulating leptin levels: site-specific changes in fat deposition and ob mRNA expression.
In order to study the effects of diet on fat distribution, circulating leptin levels and ob mRNA expression, diets of different macronutrient composition were fed to lean mice and gold thioglucose-obese mice. A high-fat diet and 2 high-carbohydrate diets, one containing mostly high-glycaemic-index starch and the other containing low-glycaemic-index starch were fed ad libitum for 10 weeks and were compared to standard laboratory chow. Weight gain was attenuated by feeding low-glycaemic-index starch in all mice and by feeding a high-fat diet in lean mice. Reduced adiposity was seen in lean mice fed low-glycaemic-index starch, whereas increased adiposity was seen in both lean and obese mice fed on the high-fat diet. Circulating leptin levels, when corrected for adiposity, were decreased in all mice fed either the high-fat diet or the low-GI diet. In epididymal fat pads, decreased ob mRNA expression was seen after both high-fat and high-glycaemic-index starch feeding. These results show that diet macronutrient composition contributes to the variability of circulating leptin levels by the combined effects of diet on fat distribution and on site-specific changes in ob mRNA expression.


Complications and Failures of Office-Based Endoscopic Angiolytic Laser Surgery Treatment.
Although office-based laser surgery applications for benign and premalignant lesions of the larynx are appealing, there are scant data on their complications and failures. We review office-based angiolytic laser surgery in patients with benign laryngeal pathology for rates of complication and failure. Retrospective chart review. Two hundred fifty-five patients who underwent in-office angiolytic laser surgery treatment over 4 years were reviewed. The criteria for complications and failures were based on postprocedure stroboscopy and clinical findings. The majority of patients had unilateral disease, which included polyps (46%), leukoplakia (14%), papilloma (13%), scar (12%), and varix (11%). There were 382 laser treatments, of which 56% were by pulsed potassium titanyl phosphate laser. Average energy delivery was lesion specific, with papilloma receiving the most (mean 351 J) and varices receiving the least (mean 53 J) energy. Most in-office treatments were tolerated well. Four percent of patients had complications including stiffness, atrophy, and transient but prolonged hyperemia. Twenty-seven percent of patients required multiple laser treatments. Multiple treatments were more likely in papilloma and leukoplakia. While in-office laser therapy for benign vocal fold lesions is appealing, repeated treatment due to incomplete resolution may be needed. Risks of transient and long-term complications are low but real. Patient selection and standardized laser energy parameters may help in decreasing complications and need for repeat procedures.


Vibrationally coherent photochemistry in the femtosecond primary event of vision.
Femtosecond pump-probe experiments reveal the impulsive production of photoproduct in the primary event in vision. The retinal chromophore of rhodopsin was excited with a 35-femtosecond pulse at 500 nanometers, and transient changes in absorption were measured with 10-femtosecond probe pulses. At probe wavelengths within the photo-product absorption band, oscillatory features with a period of 550 femtoseconds (60 wavenumbers) were observed whose phase and amplitude demonstrate that they are the result of nonstationary vibrational motion in the ground state of the photoproduct. The observation of coherent vibrational motion of the photoproduct supports the idea that the primary step in vision is a vibrationally coherent process and that the high quantum yield of the cis-->trans isomerization in rhodopsin is a consequence of the extreme speed of the excited-state torsional motion.


Transitional cell carcinoma express vitamin D receptors.
Recently, vitamin D analogues have shown antineoplastic effect in several diseases. Vitamin D analogues exert its effect by interacting with the vitamin D receptor (VDR). Studies of VDR in transitional cell carcinoma (TCC) have not been reported. The purpose of the present study was therefore to examine whether human bladder tumor cells express VDR. Tumor biopsies were obtained from 26 patients with TCC. Expression of VDR was examined by immunohistochemical experiments. All tumors expressed VDR. Biopsies from advanced disease contained more VDR positive cells than low stage disease (p < 0.05). Similarly, also tumor grade appeared to be related to the number of cells expressing the receptor. Normal urothlium also expressed VDR but only with low intensity. Our study shows that TCC cells possess the VDR receptor which may make them capable to respond to stimulation with vitamin D, but functional studies of vitamin D's effect on TCC cells in vitro are necessary before the efficacy of treatment with vitamin D analogues in TCC can be evaluated in patients.


Blood has never been thicker: Cell-free DNA fragmentomics in the liquid biopsy toolbox of B-cell lymphomas.
Liquid biopsies utilizing plasma circulating tumor DNA (ctDNA) are anticipated to revolutionize decision-making in cancer care. In the field of lymphomas, ctDNA-based blood tests represent the forefront of clinically applicable tools to harness decades of genomic research for disease profiling, quantification, and detection. More recently, the discovery of nonrandom fragmentation patterns in cell-free DNA (cfDNA) has opened another avenue of liquid biopsy research beyond mutational interrogation of ctDNA. Through examination of structural features, nucleotide content, and genomic distribution of massive numbers of plasma cfDNA molecules, the study of fragmentomics aims at identifying new tools that augment existing ctDNA-based analyses and discover new ways to profile cancer from blood tests. Indeed, the characterization of aberrant lymphoma ctDNA fragment patterns and harnessing them with powerful machine-learning techniques are expected to unleash the potential of nonmutant molecules for liquid biopsy purposes. In this article, we review cfDNA fragmentomics as an emerging approach in the ctDNA research of B-cell lymphomas. We summarize the biology behind the formation of cfDNA fragment patterns and discuss the preanalytical and technical limitations faced with current methodologies. Then we go through the advances in the field of lymphomas and envision what other noninvasive tools based on fragment characteristics could be explored. Last, we place fragmentomics as one of the facets of ctDNA analyses in emerging multiview and multiomics liquid biopsies. We pay attention to the unknowns in the field of cfDNA fragmentation biology that warrant further mechanistic investigation to provide rational background for the development of these precision oncology tools and understanding of their limitations.


A RNA polymerase III-based two-hybrid system to study RNA polymerase II transcriptional regulators.
In a previous study, we explored the mechanisms of SNR6 gene activation by grafting a heterologous DNA-binding domain, GAL4-(1-147), to various components of the yeast RNA polymerase III transcription system. Here, we demonstrate that a modified SNR6 gene harboring GAL4-binding sites (UAS(G)-SNR6) can be efficiently activated via an intervening, unrelated protein-protein interaction, thus laying the foundations of a RNA polymerase III-based two-hybrid system. In a model system, the interacting proteins recruiting TFIIIC to DNA were PRP21 and PRP9 or PRP21 and PRP11. Mutations affecting the interaction between PRP21 and PRP9, or PRP21 and PRP11 decreased UAS(G)-SNR6 activation level proportionally. RNA polymerase II transcriptional activators, like GAL4, VP16 or p53, fused to GAL4 DNA-binding domain, did not activate the UAS(G)-SNR6 gene. However, GAL4 strongly activated UAS(G)-SNR6 when GAL80, an interacting protein, was fused to TFIIIC. This result indicates that this two-hybrid system can be used to assess the interactions between RNA polymerase II regulatory proteins and their partners.


Spatio-temporal analysis of particulate matter intake fractions for vehicular emissions: Hourly variation by micro-environments in the Greater Toronto and Hamilton Area, Canada.
Previous investigations have reported intake fraction (iF) for different environments, which include ambient concentrations (outdoor exposure) and microenvironments (indoor exposure). However, little is known about iF variations due to space-time factors, especially in microenvironments. In this paper, we performed a spatio-temporal analysis of particulate matter (PM2.5) intake fractions for vehicular emissions. Specifically, we investigated hourly variation (12:00am-11:00pm) by micro-environments (residences and workplaces) in the Greater Toronto and Hamilton Area (GTHA), Canada. We used GIS modeling to estimate air pollution data (ambient concentration, and traffic emission) and population data in each microenvironment. Our estimates showed that the total iF at residences and workplaces accounts for 85% and 15%, respectively. Workplaces presented the highest 24h average iF (1.06ppm), which accounted for 25% higher than residences. Observing the iF by hour at residences, our estimates showed the highest average iF at 2:00am (iF=3.72ppm). These estimates indicate that approximately 4g of PM2.5 emitted from motor vehicles are inhaled for every million grams of PM2.5 emitted. For the workplaces, the highest exposure was observed at 10:00am, with average iF equal to 2.04ppm. The period of the day with the lower average iF for residences was at 8:00am (average iF=0.11ppm), while for the workplaces was at 4:00am (average iF=0.47ppm). Our approach provides a new perspective on human exposure to air pollution. Our results showed significant hourly variation in iF across the GTHA. Our findings can be incorporated in future investigations to advance environmental health effects research and human health risk assessment.


