Work-related violence, lifestyle, and health among special education teachers working in Finnish basic education.
Studies have reported higher levels of absenteeism due to illness among special education teachers compared to other teachers, but it is not known which factors might contribute to this difference. We examined whether health, health behaviors, and exposure to violence at work differed between special education and general education teachers in Finnish basic education. Survey data from 5760 general and special education teachers were analyzed with multilevel logistic models adjusted for individual- and school-level confounding factors. No difference was found between the health behaviors of general and special education teachers. The differences in physical and mental health between the two groups were also relatively small. With regard to work-related violence, however, male special education teachers were 3 times more likely to be exposed to mental abuse, and 5 times more likely to be exposed to physical violence when compared to their male colleagues in general education. Although female special educators were also at an increased risk of mental abuse and physical violence compared to their female general teacher colleagues, their odds ratios for such an encounter were smaller (2- and 3-fold, respectively) than those of male special education teachers. The school-level variance of physical violence toward teachers was large, which indicates that while most schools have little physical violence toward teachers, schools do exist in which teachers' exposure to violence is common. These findings suggest that special education teachers may benefit from training for handling violent situations and interventions to prevent violence at schools.


Liquid Biopsy in Hepatocellular Carcinoma: The Significance of Circulating Tumor Cells in Diagnosis, Prognosis, and Treatment Monitoring.
Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor outcomes when diagnosed at an advanced stage. Current curative treatments are most effective in early-stage HCC, highlighting the importance of early diagnosis and intervention. However, existing diagnostic methods, such as radiological imaging, alpha-fetoprotein (AFP) testing, and biopsy, have limitations that hinder early diagnosis. AFP elevation is absent in a significant portion of tumors, and imaging may have low sensitivity for smaller tumors or in the presence of cirrhosis. Additionally, as our understanding of the molecular pathogenesis of HCC grows, there is an increasing need for molecular information about the tumors. Biopsy, although informative, is invasive and may not always be feasible depending on tumor location. In this context, liquid biopsy technology has emerged as a promising approach for early diagnosis, enabling molecular characterization and genetic profiling of tumors. This technique involves analyzing circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-derived exosomes. CTCs are cancer cells shed from the primary tumor or metastatic sites and circulate in the bloodstream. Their presence not only allows for early detection but also provides insights into tumor metastasis and recurrence. By detecting CTCs in peripheral blood, real-time tumor-related information at the DNA, RNA, and protein levels can be obtained. This article provides an overview of CTCs and explores their clinical significance for early detection, prognosis, treatment selection, and monitoring treatment response in HCC, citing relevant literature.


Influence of Escherichia coli on urease-induced crystallisation in human urine.
Urease was added to urines inoculated with Escherichia coli 24 hours earlier and to control urines not inoculated with E. coli. The inoculation did not change the concentration of the measured urine components. The urease-induced ammonium ion production and pH increase was reduced in E. coli-inoculated urines compared to control urines. This suggests that E. coli can inhibit urease. The precipitation of both phosphate and magnesium on glass rods inserted in the urine was reduced with 40-50% in the E. coli-inoculated urines. The results demonstrate that E. coli can influence urease-induced crystallisation.


Diffuse Reflectance Spectroscopy of Hidden Objects, Part I: Interpretation of the Reflection-Absorption-Scattering Fractions in Near-Infrared (NIR) Spectra of Polyethylene Films.
Investigation of a sample covered by an interfering layer is required in many fields, e.g., for process control, biochemical analysis, and many other applications. This study is based on the analysis of spectra collected by near-infrared (NIR) diffuse reflectance spectroscopy. Each spectrum is a composition of a useful, target spectrum and a spectrum of an interfering layer. To recover the target spectrum, we suggest using a new phenomenological approach, which employs the multivariate curve resolution (MCR) method. In general terms, the problem is very complex. We start with a specific problem of analyzing a system, which consists of several layers of polyethylene (PE) film and underlayer samples with known spectral properties. To separate information originating from PE layers and the target, we modify the system versus both the number of the PE layers as well as the reflectance properties of the target sample. We consider that the interfering spectrum of the layer can be modeled using three components, which can be tentatively called transmission, absorption, and scattering contributions. The novelty of our approach is that we do not remove the reflectance and scattering effects from the spectra, but study them in detail aiming to use this information to recover the target spectrum.


A new species of Acantholycosa baltoroi-group (Araneae: Lycosidae, Pardosinae) from the Russian Far East.
Acantholycosa Dahl, 1908 is relatively large genus of wolf spiders with 28 named species and one subspecies (World Spider Catalog 2016) distributed in the Holarctic, though the majority of its species (24) is known from Russia. Although the genus is well studied due to several revisions (Marusik et al. 2004; Marusik & Omelko 2011; Omelko et al. 2016), its real species diversity remains unknown. A recent study of the collections of the Zoological Museum of Moscow State University revealed one undescribed species from Khabarovsk Province of Russia, belonging to the A. baltoroi-group of species. The main goals of this publications are the description of this new species and the proposition of an identification key to males of the A. baltoroi-group.


A Cross-Sectional Study on Self-Perceived Halitosis among Undergraduate University Students in Riyadh, Saudi Arabia.
The present cross-sectional observational study was conducted to evaluate the prevalence of halitosis among undergraduate university students at Riyadh Elm University, Riyadh, Saudi Arabia. A survey of 301 participants who answered a questionnaire on their self-perceived halitosis was undertaken. The response rate was 35% (301/863). Of the total, 54.5% of participants reported that they had experienced halitosis. A majority of participants (61.4%) responded to having experienced an unpleasant bad taste in the morning when they woke up, with most participants (42.4%) stating that their breath was the worst early in the morning. A majority of respondents (59.6%) reported that they were aware of their condition. Only 27% of the respondents stated that they had admitted to having undergone an examination for bad breath from their dentist, and 22.9% of the respondents reported that they had undergone an examination for conditions associated with bad breath. The measures used to reduce the condition were evenly distributed, with approximately one-third using mouthwash (34.6%), gum/mentos (38.3%), and toothpaste (27.2%). The incidence of self-perceived halitosis that was revealed in the current study is normal compare to others studies. It is unrelated to age and sex. Non-usage of dental floss, no use of mouthwash, and smoking, on the other hand, were shown to be associated with self-perceived halitosis. Furthermore, tongue cleaning was not linked to introspection halitosis. Halitosis may be also due to underlying systemic conditions. Hence it is necessary to evaluate the condition's prevalence and examine the relationship with other etiological variables with halitosis in our country.


Update on Modern Management of Pheochromocytoma and Paraganglioma.
Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine. To minimize false-positive test results particular attention should be paid to pre-analytical sampling conditions. In addition to anatomical imaging by computed tomography (CT) or magnetic resonance imaging, new promising functional imaging modalities of photon emission tomography/CT using with somatostatin analogues such as ⁶⁸Ga-DOTATATE (⁶⁸Ga-labeled DOTA(0)-Tyr(3)-octreotide) will probably replace ¹²³I-MIBG (iodine-123-metaiodobenzylguanidine) in the near future. As nearly half of all pheochromocytoma patients harbor a mutation in one of the 14 tumor susceptibility genes, genetic testing and counseling should at least be considered in all patients with a proven tumor. Post-surgical annual follow-up of patients by measurements of plasma or urinary metanephrines should last for at least 10 years for timely detection of recurrent or metastatic disease. Patients with a high risk for recurrence or metastatic disease (paraganglioma, young age, multiple or large tumors, genetic background) should be followed up lifelong.


Paratracheal air cysts: prevalence and relevance to pulmonary emphysema and bronchiectasis using thoracic multidetector CT.
We aimed to determine the prevalence of paratracheal air cysts (PTACs) and the relationship of PTACs with emphysema and bronchiectasis through retrospective analysis of multidetector computed tomography (MDCT) findings. MDCT findings of 1027 consecutive patients who underwent routine thorax examination between January 2012 and January 2013 were evaluated retrospectively for the presence of PTACs. Localization of the PTACs, as well as their size, shape, and relationship with the trachea were examined. Presence of emphysema and bronchiectasis was recorded, and bronchiectasis severity index was calculated when present. We randomly selected 80 patients who had no visible PTACs as the control group. The findings of patients with and without PTACs were compared. PTACs were determined in 82 of 1027 patients (8%), in 8.8% of females and 7.3% of males. The presence of PTACs was determined to be independent of gender (P = 0.361). Eighty-one PTACs (98.8%) were located in the right side of the trachea and 56.1% had a tracheal connection. The presence of PTACs significantly correlated with the presence and severity of bronchiectasis (P = 0.001 and P = 0.005 respectively). There was no significant relationship between the presence of PTACs and the presence of emphysema on CT images (P = 0.125). The prevalence of PTACs was determined as 8% in this study. There was significant association between PTACs and bronchiectasis.


Business ethics and health care: a stakeholder perspective.
This article examines the recent controversy in health care delivery about whether it should be conceptualized as a business. The current debate implicitly appeals to a common understanding of business and business practices that is no longer very useful. This common notion, which the authors call "cowboy capitalism," conceptualizes business as a competitive jungle resting on self-interest and an urge for competition in order to survive. The authors suggest that stakeholder capitalism offers a more useful framework for the dialogue about health care reform.


Antibiotic tolerance of peritoneal bacterial isolates in dialysis fluids.
The objective was to test antibiotic activity against Staphylococcus epidermidis and Pseudomonas aeruginosa in fresh dianeal fluid and spent dialysate from patients undergoing chronic ambulatory peritoneal dialysis. MICs and MBCs were measured and compared with those in standard broth. For S. epidermidis, there was some reduction in cefazolin and vancomycin activity in dialysis fluids. For P. aeruginosa, ciprofloxacin and tobramycin MICs increased significantly, and all isolates were tolerant to ceftazidime and piperacillin in dialysis fluids. Dialysis fluids can significantly impair antibiotic activity. The clinical implications warrant further study of antibiotic pharmacodynamics in the treatment of peritonitis.


