Sustainable bio-production of styrene from forest waste.
A strain of Penicillium expansum was studied for the production of styrene using forest waste biomass as a feeding substrate. The fungal strain was cultivated on bark of various trees supplemented with yeast extract and the volatiles produced were collected on Tenax TA and analyzed by gas chromatography-mass spectrometry. Fungus cultured on grated soft bark of pine (Pinus sylvestris) stems (GPB) and mature bark of oak (Quercus robur) supplemented with yeast extract produced relatively the highest amounts of styrene. The maximum styrene production rate was 52.5 μg/h, 41 μg/h and 27 μg/h from fungus cultivated on 50 mL liquid media with 10 g GPB or mature bark of oak and potato dextrose broth respectively. These promising results suggest that the fungal strain could be used to produce "green" styrene plastics using renewable forest waste biomass.


Risk factors for heatstroke among Japanese forestry workers.
We examined the risk factors for heatstroke among forestry workers in Japan during the summer. We distributed a questionnaire to 124 forestry workers to determine heatstroke symptoms, degree of sweating and hydration, as well as perceived hotness and amount of sunlight at work sites. Forty of the workers (32.3%) reported experiencing heatstroke symptoms. Thirteen and 21 of them reported such symptoms during July and August, respectively. Eleven workers experienced heatstroke at around 14:00; 5 and 4 developed symptoms at around 11:00 and 10:00, respectively. Groups with and without heatstroke symptoms significantly differed in terms of perceived hotness (p<0.05), sunlight (p<0.05), degree of sweating (p<0.01) and frequency of hydration (p<0.05) while working. Heatstroke symptoms developed in 60.6% of workers aged up to 50 yr, but in only 22.0% of those over the age of 51 (p<0.01). Multiple regression analysis selected the following key variables associated with the development of heatstroke symptoms (R(2)=0.236 and p=0.006): frequency of urination, hotness, BMI and years of forestry work (standard coefficients: +0.229, +0.194, +0.280 and -0.162, respectively). The results of the present study showed that one third of forestry workers developed some symptoms of early heatstroke during summer forestry work. Furthermore, the results indicate that a short duration of forestry service was one of the risk factors contributing to the onset of heatstroke, in addition to heat stress, loss of body water and electrolytes, and obesity.


Identification of O-Glcnacylated Proteins in Trypanosoma cruzi.
Originally an anthropozoonosis in the Americas, Chagas disease has spread from its previous borders through migration. It is caused by the protozoan Trypanosoma cruzi. Differences in disease severity have been attributed to a natural pleomorphism in T. cruzi. Several post-translational modifications (PTMs) have been studied in T. cruzi, but to date no work has focused on O-GlcNAcylation, a highly conserved monosaccharide-PTM of serine and threonine residues mainly found in nucleus, cytoplasm, and mitochondrion proteins. O-GlcNAcylation is thought to regulate protein function analogously to protein phosphorylation; indeed, crosstalk between both PTMs allows the cell to regulate its functions in response to nutrient levels and stress. Herein, we demonstrate O-GlcNAcylation in T. cruzi epimastigotes by three methods: by using specific antibodies against the modification in lysates and whole parasites, by click chemistry labeling, and by proteomics. In total, 1,271 putative O-GlcNAcylated proteins and six modification sequences were identified by mass spectrometry (data available via ProteomeXchange, ID PXD010285). Most of these proteins have structural and metabolic functions that are essential for parasite survival and evolution. Furthermore, O-GlcNAcylation pattern variations were observed by antibody detection under glucose deprivation and heat stress conditions, supporting their possible role in the adaptive response. Given the numerous biological processes in which O-GlcNAcylated proteins participate, its identification in T. cruzi proteins opens a new research field in the biology of Trypanosomatids, improve our understanding of infection processes and may allow us to identify new therapeutic targets.


The amelioration of streptozotocin diabetes-induced renal damage by Wu-Ling-San (Hoelen Five Herb Formula), a traditional Chinese prescription.
Wu-Ling-San (Hoelen Five Herb Formula) is a Chinese prescription used to promote water metabolism. The present study was undertaken to characterize the effects of Wu-Ling-San on diabetic nephropathy. Streptozotocin (STZ)-diabetic rats were orally administrated with Wu-Ling-San (0.5, 1.5, 2.5 g/(kgday)) once a day for 10 weeks. Changes in the renal function related parameters in plasma and urine were analyzed at the end of 10-week administration. Kidney was isolated for pathology histology, immunohistochemistry staining and Western blot analyses. Wu-Ling-San (2.5 g/(kgday)) partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-h urinary albumin excretion rate, creatinine clearance, and glomerular mesangial matrix expansion were ameliorated by Wu-Ling-San. The increased expression of nuclear factor-kB as well as transforming growth factor-beta(1) and the progressive accumulation of fibronectin in kidney of diabetic rats were attenuated by Wu-Ling-San. Not only the elevated levels of advanced glycation end products (AGEs) and mitochondrial thiobarbituric acid-reactive substance, but also the higher levels of N(epsilon)-(carboxymethyl)lysine and receptor for AGEs in kidney of diabetic rats were ameliorated by Wu-Ling-San. : Wu-Ling-San possess an anti-diabetic property with plasma glucose lowering action accompanied with amelioration of glycation-mediated renal damage.


[Diagnosis and therapeutic follow-up of patients with massive pulmonary emboli by two-dimensional echocardiography].
The aim of the study was to analyse the role of 2D echocardiogram (ECHO) in the diagnosis of massive pulmonary embolism (PE), and in the follow-up after fibrinolytic or surgical treatment. Echocardiographic studies were retrospectively analysed in seven patients, 5 male, mean age 37 +/- 19 years, with massive pulmonary embolism (PE) confirmed by pulmonary angiography. Six of them were submitted to fibrinolytic therapy with IV streptokinase (SK), and one underwent surgery. The diagnosis of PE by ECHO was made by the detection of thrombi in the pulmonary vascular bed. ECHO measurements included the right ventricular diastolic diameter (RVDD), interventricular septal motion (IVS), acceleration time (AcT), and peak pulmonary artery pressure (PAP). The ECHO study diagnosed thrombi in five out of seven patients (71%), mainly if they were present in the right main pulmonary artery (four cases -80%). It was also able to locate one out of five patients with thrombus in the right lobar artery and one out of two patients in the left main pulmonary artery; it was unable to identify six patients with involvement of the left lobar arteries. Four out of five patients with PE, diagnosed by ECHO, were submitted to fibrinolytic therapy, and one underwent surgery. The follow-up study showed dissolution of the thrombus in three of those with SK and in the one with surgical treatment. The initial ECHO study showed five out of 7 patients with increased RVDD, 5/7 patients with abnormal IVS motion, and all of them with decreased AcT (64 +/- 16 ms). The PSP was 64.4 +/- 22.8 mmHg by ECHO, versus 75.4 +/- 24.03 mmHg by angiography (r = 0.78; p = 0.11). There was a reduction of the RVDD (30 +/- 5.02 to 23 +/- 2.2) and an increased of the AcT (50 +/- 10.8 to 106.67 +/- 16) at the serial examination. The ECHO study is an important tool for the diagnosis of PE, informing about pulmonary pressure, presence and position of thrombus, and treatment results.


[Ulcerative colitis in hairy cell leukemia. A case report].
Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder sometimes affected by autoimmune complications. The use of human recombinant alpha-interferon (alpha-IFN) in the therapy of this disease may also lead to the development or the exacerbation of autoimmune pathology. We report the case of a HCL patient, treated with IFN, who developed ulcerative colitis two years later and we discuss the possible correlations of these two entities.


The GNB3 C825T polymorphism and depression among subjects with alcohol dependence.
The T allele of the C825T polymorphism in the G-protein beta(3) subunit gene (GNB3) is related to the increase of signal transduction by the G-protein. G-proteins are intermediary paths in signal transduction from receptors involved in mood regulation and substance dependence. We studied the C825T polymorphism in individuals with (i) alcohol and nicotine dependence (n = 109), (ii) nicotine dependence only (n = 117) and (iii) non-dependent controls (n = 108). We also tested for possible associations with psychiatric comorbidities among alcohol-dependent individuals. No differences were detected for allele and genotype frequencies in individuals with or without dependencies. Alcohol-dependent individuals with the heterozygous genotype presented more frequently major depressive disorder (chi(2) = 12.34; p = 0.002). These findings, taken together with other studies suggesting an influence of the C825T polymorphism in major depressive disorder, support the hypothesis of the involvement of G-proteins in mood regulation.


Characteristics of listener sensitivity to talker-specific phonetic detail.
Previous research shows that listeners are sensitive to talker differences in phonetic properties of speech, including voice-onset-time (VOT) in word-initial voiceless stop consonants, and that learning how a talker produces one voiceless stop transfers to another word with the same voiceless stop [Allen, J. S., and Miller, J. L. (2004). J. Acoust. Soc. Am. 115, 3171-3183]. The present experiments examined whether transfer extends to words that begin with different voiceless stops. During training, listeners heard two talkers produce a given voiceless-initial word (e.g., pain). VOTs were manipulated such that one talker produced the voiceless stop with relatively short VOTs and the other with relatively long VOTs. At test, listeners heard a short- and long-VOT variant of the same word (e.g., pain) or a word beginning with a different voiceless stop (e.g., cane or coal), and were asked to select which of the two VOT variants was most representative of a given talker. In all conditions, which variant was selected at test was in line with listeners' exposure during training, and the effect was equally strong for the novel word and the training word. These findings suggest that accommodating talker-specific phonetic detail does not require exposure to each individual phonetic segment.


Angiographic analysis of blood flow modification in cerebral aneurysm models with a new asymmetric stent.
We have built new asymmetric stents for minimally invasive endovascular treatment of cerebral aneurysms. Each asymmetric stent consists of a commercial stent with a micro-welded circular mesh patch. The blood flow modification in aneurysm-vessel phantoms due to these stents was evaluated using x-ray angiographic analysis. However, the density difference between the radiographic contrast and the blood gives rise to a gravity effect, which was evaluated using an initial optical dye-dilution experiment. For the radiographic evaluations, curved-vessel phantoms instead of simple straight side-wall aneurysm phantoms were used in the characterization of meshes/stents. Six phantoms (one untreated, one treated with a commercial stent, and four treated with different asymmetric stents) with similar morphologies were used for comparison. We calculated time-density curves of the aneurysm region and then calculated the peak value (Pk) and washout rate (1/τ) after analytical curve fitting. Flow patterns in the angiograms showed reduction of vortex flow and slow washout in the dense mesh patch treated aneurysms. The meshes reduced Pk down to 21% and 1/τ down to 12% of the values for the untreated case. In summary, new asymmetric stents were constructed and their evaluation demonstrates that they may be useful in the endovascular treatment of aneurysms.