Episodic angioedema with eosinophilia (Gleich syndrome) is a multilineage cell cycling disorder.
Episodic angioedema with eosinophilia (Gleich syndrome) is a rare disorder characterized by episodes of angioedema and eosinophilia that occur at monthly intervals and resolve spontaneously without therapy. Despite the striking periodicity of this disorder, its similarity to other cyclic hematopoietic disorders with multilineage involvement has not been assessed. To characterize the involvement of cell lineages in the etiology and pathogenesis of episodic angioedema with eosinophilia, four subjects were evaluated by blood counts and other analyses over the course of 1-2 months. Surface marker expression was assessed on T cells by flow cytometry and clonality by polymerase chain reaction. Intracellular cytokine evaluation, bone marrow and skin biopsies were performed during different parts of the cycle. Cycling of multiple cell lineages, including neutrophils, lymphocytes and eosinophils, was observed in the four subjects with the disorder with a periodicity of 25-35 days. An aberrant CD3(-)CD4(+) T-cell population was detected in all four subjects, and T-cell receptor rearrangement studies showed a clonal pattern in three subjects. A peak of type II cytokines was detected in the serum of subjects prior to the onset of symptoms and eosinophil cycling and corresponded to ex-vivo type II cytokines detected intracellularly in CD3(+)CD4(+)CD154(+) T cells. Although the etiology of episodic angioedema with eosinophilia is not yet known, multiple lineages, including lymphocytes, neutrophils and mast cells, are involved and may be related to disease pathogenesis. Whether these cells act directly or promote eosinophilia and eosinophil activation remains to be elucidated. All subjects gave informed consent and were evaluated under an Institutional Review Board-approved protocol (NCT00001406).


Dramatic impact of metric choice on biogeographical regionalization.
For a quantitative biogeographical regionalization, the choice of an appropriate dissimilarity index to measure pairwise distances is crucial. Several different metrics have been used, but there is no specific study to test the impact of metric choice on biogeographical regionalization. We herein applied a hierarchical cluster analysis on the mean nearest taxon distance (MNTD) and the phylogenetic turnover component of the Sørensen dissimilarity index (pβsim) pairwise distances to generate two schemes of phylogenetic regionalization of the Chinese flora, and then evaluated the effect of metric choice. Floristic regionalization based on MNTD was influenced by richness differences, but regionalization based on pβsim can clearly reflect the evolutionary history of the Chinese flora. We provided a brief description of the five regions identified by pβsim, and the regionalization can help develop strategies to effectively conserve the taxa and floristic regions with different origins and evolutionary histories.


Aging ballistic Lévy walks.
Aging can be observed for numerous physical systems. In such systems statistical properties [like probability distribution, mean square displacement (MSD), first-passage time] depend on a time span t_{a} between the initialization and the beginning of observations. In this paper we study aging properties of ballistic Lévy walks and two closely related jump models: wait-first and jump-first. We calculate explicitly their probability distributions and MSDs. It turns out that despite similarities these models react very differently to the delay t_{a}. Aging weakly affects the shape of probability density function and MSD of standard Lévy walks. For the jump models the shape of the probability density function is changed drastically. Moreover for the wait-first jump model we observe a different behavior of MSD when t_{a}≪t and t_{a}≫t.


Ecology of urban malaria vectors in Niamey, Republic of Niger.
Urbanization in African cities has major impact on malaria risk. Niamey, the capital of the Republic of Niger, is situated in the West African Sahel zone. The short rainy season and human activities linked with the Niger River influence mosquito abundance. This study aimed at deciphering the factors of distribution of urban malaria vectors in Niamey. The distribution of mosquito aquatic stages was investigated monthly from December 2002 to November 2003, at up to 84 breeding sites, throughout Niamey. An exploratory analysis of association between mosquito abundance and environmental factors was performed by a Principal Component Analysis and confirmed by Kruskall-Wallis non-parametric test. To assess the relative importance of significant factors, models were built for Anopheles and Culicinae. In a second capture session, adult mosquitoes were collected weekly with pyrethrum sprays and CDC light-traps from June 2008 to June 2009 in two differentiated urban areas chosen after the study's first step. Members of the Anopheles gambiae complex were genotyped and Anopheles females were tested for the presence of Plasmodium falciparum circumsporozoite antigens using ELISA. In 2003, 29 % of 8420 mosquitoes collected as aquatic stages were Anopheles. They were significantly more likely to be found upstream, relatively close to the river and highly productive in ponds. These factors remained significant in regression and generalized linear models. The Culicinae were found significantly more likely close to the river, and in the main temporary affluent stream. In 2009, Anopheles specimens, including Anopheles gambiae s.l. (95 %), but also Anopheles funestus (0.6 %) accounted for 18 % of the adult mosquito fauna, with a large difference between the two sampled zones. Three members of the An. gambiae complex were found: Anopheles arabiensis, Anopheles coluzzii, and An. gambiae. Nineteen (1.3 %) out of 1467 females tested for P. falciparum antigen were found positive. The study provides valuable update knowledge on malaria vector ecology and distribution in Niamey. The identification of spatial and environmental risk factors could pave the way to larval source management strategy and allow malaria vector control to focus on key zones for the benefit of the community.


Nanoscopic length scale dependence of hydrogen bonded molecular associates' dynamics in methanol.
In a recent paper [C. E. Bertrand et al., J. Chem. Phys. 145, 014502 (2016)], we have shown that the collective dynamics of methanol shows a fast relaxation process related to the standard density-fluctuation heat mode and a slow non-Fickian mode originating from the hydrogen bonded molecular associates. Here we report on the length scale dependence of this slow relaxation process. Using quasielastic neutron scattering and molecular dynamics simulations, we show that the dynamics of the slow process is affected by the structuring of the associates, which is accessible through polarized neutron diffraction experiments. Using a series of partially deuterated samples, the dynamics of the associates is investigated and is found to have a similar time scale to the lifetime of hydrogen bonding in the system. Both the structural relaxation and the dynamics of the associates are thermally activated by the breaking of hydrogen bonding.


Mourning the body as bedrock: developmental considerations in treating transsexual patients analytically.
This paper introduces the concept of massive gender trauma, a clinical syndrome arising at the onerous intersection of the misgendering of transgender patients and the subjective, anguished experience of the natal body. Analysts have become increasingly aware in recent years of the complex interactions between psyche, soma, and culture. Consequently, the field is increasingly hospitable to considering the psychic risks inherent in misgendering. However, patients' body dysphoria is often left unaddressed even by analysts who seek to work within their analysands' gendered experience. Through a detailed, in-depth account of work with a five-year-old trans girl (female-identified, male-bodied), the developmental implications of the natal body's not becoming sufficiently mentalized in the course of treatment are tracked and explored. Attention to unconscious fantasy and its transformations shows the importance of helping transgender patients whose bodies are a source of suffering to be able to psychically represent their pain as a critical step in the process of a psychologically healthy transition.


CASRdb: calcium-sensing receptor locus-specific database for mutations causing familial (benign) hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia.
Familial hypocalciuric hypercalcemia (FHH) is caused by heterozygous loss-of-function mutations in the calcium-sensing receptor (CASR), in which the lifelong hypercalcemia is generally asymptomatic. Homozygous loss-of-function CASR mutations manifest as neonatal severe hyperparathyroidism (NSHPT), a rare disorder characterized by extreme hypercalcemia and the bony changes of hyperparathyroidism, which occur in infancy. Activating mutations in the CASR gene have been identified in several families with autosomal dominant hypocalcemia (ADH), autosomal dominant hypoparathyroidism, or hypocalcemic hypercalciuria. Individuals with ADH may have mild hypocalcemia and relatively few symptoms. However, in some cases seizures can occur, especially in younger patients, and these often happen during febrile episodes due to intercurrent infection. Thus far, 112 naturally-occurring mutations in the human CASR gene have been reported, of which 80 are unique and 32 are recurrent. To better understand the mutations causing defects in the CASR gene and to define specific regions relevant for ligand-receptor interaction and other receptor functions, the data on mutations were collected and the information was centralized in the CASRdb (www.casrdb.mcgill.ca), which is easily and quickly accessible by search engines for retrieval of specific information. The information can be searched by mutation, genotype-phenotype, clinical data, in vitro analyses, and authors of publications describing the mutations. CASRdb is regularly updated for new mutations and it also provides a mutation submission form to ensure up-to-date information. The home page of this database provides links to different web pages that are relevant to the CASR, as well as disease clinical pages, sequence of the CASR gene exons, and position of mutations in the CASR. The CASRdb will help researchers to better understand and analyze the mutations, and aid in structure-function analyses.


[The genetic variability in the amylase isoenzymes of hybrid muscovy (Cairina moshata) and domestic (Anas platyrhynchos) ducks compared to the initial species].
Genetically conditioned polymorphism of alpha-amylases in musk ducks, domestic ones and their hybrids has been described. Two isoenzymes (AMY-1, AMY-2) are in blood serum of the ducks. One of them is apparently formed in crope gland and other--in pancreas. AMY-2 is monomorphic in both species. AMY-2 is polymorphic with three alleles (Amy-1A, Amy-1B, Amy-1B) in musk ducks and monomorphic in domestic ducks (Amy-1C). The hybrids have also allele obtained by them from domestic ducks.


Infliximab-induced nonspecific interstitial pneumonia.
Infliximab has well-established complications including injection site and allergic reactions, cytopenias, induction of autoimmune and demyelinating diseases and malignancy, especially lymphoma. Pulmonary complications are well documented and include serious respiratory infections from tuberculosis, fungal and opportunistic pathogens. This has prompted a Food and Drug Administration black-box warning recommending close surveillance for these diseases. Nonspecific interstitial pneumonitis (NSIP) secondary to tumor necrosis factor-alpha inhibitor (TNF-alpha) therapy is less well described. Rarely, TNF-alpha inhibitor therapy has been reported to cause NSIP when used in conjunction with other immunosuppressive agents. Literature search revealed 12 independent patients with presumed infliximab-induced NSIP in 8 separate publications; all patients were on concomitant steroid sparing immunosuppressive agents, complicating cause and effect. The authors report a case in which infliximab is surmised to cause NSIP in the absence of other steroid sparing immunosuppressants in a young female with ulcerative colitis. Of importance, the patient was taking no additional steroid sparing immunomodulating agents. The diagnosis was based on clinical presentation and radiologic and histopathological data. Cessation of infliximab and high-dose steroid therapy resulted in complete resolution of the patient's presenting signs and symptoms.