A Novel NCSTN Mutation in a Three-Generation Chinese Family with Hidradenitis Suppurative.
Hidradenitis suppurativa (HS) is a rare autosomal dominant condition characterized by inflamed nodules, cysts, deep abscesses, draining sinuses in the axillae, inguinal, and anogenital regions. Mutations in the NCSTN gene have been perceived to be responsible for the major underlying changes in the disorder. The purpose of this study is to identify a novel gene mutation in a Chinese family with HS. A Chinese family with HS present was investigated. The proband had manifested with multiple draining sinuses on the posterior neck, chest, bilateral axillae, and perineal regions. DNA was isolated from the peripheral blood of the family members. The encoding exons with introns of the NCSTN gene were analyzed by polymerase chain reactions (PCR) and direct DNA sequencing. Sanger sequencing was performed to confirm the next-generation sequencing results and to analyze each mutation's familial segregation. Furthermore, the identified mutation was localized onto a 3D structure model using the DeepView Swiss-PdbViewer 4.1 software. In this family comprising 10 HS patients, one novel mutation of the NCSTN gene was identified, involving a deletion mutation (c.447delC(p.N150Ifs∗52)) in the NCSTN gene resulting in a frameshift and the new formation of a hydrogen bond. Our study reports the identification of a novel mutation that causes familial HS and could expand the spectrum of mutations in the γ-secretase genes underlying HS.


Immunotherapy of elderly acute myeloid leukemia: light at the end of a long tunnel?
Although it is possible to induce remission in the majority of the patients with acute myeloid leukemia (AML), many patients still die due to disease relapse. Immunotherapy is an attractive option. It is more specific. The memory T cells induced by immunotherapy may also provide the long-term tumor immunosurveillance to prevent disease relapse. Although immunotherapy of AML started in the early 1970s, its clinical impact has been disappointing. Recent advances in tumor immunology and immunotherapeutic agents have rekindled interest. Here, we provide a review of the history of AML immunotherapy, discuss why AML is well suited for immunotherapeutic approaches and present the biological obstacles that affect the success of immunotherapy. Finally, we put forward a new paradigm of AML immunotherapy that utilizes a combination of immunotherapeutic agents sequentially to enhance the in vivo tumor immunogenicity and effective priming and propagation of tumor-specific cytotoxic T cells.


Lung morphology in experimental acute paraquat poisoning. SEM observations.
The authors describe the SEM ultrastructural aspects of rat lungs following acute paraquat poisoning. The results obtained confirmed previous TEM observations and suggest an early inhibition of secretory activity in type II alveolar cells. This morphological aspect can be related to the generally known early development of respiratory difficulties following acute paraquat poisoning. The technique employed allows a precise study of alveolar reepithelization in further stages of poisoning. These last observations agree with the hypothesis of reepithelization by type II alveolar cells.


Observations on lens epithelial cells and their removal in anterior capsule specimens.
We studied the morphology and removal of lens epithelial cells in the following ways. In 49 senile cataractous eyes with a mean (+/- SD) age of 69 +/- 9 years, mean (+/- SD) cell density was 3574 +/- 512 cells/mm2 and mean (+/- SD) cell size was 281 +/- 48 micron 2. With age there was a significant decrease in cell density and an increase in cell size. Immediately after each of the following procedures was performed on the central anterior capsule during routine cataract surgery, the capsule was removed and observed. Procedures used were (1) aspiration, (2) aspiration with ultrasound, (3) instant single cryopexy application, (4) double cryopexy, and (5) double cryopexy followed by aspiration with ultrasound. Each procedure could destroy or remove lens epithelial cells completely. The procedure that we recommend is single cryopexy application followed by aspiration with ultrasound.


Immunoassay screening of lysergic acid diethylamide (LSD) and its confirmation by HPLC and fluorescence detection following LSD ImmunElute extraction.
In all, 3872 urine specimens were screened for lysergic acid diethylamide (LSD) using the CEDIA DAU LSD assay. Forty-eight samples, mainly from psychiatric patients or drug abusers, were found to be LSD positive, but only 13 (27%) of these could be confirmed by high-performance liquid chromatography with fluorescence detection (HPLC-FLD) following immunoaffinity extraction (IAE). Additional analysis for LSD using the DPC Coat-a-Count RIA was performed to compare the two immunoassay screening methods. Complete agreement between the DPC RIA assay and HPLC-FLD results was observed at concentrations below a cutoff concentration of 500 pg/mL. Samples that were LSD positive in the CEDIA DAU assay but not confirmed by HPLC-FLD were also investigated for interfering compounds using REMEDI HS drug-profiling system. REMEDI HS analysis identified 15 compounds (parent drugs and metabolites) that are believed to cross-react in the CEDIA DAU LSD assay: ambroxol, prilocaine, pipamperone, diphenhydramine, metoclopramide, amitriptyline, doxepine, atracurium, bupivacaine, doxylamine, lidocaine, mepivacaine, promethazine, ranitidine, and tramadole. The IAE/HPLC-FLD combination is rapid, easy to perform and reliable. It can reduce costs when standard, rather than more advanced, HPLC equipment is used, especially for labs that perform analyses for LSD infrequently. The chromatographic analysis of LSD, nor-LSD, and iso-LSD is not influenced by any of the tested cross-reacting compounds even at a concentration of 100 ng/mL.


Identification and functional characterization of a novel locust peptide belonging to the family of insect growth blocking peptides.
Growth blocking peptides (GBPs) are recognized as insect cytokines that take part in multifaceted functions including immune system activation and growth retardation. The peptides induce hemocyte spreading in vitro, which is considered as the initial step in hemocyte activation against infection in many insect species. Therefore, in this study, we carried out a series of in vitro bioassay driven fractionations of Locusta migratoria hemolymph combined with mass spectrometry to identify locust hemocyte activation factors belonging to the family of insect GBPs. We identified the locust hemocyte spreading peptide (locust GBP) as a 28-mer peptide encoded at the C-terminus of a 64 amino acid long precursor polypeptide. As demonstrated by QRT-PCR, the gene encoding the locust GBP precursor (proGBP) was expressed in large quantities in diverse locust tissues including fat body, endocrine glands, central nervous system, reproductive tissues and flight muscles. In contrary, hemocytes, gut tissues and Malpighian tubules displayed little expression of the proGBP transcript. The bioactive peptide induces transient depletion of hemocytes in vivo and when injected in last instar nymphs it extends the larval growth phase and postpones adult molting. In addition, we identified a functional homologous hemocyte spreading peptide in Schistocerca gregaria.


Palladium-catalyzed alkenylation and alkynylation of ortho-C(sp2)-H bonds of benzylamine picolinamides.
An efficient functionalization of ortho-C(sp(2))-H bonds of picolinamide (PA)-protected benzylamine substrates with a range of vinyl iodides as well as acetylenic bromide is reported. ortho-Phenyl benzoic acid (oPBA) acts as an effective promoter in this reaction system. This method provides a practical strategy to access highly functionalized benzylamine compounds for organic synthesis.


Juvenile hyaline fibromatosis: a case report.
Juvenile hyaline fibromatosis (JHF) is a rare, autosomal recessively inherited disorder characterized histologically by deposition of hyaline, collagen like substance aberrantly synthesized by the cells of the connective tissue and deposited within many organs, typically within the skin, gingiva, joints and bones. We report this rare case of Juvenile hyaline fibromatosis in a young boy who presented clinically with multiple papulonodular skin lesions, non tender soft tissue masses over the scalp, face, anterior chest wall, back, periarticular regions of the extremities with restricted mobility of joints and gingival hypertrophy. Calcifications were seen within the tumor shadows in the skull X-Rays. Histopathological study revealed characteristic features consistent with Juvenile hyaline fibromatosis. We report this case in view of its rarity.


Phytocontact Dermatitis due to Mustard Seed Mimicking Burn Injury: Report of a Case.
Mustard seeds have been used in traditional folk medicine as a stimulant, diuretic, and purgative and to treat a variety of ailments including peritonitis and neuralgia. Mustards are still used today in mustard plasters to treat rheumatism, arthritis, chest congestion, aching back, and sore muscles. To make a mustard plaster, mix equal parts of flour and powdered mustard and spread it as a paste on a doubled piece of soft cloth. Apply mustard plaster to the affected area for a maximum of 15 minutes. Prolonged application can result in burns to the skin and nerve damage. Skin lesions occur within hours after exposure, and there is no significant therapy procedure. This case report is about a patient with second-degree burn, occurred when a mixture including mustard seed was exposed to her skin in the pain therapy of the osteoarthritis in her left knee. There are no studies analyzing treatment of skin burns induced by mustard seed in the literature. While in this type of burns our experience is limited, we think that conservative approach should be first choice of treatment.


Roles of isoamylase and ADP-glucose pyrophosphorylase in starch granule synthesis in rice endosperm.
Amyloplast-targeted green fluorescent protein (GFP) was used to monitor amyloplast division and starch granule synthesis in the developing endosperm of transgenic rice. Two classical starch mutants, sugary and shrunken, contain reduced activities of isoamylase1 (ISA1) and cytosolic ADP-glucose pyrophosphorylase, respectively. Dividing amyloplasts in the wild-type and shrunken endosperms contained starch granules, whereas those in sugary endosperm did not contain detectable granules, suggesting that ISA1 plays a role in granule synthesis at the initiation step. The transition from phytoglycogen to sugary-amylopectin was gradual in the boundary region between the inner and outer endosperms of sugary. These results suggest that the synthesis of sugary-amylopectin and phytoglycogen involved a stochastic process and that ISA1 activity plays a critical role in the stochastic process in starch synthesis in rice endosperm. The reduction of cytosolic ADP-glucose pyrophosphorylase activity in shrunken endosperm did not inhibit granule initiation but severely restrained the subsequent enlargement of granules. The shrunken endosperm often developed pleomorphic amyloplasts containing a large number of underdeveloped granules or a large cluster of small grains of amyloplasts, each containing a simple-type starch granule. Although constriction-type divisions of amyloplasts were much more frequent, budding-type divisions were also found in the shrunken endosperm. We show that monitoring GFP in developing amyloplasts was an effective means of evaluating the roles of enzymes involved in starch granule synthesis in the rice endosperm.