Camouflage therapy.
Camouflage cream was introduced over 50 years ago to assist in the rehabilitation of severely burned pilots injured during World War II. Today, camouflage therapy can be used to conceal discoloration such as postoperative bruising and erythema. Pre and postoperative teaching regarding camouflage therapies are very important parts of the healing process, and dermatology nurses can play a vital role in the teaching and healing process.


Challenges of emerging adulthood-transition from paediatric to adult diabetes.
Diabetes mellitus is a complex condition with far reaching physical, psychological and psychosocial effects. These outcomes can be significant when considering the care of a youth transferring from paediatric through to adult diabetes services. The art of mastering a smooth care transfer is crucial if not pivotal to optimising overall diabetic control. Quite often the nature of consultation varies between the two service providers and the objectives and outcomes will mirror this. The purpose of this review is to analyse the particular challenges and barriers one might expect to encounter when transferring these services over to an adult care provider. Particular emphasis is paid towards the psychological aspects of this delicate period, which needs to be recognised and appreciated appropriately in order to understand the particular plights a young diabetic child will be challenged with. We explore the approaches that can be positively adopted in order to improve the experience for child, parents and also the multi- disciplinary team concerned with the overall delivery of this care. Finally we will close with reflection on the potential areas for future development that will ultimately aim to improve long-term outcomes and experiences of the young adolescent confronted with diabetes as well as the burden of disease and burden of cost of disease.


Performance of median kriging with robust estimators of the variogram in outlier identification and spatial prediction for soil pollution at a field scale.
Median kriging with robust estimators of the variogram has been proposed in literature to reduce the influences of outliers in spatial data of soil pollution, because median kriging can utilize outliers in spatial prediction and robust estimators can overcome the bias caused by outliers. However, performance of the method at a field scale remains unknown. This study compared the method in two case studies of soil Pb pollution with two other commonly used methods for outlier identification, including box-plot and standardized kriging prediction error (SKPE), and with two classical geostatistical approaches for spatial prediction, including kriging with and without outliers. One case was based on data with 359 samples collected in an area of 14.5km2 in Jura, Swiss. The other was based on data with 242 samples collected in an area of 2.8km2 in Zhuzhou, China. Results showed that the method identified both global and local outliers, while the method did not identify all global outliers based on the box-plot. For the Jura data which were more seriously affected by outliers than the Zhuzhou data, the method identified 49 outliers, sharing 39 with SKPE which identified a total of 46 outliers. For the Zhuzhou data, the method found just three outliers, much fewer than the 12 outliers identified by SKPE. In the case of Jura, kriging prediction with outliers winsorized by the method was negligibly more accurate than prediction without outliers identified by SKPE, e.g., 0.15% in terms of root mean square error (RMSE). However, in the case of Zhuzhou, the former prediction was slightly less accurate than the latter, e.g., 2.39% in terms of RMSE. This study suggested that the method performed well for data which were seriously affected by outliers, but not so well for data slightly affected by outliers.


Application of the Digital Articulator in Surgery-First Approach.
Orthognathic surgery with surgery-first concept inevitably leads to an increase in posterior vertical dimension and anterior mandibular movement, causing a relapse. This case report introduces a digital technique for predictable surgical outcome in mandibular setback with the surgery-first orthognathic concept using digital articulator. Intraoral scans and a digital articulator were used to simulate the mandibular position after surgery and to predict postoperative increase in vertical dimension and its expecting forward movement of mandibile. This was incorporated in surgical planning. Sequential cone-beam computed tomography evaluation showed stable condylar position at 3 and 6 months after surgery. Thus, a digital articulator can be used to simulate the surgical outcome and to predict postsurgical increase in vertical dimension for better treatment planning.


Efficacy and safety of bevacizumab in Turkish patients with metastatic and recurrent cervical cancer.
To evaluate the efficacy of bevacizumab a monoclonal, antivascular endothelial growth factor antibody in combination with cytotoxic chemotherapy in Turkish patients with recurrent and metastatic cervical cancer. Data of 64 patients with metastatic or recurrent cervical cancer, receiving bevacizumab with first-line cisplatin or carboplatin and paclitaxel chemotherapy between 2013 and 2017 were retrospectively evaluated. The mean age of the patients was 49 years (range, 28-68), the median follow-up time was 12 months (range, 2-53), the median progression-free survival (PFS) was eight months, and the median overall survival (OS) was 23 months. All 64 patients received a median of 6 (range, 1-12) bevacizumab and 6 (range, 2-12) chemotherapy cycles. The chemotherapy regimens used with bevacizumab were cisplatin and paclitaxel in 31 (48%) and carboplatin and paclitaxel in 33 (52%) patients. The survival in patients treated with bevacizumab and cisplatin plus paclitaxel was better-particularly in patients with no previous cisplatin-based radiosensitizer therapy-than those treated with carboplatin, paclitaxel, and bevacizumab (p=0.023). The bevacizumab dose was 7.5 mg/kg in 30 patients (47%) and 15 mg/kg in 34 patients (53%) every 21 days. No significant difference was reported in the OS and the PFS between the two groups. While the most common all-grades adverse events were nausea, neutropenia, anemia, and peripheral sensory neuropathy, the most common grade ≥3 adverse events were neutropenia, anemia, and peripheral sensory neuropathy. Adding bevacizumab to platinum and paclitaxel chemotherapy in a case of metastatic or recurrent cervical cancer is an effective and tolerable treatment for Turkish patients.


Exchange transfusion with synthetic oxygen-carrying plasma protein "albumin-heme" into an acute anemia rat model after seventy-percent hemodilution.
Recombinant human serum albumin (rHSA) incorporating the synthetic heme "albumin-heme" is an oxygen-carrying plasma protein that has the potential to be a red blood cell substitute. The physiological responses to a 30% exchange transfusion with two types of albumin-heme (rHSA-FecycP, rHSA-FepivP) solutions after 70% isovolemic hemodilution with 5 g/dL rHSA were investigated using anesthetized rats. The circulation parameters, blood parameters, renal cortical oxygen pressure (pO2), and muscle tissue pO2 were carefully monitored for 60 min after the injection. The declined mean arterial pressure and the mixed venous partial pO2 significantly recovered to 70.8 and 91.9% of the basal values by intravenous infusion of albumin-hemes, respectively. The lowered renal cortical pO2 also increased, indicating oxygen transport by this synthetic hemoprotein. The administration of albumin-heme into the acute anemia rat model after hemorrhage improved the circulatory volume and resuscitated the shock state. Both rHSA-FecycP and rHSA-FepivP transported oxygen through the body.


[The simple method of direct estimation of infectious process in mice and rats aerogenically infected with influenza virus].
Multiplication of influenza virus in laboratory animals (mice and rats) after aerogenic inoculation was recorded directly (by the agent accumulation in the lungs and trachea) and indirectly (by interferon concentration in the lungs of mice). Thermal inactivation of influenza virus in chick embryo allantoic fluid was observed (by 4.5-6 Ig within 48 h at 37 degrees C). The authors claim that influenza (strain A/Aichi/2/68) infection in the respiratory tract of mice and rats can be experimentally validated by inoculation of chick embryos with 10 and 20% mouse or rat lung homogenate (undiluted or diluted 10-fold) or with 1 and 5% mouse and rat trachea homogenate, respectively, 48 h after aerogenic inoculation of animals, and the virus AID50 be thus determined.


Suppressed severity of collagen-induced arthritis by in vivo transfection of nuclear factor kappaB decoy oligodeoxynucleotides as a gene therapy.
In both rheumatoid arthritis and collagen-induced arthritis (CIA), the nuclear factor kappaB (NF-kappaB) transcription factor plays a pivotal role in the coordinated transactivation of many cytokines related to pathogenesis. This study investigated whether synthetic double-stranded DNA that show a high affinity for NF-kappaB could be introduced in vivo as "decoy" cis elements to bind the transcription factor and block the activation of such proinflammatory cytokine genes as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha), and thus suppress the severity of joint destruction. NF-kappaB decoy oligonucleotides (ODN) were introduced by an intraarticular injection into the bilateral hind ankle joints of CIA rats using the hemagglutinating virus of Japan (HVJ)-liposome method. Joint destruction was evaluated by histology and radiography. IL-1 and TNFalpha levels were assessed by enzyme-linked immunosorbent assay and Northern blot analysis. Using the HVJ-liposome method, the presence of fluorescein isothiocyanate-labeled ODN in the synovium was confirmed until 28 days after intraarticular injection. In vivo transfection of NF-kappaB decoy ODN by an intraarticular injection into CIA rats decreased the severity of hind-paw swelling. Histologic and radiographic studies showed a marked suppression of joint destruction treated by NF-kappaB decoy ODN transfection. This treatment method also suppressed the production of IL-1 and TNFalpha in the synovium of arthritic joints. The present results demonstrate that administration of NF-kappaB decoy ODN in arthritic joints of rats with CIA led to an amelioration of arthritis. These findings suggest that intraarticular transfection of NF-kappaB decoy ODN may provide a useful therapeutic approach for the treatment of inflammatory arthritis.


High performance of N-alkoxycarbonyl-imines in triethylborane-mediated tin-free radical addition.
Triethylborane-mediated tin-free radical alkylation of N-alkoxycarbonyl-imines, such as N-Boc-, N-Cbz-, and N-Teoc-imines, proceeded smoothly at a low temperature (-78 to -20 °C) to give the corresponding adducts in high yield. Although the formation of isocyanate was the major unfavorable reaction at room temperature, a one-pot conversion of N-Boc-imine to N-ethoxycarbonyl-adduct was possible through the corresponding isocyanate generated in situ. The higher performance of N-alkoxycarbonyl-imine than those of N-Ts- and N-PMP-imines is rationalized by a moderate electron-withdrawing character of an alkoxycarbonyl group that makes both addition of alkyl radical and trapping of the resulting aminyl radical by triethylborane efficiently fast.