Endovascular Approach for Management of Bullet Embolization to the Heart.
Bullet embolization to the right heart through the vasculature is seen infrequently in cases presenting with penetrating trauma. Patients with unstable hemodynamic status are managed operatively. For a patient with stable hemodynamic parameters, diagnostic evaluation such as computed tomography angiogram, echocardiogram, or angiography could be performed to select the best treatment option. Endovascular treatment is employed infrequently in these cases but can be a viable option for select patients. We present a case of a bullet embolus to the right ventricle treated successfully with endovascular approach and discuss the technical aspects of this approach.


Does Smoking Cessation at Primary Diagnosis Reduce the Recurrence Risk of Nonmuscle-Invasive Bladder Cancer? Results of a Prospective Study.
Evidence that smoking cessation at first diagnosis of nonmuscle-invasive bladder cancer (NMIBC) reduces the risk of recurrence is lacking. The aim of our prospective study was to analyze the association between patients' changes in smoking habits after diagnosis and recurrence-free survival (RFS). After transurethral resection of primary NMIBC, patients were classified as "ex-smokers," i.e., those definitively stopping, and as "active smokers," i.e., those continuing or restarting to smoke. Smoking status was reassessed every 3 months during the first year and every 6 months thereafter. Data on patients' demographics, smoking status, tumor characteristics, treatments, and follow-up were collected. Statistical analysis was performed adopting SPSS 15.0.1 and R3.4.2 software. Out of 194 patients, 67 (34.5%) quit smoking after the diagnosis, while 127 (65.5%) did not. The clinical and pathological characteristics were homogeneously distributed. At a median follow-up of 38 months, 106 patients (54.6%) recurred, 33 (49.2%) ex- and 73 (60.3%) active smokers with a 3-year RFS of 42.3 and 50.7%, respectively (p = 0.55). No statistically significant association between recurrence, pathological features of the primary tumor, and patient smoking habits after diagnosis was detected. Results were not statistically influenced by the intensity (cigarette/day) and duration (years) of smoking. In multivariate analysis, cigarette smoking cessation at diagnosis did not significantly reduce tumor recurrence. In our prospective study, more than half of our patients recurred at 3 years. In multivariate analysis, smoking cessation did not significantly reduce tumor recurrence. However, the 8.4% reduction in favor of the ex-smokers suggests the need of larger studies with longer follow-ups. Surprisingly, only 35% of smokers definitively quit after diagnosis. The urologists should play a more active role to persuade the patients to stop smoking at first cancer diagnosis.


Learning disability and mental health.
Essential facts [Figure: see text] Learning disabilities affect about 1.5 million people in the UK. The prevalence of mental health problems is considerably higher for those with learning disabilities than for the general population; estimates suggest 30-50% of adults are affected.


Rising atmospheric CO2 concentration may imply higher risk of Fusarium mycotoxin contamination of wheat grains.
Increasing atmospheric CO2 concentration not only has a direct impact on plants but also affects plant-pathogen interactions. Due to economic and health-related problems, special concern was given thus in the present work to the effect of elevated CO2 (750 μmol mol-1) level on the Fusarium culmorum infection and mycotoxin contamination of wheat. Despite the fact that disease severity was found to be not or little affected by elevated CO2 in most varieties, as the spread of Fusarium increased only in one variety, spike grain number and/or grain weight decreased significantly at elevated CO2 in all the varieties, indicating that Fusarium infection generally had a more dramatic impact on the grain yield at elevated CO2 than at the ambient level. Likewise, grain deoxynivalenol (DON) content was usually considerably higher at elevated CO2 than at the ambient level in the single-floret inoculation treatment, suggesting that the toxin content is not in direct relation to the level of Fusarium infection. In the whole-spike inoculation, DON production did not change, decreased or increased depending on the variety × experiment interaction. Cooler (18 °C) conditions delayed rachis penetration while 20 °C maximum temperature caused striking increases in the mycotoxin contents, resulting in extremely high DON values and also in a dramatic triggering of the grain zearalenone contamination at elevated CO2. The results indicate that future environmental conditions, such as rising CO2 levels, may increase the threat of grain mycotoxin contamination.


CT findings related to exposure to polyvinyl chloride.
Although some adverse health effects of exposure to polyvinyl chloride (PVC) are well known, there is limited evidence of its effects on the respiratory system. To assess the pulmonary effects of exposure to PVC with high-resolution computed tomography (HRCT). Workers and administrative staff of two PVC production plants completed questionnaires and went through pulmonary function testing and HRCT. Analysis of PVC dust in the work environment was performed by the Directorate of Occupational Health and Safety. In total, 104 PVC-exposed workers and 43 administrative controls participated. HRCT revealed pleural and/or parenchymal changes in 55% of the exposed subjects. Pleural thickening was detected in 14 subjects, 13 of whom were in the exposed group (P < 0.05). Isolated pleural thickening without parenchymal involvement was present in seven workers, who were all in the exposed group (P < 0.05). Pleural thickening was frequently bilateral and localized to the parietal and visceral pleura. Round opacities, heterogeneous attenuation and ground-glass opacities were only detected in the exposed group (P < 0.05). Exposure to dust increased the risk of findings on HRCT (odds ratio (OR) 4.2, P < 0.05). There were no correlations between pulmonary function tests or respiratory symptoms and HRCT findings. HRCT changes were more common in subjects with forced mid-expiratory flow (FEF(25-75)) < 50% (P < 0.001). This study found that exposure to PVC dust, at levels below the legal limit for respirable particulate matter, was associated with parenchymal changes and pleural thickening on HRCT.


Clonal T-cell populations in pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease).
Patients with the skin disorder pityriasis lichenoides et varioliformis acuta (PLEVA) develop recurrent, self-healing papulonecrotic lesions that contain infiltrates of cytologically and antigenically normal T lymphocytes. DNA extracted from the lesions of 3 patients with PLEVA was analyzed for rearrangement of beta-T-cell receptor genes for the purpose of assessing the clonality of T lymphocytes within the tissues of this disease. Lesions from all 3 cases showed clonal gene rearrangements. In each of 2 cases from which two separate lesions were biopsied, identical rearrangements were found in specimens from both sites. DNA from a variety of inflammatory lesions obtained from patients with other types of skin diseases failed to show detectable rearrangements of beta-T-cell receptor genes. These results suggest that PLEVA represents a T-cell lymphoproliferative process, rather than an inflammatory disorder, as had been previously thought.


Influence of Tumor Volume on the Fluence Rate Within Human Breast Model Using Continuous-Wave Diffuse Optical Imaging: A Simulation Study.
Objective: This article investigates the effect of varying breast tumor size on the fluence rate distribution within a breast model during the diffuse optical imaging procedure. Background: Early detection of breast cancer is of significant importance owing to its wide spread among women worldwide. Mastectomy surgery became very common due to the late detection of breast cancers by the conventional diagnostic methods such as X-ray mammography and magnetic resonance imaging. On the contrary, optical imaging techniques provide a safe and more sensitive methodology, which is suitable for the early detection criteria. Methods: The implementation was performed based on simulating multiple detectors placed on the outer surface of a human breast model to compute the optical fluence rate after probing the breast (normal and different tumor sizes) with laser irradiation. Different laser wavelengths ranging from the red to near-infrared rays spectral range were examined to determine the optimum fluence rate that shows the highest capability to differentiate between normal and cancerous breasts. A three-dimensional breast model was created using the COMSOL multiphysics package where the optical fluence rate was estimated based on the finite-element solution of the diffusion equation. Results: To evaluate the efficiency of the suggested technique for identifying cancers and discriminate them from normal breast at various wavelengths (600-1000 nm) and several tumor sizes. Conclusions: The obtained results reveal different fluence rate distributions in the breast with different radius tumors, especially at 600 nm due to the significant differences in the scattering coefficient between malignancies and healthy tissue.


[Isoharringtonine induces apoptosis in human leukemia HL-60 cell].
Harringtonine (HT), homoharringtonine (HHT) and isoharringtonine (IHT) are cephalotaxine alkaloids with anticancer activities which were isolated from Cephalotaxus hainanensis indigenous to China. Since the 1970s, HT and HHT have been developed as effective anticancer drugs in China and have been used widely in the treatment of acute nonlymphoid leukemia and chronic granulocyte leukemia. Although IHT has the advantage of low toxicity, it has not been developed as an anticancer drug because of its very low content in the plant. The cell apoptosis induced by isoharringtonine was investigated in human acute promyelocytic leukemia HL-60 cells by agarose gel electrophoresis of DNA, flow cytometry and transmission electron microscopy. In these experiments IHT showed significant and rapid apoptotic inductive effect on HL-60 cells in both concentration- and time-dependent fashion. The characteristic apoptosis-related features could be seen in IHT treated HL-60 cells. Transmission electron microscopy of IHT treated HL-60 cells displayed chromatin condensation and aggregation under the nuclear membrane, nuclear fragmentation and apoptosis body formation. Typical DNA ladder in agarose gel electrophoresis and pre-G1 peak in flow cytometric analysis were also observed in the cells exposed to IHT. The apoptotic rate could reach 43.8% in the HL-60 cells treated for 120 minutes with IHT 10(-7) mol.L-1. The cytotoxicity of IHT paralleled with cell apoptosis indicating that the anticancer activity of IHT results from the induction of apoptosis. These results are important impetus for further research and development of IHT as an anticancer agent.