Wide-view charge exchange recombination spectroscopy diagnostic for Alcator C-Mod.
This diagnostic measures temperature, density, and rotation for the fully stripped boron ion between the pedestal top and the plasma core with resolution consistent with the profile gradients. The diagnostic neutral beam used for the measurements generates a 50 keV, 6 A hydrogen beam. The optical systems provide views in both poloidal and toroidal directions. The imaging spectrometer is optimized to simultaneously accept 45 views as input with minimum cross-talk. In situ calibration techniques are applied for spatial location, spectral intensity, and wavelength. In the analysis, measured spectra are fitted to a model constructed from a detailed description of the emission physics. Methods for removal of interfering spectra are included. Applications include impurity and thermal transport.


Efficient ligandless palladium-catalyzed Suzuki reactions of potassium aryltrifluoroborates.
[reaction: see text] The ligandless palladium-catalyzed Suzuki cross-coupling reaction of potassium aryl- and heteroaryltrifluoroborates with aryl- or heteroaryl halides or triflates proceeds readily with very good yields. The cross coupling can be effected in methanol or water, in the open air, using Pd(OAc)(2) as a catalyst in the presence of K(2)CO(3). A variety of functional groups are tolerated.


The impact of Parkinson's disease on vocal-prosodic communication from the perspective of listeners.
An expressive disturbance of speech prosody has long been associated with idiopathic Parkinson's disease (PD), but little is known about the impact of dysprosody on vocal-prosodic communication from the perspective of listeners. Recordings of healthy adults (n=12) and adults with mild to moderate PD (n=21) were elicited in four speech contexts in which prosody serves a primary function in linguistic or emotive communication (phonemic stress, contrastive stress, sentence mode, and emotional prosody). Twenty independent listeners naive to the disease status of individual speakers then judged the intended meanings conveyed by prosody for tokens recorded in each condition. Findings indicated that PD speakers were less successful at communicating stress distinctions, especially words produced with contrastive stress, which were identifiable to listeners. Listeners were also significantly less able to detect intended emotional qualities of Parkinsonian speech, especially for anger and disgust. Emotional expressions that were correctly recognized by listeners were consistently rated as less intense for the PD group. Utterances produced by PD speakers were frequently characterized as sounding sad or devoid of emotion entirely (neutral). Results argue that motor limitations on the vocal apparatus in PD produce serious and early negative repercussions on communication through prosody, which diminish the social-linguistic competence of Parkinsonian adults as judged by listeners.


Measurement of free fraction, total concentration and protein binding for testosterone, triiodothyronine and thyroxine.
Aims: Measuring the total and free concentrations of hormones is useful, but the technology to do this simultaneously is lacking. Methods: A new method offers the ability to measure these parameters concurrently for testosterone, thyroxine and triiodothyronine. Results: The free concentrations showed significant correlations with patients' vital statistics. Overall, 67% of correlations for total concentration showed that the new and classical methods had equal accuracy, or that comprehensive ultrafiltration was more accurate. The protein binding term was found to correlate significantly with the patients' luteinizing hormone, prostate-specific antigen and height. Conclusion: Comprehensive ultrafiltration for measuring the total concentration, free concentration and protein binding term uses less sample and is much faster than measuring these parameters with three separate methods.


Treatment of multidrug-resistant pulmonary tuberculosis with interferon-gamma via aerosol.
Multidrug-resistant tuberculosis (MDR-TB) is associated with substantial morbidity, despite drug therapy. Interferon-gamma, a cytokine produced mainly by CD4 T lymphocytes, can activate alveolar macrophages, important effector cells in host immunity against Mycobacterium tuberculosis. We investigated safety and tolerability of aerosolised interferon-gamma in patients with MDR-TB, and assessed its efficacy in terms of sputum-smear grades. We did an open-label trial of aerosol interferon-gamma given to five patients with smears and cultures positive for pulmonary MDR-TB, despite documented adherence to therapy. The patients received aerosol interferon-gamma 500 micrograms three times a week for 1 month. Safety and tolerability were assessed, and, as well as routine clinical assessments, sputum samples for smear and culture were collected at entry and weekly. Computed tomography scans of the chest were done at baseline and after therapy ended. Interferon-gamma was well tolerated by all patients. In all five, bodyweight stabilised or increased. Sputum acid-fast-bacillus smears became negative in all patients, and the time to positive culture increased (from 17 to 24 days, not significant), which suggested that the mycobacterial burden had decreased. The size of cavitary lesions was reduced in all patients, 2 months after treatment had ended. Preliminary data suggest that aerosol interferon-gamma is a well-tolerated treatment that may be useful as adjunctive therapy in patients with MDR-TB who are otherwise not responding well to therapy.


Undetected Small Accessory Mental Foramina Using Cone-Beam Computed Tomography.
The accessory foramina could not be identified on some imaging modalities such as surface-rendered images. The purpose of this study was to investigate the ability of surface-rendered images in detecting these foramina. We analyzed 20 accessory mental foramina (AMF) in nine mandibles removed from cadavers with cone-beam computed tomography (CBCT) and assessed in surface-rendered images. All AMF were divided into three groups depending on their visibility. Group 1 included AMF that were clearly visible as foramina, Group 2 were not clearly visible but could be recognized with concave parts, and Group 3 were not visible and the smooth surface of the bone was observed. Group 1 ranged from 1.3 to 5.1 mm2, Group 2 from 0.3 to 3.8 mm2, and Group 3 from 0.2 to 1.1 mm2. A statistically significant difference in the mean size between Groups 1 and 3 was observed. Even if the AMF are smaller (e.g., 1 mm in diameter), they should still be avoided to prevent injury. The clinician should be aware that smaller foramina might not be detected on these images.


Aberrant MCT4 and GLUT1 expression is correlated with early recurrence and poor prognosis of hepatocellular carcinoma after hepatectomy.
The tumor microenvironment is a key determinant of cancer cell biology. The microenvironment is a complex mixture of tumor cells, stromal cells, and proteins, extracellular matrix, oxygen tension, and pH levels surrounding the cells that regulate the tumor progress. This study identified the prognostic factors associated with hepatocellular carcinoma (HCC) and MCT4 and GLUT1 expression levels in HCC specimens. In this study, we analyzed MCT4 and GLUT1 expression levels in tissue samples from 213 patients with HCC by immunohistochemical analyses and in HCC tumor tissues and matched adjacent nonneoplastic tissues by quantitative real-time PCR. We conducted a prognostic analysis of the overall survival (OS) and time to recurrence (TTR) using immunoreactivity and other common clinical and pathological parameters. All variables with prognostic impact were further analyzed by multivariate analysis. We found that MCT4 and GLUT1 expression levels were significantly higher in tumor tissues than in adjacent nontumor tissues, and they were positively correlated with tumor size. Survival analysis showed that patients with high expression levels of MCT4 or GLUT1 had a poor OS and TTR. In patients with HCC, MCT4 expression was an independent negative prognostic factor for OS (hazard ratio [HR] = 1.617; 95% confidence interval [CI] = 1.102-2.374; P = 0.014), and metabolic indicators were independent prognostic factors for OS (HR = 1.617, 95% CI = 1.102-2.374, P = 0.006) and TTR (HR = 1.348, 95% CI = 1.079-1.685, P = 0.009). Interestingly, patients with positive metabolic indicator expression in tumor cells had a significantly shorter OS and earlier TTR than those with negative metabolic indicator expression in tumor cells in the ≤5 cm and >5 cm subgroups. In summary, using the expression of MCT4 and GLUT1 and their metabolic parameters to determine the metabolic status of tumors is promising for predicting the prognosis of patients with HCC.


Gobichelin A and B: Mixed-Ligand Siderophores Discovered Using Proteomics.
"Omic" strategies have been increasingly applied to natural product discovery processes, with (meta-)genome sequencing and mining implemented in many laboratories to date. Using the proteomics-based discovery platform called PrISM (Proteomic Investigation of Secondary Metabolism), we discovered two new siderophores gobichelin A and B from Streptomyces sp. NRRL F-4415, a strain without a sequenced genome. Using the proteomics information as a guide, the 37 kb gene cluster responsible for production of gobichelins was sequenced and its 20 open reading frames interpreted into a biosynthetic scheme. This led to the targeted detection and structure elucidation of the new compounds produced by nonribosomal peptide (NRP) synthesis.


DNA technology, interstate commerce, and the likely origin of formosan subterranean termite (Isoptera: Rhinotermitidae) infestation in Atlanta, Georgia.
This study was the first to use DNA sequencing data to infer the origin of a Formosan subterranean termite, Coptotermes formosanus Shiraki, infestation. Cytochrome oxidase II gene sequence was used to define eight specific maternal lineages from 14 geographic locations across the southeastern United States, Hawaii, and China. One maternal lineage, A, was unique to all the Atlanta collections and one New Orleans collection, which indicated that termites at these sites shared a common maternal ancestor. The impact of interstate commerce in terms of Formosan subterranean termite introductions is addressed as is the industry response needed to arrest the spread of these termites via commercial traffic in used railroad cross ties.


Tetrac Delayed the Onset of Ocular Melanoma in an Orthotopic Mouse Model.
Ocular melanoma research, the most common primary intraocular malignancy in adults, is hindered by limited in vivo models. In a series of experiments using melanoma cells injected intraocularly into mouse eyes, we developed a model for ocular melanoma. Inoculation of 5 × 105 B16F10 cells led to rapid tumor growth, extensive lung metastasis, and limited animal survival, while injection of 102 cells was sufficient for intraocular tumors to grow with extended survival. In order to improve tumor visualization, 102 melanoma cells (B16F10 or B16LS9) were inoculated into Balb/C albino mouse eyes. These mice developed intraocular tumors that did not metastasize and exhibited extended survival. Next, we studied the therapeutic potential of inhibitor of the thyroid hormones-αvβ3 integrin signaling pathway in ocular melanoma. By utilizing tetraiodothyroacetic acid (tetrac), a thyroid hormone derivative, a delay in tumor onset in the B16F10 (integrin+) arm was observed, compared to the untreated group, while in the B16LS9 cells (integrin-) a similar rate of tumor onset was noticed in both experimental and control groups. In summary, following an optimization process, the mouse ocular melanoma model was developed. The models exhibited an extended therapeutic window and can be utilized as a platform for investigating various drugs and other treatment modalities.