Endoscopic Removal Through a Gastrostomy of Swallowed Acupuncture Needles.
Acupuncture is a representative treatment field in oriental medicine that is used widely in various medical conditions. Although acupuncture is considered a safe procedure, it can cause complications. This paper reports the case of a 44-year-old quadriplegic woman who received a percutaneous gastrostomy (PEG) tube and was referred for the endoscopic removal of swallowed acupuncture needles. The needles were removed successfully by endoscopy through the PEG tube using the rendezvous technique without significant complications.


Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation.
Hypoxia-inducible factor 1 (HIF-1), the major transcription factor specifically activated during hypoxia, regulates genes involved in critical aspects of cancer biology, including angiogenesis, cell proliferation, glycolysis and invasion. The HIF-1a subunit is stabilized by low oxygen, genetic alteration and cobaltous ions, and its over-expression correlates with drug resistance and increased cancer mortality in various cancer types, therefore representing an important anticancer target. Zinc supplementation has been shown to counteract the hypoxic phenotype in cancer cells, in vitro and in vivo, hence, understanding the molecular pathways modulated by zinc under hypoxia may provide the basis for reprogramming signalling pathways for anticancer therapy. Here we performed genome-wide analyses of colon cancer cells treated with combinations of cobalt, zinc and anticancer drug and evaluated the effect of zinc on gene expression patterns. Using Principal Component Analysis we found that zinc markedly reverted the cobalt-induced changes of gene expression, with reactivation of the drug-induced transcription of pro-apoptotic genes. We conclude that the hypoxia pathway is a potential therapeutic target addressed by zinc that also influences tumor cell response to anticancer drug.


Annoyance from industrial noise: indicators for a wide variety of industrial sources.
In the study of noises generated by industrial sources, one issue is the variety of industrial noise sources and consequently the complexity of noises generated. Therefore, characterizing the environmental impact of an industrial plant requires better understanding of the noise annoyance caused by industrial noise sources. To deal with the variety of industrial sources, the proposed approach is set up by type of spectral features and based on a perceptive typology of steady and permanent industrial noises comprising six categories. For each perceptive category, listening tests based on acoustical factors are performed on noise annoyance. Various indicators are necessary to predict noise annoyance due to various industrial noise sources. Depending on the spectral features of the industrial noise sources, noise annoyance indicators are thus assessed. In case of industrial noise sources without main spectral features such as broadband noise, noise annoyance is predicted by the A-weighted sound pressure level L(Aeq) or the loudness level L(N). For industrial noises with spectral components such as low-frequency noises with a main component at 100 Hz or noises with spectral components in middle frequencies, indicators are proposed here that allow good prediction of noise annoyance by taking into account spectral features.


Gender and the capacity of women with NIDDM to implement medical advice.
This qualitative study of women with non-insulin dependent diabetes mellitus (NIDDM) examined constructions of their diabetes management and socio-familial relationships as potential sources of support. Semi-structured interview data was collected from 16 women. The transcripts were analysed with the aim of examining the ways in which gender relations structured women's accounts of health-related behaviours. Women talked about themselves as wives, mothers, being pregnant and parenting, and friends of other women in ways that demonstrated how caring for others impeded their capacity to care for themselves. Meeting the food preferences of husbands and dietary requirements of diabetic husbands were dominant themes in women's accounts of marriage, and in various ways women justified their husbands' lack of support. Furthermore, the care of others during pregnancy and parenting was also an obstacle to women caring for themselves. An awareness of the gender politics inherent within social and family contexts is crucial to improving the effectiveness of medical advice for diabetes management.


Effect of leaf water deficit on stomatal and nonstomatal regulation of net carbon dioxide assimilation.
The effect of leaf water deficit on net CO(2) assimilation was studied under two conditions: in one, the stomata were allowed to contribute to the regulation of CO(2) assimilation; in the other, air was forced through the leaf at a constant rate to overcome the effects of change in stomatal resistance accompanying changes in leaf water deficit. When the stomata were allowed to regulate the gaseous diffusive resistance of the leaf, CO(2) assimilation decreased with increasing leaf water deficit. However, when air was forced through the leaf, the rate of assimilation was not inhibited by increasing leaf water deficit. The results indicate that the inhibition of net CO(2) assimilation with increasing leaf water deficit is a consequence of an increase in the diffusive resistance to gas exchange and not of a change in apparent mesophyll resistance.


Regional assignment of two genes of the human branched-chain alpha-keto acid dehydrogenase complex: the E1 beta gene (BCKDHB) to chromosome 6p21-22 and the E2 gene (DBT) to chromosome 1p31.
Maple syrup urine disease (MSUD) is caused by the deficiency of the mitochondrial branched-chain alpha-keto acid dehydrogenase complex. The multienzyme complex is a macromolecule (Mr 4 X 10(6] consisting of at least six distinct subunits. In this study, the human E1 beta gene (BCKDHB) has been localized to human chromosome 6 by hybrid somatic cell analysis, and regionally assigned to chromosome bands 6p21-22 by in situ hybridization. The E2 gene (DBT), which was previously localized to chromosome 1, is regionally assigned to the chromosome band 1p31 also by in situ hybridization. Localization of the E1 beta gene to chromosome 6p21-22 assigns another major human disease locus to a region that contains several important genes, including the major histocompatability complex, tumor necrosis factor, and heat-shock protein HSP70. Mapping of the E1 beta and the E2 genes may provide information for the linkage analysis of MSUD families with mutations in these two loci.


The nitrogen nutrition potential of arable soils.
Soils are an important source of nitrogen in many of the world's cropping systems. Especially in low-input production systems, nitrogen release from soil organic matter turn-over is the major part of the crop's nitrogen supply and research suggests that this process is significantly affected by changes in climate. The knowledge of the amount of nitrogen being accountable for crop nutrition is purely empirical in many production areas in the world and data as a foundation of global-scale climate change and food security assessments is scarce. Here we demonstrate that nitrogen mineralisation in general follows similar rules as for carbon, but with different implications for agricultural systems. We analysed 340 data sets from previously published incubation experiments for potential nitrogen mineralisation which covered a large range of soils and climate conditions. We find that under warm and all-year humid conditions the share of potentially mineralisable nitrogen in the soil's total nitrogen is significantly smaller than in dry or temperate environments. We conclude that - despite relatively high soil nitrogen stocks - soil-borne nitrogen supply for crop production is very low in tropical and humid subtropical environments, which is a critical piece of information for global assessments of agricultural production and food security.


An analytical derivation of a popular approximation of the Voigt function for quantification of NMR spectra.
The approximation of the Voigt line shape by the linear summation of Lorentzian and Gaussian line shapes of equal width is well documented and has proved to be a useful function for modeling in vivo (1)H NMR spectra. We show that the error in determining peak areas is less than 0.72% over a range of simulated Voigt line shapes. Previous work has concentrated on empirical analysis of the Voigt function, yielding accurate expressions for recovering the intrinsic Lorentzian component of simulated line shapes. In this work, an analytical approach to the approximation is presented which is valid for the range of Voigt line shapes in which either the Lorentzian or Gaussian component is dominant. With an empirical analysis of the approximation, the direct recovery of T(2) values from simulated line shapes is also discussed.


[Reticulocyte as indication of the erythroid hematopoiesis: reticulocyte fractions in peripheral blood and bone marrow].
Reticulocyte fractions of peripheral blood and bone marrow were measured for hematological disease in 235 patients using automated fluorescent reticulocyte analysis of Sysmex R-3000. The comparison with R-3000 and the manual method of bone marrow measurement showed an excellent agreement with a correlation coefficient of r = 0.933. In the ratio of reticulocyte fractions of marrow blood and peripheral blood, the marrow blood rate of reticulocytes, HFR, MFR, and LFR was 3.3, 6.2, 1.6, and 0.9 times higher than the peripheral blood rate, respectively. Cases in which the marrow reticulocyte rate was over ten times higher than the peripheral blood rate were observed in MDS and megaloblastic anemia at ratio of 55% and 100%, respectively. These findings suggest ineffective hematopoiesis in bone marrow. Immature reticulocyte fraction(10% or more) showed an excellent agreement with granulocyte(500/microliter or more) as an indication of the engraftment of allotransplantation of bone marrow, in which the analysis of reticulocyte fractions showed a useful indication of engraftment. In cases of death after bone marrow transplantation unlike in survivors, reticulocyte fractions decreased after engraftment.


Sequence analysis of Tnf as a candidate for Idd16.
Linkage analysis and congenic mapping have localized 18 loci (Idd1-18) that contribute to the development of autoimmune type 1 diabetes in the nonobese diabetic (NOD) mouse. By using a congenic NOD strain which possesses recombinant MHC from a closely related CTS strain, a susceptible region (Idd16) was mapped to the segment adjacent to, but distinct from class II A and E genes (Idd1). The tumor necrosis factor alpha gene (Tnf), which is located within the Idd16 region, has been suspected to be a candidate gene for type 1 diabetes in the NOD mouse. Although the protein-coding region in Tnf has been sequenced in the NOD mouse and its related strains, the complete upstream region (approximately 1400 bp, including the 5'-untranslated region) has not yet been studied. To study the possible contribution of the transcriptional regulation of Tnf to susceptibility to type 1 diabetes, we determined the complete nucleotide sequences of the NOD strain and its related strain, CTS, in comparison with the non-diabetic control strain, C57BL/6. The nucleotide sequence of the 5'-upstream region in the NOD mouse was identical to that in the C57BL/6 mouse, but different from that in the CTS mouse. In particular, a C to A substitution at position 3408 in the CTS mouse creates a new GATA family binding site, which may be responsible for the lower incidence of type 1 diabetes in the NOD. CTS-H-2 congenic strain despite the presence of the same class II MHC.


What Is the Role of Accreditation in Achieving Medical School Diversity?
Diversity standards in medical education accreditation do not guarantee diversity but do stimulate schools' activities to recruit and retain diverse students and faculty. The Liaison Committee on Medical Education's (LCME's) accreditation standard addressing medical school diversity neither mandates which categories of diversity medical schools must use nor defines quantitative outcomes they should achieve. Rather, each medical school is required to (1) identify diversity categories that motivate its mission and reflect its environment and (2) use those categories to implement programs to promote diverse representation of students and faculty. When the LCME assesses each medical school's compliance with these requirements, it considers single point-in-time diversity numbers, trends in student and faculty diversity, and outcomes of programs implemented by the school to promote diversity in the categories it identifies as key to its mission.