Criteria for the addition of prone imaging to myocardial perfusion single-photon emission computed tomography for inferior wall.
Myocardial perfusion single-photon emission computed tomography (SPECT) is occasionally suspected to generate images that represent either ischemia or infarction for the inferior wall [right coronary artery (RCA) disease] or attenuation artifacts because of the diaphragm. We often encounter this. The application of prone imaging is advantageous in the differentiation of RCA disease because of attenuation artifacts. If decreased accumulation of radioisotopes is observed at the site with either RCA disease or attenuation artifacts, then a criterion that enables the addition of prone imaging should be implemented. Then, we evaluated sites where RCA disease and attenuation artifacts would likely appear and investigated the threshold of decreased accumulation that enables utilization of prone imaging. The patients in this study were divided into two groups: group A (20 patients) suspected to have attenuation artifacts because of the diaphragm and group B (14 patients) with RCA disease. Additional evaluation by prone imaging was performed in all patients. We utilized a 20-segment quantitative perfusion SPECT polar map in the supine and prone positions to compare the percentage increase in Thallium chloride (Tl) in both groups. We then investigated the percent uptake (%uptake) value of decreased accumulation in the inferior wall for the addition of prone imaging. The highest %uptake was present in segments 3, 4, 5, and 10 in group A after the prone imaging. Detection of attenuation artifacts from the diaphragm was easy in segments 3, 4, 5, and 10, and we set the %uptake threshold at 62, 61, 71, and 76%, respectively, in the supine position for the addition of prone imaging. A decrease of the %uptake in segments 3, 4, 5, and 10 after supine imaging is presumed to result from attenuation artifact or RCA disease. We established evaluation criteria for the addition of prone imaging in patients with decreased accumulation in the inferior wall during supine imaging.


[Neuroleptic malignant syndrome in elderly hospital patients].
Neuroleptic malignant syndrome (NMS) has gained increasing attention over the past decade. Diagnostic features include exposure to major tranquilizers, acute onset of high fever, extrapyramidal symptoms and markedly elevated CPK. Other common signs include changes in mental status, tachycardia and leukocytosis. It usually runs its course within 10 days. Greater awareness and improved treatment have resulted in markedly decreased mortality. However, failure to diagnose and treat properly results in a significant risk of death. Most cases of NMS reported have been in those with psychiatric illness. Few cases have been reported in elderly patients without a psychiatric history. We describe an 85-year-old man, without previous psychiatric illness, who developed NMS while hospitalized on a general medical ward.


(18)F-FDG PET/CT in primary right eyelid lymphoma.
A 74-year-old man with right upper eyelid swell accepted FDG PET/CT examination, which showed an intensely FDG-avid soft tissue nodular mass within the eyelid. It was suggestive of malignancy. There was no evidence of active neoplastic disease elsewhere. The nodule was excised by surgery. Histopathological findings showed characteristic findings of diffuse large B-cell lymphoma. This case highlights the utility of FDG PET/CT in identifying rare types of lymphoma.


Spontaneous coronary artery dissection and woven coronary artery: three cases and a review of the literature.
Spontaneous coronary artery dissection (SCAD) and woven coronary artery anomaly (WCAA) are relatively rare. A few of the previously reported woven coronary artery cases have involved in a single coronary artery. We present an unusual woven case involving all coronary arteries and two patient with SCAD. We have also reviewed the literature related to these disease, as they resemble one another.


The investigation of a compact auto-connected wire-wrapped pulsed transformer.
For the power conditioning circuit used to deliver power efficiently from flux compression generator (FCG) to the load with high impedance, an air-cored and wire-wrapped transformer convenient in coaxial connection to the other parts is investigated. To reduce the size and enhance the performance, an auto-connection is adopted. A fast and simple model is used to calculate the electrical parameters of the transformer. To evaluate the high voltage capability, the voltages across turns and the electric field distribution in the transformer are investigated. The calculated and the measured electrical parameters of the transformer show good agreements. And the safe operating voltage is predicted to exceed 500 kV. In the preliminary experiments, the transformer is tested in a power conditioning circuit with a capacitive power supply. It is demonstrated that the output voltage of the transformer reaches -342 kV under the input voltage of -81 kV.


Fusobacterium's link to colorectal neoplasia sequenced: A systematic review and future insights.
To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development. Two independent investigators systematically reviewed all original scientific articles published between January, 2000, and July, 2017, using PubMed, EMBASE, and MEDLINE. A total of 355 articles were screened at the abstract level. Of these, only original scientific human, animal, and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer (CRC) were included in the analysis. Abstracts, review articles, studies investigating other colonic diseases, and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates, resolving disagreements between the two reviewers, and applying the above criteria. Studies have consistently identified positive associations between Fusobacterium, especially Fusobacterium nucleatum (F. nucleatum), and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and CpG island methylator phenotype (CIMP)-high CRCs. There was evidence of temporality and a biological gradient, with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment; evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear; however, the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin (Gal-GalNAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors through interaction with an F. nucleatum protein, fibroblast activation protein 2 (FAP2). The clinical significance of detection or enrichment of Fusobacterium in colorectal neoplasia is ambiguous, but data suggest a procarcinogenic effect of F. nucleatum, likely due to activation of oncogenic and inflammatory pathways and modulation of the tumor immune environment. This is hypothesized to be mediated by certain F. nucleatum strains carrying invasive properties and virulence factors such as FadA and FAP. Evidence suggests a potential active role of Fusobacterium, specifically F. nucleatum, in CRC. Future prospective and experimental human studies would fill an important gap in this literature.


Estimation of additive genetic and environmental sources of quantitative trait variation using data on married couples and their siblings.
Twin studies have been used to understand the sources of genetic and environmental variation in body height, body weight and other common human quantitative traits. However, it is rather unclear whether these two sources of variation could be really separated in practice. Here, we consider a special study design where phenotype data from married couples and their siblings have been collected. The marital status gives information about the shared environment, while siblings give information about both genetic and environmental variation. To dissect sources of variation and to allow some deviations and pedigree errors in the data, we model such data using a robust polygenic model with finite genome length assumption. As a summary, we provide the estimates for age-dependent proportions of total variation which are due to polygenic and environmental effects. Here, these estimates are provided for body height, weight, systolic blood pressure and total serum cholesterol measured from subjects of the Indian Migration Study.


Capillary electrophoresis-driven synthesis of water-soluble CdTe quantum dots in nanoliter scale.
'Green nanotechnology' is a term used for the design of nanomaterials and processes that reduce or eliminate the use and/or generation of hazardous substances. In this paper, a capillary electrophoresis (CE)-driven synthesis of CdTe quantum dots (QDs) and their subsequent conjugation with a metal-binding protein metallothionein (isofom MT1) is reported. Even though the toxic materials (cadmium and potassium borohydride) were used for synthesis, the proposed method can be labeled as 'environmentally friendly' because the whole process (synthesis of QDs and MT1 conjugation) was carried out under mild conditions: ultra-low volume (nanoliter scale), relatively low temperature (50 °C), atmospheric pressure, and completed in a short time (under 90 s). Prepared QDs were also characterized by classical fluorescence spectroscopy and transmission electron microscopy. This study opens up new possibilities for the utilization of classical CE in the synthesis of nanoparticles and on-line labeling of biomolecules in the nanoliter scale in short period of time.


Computer-aided detection for virtual colonoscopy.
Colon cancer is one of the leading causes of cancer deaths in the developed countries. Most colon cancers can be prevented if precursor colon polyps are detected and removed. Virtual colonoscopy, or CT colonography, has shown promise to be the future screening tool for polyp detection, with a number of studies performed at academic institutions showing high sensitivity and specificity. Two main factors limiting CT colonography in general use are its excessive interpretation time and the variable sensitivity among readers. This article discusses the potential of computer-aided detection to address these problems. We also review the current state of research in this field and the future roles and challenges of CAD for CT colonography.


An update on short-course episodic and prevention therapies for herpes genitalis.
The prevalence of herpes genitalis (genital herpes) has increased markedly over the past three decades. The most common cause is infection with the herpes simplex virus type 2 (HSV-2), but it can also occur as a result of HSV-1 infection. Herpes genitalis can cause substantial psychosexual as well as physical morbidity and, in immunocompromised individuals, such as those who are HIV-positive, HSV infection can result in severe disease with progressive and extensive lesions. The natural history of herpes genitalis and the pathways of infection are now well known; however, the factors associated with reactivation have yet to be fully defined. A number of management approaches with antiviral medications are commonly used, including episodic and suppressive treatments. For episodic therapy, the duration of both lesions and symptoms, as well as the proportion of aborted episodes, are the most important measures of efficacy. For suppressive therapy, the time to first recurrence and frequency of recurrences over time are the most important clinical measures of antiviral benefit. Regarding the duration of episodic regimens, comparisons of 1-, 2- and 3-day antiviral courses with standard 5-day regimens show similar benefits on healing and relief of symptoms, with the obvious improvement in convenience, economy and compliance. In HIV-positive patients, antiherpes therapy has proved effective in speeding healing of lesions and reducing subclinical shedding, and can be used to treat genital HSV-2 infections in this group. Suppressive antiviral therapy has been shown to decrease the risk of HSV transmission in heterosexual couples. New approaches to the prevention of HSV infection, including vaccines and topical microbicides, are under investigation.