Inhibition of phage-resistant bacterial pathogen re-growth with the combined use of bacteriophages and EDTA.
The combined effects of ethylenediaminetetraacetic acid (EDTA) and bacteriophage (phage) treatment of foodborne pathogens were investigated. Although viable counts for Campylobacter jejuni decreased by 1.5 log after incubation for 8 h in the presence of phage PC10, re-growth was observed thereafter. The combination of phage PC10 and 1 mM EDTA significantly inhibited the re-growth of C. jejuni. The viable counts for C. jejuni decreased by 2.6 log (P < 0.05) compared with that of the initial count after 24 h. Moreover, EDTA at 0.67 or 1.3 mM, combined with the specific lytic phages, also effectively inhibited the re-growth of phage-resistant cells of Campylobacter coli, Salmonella enterica serovar Enteritidis, and Salmonella enterica serovar Typhimurium. In addition, the combined effects of lytic phages and EDTA were investigated on the viability of Campylobacter in BHI broth at low temperatures followed by the optimum growth temperature. The re-growth of C. coli was significantly inhibited by the coexistence of 1.3 mM EDTA, and the viable counts of surviving bacteria was about the same as the initial viable count after the incubation. This is the first study demonstrating the combined use of lytic phages and EDTA is effective in inhibiting the re-growth of phage-resistant bacteria in Gram-negative bacteria.


Transient behavior of an electrolytic diode.
The transient behavior of an electrolytic diode system was studied. A gel-like electrolytic diode was incorporated in a capillary microfluidic chip. The microfluidic platform guaranteed a constant composition of solutions on the diode boundaries. The current responses of the electrolytic diode to step-like changes of the imposed DC electric voltage were measured. Some of these transients were accompanied by a short-time overshoot of electric current density. In order to explain this phenomenon, a mathematical model of the electrolytic diode system was developed. Dynamical analysis of the model equations confirmed the existence of the electric current overshoots. Because the results of the experimental and the numerical transient studies were quite similar, we have explained the physical meaning of three selected overshoots by means of an analysis of the reaction-transport processes inside the electrolytic diode system. The transient experiments carried out in this study indicate that our physical concept of the electrolytic diode system presented in previous papers is correct.


Unilateral tilted disc and ipsilateral keratoconus in the same eye.
The objective of this case was to report unilateral tilted disc in a boy with ipsilateral keratoconus. The tilted disc syndrome is a non-hereditary bilateral condition. This configuration is accompanied by situs inversus of the retinal vessels, congenital inferonasal conus, thinning of the inferonasal retinal pigment epithelium and choroid, and myopic astigmatism. Unilateral tilted disc syndrome is a rare condition. Keratoconus is a disorder characterised by progressive corneal steepening. The author present a case of unilateral tilted disc in a boy with ipsilateral keratoconus. Pterygium is a common disorder and tilted disc syndrome is a bilateral condition. But unilateral tilted disc in a boy with ipsilateral keratoconus is the first report in literature. Due to these clinical presentation, this report is an exception in literature and reported an unknown clinical coincident.


Periplasmic proteases of Escherichia coli.
In the course of examining the turnover of enzymes and proteins subject to catabolite inhibition and/or catabolite repression in Escherichia coli, we have observed at least three novel calcium- or manganese-activated proteolytic activities restricted to the periplasmic space. The occurrence and level of these proteolytic activities vary with the stage of cell growth and carbon source. Each of these proteases are neutral metalloendoproteases capable of degrading test substrates such as casein, insulin, globin, and protamine and appear to be unique when compared with the known periplasmic proteases in E. coli. One of these proteases (designated protease VII) has been purified to homogeneity and characterized in regard to subunit structure, sensitivity to protease inhibitors and metal ions, and substrate specificity. Immunological and genetic approaches are being employed to determine if these novel proteases arise from a common gene product. The physiological role of these proteases remains to be established.


Neurofibromatosis--review of the literature and case report.
Neurofibromatoses are genetic disorders of the nervous system that primarily affect the development and growth of neural (nerve) cell tissues. These disorders cause tumors to grow on nerves, and produce other abnormalities such as skin changes and bone deformities. Although many affected persons inherit the disorder, between 30 and 50 percent of new cases arise spontaneously through mutation in the individual's genes. We report on seven cases of type 1 neurofibromatosis (NF1) diagnosed from 2001 to 2006 at our Department. There were four female and three male patients, mean age 46.1 and 49 years, respectively. All patients showed neurofibromas accompanied by fibromas, café au lait spots, cases showed five axillary freckling (lentigines) and one case showed five plexiform neurofibromas and pruritus belonging to NF1 category. All patients had affected first degree relatives. Systemic findings were rare and included optic glioma in one case and Lisch hamartoma nodules in three cases. In all cases, the diagnosis was established according to the National Institutes of Health criteria, including at least two of the diagnostic criteria for NF1 diagnosis. None of our cases had malignancies or gastrointestinal tract involvement.


Aspirin-Induced Small-Bowel Injury Presenting Portal Venous Gas.
Aspirin is well known to damage small intestinal mucosa; however, little is known about the extra-intestinal manifestations of this aspirin-induced small-bowel injury. Herein, we report a case of aspirin-induced small-bowel injury in an 84-year-old Japanese man who presented with portal venous gas. Six weeks after the aspirin was stopped, his abdominal pain gradually resolved. Various intestinal disorders can manifest portal venous gas, and understanding the pathophysiology in such situations can help physicians to avoid anchoring bias in diagnosis.


Fibroepithelial polyp of the ureter presenting incidentally in a patient with a diverticular abscess.
We report on a patient with a fibroepithelial polyp of the distal ureter in whom the diagnosis was made incidentally while being examined for a diverticular abscess draining into the vagina. This patient's lack of symptoms and a possible relationship with the diverticular abscess is also explored.


[Preoperative leukocytosis as a predictor of intrabdominal injury in penetrating abdominal trauma].
in Mexico, the management of abdominal penetrating trauma doesn't follow the algorithms of Trauma Center level I, because of our limitations, and laparotomies are inevitable in this context. Is possible use some grade of leukocytosis suspect in-trabdominal lesion? study retrospective, descriptive and analytic that inclu-ded patients with abdominal penetrating trauma that suffered exploratory laparotomy. We excluded patients' whit severe damage to soft tissues in extremities, thoracic affection, fractures, or da-mage in nervous system. We divided the patients into 2 groups: group I (therapeutic laparotomy) and group II (non-therapeutic laparotomy). Dependent variables were; age, gender, type of injury, number of lesions, peripheral lesions, time between injury and, from a laboaratory blood sample, leukocytosis mean, percentage of neutrophils, leukocytosis ≥ 12,500 /mm(3), and hemoperitoneum. We compared variables between two groups and use Pearson's χ(2) test and T-Student, and percentages as summary of measures. we included 231 patients, group I with 159 patients and group II with 72 patients. Leukocytosis global was 13.2 mil/mm(3) and neutrophil range of 70.3%. 26% of patients did not have leukocytosis at arrival and evaluation, however they were laparotomized because of present peritoneal irritation. Leukocytosis ≥ 12.5 mil/mm(3) was statistically significant in patients with intrabdominal lesions (74.2% vs 27.7%, p < 0.001). leukocytosis ≥ 12.5 mil/mm(3) could be an early serum marker abdominal penetrating trauma.


Prospective analysis of 40 initial laparoscopic colorectal resections: a plea for a randomized trial.
The experience reported herein is on our initial 40 cases of laparoscopic-assisted (LA) colorectal resection that were prospectively evaluated. The operations were performed for colonic tumors of the right segment (n = 4), sigmoid (n = 11), or rectum (n = 7), diverticular disease (n = 17), and chronic constipation (n = 1). Among 22 tumors, 11 were malignant. The operative procedures were 4 right hemicolectomies, 28 segmental left colectomies, 5 anterior resections, 2 abdominoperineal resections, and 1 total colectomy. Thirty-one patients (77.5%) had a successfully completed LA resection. The reasons for conversion in the majority of the cases (66.6%) were difficulties in dissection. In the entirely LA procedures, the mean flatus postoperative day was 3, the mean postoperative hospitalization was 10.7 days, and there were 8 complications (25%) in 7 patients. Two patients were reoperated 2 and 3 months later for adhesion and ischemic stenosis of the colon above the anastomosis. There was 1 death in the LA group (3.2%). The length of operative specimen was 19.6 cm, and the mean number of resected lymph node was six. In contrast to laparoscopic biliary surgery, the benefits of LA colorectal surgery are not obvious. A randomized trial comparing LA and open colorectal resection must be carried out.


Aquaporins in Renal Diseases.
Aquaporins (AQPs) are a family of highly selective transmembrane channels that mainly transport water across the cell and some facilitate low-molecular-weight solutes. Eight AQPs, including AQP1, AQP2, AQP3, AQP4, AQP5, AQP6, AQP7, and AQP11, are expressed in different segments and various cells in the kidney to maintain normal urine concentration function. AQP2 is critical in regulating urine concentrating ability. The expression and function of AQP2 are regulated by a series of transcriptional factors and post-transcriptional phosphorylation, ubiquitination, and glycosylation. Mutation or functional deficiency of AQP2 leads to severe nephrogenic diabetes insipidus. Studies with animal models show AQPs are related to acute kidney injury and various chronic kidney diseases, such as diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma. Experimental data suggest ideal prospects for AQPs as biomarkers and therapeutic targets in clinic. This review article mainly focuses on recent advances in studying AQPs in renal diseases.


Intracytoplasmic inclusions in benign prostatic epithelium.
Prostatic glandular tissue in man is associated with varying forms of acellular structures. These include corpora amylacea, as well as more recently described prostatic crystalloids. We describe, for the first time to our knowledge, intracytoplasmic inclusions in benign prostatic epithelial cells of the central and transition zones of the prostate gland. Despite extensive histochemical, immunohistologic, and electron microscopic investigation, the exact nature of these inclusions remains obscure.


Construction of defined galE mutants of Salmonella for use as vaccines.
We describe the molecular cloning of the gal operon of Salmonella typhimurium LT2 and the localization of the gal promoter and the genes galE, galT, and galK. The order of the genes and the direction of transcription was the same as in Escherichia coli K12. A restriction enzyme map of the operon was obtained, and the approximate termini of the gal genes were located by using transposon insertion mutagenesis and minicell analysis. We constructed a plasmid that contained a defined 0.4-kilobase deletion in the galE but still expressed galT and galK activities from the gal promoter. This galE deletion was recombined into the chromosomal gal operons of S. typhimurium and Salmonella typhi Ty2. The resulting strains were vigorous, nonreverting galE mutants that were sensitive to galactose-induced lysis at 0.2 mM galactose. The S. typhimurium galE derivatives were avirulent and protective in mice.