Simple and novel technique of using lampblack soot as a corneal tattoo for disfiguring corneal opacities.
The aim of this study was to report a series of corneal tattooing in three eyes of three patients with disfiguring corneal scar and no visual potential, which underwent the procedure using the lampblack prepared in the operating room (OR), and to describe the novel technique of lampblack preparation for the surgery. The depth of corneal opacity was carefully assessed and a superficial lamellar pocket was made by lamellar separation using corneal dissectors, following which the prepared lampblack soot using materials available in the OR was deposited in the pocket. At a mean follow-up of 6 months, all the eyes had a stable corneal surface with an acceptable cosmetic outcome. Corneal tattoo using lampblack gives a satisfactory cosmetic result with good patient satisfaction and improved quality of life in the eyes with disfiguring corneal scar.


Thrombin generation in morbid obesity: significant reduction after weight loss.
Patients with morbid obesity (MO; body mass index > 40 kg m(-2)) suffer from an increased risk of cardiovascular disease, stroke, venous thromboembolism and all-cause mortality. Because weight loss by bariatric surgery reduces cardiovascular and all-cause mortality, we hypothesized that the plasmatic clotting system might be involved in cardiovascular risk. Thirty-six MO patients [mean age 42 (+/-13) years; 29 female) were investigated before and 2 years after bariatric surgery. Thrombin generation was measured with a commercially available assay (Technothrombin-TGA,Technoclone). Metabolic parameters and parameters of the hemostatic system, such as tissue factor (TF), TF pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1) and prothrombinfragment 1.2 (F1.2), were determined. To investigate associations of changing parameters, deltas were calculated. Metabolic parameters improved with a mean weight loss of 41 (+/-19) kg. Postoperatively, the lag phase was significantly extended compared with preoperative values [median (25th-75th percentile), 7 (4-12) vs. 12 (7-19) min, P = 0.005]. Peak thrombin decreased after weight loss from 345 (232-455) to 282 (111-388) nm (P = 0.015) and the area under the curve from 3962 (3432-5023) to 3227 (2202-4030) nm thrombin (P < 0.001). TF, PAI-1 and F1.2 significantly decreased after weight loss. Analyses of the deltas showed a significant correlation between peak thrombin and total cholesterol (r = 0.50), triglycerides (r = 0.46) and HbA1c (r = 0.55). Moreover, an inverse correlation was found between insulin resistance and the lag phase (r = -0.46). Thrombin generation, a marker of the overall coagulation potential, decreased significantly with weight reduction. This might, at least in part, explain the decreased risk of cardiovascular disease after bariatric surgery.


Let's cross-link: diverse functions of the promiscuous cellular transglutaminase factor XIII-A.
Essentials Plasma Factor XIII, a heterodimer of A and B subunits FXIIIA2 B2 , is a transglutaminase enzyme with a well-established role in haemostasis. Cells of bone marrow and mesenchymal lineage express the FXIII-A gene (F13A1) that encodes the cellular form of the transglutaminase, a homodimer of the A subunits, FXIII-A. FXIII-A was presumed to function intracellularly, however, several lines of evidence now indicate that FXIII-A is externalised by an as yet unknown mechanism This review describes the mounting evidence that FXIII-A is a diverse transglutaminase with many intracellular and extracellular substrates that can participate in an array of biological processes SUMMARY: Factor XIII is a tranglutaminase enzyme that catalyzes the formation of ε-(γ-glutamyl)lysyl isopeptide bonds in protein substrates. The plasma form, FXIII-A2 B2 , has an established function in hemostasis, where its primary substrate is fibrin. A deficiency in FXIII manifests as a severe bleeding diathesis, underscoring its importance in this pathway. The cellular form of the enzyme, a homodimer of the A-subunits, denoted FXIII-A, has not been studied in as extensive detail. FXIII-A was generally perceived to remain intracellular, owing to the lack of a classical signal peptide for its release. In the last decade, emerging evidence has revealed that this diverse transglutaminase can be externalized from cells, by an as yet unknown mechanism, and can cross-link extracellular substrates and participate in a number of diverse pathways. The FXIII-A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage, notably megakaryocytes, monocytes/macrophages, dendritic cells, chrondrocytes, osteoblasts, and preadipocytes. The biological processes that FXIII-A is coupled with, such as wound healing, phagocytosis, and bone and matrix remodeling, reflect its expression in these cell types. This review describes the mounting evidence that this cellular transglutaminase can be externalized, usually in response to stimuli, and participate in extracellular cross-linking reactions. A corollary of being involved in these biological pathways is the participation of FXIII-A in pathological processes. In conclusion, the functions of this transglutaminase extend far beyond its role in hemostasis, and our understanding of this enzyme in terms of its secretion, regulation and substrates is in its infancy.


The Relationship Between Sacral Slope and Symptomatic Isthmic Spondylolysis in a Cohort of High School Athletes: A Retrospective Analysis.
Spondylolysis with and without anterolisthesis is the most common cause of structural back pain in children and adolescents, but few predictive factors have been confirmed. An association between abnormal sacropelvic orientation and both spondylolysis and spondylolisthesis has been supported in the literature. Sacral slope and other sacropelvic measurements are easily accessible variables that could aid clinicians in assessing active adolescents with low back pain, particularly when the diagnosis of spondylolysis is suspected. To examine the relationship between sacral slope and symptomatic spondylolysis in a cohort of active adolescents. Case-control retrospective study. Academic outpatient physiatry practice. Seventy-four patients of primarily adolescent age (between 12 and 22 years old) with a chief complaint of low back pain and presence of lateral radiographs of the lumbar spine were enrolled. Cases (n = 37) were defined as subjects with evidence of spondylolysis on both radiograph and magnetic resonance imaging of the lumbar spine. Controls (n = 37) were defined as subjects without spondylolysis. Using a single sagittal radiograph, taken with the patient standing, a fellowship-trained interventional spine physiatrist measured the sacral slope of each subject (angle between the superior plate of S1 and a horizontal reference on sagittal imaging of the lumbosacral spine). Ages and genders were collected from medical records. The primary outcome was mean sacral slope. Mean sacral slope of cases was compared with mean sacral slope of controls with the Student t-test. Ages ranged from 12 to 22 for both groups, with no significant differences in age between the groups (cases: 16.8 ± 2.3 years; controls: 17.7 ± 2.7 years). The patients with spondylolysis (cases) consisted of 29 male and 8 female patients, whereas those without spondylolysis (controls) consisted of 15 male and 21 female patients (gender details for 1 patient were not available). The mean sacral slope among cases was 42.4°, whereas the mean sacral slope among controls was 37.4°. The difference achieved significance (P = .014). The interdependence of positional parameters, such as sacral slope, with anatomic parameters, such as pelvic incidence, can affect lumbar lordosis and therefore upright positioning and loading of the spine. Sacral slope may be an important variable for clinicians to consider when caring for young athletes with low back pain, particularly when the index of suspicion for spondylolysis is high. IV.


Drug release from irradiated PLGA and PLLA multi-layered films.
Poly(lactide-co-glycolic acid) (PLGA) and poly(L-lactide) (PLLA) films are widely studied for various biomedical applications. Because of their use for drug delivery, achieving controlled release from these biodegradable films has become an area of intense research. The objective of this study is therefore to investigate how PLGA and PLLA films fabricated through an irradiated-multi-layer approach can be a viable technique to achieve controlled drug delivery. In this study, lidocaine base (lido-base) and lidocaine salt (lido-salt) were used as model hydrophobic and hydrophilic drugs, respectively. Results show that multi-layer PLGA underwent pseudo surface degradation, while multi-layer PLLA degraded to a lesser extent over the same study period. Triphasic release was observed for lido-base, whereas lido-salt was released through a biphasic profile, from both polymer systems. The two dominating release phases for both drugs were diffusion and zero-order release, where the latter is characterized by the onset of mass loss. It was shown that PLGA had a shorter diffusion phase and a longer zero-order phase, while the contrary was true for PLLA. This difference was due to the faster degradation for PLGA. In conclusion, the hydrophilic gradient induced from an irradiated-multi-layer film system shows potential for controlled and sustained release of drugs.


Identification and functional study of cytokines and chemokines involved in tumorigenesis.
Tumorigenesis may be affected by various cellular components in the tumor cells and/or by tumor microenvironmental factors. Cytokines, including chemokines (chemotactic cytokines) are polypeptides or small soluble proteins generated by leukocytes and non-leukocytes, including cancer cells and stromal cells, for example, fibroblasts, mesenchymal stem cells (MSCs) and epithelial cells. Cytokines exert their functions on the cells that secrete them, on nearby cells, or on distant cells. Chemokines have expanded beyond their initial roles in impinging on every aspect of the immune system and leukocyte biology. They display multifunctional effects for regulating angiogenesis, tumor cell proliferation and apoptosis, mediating tumor cell metastasis in an organ-specific manner. This review will focus on the structural and functional aspects of chemokines as well as the roles that cytokines and their receptors play in angiogenesis, tumor invasion and metastasis, and discuss their potential value as important therapeutic targets for intervention in cancer.


Empiric, broad-spectrum antibiotic therapy with an aggressive de-escalation strategy does not induce gram-negative pathogen resistance in ventilator-associated pneumonia.
Early, empiric, broad-spectrum antibiotics followed by de-escalation to pathogen-specific therapy is the standard of care for ventilator-associated pneumonia (VAP). In our surgical intensive care unit (SICU), imipenem-cilastatin (I-C) in combination with tobramycin (TOB) or levofloxacin (LEV) has been used until quantitative bronchoalveolar lavage results are finalized, at which time de-escalation occurs to pathogen-specific agents. With this practice, however, alterations in antimicrobial resistance remain a concern. Our hypothesis was that this strict regimen does not alter antimicrobial susceptibility of common gram-negative VAP pathogens in our SICU. After Institutional Review Board approval, a retrospective review of SICU-specific antibiograms was performed for the sensitivities of common gram-negative VAP pathogens. Time periods were defined as early (January-June 2005) and late (July-December 2006). Chart review of empiric and de-escalation antibiotic usage was obtained. Data were collated, and statistical significance was assessed with the chi-square test using the on-line Simple Interactive Statistical Analysis tool. Imipenem-cilastatin was used 198 times for empiric VAP coverage (811 patient-days), whereas TOB and LEV were given a total of 149 (564 patient-days) and 61 (320 patient-days) times, respectively. Collectively, the susceptibility of gram-negative organisms to I-C did not change (early 91.4%; late 97%; p = 0.33). Individually, non-significant trends to greater sensitivity to I-C were noted for both Pseudomonas aeruginosa (early 85.7%; late 90.9%; p = 0.73) and Acinetobacter baumannii (early 80%; late 100%; p = 0.13). Further, both TOB (early 77.1%; late 70.0%; p = 0.49) and LEV (early 74.3%; late 70.0%; p = 0.67) were found to maintain their susceptibility profiles. The frequency of resistant gram-positive VAPs was unchanged during the study period. Our de-escalation compliance (by 96 h) was 78% for I-C, 77.2% for TOB, and 59% for LEV. When infections requiring I-C were removed from the analysis, de-escalation compliance was improved to 92%. In our SICU, early, empiric broad-spectrum VAP therapy followed by de-escalation to pathogen-specific agents did not alter antimicrobial resistance and is a valid practice. Further, our compliance with de-escalation practices was higher than published rates.