Portal vein thrombosis as a rare cause of abdominal pain: When to consider?
Extrahepatic portal vein thrombosis (PVT) is a rare condition that is characterized by the presence of thrombus within any segment of the portal vein, including the right and left intrahepatic branches. It may also extend to the splenic or superior mesenteric veins. Portal vein thrombosis may be related to cirrhosis or liver malignancy as well as to local inflammatory conditions in the abdomen and genetic or acquired thrombophilic diseases. Currently, PVT is being increasingly diagnosed due to advances in modern imaging techniques. The clinical presentation has a wide range, from an asymptomatic lesion to a potentially life-threatening situation. In this study, we present three patients with PVT. The diagnosis was made by radiologic and clinical findings. In the first patient, genetic testing revealed factor V Leiden mutation as the cause of PVT. The second patient was diagnosed with lupus anticoagulant syndrome as the cause of PVT. Portal vein thrombosis was associated with intra abdominal infection due to anastomotic leakage in the third patient. Two patients were successfully treated with anticoagulant therapy. This report emphasizes that even though PVT is a rare cause of abdominal pain, timely diagnosis and appropriate management is vital due to its lethal complications such as mesenteric ischemia and mesenteric infarct.


Species level identification of coagulase negative Staphylococcus spp. from buffalo using matrix-assisted laser desorption ionization-time of flight mass spectrometry and cydB real-time quantitative PCR.
Incorrect identification of Staphylococcus spp. can have serious clinical and zoonotic repercussions. Accordingly, the aim of this study was to determine if matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and/or cydB real- time quantitative PCR (qPCR) could be used to accurately identify coagulase negative Staphylococcus spp. (CoNS) obtained from buffalo milk and milking environment samples. Seventy-five of 84 CoNS isolates could be identified to the species level (score value >1.99) using MALDI-TOF MS. However, as determined by cytochrome d ubiquinol oxidase subunit II (cydB) qPCR and by 16S RNA and cydB gene sequencing, 10S. agnetis strains were wrongly identified as S. hyicus by MALDI-TOF MS. In addition, 9 isolates identified by MALDI-TOF only to the genus level (score values between 1.70 and 1.99) could be identified to species by cydB qPCR. Our findings suggest that MALDI-TOF MS is a reliable method for rapid identification of S. chromogenes and S. epidermidis (species of interest both in human and veterinary medicine) and may be able to correctly identify other Staphylococcus spp. However, at present not all Staphylococcus spp. found in buffalo milk can be accurately identified by MALDI-TOF MS and for these organisms, the cydB qPCR developed in the current study may provide a reliable alternative method for rapid identification of CoNS species.


Separator Membrane from Crosslinked Poly(Vinyl Alcohol) and Poly(Methyl Vinyl Ether-alt-Maleic Anhydride).
In this work, we report separator membranes from crosslinking of two polymers, such as poly vinyl alcohol (PVA) with an ionic polymer poly(methyl vinyl ether-alt-maleic anhydride) (PMVE-MA). Such interpolymer-networked systems were extensively used for biomedical and desalination applications but they were not examined for their potential use as membranes or separators for batteries. Therefore, the chemical interactions between these two polymers and the influence of such crosslinking on physicochemical properties of the membrane are systematically investigated through rheology and by critical gel point study. The hydrogen bonding and the chemical interaction between PMVE-MA and PVA resulted in highly cross-linked membranes. Effect of the molecular weight of PVA on the membrane properties was also examined. The developed membranes were extensively characterized by studying their physicochemical properties (water uptake, swelling ratio, and conductivity), thermal and electrochemical properties using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), thermo-gravimetric analysis (TGA) and electrochemical impedance spectroscopy (EIS). The DSC study shows the presence of a single Tg in the membranes indicating compatibility of the two polymers in flexible and transparent films. The membranes show good stability and ion conductivity suitable for separator applications.


Bone marrow repopulation capacity after transplantation of lymphocyte-depleted allogeneic bone marrow using counterflow centrifugation.
Bone marrow from six allogeneic HLA-matched and MCL nonreactive siblings was fractionated by means of isopycnic flotation centrifugation and subsequent counterflow centrifugation. The low density fraction (d less than or equal to 1.070 g/ml) obtained by IFC contained 20% of the nucleated cells and more than 90% of the myeloid and erythroid progenitors. The putative stem cell fraction obtained by CC showed a satisfactory recovery (88%) of the CFU-GM and BFU-E and only 3.5% of the original number of T lymphocytes. Bone marrow repopulation capacity was not impaired in comparison with a comparable group of patients. Despite the average high age of this group (29.6 years), only one of the four evaluable patients developed graft-versus-host disease.


Effects of Estrogens on Platelets and Megakaryocytes.
In women, oral menopausal hormonal therapy (MHT) is associated with adverse effects including an increased incidence of thromboembolic events, classically attributed to an increase in several liver-derived coagulation factors due to hepatic first pass. While platelets are central players in thrombus constitution, their implication in women treated with estrogens remains incompletely characterized. Platelets and their medullar progenitors, megakaryocytes, express estrogen receptors (ER) that may explain, at least in part, a sensitivity to hormonal changes. The purpose of this review is to summarize our current knowledge of estrogen actions on platelets and megakaryocytes in mice following in vivo administration and in women using MHT.


The effect of sub-inhibitory concentrations of rifaximin on urease production and on other virulence factors expressed by Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus.
Rifaximin, a topical derivative of rifampin, inhibited urease production and other virulence factors at sub-MIC concentrations in strains involved in hepatic encephalopathy and the expression of methicillin resistance in Staphylococcus aureus. In particular, urease production was affected in all Proteus mirabilis and Klebsiella pneumoniae strains as well as in all tested Pseudomonas aeruginosa isolates. Other exotoxins, synthesized by P. aeruginosa, such as protease, gelatinase, lipase, lecithinase and DNAse were also not metabolized in the presence of rifaximin. This antibiotic inhibited pigment production in both P. aeruginosa and Chromobacterium violaceum, a biosensor control strain. Lastly, rifaximin affected haemolysin production in S. aureus and was able to restore cefoxitin susceptibility when the strain was cultured in the presence of sub-MICs of the drug. The present findings confirm and extend previous observations about the beneficial effects of rifaximin for the treatment of gastrointestinal diseases, since in this anatomic site, it reaches a large array of concentrations which prevents enterobacteria from thriving and/or producing their major virulence factors.


Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma.
The prevalence of circulating thyroid autoantibodies (TgAb or antithyroid peroxidase) was increased nearly 3-fold in patients with differentiated thyroid cancers (DTC) compared with the general population (40% vs. 14%, respectively). Serum TgAb (with or without antithyroid peroxidase) was present in 25% of DTC patients and 10% of the general population. Serial postsurgical serum TgAb and serum Tg patterns correlated with the presence or absence of disease. Measurements of serum Tg were made in 87 TgAb-positive sera by a RIA and two immunometric assay (IMA) methods to study TgAb interference. TgAb interference, defined as a significant intermethod discordance (>41.7% coefficient of variation) between the Tg RIA and Tg IMA values relative to TgAb-negative sera, was found in 69% of the TgAb-positive sera. TgAb interference was characterized by higher Tg RIA vs. IMA values and was, in general, more frequent and severe in sera containing high TgAb concentrations. However, some sera displayed marked interference when serum TgAb was low (1-2 IU/mL), whereas other sera with very high TgAb values (>1000 IU/mL) displayed no interference. An agglutination method was found to be too insensitive to detect low TgAb concentrations (1-10 IU/mL) causing interference. Exogenous Tg recovery tests were an unreliable means for detecting TgAb interference. Specifically, the exogenous Tg recovered varied with the type and amount of Tg added and the duration of incubation employed. Further, recoveries of more than 80% were found for some sera displaying gross serum RIA/IMA discordances. The measurement of serum Tg in DTC patients with circulating TgAb is currently problematic. It is important to use a Tg method that provides measurements that are concordant with tumor status. IMA methods are prone to underestimate serum when TgAb is present, increasing the risk that persistent or metastatic DTC will be missed. The RIA method used in this study provided more clinically appropriate serum Tg values in the group of TgAb-positive patients with metastatic DTC. Furthermore, as serial serum TgAb measurements paralleled serial serum Tg RIA measurements, TgAb concentrations may be an additional clinically useful tumor marker parameter for following TgAb-positive patients. Disparities between serial serum Tg and TgAb measurements might alert the physician to the possibility of TgAb interference with the serum Tg measurement and prompt a more cautious use of such data for clinical decision-making.