[Cost-effectiveness of community-based treatment of chronic hepatitis B in China].
Objective: Since eliminating hepatitis B in China would need considerable public health resources, the economics problem of the strategy of community-based antiviral treatment for chronic hepatitis B (CHB) has become an important issue. The cost-effectiveness and affordability of the strategy were evaluated in this study. Methods: According to the advocacy on eliminating hepatitis B by WHO and the comprehensive protocol of community based prevention of major infectious diseases and the guideline for CHB prevention and treatment in China, the decision analytic Markov model was constructed with the parameters from national surveys or Meta-analysis. A cohort population aged 20-59 years was used as study subjects. The strategy of CHB antiviral treatment was compared with the strategies of hepatitis B vaccination and non-intervention, respectively. The costs and disability-adjusted life years (QALYs) of the strategies were calculated from the societal and payer perspectives. The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness ratio (CER) were calculated for the comparison of the strategies. One-way and probability sensitivity analysis were performed for uncertainty of the results. And the cost-effectiveness and affordability curves were introduced to estimate the budget impact on the strategies. Results: In the Chinese aged 20-59 years, the ICER of CHB antiviral treatment was 37 598.6 yuan (RMB) per QALYs and the ICERs were smaller in the low age groups, indicating that the antiviral treatment strategy is cost-effective and low age groups should be the priority population. The ICER of hepatitis B vaccination was -64 000.0 yuan (RMB) per QALYs, indicating that hepatitis B vaccination is cost saving. The CER of CHB antiviral treatment ranged from 731.8 to 1 813.3 yuan (RMB) per QALYs compared with hepatitis B vaccination, and the CER of CHB antiviral treatment was higher than that of hepatitis B vaccination in all age groups, indicating that hepatitis B vaccination would be more cost-effective than CHB antiviral treatment. The price of antiviral drug, entercavir, can influence the cost effectiveness of CHB antiviral treatment. If the price of entercavir declined half, CHB antiviral treatment would be cost-saving. The probability sensitivity analysis showed that people's willing to pay for CHB antiviral treatment should not be ignored, although the results of economics evaluation of CHB antiviral treatment were reliable. The results of affordability analysis indicated that the antiviral treatment strategy could not be implemented with the budget lower than 30 million yuan (RMB), the probability of implementing the strategy was 42.6% if the budget reaches 127 million yuan (RMB), and only when the budget reaches 269 million yuan (RMB), the goal of CHB antiviral treatment strategy can be fully realized. Conclusions: Although the strategy of CHB antiviral treatment as prevention in Chinese aged 20-59 years is cost-effective, it is not an appropriate public health measure due to the high cost. The cost effectiveness would be higher by conducting hepatitis B vaccination and then antiviral treatment in susceptible population.


Nuclear receptor agonists as potential differentiation therapy agents for human osteosarcoma.
This study was designed to investigate whether nuclear receptor agonists can be used as potential differentiation therapy agents for human osteosarcoma. Four osteosarcoma cell lines (143B, MNNG/HOS, MG-63, and TE-85) were treated with proliferator-activated receptor (PPAR)gamma agonists, troglitazone and ciglitazone, and a retinoid X receptor (RXR) ligand, 9-cis retinoic acid. The proliferation and induction of apoptosis in the treated cells were assessed, as was the induction of alkaline phosphatase, a differentiation marker of osteoblasts. The expression of PPARgamma was readily detected in all tested osteosarcoma lines. On treatment with the PPARgamma and RXR ligands, all four osteosarcoma lines exhibited a significantly reduced proliferation rate and cell viability. Among the four lines, 143B and MNNG/HOS were shown to be more sensitive to ligand-induced apoptosis, as demonstrated by the Crystal Violet and Hoechst staining assays. Of the three tested ligands, troglitazone was shown to be the most effective in inducing cell death, followed by 9-cis retinoic acid. Moreover, a strong synergistic effect on the induction of cell death was observed when both troglitazone and 9-cis retinoic acid or ciglitazone and 9-cis retinoic acid were administered to osteosarcoma cells. Troglitazone was shown to effectively induce alkaline phosphatase activity, a well-characterized hallmark for osteoblastic differentiation. Our findings suggest that PPARgamma and/or RXR ligands may be used as efficacious adjuvant therapeutic agents for primary osteosarcoma, as well as potential chemopreventive agents for preventing the recurrence and metastasis of osteosarcoma after the surgical removal of the primary tumors.


A model independent S/W framework for search-based software testing.
In Model-Based Testing (MBT) area, Search-Based Software Testing (SBST) has been employed to generate test cases from the model of a system under test. However, many types of models have been used in MBT. If the type of a model has changed from one to another, all functions of a search technique must be reimplemented because the types of models are different even if the same search technique has been applied. It requires too much time and effort to implement the same algorithm over and over again. We propose a model-independent software framework for SBST, which can reduce redundant works. The framework provides a reusable common software platform to reduce time and effort. The software framework not only presents design patterns to find test cases for a target model but also reduces development time by using common functions provided in the framework. We show the effectiveness and efficiency of the proposed framework with two case studies. The framework improves the productivity by about 50% when changing the type of a model.


Tailor-made nanoparticles via gas-phase synthesis.
Gas-phase synthesis is a well-known chemical manufacturing technique for an extensive variety of nanoscale particles. Since the potential of ultrafine and, in particular, nanoscale particles in high-performance applications has been identified, scientific and commercial interest has increased immensely, thus identifying this field as a most important technology of the future. However, nanomaterials can perform their multifunctional tasks only if they are customized in terms of chemical composition, size, and morphology to suit the application at hand. Profound knowledge of the synthesis and precise process control is crucial in meeting the stringent specifications. Although the gas-phase synthesis of ultrafine materials has been known and commercially exploited for decades, existing knowledge is based almost exclusively on empirical know-how. Process simulation is a very suitable tool for expanding the understanding of the synthesis-relevant processes, particle formation mechanisms, and operating parameters. Based on the resulting expertise some special nanoscale gas-phase products of high innovative potential have been developed.


Control of alternative splicing by forskolin through hnRNP K during neuronal differentiation.
The molecular basis of cell signal-regulated alternative splicing at the 3' splice site remains largely unknown. We isolated a protein kinase A-responsive ribonucleic acid (RNA) element from a 3' splice site of the synaptosomal-associated protein 25 (Snap25) gene for forskolin-inhibited splicing during neuronal differentiation of rat pheochromocytoma PC12 cells. The element binds specifically to heterogeneous nuclear ribonucleo protein (hnRNP) K in a phosphatase-sensitive way, which directly competes with the U2 auxiliary factor U2AF65, an essential component of early spliceosomes. Transcripts with similarly localized hnRNP K target motifs upstream of alternative exons are enriched in genes often associated with neurological diseases. We show that such motifs upstream of the Runx1 exon 6 also bind hnRNP K, and importantly, hnRNP K is required for forskolin-induced repression of the exon. Interestingly, this exon encodes the peptide domain that determines the switch of the transcriptional repressor/activator activity of Runx1, a change known to be critical in specifying neuron lineages. Consistent with an important role of the target genes in neurons, knocking down hnRNP K severely disrupts forskolin-induced neurite growth. Thus, through hnRNP K, the neuronal differentiation stimulus forskolin targets a critical 3' splice site component of the splicing machinery to control alternative splicing of crucial genes. This also provides a regulated direct competitor of U2AF65 for cell signal control of 3' splice site usage.


Different effects of heparin in males and females.
To determine whether women have a Pharmacological predisposition to bleeding and a worse outcome than men during heparin therapy, in light of recent studies showing that women have a higher risk of bleeding complications following anticoagulant therapy for thrombotic disorders than men. Prospectively planned subgroup analysis of a double-blind randomized study. Academic tertiary care hospitals in Hamilton, Ont. A total of 199 consecutive patients (105 women, 93 men) presenting with proximal deep vein thrombosis. (One patient was not included due to incomplete data). Activated partial thromboplastin time (APTT) values and heparin levels were assessed every 4 to 6 hours after a standard heparin bolus and infusion. The effect of sex on heparin doses and levels was also assessed after stable therapeutic heparin infusions were achieved. The women had higher heparin levels than the men (0.560 [standard error of the mean, SEM 0.056] units/mL v. 0.347 [SEM 0.062] units/mL, p < 0.0001) and higher APTT values (94.9 [SEM 0.50] seconds v. 81.2 [SEM 0.53] seconds, p = 0.0002) 4 to 6 hours after being given the same heparin bolus and infusion doses. After achieving therapeutic APTT values, the women received lower heparin doses than the men (27.9 [SEM 0.24] 1000 units/24 hours v. 34.5 [SEM 0.24] 1000 units/24 hours, p < 0.0001) but had higher heparin levels (0.349 [SEM 0.035] units/mL v. 0.292 [SEM 0.036] units/mL, p = 0.034). The effect of sex was also determined after correcting for the known effects of weight and age on heparin therapy. After adjusting for patient weight, among the women, older women had higher heparin levels but, among the men, there was little effect of age. There were no sex differences with respect to bleeding complications or recurrent thromboembolic disease. Women showed alterations in the pharmacokinetics of heparin, which could explain a predisposition to bleeding complications. Under the heparin protocol used in this study, heparin doses were rapidly adjusted, which may explain why rates of bleeding complications and recurrent thromboembolism were similar in men and women. We do not recommend changes in heparin therapy based on these results, but suggest the use of protocols that assess coagulation parameters frequently and then adjust heparin doses rapidly, in order to individualize therapy. Further study is required to determine whether there are sex differences in bleeding complications associated with anticoagulant therapy, and to confirm the altered pharmacokinetics of heparin in women.