Pregnancy outcomes among farming households of Nueva Ecija with conventional pesticide use versus integrated pest management.
A retrospective cohort study was conducted to compare pregnancy outcomes in farming households that used pesticides conventionally with those that practiced integrated pest management (IPM) in Nueva Ecija, Philippines, in the period 1998-1999. Conventional pesticide users (CPUs) were defined as pesticide appliers who used pesticides routinely and regularly, whereas users of IPM were those who used pesticides as necessary, and on economically injured crop areas only. The data sets were subjected to the chi-square test of association, Fisher's exact probability test, and logistic regression analysis. At a significance level at 0.05, spontaneous abortion occurred significantly more often among the 345 CPU households than among the 331 IPM households (adjusted risk ratio 6.17). Likewise, birth defects were significantly more common in the CPU group (adjusted risk ratio 4.56). Thus, people of reproductive age who plan to have children should avoid any use of pesticides.


Red-far red reversibility of anthocyanin synthesis in dark-grown and light-pretreated seedlings.
The rate of escape from red-far red reversibility for anthocyanin synthesis is lower in dark-grown than in light-pretreated seedlings of Brassica oleracea L. Red Acre, Secale cereale L. Cougar, and Lycopersicon esculentum Mill. Beefsteak. This observation is consistent with the suggestion that there might be two pools of phytochrome, a labile one, characterized by fast disappearance of phytochrome-far-red absorbing form, and a stable one, characterized by slow disappearance of phytochrome-far-red absorbing form, and that the proportion between the two pools might be different in dark-grown and light-pretreated seedlings.


Functional and structural outcome after arthroscopic full-thickness rotator cuff repair: single-row versus dual-row fixation.
The purpose of this study was to compare the functional as well as the structural outcomes of single-row and dual-row fixation after arthroscopic full-thickness rotator cuff repair. Retrospective cohort study. A consecutive series of 80 shoulders in 78 patients with full-thickness rotator cuff tears was evaluated using the rating scale of the University of California Los Angeles (UCLA) and the shoulder index of the American Shoulder and Elbow Surgeons (ASES) at an average of 35 months (range, 24 to 60 months) after arthroscopic rotator cuff repair. Thirty-nine shoulders were repaired using the single-row technique and 41 shoulders using the dual-row technique. Postoperative cuff integrity was determined through magnetic resonance imaging and was classified into 5 categories: type I, sufficient thickness with homogenously low intensity; type II, sufficient thickness with partial high intensity; type III, insufficient thickness without discontinuity; type IV, presence of a minor discontinuity; type V, presence of a major discontinuity. The average UCLA score improved significantly to 32.4 in the single-row and to 33.1 in the dual-row group. The ASES shoulder index improved significantly to 93.0 in the single-row group and to 94.6 in the dual-row group. However, there was no statistical difference between the groups in the postoperative scores. Postoperative MRI revealed 11 type I, 6 type II, 12 type III, 4 type IV, and 6 type V in the single-row group, and 22 type I, 8 type II, 7 type III, 4 type IV, and no type V in the dual-row group. A statistical difference was observed between the groups (P < .01). Arthroscopic rotator cuff repair yielded successful functional outcomes without significant difference between single and dual-row fixation techniques. However, dual-row repairs excelled in structural outcome over the single-row technique. Level III.


Prevalence of metabolic syndrome in obese Turkish children and adolescents.
The aim of our study was to assess the prevalence of metabolic syndrome and the other metabolic features in obese children. We have studied 169 obese children and adolescents (body mass index>95th percentile), 100 prepubertal and 69 pubertal, aged between 7 and 18 years. Each subject was submitted to an oral glucose tolerance test. The diagnosis of impaired glucose tolerance, type 2 diabetes and metabolic syndrome were defined according to modified WHO criteria adapted for children. Metabolic syndrome was found in 27.2%, with a significantly higher rate among adolescents aged 12-18 years (37.6%) than among children aged 7-11 years (20%) (p < 0.001). There were no significant differences in the prevalence of metabolic syndrome by sex. The prevalences of insulin resistance, glucose intolerance and type 2 diabetes were 29, 19 and 2% among prepubertal children and 56.5, 27.5 and 4.3% among pubertal group, respectively. The prevalence of fasting hyperinsulinemia in pubertal group was significantly higher than prepubertal children (p < 0.001). Hyperinsulinemia was also more frequent in pubertal children with significant difference (20% versus 43.7%, p < 0.001). Hypertension was significantly more common in adolescents (31.8%) than children (15%) with obesity, as expected (p < 0.013). Overall, dyslipidaemia in prepubertal and pubertal groups was identified in 42 and 55%, respectively, with no significant differences (p = 0.085). Type 2 diabetes mellitus and metabolic syndrome prevalences among adolescents are quite high in the urban area of Konya, central Anatolia, with abnormal lipid profiles, obesity and nutritional mistakes.


Genetic variants in the C-reactive protein gene are associated with microangiopathic ischemic stroke.
C-reactive protein (CRP) is an independent risk factor for cardiovascular disease and ischemic stroke. CRP serum levels are influenced by genetic variation in the CRP gene. Studies investigating the relationship between ischemic stroke and polymorphisms in the CRP gene produced equivocal results. Here we investigate single-nucleotide polymorphisms (SNPs) in the CRP gene in a large German ischemic stroke sample. In a case-control design, 1,669 patients with ischemic stroke due to large-artery atherosclerosis, cardioembolism or cerebral microangiopathy were genotyped for 4 haplotype tagging SNPs (rs3093075, rs1205, rs1130864 and rs1800947) in the CRP gene which have been shown to influence CRP serum concentrations. Geographically matched controls were drawn from 2 prospective population-based studies, the Dortmund Health Study and the Study of Health in Pomerania. The genetic association between the SNPs and stroke was assessed using SNP and haplotype approaches. Results were adjusted for covariates by logistic regression. All 4 CRP SNPs reside in one linkage disequilibrium block. None of the SNPs or SNP haplotypes were associated with ischemic stroke as a whole. Three SNPs (rs3093075, rs1130864 and rs1800947) showed a significant association with microangiopathic stroke. A common 4-SNP haplotype was protective while 2 rarer haplotypes conferred susceptibility to microangiopathic stroke. All associations remained significant after adjustment for sex, age, hypertension, diabetes mellitus and hypercholesterolemia and after correction for multiple testing using the 'false discovery rate' method. Genetic variation in the CRP gene is associated with microangiopathic but not macroangiopathic or cardioembolic stroke in a large German stroke sample.


Malignant proliferating trichilemmal tumor: a case report and review of literature.
Proliferating trichilemmal tumor (PTT) is an uncommon appendageal skin tumor that affects mainly elderly women. It arises from the external root sheath of the hair follicle and is most commonly observed on the scalp. Although most cases pursue a favorable clinical course and surgical excision is curative, malignant transformation has rarely been reported in these lesions. Because of limited number of cases reported in the literature, management of malignant PTT is controversial and mainly entails wide local excision. Many other adjuvant modalities have been tried. In this report, we present a case of malignant PTT in a 65-year-old male patient who presented with ulceroproliferative growth over occipital region since 4 months.


Congenital Heart Disease Genetics Uncovers Context-Dependent Organization and Function of Nucleoporins at Cilia.
Human genomics is identifying candidate genes for congenital heart disease (CHD), but discovering the underlying mechanisms remains challenging. In a patient with CHD and heterotaxy (Htx), a disorder of left-right patterning, we previously identified a duplication in Nup188. However, a mechanism to explain how a component of the nuclear pore complex (NPC) could cause Htx/CHD was undefined. Here, we show that knockdown of Nup188 or its binding partner Nup93 leads to a loss of cilia during embryonic development while leaving NPC function largely intact. Many data, including the localization of endogenous Nup188/93 at cilia bases, support their direct role at cilia. Super-resolution imaging of Nup188 shows two barrel-like structures with dimensions and organization incompatible with an NPC-like ring, arguing against a proposed "ciliary pore complex." We suggest that the nanoscale organization and function of nucleoporins are context dependent in a way that is required for the structure of the heart.


Blood pressure, change in blood pressure, and cardiovascular event rates in placebo-treated patients in the Medical Research Council Trial.
The relationship between cardiovascular event rate (stroke + coronary events), entry blood pressure (BP), change in BP over 6 months, and other variables was examined in the 8,654 placebo-treated patients in the Medical Research Council (MRC) trial. Entry BP was greater than screening pressures and fell significantly after randomization to placebo. The entry pressure was significantly greater but the fall after entry was less in those who had a cardiovascular event during 5.5 years of follow-up. Thus, patients with high entry pressure that remained elevated during follow-up had the highest event rates. This pattern was marked for stroke but was also found for coronary events. Other variables strongly related to event occurrence were sex, age, and smoking habit. Discriminant analysis based on these variables correctly identified 67% of those who had an event but incorrectly classified 40% of the much larger group who did not. These results suggest that failure of BP to fall after screening examinations is a cardiovascular risk factor. Thus, high-risk patients may be identified by repeated measurements of BP before treatment is started.