Palliative treatment of advanced non small cell lung cancer with weekly fraction radiotherapy.
Various hypofractionated radiotherapy schedules of radiotherapy have been tried in patients of advanced NSCLC with no conclusive superiority of either a more protracted low dose per fraction schedule or a rapid course of large fraction size. Present study evaluates the role of weekly high dose radiotherapy for the palliation of various intrathoracic symptoms like cough, chest pain, hemoptysis, dyspnoea. A total of 47 patients of advanced non-small cell lung cancer were treated with four weekly fraction of 5 Gy to a total dose of 20 Gy. Mean age at presentation was 53 years. Majority of patients had stage III disease. Pain relief was seen in 77% (23/30) patients with complete relief in 57%; haemoptysis was completely relieved in 77% patients (17/22); and cough was relieved in 68% (19/28) patients. Complete relief from dyspnoea was seen in only 5/12 (42%) patients whereas 2/12 (17%) patients had partial response. The present regime of 20 Gy in four weekly fractions was well tolerated by the patients without any identifiable acute toxicity and was simple and convenient to the patients, who traverse a long distance for radiotherapy in India. To conclude, weekly schedule af EBRT provide effective palliation of various intrathoracic symptoms in the patients with advanced NSCLC.


Pharmacological inhibition of microsomal prostaglandin E synthase-1 suppresses epidermal growth factor receptor-mediated tumor growth and angiogenesis.
Blockade of Prostaglandin (PG) E(2) production via deletion of microsomal Prostaglandin E synthase-1 (mPGES-1) gene reduces tumor cell proliferation in vitro and in vivo on xenograft tumors. So far the therapeutic potential of the pharmacological inhibition of mPGES-1 has not been elucidated. PGE(2) promotes epithelial tumor progression via multiple signaling pathways including the epidermal growth factor receptor (EGFR) signaling pathway. Here we evaluated the antitumor activity of AF3485, a compound of a novel family of human mPGES-1 inhibitors, in vitro and in vivo, in mice bearing human A431 xenografts overexpressing EGFR. Treatment of the human cell line A431 with interleukin-1beta (IL-1β) increased mPGES-1 expression, PGE(2) production and induced EGFR phosphorylation, and vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) expression. AF3485 reduced PGE(2) production, both in quiescent and in cells stimulated by IL-1β. AF3485 abolished IL-1β-induced activation of the EGFR, decreasing VEGF and FGF-2 expression, and tumor-mediated endothelial tube formation. In vivo, in A431 xenograft, AF3485, administered sub-chronically, decreased tumor growth, an effect related to inhibition of EGFR signalling, and to tumor microvessel rarefaction. In fact, we observed a decrease of EGFR phosphorylation, and VEGF and FGF-2 expression in tumours explanted from treated mice. Our work demonstrates that the pharmacological inhibition of mPGES-1 reduces squamous carcinoma growth by suppressing PGE(2) mediated-EGFR signalling and by impairing tumor associated angiogenesis. These results underscore the potential of mPGES-1 inhibitors as agents capable of controlling tumor growth.


Growth and remodelling of the autologous bone transplant used in a pediatric femoral reconstruction.
The aim of the present work was to assess how growth and remodelling changed the morphology of the transplanted fibula used to reconstruct the proximal femur of a 5 year old child affected by a Ewing's sarcoma during the first 3 years of follow-up. The morphological evolution of the transplant was quantitatively assessed on diagnostic images. Special software was developed to perform three-dimensional measurements on computed tomography (CT) datasets, while state-of-the-art image processing software was used for conventional radiography. The measurements were then correlated with the loads expected to act on the hip during the various stages of the rehabilitation protocol. A simple cantilever beam model was used for a gross estimate of the risk of fracture of the transplant. The results of the analysis showed that there is no clear correlation between the morphological changes of the autograft and the hip loading conditions experienced. Apart from a drastic increase in the periosteal radius in the frontal plane, occurring in the first 10 months after the operation, the growth of the transplanted fibula seems well within the ranges of the normal fibular growth. The cantilever beam model suggested that, although the autograft is currently subjected to subcritical stresses. morphological evolution could increase the risk of fracture in the next few years if a normal level of loading were allowed.


Effect of subsurface oxygen on the reactivity of the Ag(111) surface.
Periodic, self-consistent, density functional theory calculations have been performed to demonstrate that subsurface oxygen (O(sb)) dramatically increases the reactivity of the Ag(111) surface. O(sb) greatly facilitates the dissociation of H2, O2, and NO and enhances the binding of H, C, N, O, O2, CO, NO, C2H2, and C2H4 on the Ag(111) surface. This effect originates from an O(sb)-induced upshift of the d-band center of the Ag surface and becomes more pronounced at higher O(sb) coverage. Our findings point to the important role that near-surface impurities, such as O(sb), can play in determining the thermochemistry and kinetics of elementary steps catalyzed by transition metal surfaces.


Directly measuring spinal cord blood flow and spinal cord perfusion pressure via the collateral network: correlations with changes in systemic blood pressure.
During thoracoabdominal surgery in which segmental arteries are sacrificed over a large area, blood supply routes from collateral networks have received attention as a means of avoiding spinal cord injury. The aim of this study was to investigate spinal cord blood supply through a collateral network by directly measuring spinal cord blood flow and spinal cord perfusion pressure experimentally. In beagle dogs (n = 8), the thoracoabdominal aorta and segmental arteries L1-L7 were exposed, and a temporary bypass was created for distal perfusion. Next, a laser blood flow meter was placed on the spinal dura mater in the L5 region to measure the spinal cord blood flow. The following were measured simultaneously when the direct blood supply from segmental arteries L2-L7 to the spinal cord was stopped: mean systemic blood pressure, spinal cord perfusion pressure (blood pressure within the aortic clamp site), and spinal cord blood flow supplied via the collateral network. These variables were then investigated for evidence of correlations. Positive correlations were observed between mean systemic blood pressure and spinal cord blood flow during interruption of segmental artery flow both with (r = 0.844, P < .01) and without (r = 0.834, P < .01) distal aortic perfusion. In addition, we observed significant correlations between spinal cord perfusion pressure and spinal cord blood flow with and without distal perfusion (r = 0.803, P < .001 and r = 0.832, P < .01, respectively), and between mean systemic blood pressure and spinal cord perfusion pressure with and without distal perfusion (r = 0.898, P < .001 and r = 0.837, P < .001, respectively). The spinal cord was perfused from the collateral network from outside the interrupted segmental arteries, and high systemic blood pressure (∼1.33-fold higher) was needed to obtain the preclamping spinal cord blood flow, whereas 1.68-fold higher systemic blood pressure was needed when distal perfusion was halted. Spinal cord blood flow is positively correlated with mean systemic blood pressure and spinal cord perfusion pressure under spinal cord ischemia caused by clamping a wide range of segmental arteries. In open and endovascular thoracic and thoracoabdominal surgery, elevating mean systemic blood pressure is a simple and effective means of increasing spinal cord blood flow, and measuring spinal cord perfusion pressure seems to be useful for monitoring perioperative spinal cord blood flow.


Chip-based time-continuous monitoring of toxic effects on stem cell differentiation.
Pesticides used to control unwanted insects are potentially toxic to humans. In assessing the risk involved in exposure to pesticides or complex chemical mixtures, an in vitro cell-based test can provide useful information regarding danger to human health. Cell differentiation is a biological process of fundamental importance in developing and adult organisms. In this paper, we propose a cell-based test system for continuous, label-free monitoring of the effect of test substances on stem cell differentiation. Using a prefabricated electrode-based chip and impedance measurement system, we investigated the influence of chlorpyrifos (a pesticide) on the differentiation of human mesenchymal stem cells (hMSCs) to adipocytes. The state of hMSCs on electrodes during adipogenic differentiation or after application of the cytotoxic substance was clearly reflected in the impedance measurement. Chlorpyrifos caused a partially uncovered electrode area with a decreased number of lipid vacuoles, thus leading to a rapid decrease in resistance in the cell layer. After removal of the chlorpyrifos, the cell layer resistance was regained due to the renewed covering of the electrodes by hMSCs. However, an increase in lipid vacuoles was not observed. From this, it was concluded that the measured resistance of hMSCs is determined by the electrical properties in the extra cellular space (e.g., cell/electrode or cell/cell gap), but not by the lipid vacuoles appearing in intracellular space during adipogenic differentiation.


[Component analysis of bone matrix via cell extraction].
To investigate the preparation of bone acellular extra-cell matrix(AECM) and to analyze its component. With low-osmosis theory and method of cell extraction by detergent, bone acellular extra-cell matrix was prepared. We observed morphologic changes with HE, Mallory-Heidenhain rapid one-step dyeing and Alcian blue dyeing and examined fibronectin(FN) and laminin(LN) with immunohistochemistry. Light microscope showed that the collagen fibers arranged regularly in AECM with blankness of bone lacunas by HE, Mallory-Heidenhain rapid one-step dyeing and that the region around bone lacunas was stained different degrees of blue-green by Alcian blue dyeing. The result of immunohistochemistry showed there are positive markers of FN and LN in ECM. This method for preparation of bone acellular extra-cell matrix is effective, and it can keep natural structure of collagen fibers and maintain components of ECM, such as proteoglycan, FN and LN.


Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels.
Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is a major signaling molecule implicated in the regulation of various ion transporters and channels. Here we show that PIP(2) and intracellular MgATP control the activity of the KCNQ1/KCNE1 potassium channel complex. In excised patch-clamp recordings, the KCNQ1/KCNE1 current decreased spontaneously with time. This rundown was markedly slowed by cytosolic application of PIP(2) and fully prevented by application of PIP(2) plus MgATP. PIP(2)-dependent rundown was accompanied by acceleration in the current deactivation kinetics, whereas the MgATP-dependent rundown was not. Cytosolic application of PIP(2) slowed deactivation kinetics and also shifted the voltage dependency of the channel activation toward negative potentials. Complex changes in the current characteristics induced by membrane PIP(2) was fully restituted by a model originally elaborated for ATP-regulated two transmembrane-domain potassium channels. The model is consistent with stabilization by PIP(2) of KCNQ1/KCNE1 channels in the open state. Our data suggest a striking functional homology between a six transmembrane-domain voltage-gated channel and a two transmembrane-domain ATP-gated channel.


[Current directions of studies for development of methods for specific diagnostics of allergic diseases in vitro].
Results of studies as well as perspectives for development and use of modern in vitro methods of allergic diseases diagnostics are presented. High prevalence of allergic diseases dictates the need of high-quality etiologic diagnosis for conducting relevant etiopathogenetic treatment - allergen-specific immunotherapy and prophylactic measures. Interest to in vitro diagnostic methods due to their high specificity and commonality is rising. They are directed to identification of various elements of "material substrate" of allergic reaction - specific antibodies, cell elements, cytokines as well as genes, which encode them. Intensively developing methods based on immunoenzyme, immunofluorescent, and immunochemiluminescent reactions are widely used now. Methods based on the use of various monoclonal antibodies for identification of lymphocytic markers, cytokines, antigen-presenting cells by laser flowcytometry are also very promising. ELISPOT technology is also intensively used for diagnostics of allergic diseases. From immunogenetic methods great potential belongs to molecular biologic methods of assessment of genome specificity characterizing sensitization to given antigen.


Finite strain crack tip fields in soft incompressible elastic solids.
A finite element model (FEM) is used to study the behavior of the large deformation field near the tip of a crack in a soft incompressible plane stress fracture specimen loaded in mode I. Results are obtained for the case of a neo-Hookean solid (ideal rubber) and a hyperelastic solid with exponentially hardening behavior. In contrast to the predictions of linear elastic fracture mechanics (LEFM), the near tip stress fields are dominated by the opening stress which shows a 1/R singularity for the neo-Hookean material and a -1/(R ln R) singularity for the exponential hardening solid. We found very similar qualitative behavior in the near tip stress fields despite the very large difference in strain hardening behavior of the two material models. Our result shows that the near tip opening stress is controlled by the far field energy release rate for large applied loads.


[Modeling of pemphigus vulgaris in guinea pigs].
In 146 guinea pigs with body weight of 150-200 g pemphigus vulgaris (PV) was induced using screening techniques. The animals were injected with PV patients' IgG (IgGPV) and blister fluid (PVBF) with the PV patient mononuclears. Intraperitoneal administration of IgGPV caused dystrophy in epidermis of experimental animals while intracutaneous injection of PVBF resulted in balloon dystrophy. Clinical manifestations of -PV were obtained after two-day intraperitoneal IgGPV administration in a total dose of 1.5 g (6 mg/g) following a cycle of intracutaneous injections of 2.0 ml PVBF in 10-15 sites of guinea pig back. The presence of acantholysis, intraepidermal localization of blisters, pemphigus antibodies fixation on spinous cell surface, and almost 100% mortality of experimental animals were the major criteria for the developed model of PV in guinea pigs. Experimental PV in guinea pigs was abolished due to treatment of PVBF with dexamethasone, contrykal, heating (56 degrees C, 30 min), preincubation with human skin samples, and PVBF cell-free supernatant application. The conclusion was made that for occurrence of pemphigus in laboratory animals a combined effect of pemphigus antibodies, sensitized mononuclears, complement and endogenous proteinases is required.


Aggregated occurrence records of the invasive alien striped field mouse (Apodemus agrarius Pall.) in the former USSR.
Open access to occurrence records of the most dangerous invasive species in a standardised format have important potential applications for ecological research and management, including the assessment of invasion risks, formulation of preventative and management plans in the context of global climate and land use changes in the short and long perspective. The striped field mouse (Apodemus agrarius Pallas, 1771) is a common species in the temperate latitudes of the Palaearctic. Due to land use and global climate changes, several waves of expansion of the range of this species have been observed or inferred. By intrusion into new regions, the striped field mouse has become an alien species there. Apodemus agrarius causes significant harm to agriculture and is one of the most important pests of grain crops. In tree nurseries, A. agrarius destroys seeds of valuable tree species and gnaws at the bark of saplings of broadleaf species and berry bushes. It is one of the most epidemiologically important rodents, involved in the circulation of the causative agents of haemorrhagic fever with renal syndrome (HFRS) and many other zoonotic infections. The foregoing allows us to classify the striped field mouse as a dangerous invasive alien species in the expanding part of the range. A lot of data accumulated for this species are of interest from both ecological and applied points of view. The accumulation and aggregation of data on the occurrence records of A. agrarius is relevant for the study of ecology, biogeography and construction of the spatial distribution and ecological niche models in the context of global climate change. We have created a dataset of 1603 occurrence records of this species, collected from 1936 to December 2020 by various zoologists, previously published or original. These records relate to a significant part of the striped field mouse's range in Russia (1264 records) and neighbouring countries (339 records). The dataset shows the position of the northern and central parts of A. agrarius range, the disjunction of the range in Transbaikalia and isolated populations in the north of the range. The data were obtained in different formats from literature, indicating different degrees of accuracy of geographic coordinates and with several variations of the species' name. In the process of aggregating and fixing errors, we created a set of georeferenced occurrence records, adopted a controlled vocabulary, removed duplicates and standardised the format of records using unified data structure. We examined the dataset for inconsistencies with the taxonomic position of A. agrarius and removed the incorrect records. This paper presents the resulting dataset of A. agrarius occurrence records in the territory of Russia and neighbouring countries in a standardised format. This is a validated and comprehensive dataset of occurrence records of A. agrarius, including both our own observations and records from literature. This dataset is available for extension by other researchers using a standard format in accordance with Darwin Core standards. In different countries, there are a lot of occurrence records for the striped field mouse, but the overwhelming part of them is presented in separate literary sources, stored in the form of maps and in zoological collections. Prior to this project, such information was not available to a wide range of researchers and did not allow the use of these spatial data for further processing by modern methods of analysis, based on geographic information systems (GIS technologies). The created dataset combines species occurrence records of many Soviet zoologists who studied the distribution of the striped field mouse over a significant part of its recent range, in Russia and neighbouring countries (within the former USSR). The final set of records was created by combining the species occurrence records using a uniform data structure, checking geographic coordinates and removing duplicate and erroneous records. The dataset expands the available information on the spatial and temporal distribution of the dangerous invasive species in Russia and neighbouring countries of the former USSR (Estonia, Latvia, Lithuania, Belarus, Ukraine, Moldova, Georgia, Azerbaijan, Kazakhstan and Kyrgyzstan).


Endogenous Aeromonas hydrophila endophthalmitis.
Aeromonas hydrophila as the etiologic agent of endophthalmitis is rare, having only been reported in association with a perforating injury of the eye. We describe a case of isolated spontaneous, endogenous endophthalmitis due to this agent, with no apparent source.


An innovative approach to the care of patients on phase I and phase II clinical trials: the role of the experimental therapeutics nurse.
The tremendous strides in survival rates for childhood malignancies in large part can be attributed to the clinical trial mechanism. New and innovative therapies are being developed in the laboratory in an attempt to find a cure for those children who have relapsed or have refractory disease. Phase I and phase II clinical trials move this science from the laboratory to the patient's bedside. With increasing frequency, the oncology staff nurse may be managing the care of a patient receiving a phase I or phase II study drug. Administration of these agents goes beyond what is familiar, requires specialized knowledge, and demands a skill set beyond what is required for standard oncology care. At The Children's Hospital of Philadelphia, the role of the experimental therapeutics nurse was created in an effort to improve the process for identification, treatment, and follow-up of patients receiving these therapies. The broader role of nursing in clinical trials, the multidisciplinary challenges of experimental therapies, and the development of an innovative approach to caring for patients on phase I/II studies are discussed.


Examining the longitudinal association between oppositional defiance and autonomy in adolescence.
In this longitudinal study, we tested whether the association between oppositional defiance to parental authority (i.e., adolescents' tendency to bluntly reject parental rules) and autonomy would depend upon the specific conceptualization of autonomy. Whereas oppositional defiance would yield more interpersonal distance from parents, because it involves turning away from parental authority, it would also yield less volitional functioning, as oppositional defiance would come at the expense of acting upon one's personal values and interests. A sample of 387 middle and late adolescents (age range = 14-20 years at Time 1) filled out questionnaires at 2 time points, separated by a 2-year interval. With increasing age, adolescents reported less oppositional defiance and more volitional functioning. Late adolescents in particular reported less interpersonal distance from their parents. Cross-lagged analyses indicated that oppositional defiance predicted increases in interpersonal distance as well as decreases in volitional functioning across time. Conversely, higher scores on volitional functioning predicted decreases in oppositional defiance. These findings emphasize the necessity of a differentiated approach to autonomy.