Farming, well water consumption, rural living, and pesticide exposure in early life as the risk factors for Parkinson disease in Igdir province.
To investigate potential risk factors for Parkinson`s disease (PD) in elderly individuals rural living in Turkey. In total, 72 consecutive elderly Parkinson disease patients referred to the Neurology Clinic, Igdir State Hospital, Igdir, Turkey were included in the study. A structured questionnaire comprising questions on history of pastoral living, pit water consumption, and exposure to ionizing radiation and pesticides was administered to the patients. The patients were divided into 2 groups on the basis of water consumption: well water consumption group and city network consumption group. Of 72 patients with PD, 49 (68.1%) exposed to well water while 23 (31.9%) did not exposed to well water. The average duration of well water consumption was 20 (standard deviation 6) years (p less than 0.01) in group 1. Nitrate, sulfate and heavy metal levels were significantly higher in well water than in city network water (p less than 0.05). Consumption of well water containing heavy metals and nitrates in early life may contribute to the etiology of Parkinson disease in elderly individuals in Igdir province of Turkey.


Closure of a Chronic Traumatic Macular Hole Following Phacoemulsification Surgery.
To report a case of chronic traumatic macular hole closure following an uncomplicated phacoemulsification surgery. Retrospective chart review with optical coherence tomography imaging. 42-year-old woman with a 20-year history of a traumatic macular hole and cataract in the right eye underwent an uncomplicated phacoemulsification surgery. Following surgery, the patient was prescribed prednisolone acetate 1% four times per day, which was tapered off by postoperative month 1. By postoperative month 1, the full-thickness macular hole had closed. This unique case illustrates the closure of a full-thickness macular hole following cataract surgery. We hypothesize that closure of the macular hole was aided by the use of topical steroids in the postoperative period, allowing for resolution of the cystic intraretinal fluid and hole closure.


Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer.
Muscle Invasive Bladder Cancer (MIBC) has a poor prognosis. Whilst patients can achieve a 6% improvement in overall survival with Neo-Adjuvant Chemotherapy (NAC), many do not respond. Body fluid mutant DNA (mutDNA) may allow non-invasive identification of treatment failure. We collected 248 liquid biopsy samples including plasma, cell pellet (UCP) and supernatant (USN) from spun urine, from 17 patients undergoing NAC. We assessed single nucleotide variants and copy number alterations in mutDNA using Tagged-Amplicon- and shallow Whole Genome- Sequencing. MutDNA was detected in 35.3%, 47.1% and 52.9% of pre-NAC plasma, UCP and USN samples respectively, and urine samples contained higher levels of mutDNA (p = <0.001). Longitudinal mutDNA demonstrated tumour evolution under the selective pressure of NAC e.g. in one case, urine analysis tracked two distinct clones with contrasting treatment sensitivity. Of note, persistence of mutDNA detection during NAC predicted disease recurrence (p = 0.003), emphasising its potential as an early biomarker for chemotherapy response.


Room temperature, high-yield synthesis of multiple shapes of gold nanoparticles in aqueous solution.
A seed-mediated growth method was used to control the morphology and dimensions of Au nanocrystals by the manipulation of the experimental parameters in aqueous solution at room temperature. This chemical route produces various structural architectures with rod-, rectangle-, hexagon-, cube-, triangle-, and starlike profiles and branched (such as bi-, tri-, tetra-, and multipod) Au nanocrystals of various dimensions in high yield in the presence of a single surfactant, cetyltrimethylammonium bromide.


High-resolution spherical grating monochromator for the undulator beamline (BL-16B) at the Photon Factory.
The design and performance of a 24 m high-resolution spherical grating monochromator (H-SGM) for the undulator beamline (BL-16B) at the Photon Factory are described. With three interchangeable gratings of 400, 900 and 2000 lines mm(-1), the H-SGM is designed to cover the photon energy range 40-600 eV. With a resolving power of approximately 2000 in the photon energy range 40-530 eV, more than 10(11) photons s(-1) have been measured. The best resolutions obtained so far, at a substantially lower photon flux, are greater than 10 000 at 250 eV and 8000 at 400 eV


Enantioselective pharmacokinetics of ketoprofen in calves after intramuscular administration of a racemic mixture.
The pharmacokinetic properties of ketoprofen were determined in 4-week-old calves after intramuscular (i.m.) injection of a racemic mixture at a dose of 3 mg/kg body weight. Due to possible enantioselective disposition kinetics and chiral inversion, the plasma concentrations of the R(-) and S(+) enantiomer were quantified separately, using a stereospecific HPLC-UV assay. A distinct predominance of the S(+) enantiomer was observed, as well as significantly different pharmacokinetic parameters between R(-) and S(+) ketoprofen. More in specific, a greater value for the mean area under the plasma concentration-time curve (AUC(0→∞)) (46.92 ± 7.75 and 11.13 ± 2.18 μg·h/mL for the S(+) and R(-) enantiomer, respectively), a lower apparent clearance (Cl/F) (32.8 ± 5.7 and 139.0 ± 25.1 mL/h·kg for the S(+) and R(-) enantiomer, respectively) and a lower apparent volume of distribution (V(d)/F) (139 ± 14.7 and 496 ± 139.4 mL/kg for the S(+) and R(-) enantiomer, respectively) were calculated for the S(+) enantiomer, indicating enantioselective pharmacokinetics for ketoprofen in calves following i.m. administration.


[Sexually transmitted infections in patients with condylomata acuminata].
42 patients (26 males, 16 females) with genital and perianal warts were submitted to serological testing for HBV markers, anti HSV antibodies and syphilis. Specimens were also collected for microscopic and cultural examination for Neisseria gonorrhoeae, Chlamydia Trachomatis, Trichomonas vaginalis, Candida albicans and other pathogenic bacteria from urethra in men and from urethra, vagina and cervix in women. Women had also cytologic examination from cervix with Papanicolau method. We have found an high incidence of urethral and vaginal asymptomatic infections, of positivity for HBV markers and some positivities of tests for syphilis. Importance of these screening examinations in the management of patients with genital warts is then discussed.


Influence of zygapophyseal joint orientation on hyaline cartilage at the thoracolumbar junction.
Hyaline articular cartilage from 102 thoracolumbar junction zygapophyseal joints was examined using light microscopy. One section from the upper, middle and lower third of each joint at the T10-11, T11-12, T12-L1 and L1-2 spinal levels was photographed using 35 mm color film. Hyaline articular cartilage cross-sectional area of the superior and inferior articular processes of each joint pair, at each level, was digitized using computer-aided planimetry. Differences in area were compared with joint orientation (symmetry or tropism) and geometry of each joint pair at each spinal level. Variation in hyaline cartilage cross-sectional area between joint pairs could be attributed to: a) geometric differences, b) the presence of a mortice joint, or c) osteoarthritic changes, with or without tropism. These findings were most frequently demonstrated at the transitional levels of T11-12 and T12-L1.


Urban air pollution: state of the science.
Urban air pollution is comprised of a highly complex mixture of gaseous and particulate components. Much progress has been made in our understanding of the detailed chemistry and physics of air pollution, but important areas of uncertainty still remain.


Staining and histochemistry of undecalcified bone embedded in a water-miscible plastic.
Undecalcified bone fixed in a variety of fixatives and embedded in a new formulation of 2-hydroxypropyl methacrylate at 4 c has been sectioned at 1 to 5 microns. The embedding mixture contains 2-butoxyethanol as plasticizer and triethyleneglycol dimethacrylate as cross-linker. The accelerator was benzoyl peroxide and the catalyst was N,N-dimethylaniline. With proper embedding and care in sectioning it is possible to obtain sections with relatively little bone compression, excellent preservation of cellular elements, and a minimum of wrinkling. A wide variety of stains have been used for these sections and those reported here are Gill's hematoxylin-eosin, Nocht's azure-eosin, Feulgen, Hoechst 33258 (bisbenzimid H 33258), methyl green-pyronin, PAS, alizarin red, and von Kossa silver stain. There was excellent preservation of acid and alkaline phosphatase activities. A new method of prestaining immunofluorescent labeling was also applied to bone and examples of staining with anticollagen I and antifibronectin are presented.


Tuberculosis and HIV are the leading causes of adult death in northwest Ethiopia: evidence from verbal autopsy data of Dabat health and demographic surveillance system, 2007-2013.
Reliable data on causes of death form the basis for building evidence on health policy, planning, monitoring, and evaluation. In Ethiopia, the majority of deaths occur at home and civil registration systems are not yet functional. The main objective of verbal autopsy (VA) is to describe the causes of death at the community or population level where civil registration and death certification systems are weak and where most people die at home without having had contact with the health system. Causes of death were classified and prepared based on the International Classification of Diseases (ICD-10). The cause of a death was ascertained based on an interview with next of kin or other caregivers using a standardized questionnaire that draws information on signs, symptoms, medical history, and circumstances preceding death. The cause of death, or the sequence of causes that led to death, is assigned based on the data collected by the questionnaire. The complete VA questionnaires were given to two blinded physicians and reviewed independently. A third physician was assigned to review the case when disagreements in diagnosis arose. Communicable diseases (519 deaths [48.0%]), non-communicable diseases (377 deaths [34.8%]), and external causes (113 deaths [10.4%]) were the main causes of death between 2007 and 2013. Of communicable diseases, tuberculosis (207 deaths [19.7%]), HIV/AIDS (96 deaths [8.9%]) and meningitis (76 deaths [7.0%]) were the most common causes of death. Tuberculosis, HIV/AIDS, and meningitis were the most common causes of deaths among adults. Death due to non-communicable diseases showed an increasing trend. Increasing community awareness of infections and their interrelationships, tuberculosis case finding, effective local TB programs, successful treatment, and interventions for HIV are supremely important.


A Tcl/Tk based graphical interface to medical and administrative information.
FELIX is an front-end application processor, with an open systems back-end, that provides a uniform and intuitive interface to clinical and administrative information. It consists of an information browser, three clinical applications, and three management applications. FELIX was developed in a community hospital environment, but has conceptual and technical roots in medical informatics and the Internet.