IL-16 processing in sentinel node regulatory T cells is a factor in bladder cancer immunity.
In the effort of developing new immunotherapies, the sentinel node (SN) has proven a promising source from which to harness an effective antitumour T cell response. However, tumour immune escape, a process in which regulatory T cells (Tregs) play a central role, remains a major limiting factor. Therefore, there is a clear need to increase the knowledge of Treg function and signalling in sentinel nodes. Here, we set out to explore whether the proteome in SN-resident T cells is altered by the tumour and to identify key proteins in SN T cell signalling, focusing on Tregs. Five patients with muscle-invasive urothelial bladder cancer were prospectively included. Mass spectrometry was performed on two patients, with validation and functional studies being performed on three additional patients and four healthy donors. At cystectomy, SN, non-SN lymph nodes and peripheral blood samples were collected from the patients and T cell subsets isolated through flow cytometry before downstream experiments. Proteomic analysis indicated that growth and immune signalling pathways are upregulated in SN-resident Tregs. Furthermore, centrality analysis identified the cytokine IL-16 to be central in the SN-Treg signalling network. We show that tumour-released factors, through activating caspase-3, increase Treg IL-16 processing into bioactive forms, reinforcing Treg suppressive capacity. In conclusion, we provide evidence that Tregs exposed to secreted factors from bladder tumours show increased immune and growth signalling and altered IL-16 processing which translates to enhanced Treg suppressive function, indicating altered IL-16 signalling as a novel tumour immune escape mechanism.


Nonspecific bronchial hyperresponsiveness and development of asthma in children with hay fever.
It has been suggested that patients with allergic rhinitis who present nonspecific bronchial hyperresponsiveness (BHR) are those most likely to develop asthma. Therefore, a study was conducted in children with rhinoconjunctivitis to ascertain whether BHR to methacholine might predict the development of asthma in these patients. Fifteen patients with hay fever and no previous symptoms of asthma were selected. All underwent clinical symptom tests and methacholine tests, during the pollen season in the 4 consecutive years following the start of the study. At the end of this period, 5 patients had developed asthma. It may thus be affirmed that, in this group, neither the presence nor the degree of previous BHR was useful for predicting which patients would later develop asthma.


Predicting HIV testing in low threshold community contexts among young African American women living in the Southern United States.
Southern U.S. African American women have disproportionately high HIV infection rates, and increasing HIV testing is a prevention priority. Research suggests that optimal testing conditions involve reaching out to community members and offering free tests in private, supportive contexts with minimal delays for results. These conditions were implemented with young African American women (N = 223, M age = 20.4 years) living in disadvantaged areas of a Southern U.S. city to identify participant characteristics associated with test choice. Participants were recruited using Respondent Driven Sampling. Structured field interviews assessed personal and social network characteristics, sexual practices, substance use, and behavioral impulsivity (assessed by a delay discounting task). A free HIV test was then offered, and test choice was the outcome variable. Testing was accepted by 69%, which exceeded the national lifetime test rate for this population by 7.4% (p < .05). All were sero-negative. Test refusal (31%) was associated with poorer educational performance, greater impulsivity (discounting), less social network encouragement to use birth control (ps < .05), and lower engagement in sexual risk behaviors (p < .10). Test choice did not differ by substance involvement. Thus, low threshold community testing promoted acceptance among this priority population, although a minority with specific characteristics likely need additional incentives for test acceptance.


Antitumor activity of Hygrophila spinosa on Ehrlich ascites carcinoma and sarcoma-180 induced mice.
Petroleum ether extract from H. spinosa root exhibited antitumor activity in Ehrlich ascites carcinoma and Sarcoma-180 bearing mice Processed extract suppressed significantly the tumor fluid volume at the end of 3 weeks experiment. It decreased about 50% of packed cell volume and increased life span of EAC/S-180 bearing mice in a day dependent manner. Red blood cell count, hemoglobin content and white blood cell count were more or less normal after processed extract treatment of the tumor bearing mice. In tumor control animals, neutrophils increased (273.7% in EAC and 263.4% in S-180 bearing mice respectively with respect to normal mice) whereas lymphocytes decreased (60.0% in EAC and 56.5% in S-180 bearing mice respectively with respect to normal mice). It also inhibited the rapid increase of body weight of tumor bearing mice.


APOBEC3F expression in triple-negative breast cancer is associated with tumor microenvironment infiltration and activation of cancer immunity and improved survival.
The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) causes a point mutation from cytidine to uracil in DNA and/or RNA. The role of APOBEC3A and APOBEC3B in breast cancer has been well described, whereas that of APOBEC3F remains unknown. To investigate the clinical relevance of APOBEC3F expression, we analyzed a total of 3000 breast cancer cases from multiple independent large patient cohorts including METABRIC, TCGA, GSE75688, and GSE114725. High expression of APOBEC3F was associated with improved disease-specific and overall survival in triple negative breast cancer (TNBC). APOBEC3F is not usually a reflection of cancer cell biology in TNBC or luminal breast cancer, except for homologous recombination deficiency in TNBC. In the TNBC homologous recombination deficiency group, APOBEC3F expression was not consistently associated with intratumor heterogeneity, mutation rates, or neoantigens. APOBEC3F expression did not correlate with response to any of the drugs tested in breast cancer cell lines in vitro. However, high APOBEC3F expression was associated with enrichment of several immune-related gene sets and immune activity. High APOBEC3F expression also accompanied higher infiltration of anti-cancer immune cell infiltration in TNBC. However, in luminal breast cancer, high APOBEC3F tumor significantly enriched not only immune-related gene sets, but also cell proliferation-, metastasis-, and apoptosis-related gene sets. Analysis of single-cell transcriptomes showed APOBEC3F exclusively expressed in immune cells and significantly associated with cytolytic activity of the immune cells, immune response, and immune cell proliferation. Expression of immune checkpoint genes was uniformly elevated in APOBEC3F-high tumors. We conclude that APOBEC3F is exclusively expressed in immune cells and this expression is associated with enhanced anti-cancer immune response as well as improved survival in TNBC.


A theory of macromolecular chemotaxis.
A macromolecule in a gradient of a cosolute that is preferentially (relative to the solvent) either attracted to or excluded from the domain of the macromolecule should experience a thermodynamic force and move, respectively, up or down the gradient. A theory of chemotactic forces arising from such preferential interactions, especially short-range ligand binding and excluded volume interactions, is developed via an extension of Kirkwood-Buff theory. The ligand binding result is confirmed for both non-ionic and ionic cosolutes by standard solution thermodynamics. The effect of increasing the electrolyte concentration to diminish the electrostatic free energy of a charged macromolecule is also treated formally via an electrostatic macromolecule-electrolyte preferential interaction coefficient. For short-range interactions, the induced chemotactic velocity is attributed entirely to tangential tractions at the interface between the macromolecule and its surrounding solution. The velocity of a spherical macromolecule driven by such tractions is derived by a hydrodynamic calculation for steady-state creepy flow with a partial slip boundary condition. Qualitative comparisons of theoretical predictions with experimental observations of Zheng and Pollack pertaining to charged microspheres near the surfaces of non-ionic gels suggest that the reported exclusion zones are due to chemotaxis induced by gradients of base (NaOH) (or acid (HCl)) and salt. With a single adjustable parameter, namely, the ratio of slip length to area per surface carboxyl (or amidine) group, this theory yields nearly quantitative agreement with many observations. The estimated slip length for the microspheres is comparable to that obtained for bovine serum albumen by fitting the chemotactic theory to two reported cross-diffusion coefficients. When a solution with a gradient of NaOH is placed in contact with a smooth glass wall, chemotactic surface tractions are predicted to cause convection of the solution toward the acidic end of the gradient, as observed in preliminary experiments.


Dexamethasone in Glioblastoma Multiforme Therapy: Mechanisms and Controversies.
Glioblastoma multiforme (GBM) is the most common and malignant of the glial tumors. The world-wide estimates of new cases and deaths annually are remarkable, making GBM a crucial public health issue. Despite the combination of radical surgery, radio and chemotherapy prognosis is extremely poor (median survival is approximately 1 year). Thus, current therapeutic interventions are highly unsatisfactory. For many years, GBM-induced brain oedema and inflammation have been widely treated with dexamethasone (DEX), a synthetic glucocorticoid (GC). A number of studies have reported that DEX also inhibits GBM cell proliferation and migration. Nevertheless, recent controversial results provided by different laboratories have challenged the widely accepted dogma concerning DEX therapy for GBM. Here, we have reviewed the main clinical features and genetic and epigenetic abnormalities underlying GBM. Finally, we analyzed current notions and concerns related to DEX effects on cerebral oedema, cancer cell proliferation and migration and clinical outcome.


Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells.
Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. Numerous patients are unable to be cured due to the development of resistance of the osteosarcoma cells to chemotherapeutic drugs. Therefore, reversion of drug resistance is urgently required for the treatment of osteosarcoma. Arsenic trioxide (As2O3) is an active ingredient in Traditional Chinese Medicine, but the therapeutic potential of As2O3 in osteosarcoma remains largely unexplored. The current study investigated the effects of As2O3 on MG63 osteosarcoma cells using a cell proliferation assay, flow cytometric analysis of the cell cycle and cell apoptosis, reverse transcription polymerase chain reaction to detect stathmin mRNA expression levels and western blot analysis to detect the stathmin protein expression levels. As2O3 and doxorubicin (ADM) combination treatment markedly inhibited cell proliferation in ADM-resistant MG63 (MG63/dox) osteosarcoma cells, clearly induced G2/M phase cell cycle arrest and increased the number of apoptotic MG63/dox cells. Furthermore, stathmin expression was found to be downregulated in MG63/dox cells and was sensitive to ADM treatment. Additional investigation revealed that the downregulation of stathmin expression in MG63/dox cells by stathmin small interfering RNA significantly enhanced the reversion of ADM resistance in MG63/dox by As2O3. The data indicated that As2O3 reversed ADM resistance in MG63/dox cells through downregulation of stathmin and may be a potential drug for the treatment of ADM-resistant osteosarcoma.


Inhibition of Intermediate-Conductance Calcium-Activated K Channel (KCa3.1) and Fibroblast Mitogenesis by α-Linolenic Acid and Alterations of Channel Expression in the Lysosomal Storage Disorders, Fabry Disease, and Niemann Pick C.
The calcium/calmodulin-gated KCa3.1 channel regulates normal and abnormal mitogenesis by controlling K+-efflux, cell volume, and membrane hyperpolarization-driven calcium-entry. Recent studies suggest modulation of KCa3.1 by omega-3 fatty acids as negative modulators and impaired KCa3.1 functions in the inherited lysosomal storage disorder (LSD), Fabry disease (FD). In the first part of present study, we characterize KCa3.1 in murine and human fibroblasts and test the impact of omega-3 fatty acids on fibroblast proliferation. In the second, we study whether KCa3.1 is altered in the LSDs, FD, and Niemann-Pick disease type C (NPC). Our patch-clamp and mRNA-expression studies on murine and human fibroblasts show functional expression of KCa3.1. KCa currents display the typical pharmacological fingerprint of KCa3.1: Ca2+-activation, potentiation by the positive-gating modulators, SKA-31 and SKA-121, and inhibition by TRAM-34, Senicapoc (ICA-17043), and the negative-gating modulator, 13b. Considering modulation by omega-3 fatty acids we found that α-linolenic acid (α-LA) and docosahexanenoic acid (DHA) inhibit KCa3.1 currents and strongly reduce fibroblast growth. The α-LA-rich linseed oil and γ-LA-rich borage oil at 0.5% produce channel inhibition while α-LA/γ-LA-low oils has no anti-proliferative effect. Concerning KCa3.1 in LSD, mRNA expression studies, and patch-clamp on primary fibroblasts from FD and NPC patients reveal lower KCa3.1-gene expression and membrane expression than in control fibroblasts. In conclusion, the omega-3 fatty acid, α-LA, and α-LA/γ-LA-rich plant oils, inhibit fibroblast KCa3.1 channels and mitogenesis. Reduced fibroblast KCa3.1 functions are a feature and possible biomarker of cell dysfunction in FD and NPC and supports the concept that biased lipid metabolism is capable of negatively modulating KCa3.1 expression.