Insulin signals control the competence of the Drosophila female germline stem cell niche to respond to Notch ligands.
Adult stem cells reside in specialized microenvironments, or niches, that are essential for their function in vivo. Stem cells are physically attached to the niche, which provides secreted factors that promote their self-renewal and proliferation. Despite intense research on the role of the niche in regulating stem cell function, much less is known about how the niche itself is controlled. We previously showed that insulin signals directly stimulate germline stem cell (GSC) division and indirectly promote GSC maintenance via the niche in Drosophila. Insulin-like peptides are required for maintenance of cap cells (a major component of the niche) via modulation of Notch signaling, and they also control attachment of GSCs to cap cells and E-cadherin levels at the cap cell-GSC junction. Here, we further dissect the molecular and cellular mechanisms underlying these processes. We show that insulin and Notch ligands directly stimulate cap cells to maintain their numbers and indirectly promote GSC maintenance. We also report that insulin signaling, via phosphoinositide 3-kinase and FOXO, intrinsically controls the competence of cap cells to respond to Notch ligands and thereby be maintained. Contrary to a previous report, we also find that Notch ligands originated in GSCs are not required either for Notch activation in the GSC niche, or for cap cell or GSC maintenance. Instead, the niche itself produces ligands that activate Notch signaling within cap cells, promoting stability of the GSC niche. Finally, insulin signals control cap cell-GSC attachment independently of their role in Notch signaling. These results are potentially relevant to many systems in which Notch signaling modulates stem cells and demonstrate that complex interactions between local and systemic signals are required for proper stem cell niche function.


Relief for patients with severe allergies.
For patients with severe allergies, allergen immunotherapy can lessen or eliminate reactions, reduce the need for medication, and improve quality of life. Here's what you need to know to provide this treatment safely and minimize its risks.


Lothar Jaenicke (1923-2015) zum Gedächtnis.
Among the post-war European biochemists, L. Jaenicke (1923-2015) stands out as a distinctive character with bright ideas and professional elegance, yet with personal modesty. His contributions to diverse fields such as C1 metabolic pathways, signal compounds (aquatic sex attractants) of brown algae and chemotaxis appear as distinctive features not covered by his peers. His rich scientific œuvre is documented in 291 journal articles, nine books, and a huge number of almost 570 book reviews, recensions, biographies and commentaries on the politics of science and the history of biochemistry. A quantitative approach is attempted here to make his diversified life's work more transparent through graphical analysis by the novel method of ergography. At a glance, his different strands of activities stand out clearly and speak for themselves, without the need for excessive verbal interpretation.


Expression of T-lymphoma invasion and metastasis factor on the occurrence of oral squamous cell carcinoma.
In recent years, many studies have found that tumor metastasis-related gene T-lymphoma invasion and metastasis-inducing factor 1 (TIAM1) had abnormal high expression in a variety of tumor cells; however, there are few studies regarding its expression in oral squamous cell carcinoma (OSCC). This study aimed to observe the expression of TIAM1 in OSCC and investigated its clinical significance. The expression of TIAM1 in tissues from 120 cases of OSCC and oral mucosa from 40 normal cases was detected by immunohistochemistry, and the relationship between the expression of TIAM1 and the clinicopathological parameters of OSCC was analyzed. The positive expression rate of TIAM1 in the OSCC tissues was significantly higher than that in the normal oral mucosa (92.5% vs 0%). With the decrease of histological differentiation of OSCC, the increase of tumor node metastasis (TNM) stage and the occurrence of lymph node metastasis, the TIAM1 staining positive rate was gradually increased, and the difference was statistically significant (P less than 0.05). However, the expression of TIAM1 in the OSCC tissues was in no correlation with the gender and age of the patients. The expression of TIAM1 is closely related to the occurrence, development and metastasis of OSCC, and it can be used as a new marker for reflecting its biological behaviors.


[Hereditary angioedema--neglected diagnosis].
Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare autosomal dominant inherited disorder. It is characterized by recurrent episodes of potentially life-threatening swellings without itching localized in the dermis and submucosa. We report a case of 41 years old woman with hereditary angioedema manifested as episodes of localized skin swellings and painful gastrointestinal colics. This report underlines the fact that hereditary angioedema is underdiagnosed in differential diagnoses. If hereditary angioedema is correctly diagnosed, effective treatment highly improving patients' quality of life is available.


Effect of beta-blockers on cardiac function and calcium handling protein in postinfarction heart failure rats.
The normal expression of Ca2+-handling protein is critical for efficient myocardial function. The present study was designed to test the hypothesis that beta-blocker treatment may attenuate left ventricular (LV) remodeling and cardiac contractile dysfunction in the failing heart, which may be associated with alterations of Ca2+-handling protein We investigated the change of LV remodeling and function in a rat model of heart failure due to myocardial infarction (MI) with or without carvedilol (30 mg/kg/d) or metoprolol (60 mg/kg/d) treatment for 6 weeks (n = 9 in the MI plus carvedilol group, and n = 8 in every other group). The expression of messenger RNA and proteins of sarcoplasmic reticulum Ca2+-adenosine triphosphatase (SERCA) and phospholamban in cardiomyocytes of all rats were also measured There was significant LV remodeling and cardiac contractile dysfunction in MI rats. The messenger RNA and protein expression of SERCA were down-regulated (p < 0.01), but the expression of phospholamban messenger RNA and protein were up-regulated (p < 0.01) in MI rats compared to sham-operated rats. After the treatment with beta-blockers, LV remodeling and function were clearly improved. Carvedilol was better in attenuating the weight of the LV and the relative weight of the right ventricle than metoprolol (p < 0.05). beta-Blockers restored the low expression of SERCA (p < 0.05) but showed no effect on phospholamban expression (p > 0.05). Moreover, carvedilol induced a more significant improvement of SERCA expression than metoprolol (p < 0.05) Beta-blockers are effective in preventing LV remodeling and cardiac contractile dysfunction in the failing heart. The molecular mechanism may be related to normalization of SERCA expression.


[Cryopreservation and plantlet regeneration of dormant buds of Gentiana straminea by vitrification].
To investigate the detailed techniques for cryopreservation of Gentiana straminea dormant buds by vitrification. Dormant buds as an experimental material,the influence of the different size of dormant buds,preculture and PVS etc. on cryopreservation of Gentiana straminea were studied. The optimal procedures were as follows: 10-11 mm long dormant buds which were cultured on MS medium supplemented with different sucrose concentration (0. 3,0. 5 or 0.7 mol/L) for 1 day respectively. The buds were immersed in loading solution for 20 min at 20 degrees C, and then treated in PVS2 solution for 40 min at 0 degrees C and finally plunged into liquid nitrogen quickly. After 24 hours, the buds were rapidly thawed in a water bath at 40 degrees C for 2 - 3 min and washed twice with MS medium supplemented with 1/2 MS liquid medium containing 1. 2 mol/L sucrose. Finally the buds were transferred to regeneration medium (MS + 0.5 mg/L 6-BA + 0.1 mg/L NAA + 3% sucrose + 0.7% agar), the survival rate was up to 83.3%. A high-efficiency cryopreservation protocol of Gentiana straminea is set up.


Effectiveness of a web-based screening and brief intervention with weekly text-message-initiated individualised prompts for reducing risky alcohol use among teenagers: study protocol of a randomised controlled trial within the ProHEAD consortium.
Early and excessive alcohol use is a significant threat to healthy development. Evidence supports the effectiveness of electronic alcohol interventions for young drinkers. However, effects are typically small and studies targeting under 18-year-olds are scarce. This trial is the first to evaluate the effectiveness of a single-session, brief, motivational, web-based intervention (ProWISE) plus weekly text-message-initiated individualised prompts (TIPs) in reducing alcohol consumption and alcohol-related harm among children and adolescents aged ≥ 12 years. TIPs are designed to decrease risky alcohol use by reaching youth in the contexts of their everyday lives and by providing individualised feedback on drinking intentions, actual drinking and succession in achieving personal goals for low-risk drinking or abstinence. The trial is part of the multicentre consortium ProHEAD testing e-interventions for mental health problems in children and adolescents. Participants in grades 6-13 aged ≥ 12 years will be recruited in schools which participate in ProHEAD (target N = 15,000). Main criterion for inclusion in the ProWISE-TIP trial is a positive screening for at-risk alcohol use in the CRAFFT-d questionnaire (target n = 1076). In a multicentre, four-arm, randomised controlled design the following groups will be compared: (A) web-based intervention plus TIPs for 12 weeks; (B) web-based intervention plus text-message-initiated assessment of alcohol consumption for 12 weeks; (C) web-based intervention only; and (D) alcohol-related psychoeducation. TIPs will be delivered shortly before and after high-risk situations for excessive alcohol use and will be tailored to age, gender, drinking motives and alcohol consumption. Study participants will be followed up at three, six and nine months in the ProWISE-TIP trial and at one and two years in the ProHEAD consortium. Primary outcome is alcohol use in the past 30 days at nine months after enrolment. Secondary outcomes are alcohol-related problems, co-occurring substance use, health service utilisation, mental health problems and quality of life. Trial results will generate important evidence on how to enhance effectiveness of single-session, web-based alcohol interventions for youth. The ProWISE-TIP intervention, if effective, can be used as a stand-alone alcohol intervention or as an add-on to school-based or community-based alcohol prevention programs. German Clinical Trials Register, DRKS00014606 Registered on 20 April 2018.