Emerging Tick-Borne Pathogens in Central Canada: Recent Detections of Babesia odocoilei and Rickettsia rickettsii.
Background: The spread of emerging tick-borne pathogens has steadily increased in Canada with the widespread establishment of tick vectors and vertebrate hosts. At present, Borrelia burgdorferi, the bacterium causing Lyme disease, is the most common tick-borne pathogen in Canada and primarily transmitted by Ixodes scapularis. A low prevalence of other emerging tick-borne pathogens, such as Anaplasma phagocytophilum, Babesia species, Borrelia miyamotoi, and Francisella tularensis have also been detected through surveillance efforts in Canada. Although Rickettsia rickettsii has been historically detected in Haemaphysalis leporispalustris in Canada, the current prevalence and geographic extent of this pathogen is unknown. Material and Methods: In this study, we assessed the presence and prevalence of several emerging tick-borne pathogens in ticks and hosts collected through tick dragging and small mammal trapping in Central Canada. Results: Nested PCR testing detected three pathogen species in ticks, with Babesia odocoilei and B. burgdorferi in I. scapularis in addition to R. rickettsii in H. leporispalustris. Three pathogen species were detected in small mammals by nested PCR including B. odocoilei in Blarina brevicauda, Babesia microti in Peromyscus leucopus, and a Hepatozoon species in P. leucopus and Peromyscus maniculatus. B. burgdorferi and Babesia species were the pathogens most often detected in our samples, suggesting they are widely distributed across Central Canada. We also detected B. odocoilei and R. rickettsii beyond their known geographic distribution. Conclusions: Our results provide evidence that emerging tick-borne pathogens may be present outside defined risk areas identified by current surveillance efforts in Canada. As a result, emerging tick-borne pathogens introduced by the dispersal of infected ticks by migratory birds or maintained by hosts and vectors through cryptic transmission cycles may go undetected. More comprehensive testing including all tick life stages and additional tick-borne pathogens will help detect the spread and potential risk of emerging or re-emerging tick-borne pathogens for human and wildlife populations throughout Canada.


Oxidative and nitrosative stress in brain mitochondria of diabetic rats.
Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, may involve direct neuronal damage caused by intracellular glucose. The study assesses the direct effect of chronic hyperglycemia on the function of brain mitochondria, the major site of reactive species production, in diabetic streptozotocin (STZ) rats. Oxidative stress plays a central role in diabetic tissue damage. Alongside enhanced reactive oxygen species (ROS) levels, both nitric oxide (NO) levels and mitochondrial nitric oxide synthase expression were found to be increased in mitochondria, whereas glutathione (GSH) peroxidase activity and manganese superoxide dismutase protein content were reduced. GSH was reduced and GSH disulfide (GSSG) was increased in STZ rats. Oxidative and nitrosative stress, by reducing the activity of complexes III, IV and V of the respiratory chain and decreasing ATP levels, might contribute to mitochondrial dysfunction. In summary, this study offers fresh evidence that, besides the vascular-dependent mechanisms of brain dysfunction, oxidative and nitrosative stress, by damaging brain mitochondria, may cause direct injury of neuronal cells.


Reconciling ligase ribozyme activity with Fatty Acid vesicle stability.
The "RNA world" and the "Lipid world" theories for the origin of cellular life are often considered incompatible due to the differences in the environmental conditions at which they can emerge. One obstacle resides in the conflicting requirements for divalent metal ions, in particular Mg2+, with respect to optimal ribozyme activity, fatty acid vesicle stability and protection against RNA strand cleavage. Here, we report on the activity of a short L1 ligase ribozyme in the presence of myristoleic acid (MA) vesicles at varying concentrations of Mg2+. The ligation rate is significantly lower at low-Mg2+ conditions. However, the loss of activity is overcompensated by the increased stability of RNA leading to a larger amount of intact ligated substrate after long reaction periods. Combining RNA ligation assays with fatty acid vesicles we found that MA vesicles made of 5 mM amphiphile are stable and do not impair ligase ribozyme activity in the presence of approximately 2 mM Mg2+. These results provide a scenario in which catalytic RNA and primordial membrane assembly can coexist in the same environment.


One by one: Single molecule tools for genomics.
Much of the effort in any genomics programme arises from the need to generate and purify large numbers of identical molecules, since most analytical tools rely on the analysis of bulk DNA. Biological steps such as bacterial cloning--commonly used to prepare bulk samples of defined DNA fragments--are capricious and introduce their own restrictions and distortions. The analysis of single molecules, either directly or by in vitro enzymatic amplification, makes possible the examination of native genomic DNA without the complications and restrictions of biological propagation. Techniques already exist for the in vitro propagation of genomic fragments and for genome mapping, and offer the advantages of speed, flexibility and predictable behaviour. Single molecule sequencing, for which many approaches are being developed, is more challenging, but offers even greater rewards in terms of throughput and read length.


Phosphatidylethanol mediates its effects on the vascular endothelial growth factor via HDL receptor in endothelial cells.
Previous epidemiological studies have shown that light to moderate alcohol consumption has protective effects against coronary heart disease but the mechanisms of the beneficial effect of alcohol are not known. Ethanol may increase high density lipoprotein (HDL) cholesterol concentration, augment the reverse cholesterol transport, or regulate growth factors or adhesion molecules. To study whether qualitative changes in HDL phospholipids mediate part of the beneficial effects of alcohol on atherosclerosis by HDL receptor, we investigated whether phosphatidylethanol (PEth) in HDL particles affects the secretion of vascular endothelial growth factor (VEGF) by a human scavenger receptor CD36 and LIMPII analog-I (CLA-1)-mediated pathway. Human EA.hy 926 endothelial cells were incubated in the presence of native HDL or PEth-HDL. VEGF concentration and CLA-1 protein expression were measured. Human CLA-1 receptor-mediated mechanisms in endothelial cells were studied using CLA-1 blocking antibody and protein kinase inhibitors. Phosphatidylethanol-containing HDL particles caused a 6-fold increase in the expression of CLA-1 in endothelial cells compared with the effect of native HDL. That emergent effect was mediated mainly through protein kinase C and p44/42 mitogen-activated protein kinase pathways. PEth increased the secretion of VEGF and that increase could be abolished by a CLA-1 blocking antibody. High density lipoprotein particles containing PEth bind to CLA-1 receptor and thereby increase the secretion of VEGF from endothelial cells. Ethanol-induced protective effects against coronary heart disease may be explained, at least partly, by the effects of PEth-modified HDL particles on VEGF via CLA-1-mediated mechanisms in endothelial cells.


End-grafted low-molecular-weight PNIPAM does not collapse above the LCST.
The interfacial properties of end-grafted temperature-responsive poly(N-isopropylacryamide) (PNIPAM) were quantified by direct force measurements both above and below the lower critical solution temperature (LCST) of 32 degrees C. The forces were measured between identical, opposing PNIPAM films and between a PNIPAM film and a lipid membrane. At the grafting densities and molecular weights investigated, the polymer extension did not change significantly above the LCST, and the polymers did not adhere. Below the LCST, the force-distance profiles suggest a vertical phase separation, which results in a diluter outer layer and a dense surface proximal layer. At large separations, the force profiles agree qualitatively with simple polymer theory but deviate at small separations. Importantly, at these low grafting densities and molecular weights, the end-grafted PNIPAM does not collapse above the LCST. This finding has direct implications for triggering liposomal drug release with end-grafted PNIPAM, but it increases the temperature range where these short PNIPAM chains function as steric stabilizers.


All eyes on me?! Social anxiety and self-directed perception of eye gaze.
To date, only little is known about the self-directed perception and processing of subtle gaze cues in social anxiety that might however contribute to excessive feelings of being looked at by others. Using a web-based approach, participants (n=174) were asked whether or not briefly (300 ms) presented facial expressions modulated in gaze direction (0°, 2°, 4°, 6°, 8°) and valence (angry, fearful, happy, neutral) were directed at them. The results demonstrate a positive, linear relationship between self-reported social anxiety and stronger self-directed perception of others' gaze directions, particularly for negative (angry, fearful) and neutral expressions. Furthermore, faster responding was found for gaze more clearly directed at socially anxious individuals (0°, 2°, and 4°) suggesting a tendency to avoid direct gaze. In sum, the results illustrate an altered self-directed perception of subtle gaze cues. The possibly amplifying effects of social stress on biased self-directed perception of eye gaze are discussed.


Enhanced Immune Responses by Virus-Mimetic Polymeric Nanostructures Against Infectious Diseases.
Intermittent outbreaks of global pandemic disease have spurred new sensors and medicines development for the prevention of disease spread. This perspective specifically covers recent advances, challenges, and future directions in virus-mimetic polymeric nanostructures and their application in biological medicines with a special emphasis on subunit vaccine development. With tailorable compositions and properties, polymers facilitate the ingenious design of various polymeric nanostructures. As one type of polymeric nanostructures, virus-mimetic polymeric nanostructures have been developed as an attractive platform for enhanced immune responses, since they combine the merits of polymer nanocores with the biomimetic characteristic of virus which displays multivalent epitopes on their surfaces. This perspective also provides an applicative approach to rationally design virus-mimetic polymeric platforms based on nanostructures that are self-assembled by using polymers as templates and the antigens and metal oxide clusters loaded on their surface to mimic viruses in size and surface antigenicity. Sub-200 nm virus-mimetic polymeric nanostructures are in a relatively lower level of endotoxins and can promote the antigens to elicit potent humoral and cellular immune responses against pathogenic bacteria. The promising development of virus-mimetic polymeric nanostructures will continue to protect human health from common pathogens and emerging infectious threats.


The Perspectives of Patients and Health Professionals Regarding the Tuberculosis Control Programme in Recife, Brazil: A Contribution to Evaluation.
The study objective is to describe patients and professionals' perspectives on the Tuberculosis Control Program (PCT) in Recife, Brazil, contributing to the program evaluation. A cross-sectional study was conducted in three purposively selected sites, representing the three levels of care in the public health system. All eligible PCT patients in sites A, B and C were invited to participate (n = 123). Physicians, nurses, pharmacists and community health agents providing care to PCT patients in these sites, plus their managers, were purposively selected. Data were collected by means of interviews with 44 patients and a questionnaire to 24 professionals. Instruments encompassed previously published items to capture stakeholders' perspectives (16 and 12 closed-questions, respectively), grouped into categories. The overall evaluation by patients was unsatisfactory (median score 35%; third quartile below 50%; interquartile range 21.9%). Analysis of scores by categories showed that opinions about organizational accessibility were significantly worse than about economic and geographical accessibility, taken together. Overall the median score attributed by professionals was 52% (third quartile below 65%). Professionals had significantly worse opinions about diagnosis, clinical and laboratory assistance. Patients and professionals' perspectives highlight potential opportunities for improvement. Our findings can be used by managers as a starting point for shared decision-making, potentially contributing to a better performance of the PCT in Recife and, consequently, reducing the risk posed by tuberculosis.