When to Discharge a Patient After Endoscopy: A Narrative Review.
Video endoscopy is an important modality for the diagnosis and treatment of various gastrointestinal diseases. Most endoscopic procedures are performed as outpatient basis, sometimes requiring sedation and deeper levels of anesthesia. Moreover, advances in endoscopic techniques have allowed invasion into the third space and the performance of technically difficult procedures that require the utmost precision. Hence, formulating strategies for the discharge of patients requiring endoscopy is clinically and legally challenging. In this review, we have discussed the various criteria and scores for the discharge of patients who have undergone endoscopic procedures with and without anesthesia.


[Single cell fluorescence photometry for quantification of antigens on alveolar macrophages].
The quantitation of cell surface antigens on alveolar macrophages (AM) using flow-cytometry is complicated by strong autofluorescence and wide variation of cell- size and autofluorescence. Therefore a microscope-fluorometric method was developed which allows simultaneous assessment of fluorescence of fluorochrome-labelled monoclonal antibodies and size in individual cells. Autofluorescence of smokers AM was found to be variable and considerably stronger than autofluorescence of nonsmokers AM. By means of a multi step determination of autofluorescence and specific fluorescence using different filter combinations of the microscope fluorometer density of membrane bound HLADR-antigens could be efficiently determined also in strongly autofluorescent smoker AM.


[Incidence and risk factors of extraintestinal manifestations in children with inflammatory bowel disease].
Objective: To investigate the incidence and risk factors of extraintestinal manifestations (EIMs) in children with inflammatory bowel disease (IBD). Methods: The clinical data of 161 children with IBD was collected from the electronic medical records in the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine from January 2012 to December 2017. These patients were divided into Crohn's disease (CD) group and ulcerative colitis (UC) group, accounting for 82.0% (132 cases) and 18.0%(29 cases), respectively. The incidence of EIMs in each group was analyzed. The potential risk factors of EIMs including the IBD phenotype, gender, age, location of the CD lesion, disease activity of CD, and the presence of perianal lesion were analyzed with logistic regression model. Results: Eighty-eight patients (54.7%) had EIMs. The main EIMs were immune-mediated EIMs and growth retardation, accounting for 41.0% (66/161) and 24.2% (39/161), respectively. Aphthous ulcer (39/161, 23.0%) was the most common symptom among immune-mediated EIMs, followed by arthropathy (20/161, 12.4%) and skin lesions (19/161, 11.8%). Forty-three patients (26.7%) had EIMs before being diagnosed as IBD. Fifty-eight (65.9%) patients had only one EIM during the whole course of IBD. By logistic regression analysis, CD (OR=5.536, 95%CI:1.825-16.788) and perianal disease (OR=1.969, 95%CI:1.035-3.746) were the risk factors of immune-mediated EIMs. Meanwhile, CD (OR=11.319, 95%CI: 1.487-86.179), younger than six-year-old at diagnosis (OR=8.556, 95%CI: 3.109-23.545), moderate to severe activity of CD (OR=3.447, 95%CI: 1.196-9.934) and perianal disease (OR=3.361, 95%CI: 1.720-7.793) increased the risk of growth retardation. Conclusions: The children with IBD have a high incidence of EIMs, which were more common in CD than in UC. The risk factors of developing EIMs include CD, perianal diseases, younger than six-year-old at diagnosis and moderate to severe activity of CD.


Light stress-regulated two-helix proteins in Arabidopsis thaliana related to the chlorophyll a/b-binding gene family.
The chlorophyll a/b, chlorophyll a/c, and chlorophyll a/a light-harvesting proteins are part of an extended gene family that also includes the transiently expressed stress proteins, the Elips (early light-induced proteins). Four Elip homologue proteins, encoded by single-copy nuclear genes, have been identified in the Arabidopsis thaliana database. These proteins were divided into two groups according to the expression pattern under light-stress conditions and the predicted secondary structure. Group one included two members of the Elip family with three predicted transmembrane helices and a gene expression strictly related to light stress. Group two included two proteins, the Seps (stress-enhanced proteins), which possessed two predicted transmembrane segments. The transcripts of Sep1 and Sep2 were present under low light conditions, but their level increased 4- to 10-fold during illumination of plants with high-intensity light. Preliminary data indicated that the induced transcripts were translated in vivo. Other physiological stress conditions, such as cold, heat, desiccation, salt, wounding, or oxidative stress, did not significantly influence the expression of Sep genes. In vitro import of radioactively labeled precursors of Seps into isolated chloroplasts confirmed the thylakoid membrane localization of these proteins. Considering the predicted protein structure and homology to other pigment-antenna proteins, the two-helix Seps might represent an evolutionary missing link between the one- and three-helix antenna proteins present in pro- and eukaryota.


PDB-tools web: A user-friendly interface for the manipulation of PDB files.
The Protein Data Bank (PDB) file format remains a popular format used and supported by many software to represent coordinates of macromolecular structures. It however suffers from drawbacks such as error-prone manual editing. Because of that, various software toolkits have been developed to facilitate its editing and manipulation, but, to date, there is no online tool available for this purpose. Here we present PDB-Tools Web, a flexible online service for manipulating PDB files. It offers a rich and user-friendly graphical user interface that allows users to mix-and-match more than 40 individual tools from the pdb-tools suite. Those can be combined in a few clicks to perform complex pipelines, which can be saved and uploaded. The resulting processed PDB files can be visualized online and downloaded. The web server is freely available at https://wenmr.science.uu.nl/pdbtools.


Recent Developments in Vinylsulfonium and Vinylsulfoxonium Salt Chemistry.
This review describes advances in the literature since 2000 in the area of reactions of vinylsulfonium and vinylsulfoxonium salts, with a particular emphasis on stereoselective examples. Although the chemistry of vinylsulfonium salts was first explored back in the 1950s, and that of vinylsulfoxonium salts in the early 1970s, there has been renewed interest in these compounds since the turn of the century. This has been largely due to an increased appreciation for the many synthetic possibilities associated with these valuable electrophiles. The development of improved routes to vinylsulfonium salts allowing for their in situ generation has played a part in accelerating their study. In general, reactions of the two sulfur salt classes follow a similar mechanistic pathway: initial conjugate addition of a nucleophile to the β-position, followed by protonation of an ylide intermediate, and cyclization of tethered anion to afford monocyclic or bicyclic product (e.g., cyclopropane, aziridine, oxazole, oxazolidinone, γ-lactam or γ-lactone). Alternatively, reactions involve formation of an ylide intermediate followed by intramolecular Johnson-Corey-Chaykovsky reaction (epoxidation or cyclopropanation), and subsequent cyclization to afford the desired bicyclic product (e.g., fused bicyclic epoxide or cyclopropane).


Injuries in elite women's ski jumping: surveillance through the 2017-18 FIS World Cup season.
To describe the incidence, type, aetiology and severity of injuries sustained by the International Ski Federation World Cup level female ski jumpers during the 2017-18 season. Prospective cohort study. Sixty-seven female ski jump athletes from 16 countries were followed throughout the 17-week winter season. Preseason baseline demographic data and injury history were recorded via questionnaire. Prospective biweekly reports and retrospective end-of-season interviews provided data on all injuries requiring medical attention. Seventeen injuries were recorded, corresponding to an incidence of 25.4 injuries/100 athletes/season. The incidence of time-loss and severe injuries were found to be 17.9 and 4.5, respectively. The knee was the most common site of injury (4/17; 23.5%). Fourteen injuries occurred on the ski jump hill and crash-landing was the most common mechanism of injury (10/14; 71%). Eighty-five per cent of all moderate and severe injuries occurred in snow or windy conditions. Length of jumps resulting in injury averaged 83.7% (95% CI 72.9% to 94.4%) of hill size. Moderate injuries causing 8-28 days absence from training activities were most common (7/17; 41%) and there were three severe injuries necessitating >4 weeks absence. Injuries among elite female ski jumpers are common and the majority are acute, resulting in time loss from training and competition. The knee was the most common site of injury and poor weather conditions may be a risk factor. Future studies are needed to identify risk factors for injury and to guide injury prevention initiatives.


Methods for the study of alternative splicing.
Alternative splicing multiplies the coding capacity of genes, which provides unparalleled complexity to the transcriptome and proteome. This increased complexity has clear repercussions for the regulation of gene expression in many organisms and for the balance between human health and disease. This significance, which has only recently been fully understood, has led to a growing number of studies that address the mechanisms that control alternative splicing decisions and the biological consequences of alternative RNA and protein isoforms. These studies have adapted or developed new methods and protocols that span computational biology, the biochemical analysis of in vitro reactions, model tissue culture systems, and in vivo studies. Many of these methods have been assembled in this volume to assist a newcomer to the study of alternative splicing and to expand the methodologies of laboratories already in the field.


Nociceptive signaling mediated by P2X3, P2X4 and P2X7 receptors.
Chronic pain is a debilitating condition that often occurs following peripheral tissue inflammation and nerve injury. This pain, especially neuropathic pain, is a significant clinical problem because of the ineffectiveness of clinically available drugs. Since Burnstock proposed new roles of nucleotides as neurotransmitters, the roles of extracellular ATP and P2 receptors (P2Rs) in pain signaling have been extensively studied, and ATP-P2R signaling has subsequently received much attention as it can provide clues toward elucidating the mechanisms underlying chronic pain and serve as a potential therapeutic target. This review summarizes the literature regarding the role of ATP signaling via P2X3Rs (as well as P2X2/3Rs) in primary afferent neurons and via P2X4Rs and P2X7Rs in spinal cord microglia in chronic pain, and discusses their respective therapeutic potentials.


Sex mosaics in the honeybee: how haplodiploidy makes possible the evolution of novel forms of reproduction in social Hymenoptera.
Hymenoptera are haplodiploid: females arise from fertilized, diploid eggs, while males arise from unfertilized, haploid eggs. The cytogenetic mechanisms underlying haplodiploidy enable remarkable phenomena including female cloning, male cloning and gynandromorphy (sex mosaics). We collected 11 newly emerged putative gynandromorph honeybees from a single colony, assessed the sex of various tissues morphologically and determined the genetic origin (maternal or paternal) of each tissue by genotyping. Ten bees were gynandromorphs with one to three distinct paternal origins. Remarkably, one bee carried no maternal alleles. This bee had female organs throughout, and arose from the fusion of two sperm nuclei. This is the first reported case in the Hymenoptera of sperm fusion resulting in a female, emphasizing the flexibility for social insect reproduction and potentially novel colony-level social structures.


Factors Affecting Use of Telemedicine and Telesurgery in Cancer Care (TTCC) among Specialist Physicians
Background: Considering the increasing incidence of different cancers, use of modern technologies such as TTCC can make a dramatic change in treatment of these diseases. So, if the evolution strategy conflicts with the organizational culture, national culture, and organizational structure of experts in this field, resistance will rise. Objective: The purpose of this study was to determine the effective factors on the use of TTCC in hospitals affiliated to Tehran University of Medical Sciences using the AHP model. Materials and Methods: This current descriptive study was carried out in 2018 on specialist physicians from five hospitals of Tehran University of Medical Sciences. The data gathering tool was a questionnaire consisting of two sections; demographic items and 27 effective factors influencing the implementation of TTCC technology, which was evaluated for validity and reliability. Data analysis was performed using analytical hierarchy process with expert choice and for empirical illustration are used to discuss the use of covariance-based SEM versus smart PLS software. Results: Based on AHP comparisons in the studied factors, the highest priority was the Cultural factor. In other words, commitment of senior executives to support the provision of a new technology with a weight of 0.327. The lowest priority, however, was related to support diverse approaches, innovation, creativeness, and acceptance of new ideas with a weight of 0.038. In regard with technical and organizational factors, out-of-hospital access to the intranet network and support provided by the doctors, with the weight of 0.221 and 0.205 in order, acquired the highest rates. Conclusion: Considering the high prevalence of cancer in Iran and the necessity of using new technologies in its treatment and by addressing the specialists' views and opinions in this field, organizational and national culture in the application of TTCC technology should be promoted. This target can be hit through acceptance, change in attitude, and successful use of TTCC technology by medical professionals.


γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress.
Ischemic stroke is a severe and acute neurological disorder with limited therapeutic strategies currently available. Oxidative stress is one of the critical pathological factors in ischemia/reperfusion injury, and high levels of reactive oxygen species (ROS) may drive neuronal apoptosis. Rescuing neurons in the penumbra is a potential way to recover from ischemic stroke. Endogenous levels of the potent ROS quencher glutathione (GSH) decrease significantly after cerebral ischemia. Here, we aimed to investigate the neuroprotective effects of γ-glutamylcysteine (γ-GC), an immediate precursor of GSH, on neuronal apoptosis and brain injury during ischemic stroke. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice, neuronal cell lines, and primary neurons. Our data indicated that exogenous γ-GC treatment mitigated oxidative stress, as indicated by upregulated GSH and decreased ROS levels. In addition, γ-GC attenuated ischemia/reperfusion-induced neuronal apoptosis and brain injury in vivo and in vitro. Furthermore, transcriptomics approaches and subsequent validation studies revealed that γ-GC attenuated penumbra neuronal apoptosis by inhibiting the activation of protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) in the endoplasmic reticulum (ER) stress signaling pathway in OGD/R-treated cells and ischemic brain tissues. To the best of our knowledge, this study is the first to report that γ-GC attenuates ischemia-induced neuronal apoptosis by suppressing ROS-mediated ER stress. γ-GC may be a promising therapeutic agent for ischemic stroke.


Surgical techniques of the parotid tumor.
101 cases with parotid tumors, including fourteen recurrent ones, were operated from 1976 to 1986. Surgical techniques of the recurrent cases were more complicated and difficult and often required plastic and reconstructive procedures for the skin, tissue and nerve defects. From the experiences mainly of the recurrent tumors, it was concluded that uniformly applied superficial or total parotidectomy was not always necessary but modified parotidectomy resecting sufficient and adequate tissues around the tumor should be planned individually from the prudent preoperative examinations.


Does retinitis pigmentosa relate with polycystic kidney disease?
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic disorders. A 21-year-old woman presented with temporary visual loss and gross hematuria. Fundoscopy showed retinitis pigmentosa, which was confirmed by electroretinogram. Her serum creatinine concentration was 1.6 mg/dl, and her renal ultrasonography revealed bilateral polycystic kidneys; she was unaware of having this condition. In this patient, there was probably an inherited ciliary defect, which may explain the association of ADPKD and retinitis pigmentosa.


Acute and chronic antidepressant drug treatment in the rat forced swimming test model of depression.
The forced swimming test (FST) is a widely used behavioral screen in rodents that is both sensitive and selective for clinically effective antidepressant drugs. However, antidepressant drugs produce changes in the FST within 24 hr of treatment, in contrast to weeks required for the recovery from clinical depression, and high doses seem to be required to produce effects in most animal tests. This study examined behavioral effects in the FST after subacute and chronic treatment with low doses (1-5 mg/kg) of antidepressant drugs to determine whether chronic treatment produced behavioral effects at doses that were ineffective after subacute treatment. The antidepressants studied were desipramine, a selective norepinephrine uptake inhibitor, and fluoxetine, a selective serotonin uptake inhibitor. The results indicated that low doses of desipramine and fluoxetine produced different behavioral patterns in the FST, but only after chronic administration. The results strengthen the validity of the FST as a behavioral screen for antidepressant drugs with features similar to an animal model of depression.


An update on functional electrical stimulation after spinal cord injury.
Recent advances in biomedical engineering as applied to neurologic rehabilitation have finally borne clinically relevant fruit. Nowhere is this more evident than in the field of functional electrical stimulation (FES). This article highlights the remarkable clinical progress that has been made in the use of electrical stimulation for restoring movement and function in individuals with spinal cord injury. Specific attention is given to respiratory-assist devices, hand-grasp systems, standing and walking, and bladder control. This review article features discussion of eight devices that have gone through the United States Food and Drug Administration (FDA) regulatory approval process.


[Exploration of respiratory allergies and prevention].
Respiratory allergies are found in more than 50% of the asthmatics. Allergen sources and their secondary reservoirs are better known. The different methods of exploration of allergic asthma consist of clinical history, skin tests, and in vitro tests particularly measurement of specific serum IgE. Specific challenge tests are realized with nebulized allergenic extracts as well as in the realistic manner with substances in occupational environment. It is equally important to evaluate the allergenic environment, especially by simple but informative techniques such as the Acarex test for mites. The eviction methods are the same for primary prevention (to prevent sensitization) as well as for the secondary prevention (to reduce the disease exacerbation in the patients already sensitized). The eviction methods mainly concern the allergens of mites, domestic animals, cockroaches and the molds.


Delayed hemorrhagic infarction. A cause of late neonatal germinal matrix and intraventricular hemorrhage.
Although a single perinatal or postnatal event may be directly correlated to intraventricular hemorrhage (IVH) in some infants, in other infants IVH may be related to a series of insults. Asphyxia, hypotension, and a pressure-passive low cerebral blood flow (CBF) may lead to an infarction. Subsequent events known to cause sudden rises in the CBF may then produce a hemorrhage into damaged tissues. We report two cases of this proposed model for delayed hemorrhage into infarcted tissues, or late IVH. Both neonates were severely asphyxiated, and both experienced profound hypotension and a low CBF on the first postnatal day. Late IVH was found in both neonates; at 2 to 3 months of age, one neonate was found to have computed tomographic evidence for diffuse encephalomalacia, and the other neonate was noted to have an occipital porencephalic cyst.


Shiga Toxin-A Model for Glycolipid-Dependent and Lectin-Driven Endocytosis.
The cellular entry of the bacterial Shiga toxin and the related verotoxins has been scrutinized in quite some detail. This is due to their importance as a threat to human health. At the same time, the study of Shiga toxin has allowed the discovery of novel molecular mechanisms that also apply to the intracellular trafficking of endogenous proteins at the plasma membrane and in the endosomal system. In this review, the individual steps that lead to Shiga toxin uptake into cells will first be presented from a purely mechanistic perspective. Membrane-biological concepts will be highlighted that are often still poorly explored, such as fluctuation force-driven clustering, clathrin-independent membrane curvature generation, friction-driven scission, and retrograde sorting on early endosomes. It will then be explored whether and how these also apply to other pathogens, pathogenic factors, and cellular proteins. The molecular nature of Shiga toxin as a carbohydrate-binding protein and that of its cellular receptor as a glycosylated raft lipid will be an underlying theme in this discussion. It will thereby be illustrated how the study of Shiga toxin has led to the proposal of the GlycoLipid-Lectin (GL-Lect) hypothesis on the generation of endocytic pits in processes of clathrin-independent endocytosis.


Vaccinia-induced epidermal growth factor receptor-MEK signalling and the anti-apoptotic protein F1L synergize to suppress cell death during infection.
F1L is a functional Bcl-2 homologue that inhibits apoptosis at the mitochondria during vaccinia infection. However, the extent and timing of cell death during DeltaF1L virus infection suggest that additional viral effectors cooperate with F1L to limit apoptosis. Here we report that vaccinia growth factor (VGF), a secreted virulence factor, promotes cell survival independently of its role in virus multiplication. Analysis of single and double knockout viruses reveals that VGF acts synergistically with F1L to protect against cell death during infection. Cell survival in the absence of F1L is dependent on VGF activation of the epidermal growth factor receptor. Furthermore, signalling through MEK kinases is necessary and sufficient for VGF-dependent survival. We conclude that VGF stimulates an epidermal growth factor receptor-MEK-dependent pro-survival pathway that synergizes with F1L to counteract an infection-induced apoptotic pathway that predominantly involves the BH3-only protein Bad.