Effect of isoflurane and other potent inhaled anesthetics on minimum alveolar concentration, learning, and the righting reflex in mice engineered to express alpha1 gamma-aminobutyric acid type A receptors unresponsive to isoflurane.
Enhancement of the function of gamma-aminobutyric acid type A receptors containing the alpha1 subunit may underlie a portion of inhaled anesthetic action. To test this, the authors created gene knock-in mice harboring mutations that render the receptors insensitive to isoflurane while preserving sensitivity to halothane. The authors recorded miniature inhibitory synaptic currents in hippocampal neurons from hippocampal slices from knock-in and wild-type mice. They also determined the minimum alveolar concentration (MAC), and the concentration at which 50% of animals lost their righting reflexes and which suppressed pavlovian fear conditioning to tone and context in both genotypes. Miniature inhibitory postsynaptic currents decayed more rapidly in interneurons and CA1 pyramidal cells from the knock-in mice compared with wild-type animals. Isoflurane (0.5-1 MAC) prolonged the decay phase of miniature inhibitory postsynaptic currents in neurons of the wild-type mice, but this effect was significantly reduced in neurons from knock-in mice. Halothane (1 MAC) slowed the decay of miniature inhibitory postsynaptic current in both genotypes. The homozygous knock-in mice were more resistant than wild-type controls to loss of righting reflexes induced by isoflurane and enflurane, but not to halothane. The MAC for isoflurane, desflurane, and halothane did not differ between knock-in and wild-type mice. The knock-in mice and wild-type mice did not differ in their sensitivity to isoflurane for fear conditioning. gamma-Aminobutyric acid type A receptors containing the alpha1 subunit participate in the inhibition of the righting reflexes by isoflurane and enflurane. They are not, however, involved in the amnestic effect of isoflurane or immobilizing actions of inhaled agents.


A critical re-appraisal of lymph-venous shunt in the management of massive ascites.
Lymph-venous shunt is one of most investigated procedures in the management of intractable ascites. However, there is considerable variation in the reported results. Personal experience with twenty-one operated cases reveals a dubious role for this intervention. Frequent anatomical variations and uncertain role and incidence of duct-end stenosis, in our opinion, reduces the efficacy of the procedure.


SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T cell activation.
T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain-containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain-containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor- and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2.


In Vitro Assessment of Anthelmintic Activities of Rauwolfia vomitoria (Apocynaceae) Stem Bark and Roots against Parasitic Stages of Schistosoma mansoni and Cytotoxic Study.
Schistosomiasis is a Neglected Tropical Diseases which can be prevented with mass deworming chemotherapy. The reliance on a single drug, praziquantel, is a motivation for the search of novel antischistosomal compounds. This study investigated the anthelmintic activity of the stem bark and roots of Rauwolfia vomitoria against two life stages of Schistosoma mansoni. Both plant parts were found to be active against cercariae and adult worms. Within 2 h of exposure all cercariae were killed at a concentration range of 62.5-1000 µg/mL and 250-1000 µg/mL of R. vomitoria stem bark and roots, respectively. The LC50 values determined for the stem bark after 1 and 2 h of exposure were 207.4 and 61.18 µg/mL, respectively. All adult worms exposed to the concentrations range of 250-1000 µg/mL for both plant parts died within 120 h of incubation. The cytotoxic effects against HepG2 and Chang liver cell assessed using MTT assay method indicated that both plant extracts which were inhibitory to the proliferation of cell lines with IC50 > 20 μg/mL appear to be safe. This report provides the first evidence of in vitro schistosomicidal potency of R. vomitoria with the stem bark being moderately, but relatively, more active and selective against schistosome parasites. This suggests the presence of promising medicinal constituent(s).


New baccalaureate graduates' perceptions of organizational conflict.
This study explores the process of professional socialization in a sample of newly graduated baccalaureate nurses whose first experience as practicing professionals was in a hospital organizational system. Professional socialization was defined in terms of concept of identity reassessment as proposed by Strauss and in terms of the new graduates' descriptions of their own behavior during conflictual situations in the work setting. These descriptions were identified as conflict-reporting behavior and analyzed from two aspects: the source of the conflict and the level reached by the behavior of the respondent, as defined by a model for organizational conflict proposed by Pondy. Although changes in conflict-reporting behavior with increasing experience in the hospital bureaucracy were noted, the study findings showed no significant relationships between this behavior and ideas about the nursing role and the value of organizational inducements. Some trends in conflict-reporting behavior were noted in relation to three other variables: the size of the unit on which the new graduate was working, the identity of the other persons in the conflict, and the new graduates' work experience in a hospital system while in school.


The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials.
The aim of this systematic review was to assess the quality and outcomes of clinical trials investigating the effect of St John's wort extracts on the metabolism of drugs by CYP3A. Prospective clinical trials assessing the effect of St John's wort (SJW) extracts on metabolism by CYP3A were identified through computer-based searches (from their inception to May 2005) of Medline, Cinahl, PsycINFO, AMED, Current Contents and Embase, hand-searches of bibliographies of relevant papers and consultation with manufacturers and researchers in the field. Two reviewers selected trials for inclusion, independently extracted data and recorded details on study design. Thirty-one studies met the eligibility criteria. More than two-thirds of the studies employed a before-and-after design, less than one-third of the studies used a crossover design, and only three studies were double-blind and placebo controlled. In 12 studies the SJW extract had been assayed, and 14 studies stated the specific SJW extract used. Results from 26 studies, including all of the 19 studies that used high-dose hyperforin extracts (>10 mg day(-1)), had outcomes consistent with CYP3A induction. The three studies using low-dose hyperforin extracts (<4 mg day(-1)) demonstrated no significant effect on CYP3A. There is reasonable evidence to suggest that high-dose hyperforin SJW extracts induce CYP3A. More studies are required to determine whether decreased CYP3A induction occurs after low-dose hyperforin extracts. Future studies should adopt study designs with a control phase or control group, identify the specific SJW extract employed and provide quantitative analyses of key constituents.


'Alarming but very necessary': working with staff groups around the sexual abuse of adults with learning disabilities.
This study focused on the knowledge of front line staff, as individuals and in groups, in relation to the sexual abuse of adults with learning disabilities and was designed to inform staff training and policy initiatives and to explore gender dynamics. It showed that front line staff were alert to the possibility of sexual abuse but unclear about their roles and responsibilities making this an area of great concern to them. One third knew of people who had been abused but these had been dealt with haphazardly, leaving front line staff holding disproportionate anxiety on behalf of the service as a whole.


Immunologic reactivity to work-related airborne allergens in people occupationally exposed to dust from herbs.
A group of 150 people occupationally exposed to dust from herbs were examined. The examined group consisted of 47 thyme farmers, 32 chamomile farmers, 31 sage farmers and 40 workers of herbs processing industry. As a reference group, 50 urban dwellers, not exposed to any kind of organic dust, were examined. Skin prick tests and precipitin tests were conducted with, respectively, 4 and 11 microbial antigens associated with organic dust. Both skin and precipitin tests were also conducted with herbal extracts of chamomile and sage. Precipitin tests were carried out with sera not concentrated and sera 3-fold concentrated. Tests for inhibition of leukocyte migration (MIF) were also conducted with 4 microbial antigens. People occupationally exposed to dust from herbs showed a higher frequency of positive skin reactions to microbial antigens compared to the reference group. The results of precipitin test also revealed greater reactivity to the environmental microbial antigens in the examined group, compared to the reference group. The highest frequency of positive results was noted with the antigen of Pantoea agglomerans (30.6 % with sera not concentrated and 48.3 % with sera 3-fold concentrated) - the difference compared to the reference group (12.0 %) was highly significant (p < 0.01). The frequencies of positive results of MIF test in the examined group were high with all antigens tested: Arthrobacter globiformis (12.6 %), Pantoea agglomerans (11.1 %), Saccharopolyspora rectivirgula (17.0 %), Aspergillus fumigatus (13.3 %), and, compared to the reference group with no positive result for any antigen, all the differences were significant (p < 0.05). In conclusion, the frequency of positive allergological reactions to airborne microorganisms was high in people occupationally exposed to dust from herbs and suggests a potential role of microbial allergens in the pathogenesis of work-related health disorders among herb workers. The risk of sensitization seems to be greatest among thyme farmers, who showed the highest positive response. The results confirmed the particular allergenic importance of Gram-negative bacterium Pantoea agglomerans.


Prognostic Values of Transforming Growth Factor-Beta Subtypes in Ovarian Cancer.
To explore the potential role of the transforming growth factor-beta (TGF-β) subtypes in the prognosis of ovarian cancer patients. Materials and Methods. The prognostic roles of individual TGF-β subtypes in women with ovarian cancer were retrieved from the Kaplan-Meier plotter (KM plotter) database. In addition, the Oncomine database and immunohistochemistry were used to observe the mRNA and protein expression of TGF-β subtypes between human ovarian carcinoma and normal ovarian samples, respectively. TGF-β1 and TGF-β4 were totally uncorrelated with survival outcomes in women with ovarian cancer. Increased TGF-β2 and TGF-β3 mRNA expression was markedly related to unfavorable prognosis, especially in women with serous, poorly differentiated, and late-stage ovarian carcinoma. High expression levels of TGF-β2 were related to worse progression-free survival (PFS) while TGF-β3 was linked to unfavorable overall survival (OS) and PFS in women with TP53-mutated ovarian cancer. TGF-β2 was associated with poor OS and PFS from treatment with chemotherapy with platins, Taxol, or a platin+Taxol. However, overexpression of TGF-β3 was associated with poor OS from the use of platins and poor PFS of Taxol or a platin+Taxol in women with ovarian carcinoma. Furthermore, the expression of TGF-β2 mRNA and protein was higher but only TGF-β3 mRNA expression was higher in cancerous tissues than in normal ovarian samples. Higher expression of TGF-β2 functioned as a significant predictor of poor prognosis in women with ovarian cancer, especially those with TP53 mutations or who were undergoing chemotherapy with platins, Taxol, or a platin+Taxol.