Synthesis and characterization of chitosan/ZnO nanoparticle composite membranes.
Novel chitosan/ZnO nanoparticle (CS/nano-ZnO) composite membranes were prepared via the method of sol-cast transformation and studied by UV-vis absorption spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray fluorescence spectrometry (EDX). The characterization revealed that ZnO nanoparticles dispersed homogeneously within the chitosan matrix. The mechanical and antibacterial properties of the product were investigated. The results showed that the ZnO content had an effect on the mechanical properties of CS/nano-ZnO composite membranes, and that the antibacterial activities of CS membranes for Bacillus subtilis, Escherichia coli, and Staphylococcus aureus were enhanced by the incorporation of ZnO. Further, CS/nano-ZnO composite membranes with 6-10 wt% ZnO exhibited high antibacterial activities.


Applying GRADE-CERQual to qualitative evidence synthesis findings: introduction to the series.
The GRADE-CERQual ('Confidence in the Evidence from Reviews of Qualitative research') approach provides guidance for assessing how much confidence to place in findings from systematic reviews of qualitative research (or qualitative evidence syntheses). The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. Confidence in the evidence from qualitative evidence syntheses is an assessment of the extent to which a review finding is a reasonable representation of the phenomenon of interest. CERQual provides a systematic and transparent framework for assessing confidence in individual review findings, based on consideration of four components: (1) methodological limitations, (2) coherence, (3) adequacy of data, and (4) relevance. A fifth component, dissemination (or publication) bias, may also be important and is being explored. As with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach for effectiveness evidence, CERQual suggests summarising evidence in succinct, transparent, and informative Summary of Qualitative Findings tables. These tables are designed to communicate the review findings and the CERQual assessment of confidence in each finding. This article is the first of a seven-part series providing guidance on how to apply the CERQual approach. In this paper, we describe the rationale and conceptual basis for CERQual, the aims of the approach, how the approach was developed, and its main components. We also outline the purpose and structure of this series and discuss the growing role for qualitative evidence in decision-making. Papers 3, 4, 5, 6, and 7 in this series discuss each CERQual component, including the rationale for including the component in the approach, how the component is conceptualised, and how it should be assessed. Paper 2 discusses how to make an overall assessment of confidence in a review finding and how to create a Summary of Qualitative Findings table. The series is intended primarily for those undertaking qualitative evidence syntheses or using their findings in decision-making processes but is also relevant to guideline development agencies, primary qualitative researchers, and implementation scientists and practitioners.


Tuberculous periprosthetic infection precipitated by infliximab therapy.
Biological therapy with TNF-α inhibitors have been increasingly used in the treatment of inflammatory arthritis. Systemic tuberculosis infections are often known to occur following treatment with these biological agents. However, no case of periprosthetic tuberculous infection of the hip following this therapy has been reported. We report a case of a 45-year-old man who developed periprosthetic tuberculous infection soon after infliximab injection. We also discuss the need of pretreatment awareness, high index of suspicion, early diagnosis and management of such case.


[Adaptation of hepatitis A virus strain (JaM-55) originally pathogenic for monkeys to a cell culture].
The results of adaptation of hepatitis A viral strain JaM-55 to the culture of embryo kidney cells FRhk-4 from macaque Rhesus are presented. The viral strain was isolated from a M. fascicularis suffering from spontaneous hepatitis. Before inoculating the cell culture the virus was passaged twice in the M. arctoides capable of reproducing hepatitis. FRhk-4 cell line inoculation by the monkey liver extract, containing the strain HAV-YaM-55, resulted in isolation of single viral particles of hepatitis A in the preparations obtained at the first 3 passages by the 28-31 day of cultivation. Beginning from the fourth passage the abrupt increase in the number of viral particles and hepatitis A antigen was registered. There were no traces of cytopathogenic effect at any level of viral passages in the inoculated cell culture. The adapted virus contains hepatitis A viral RNA identified by spot hybridization with the cloned cDNA of hepatitis A virus.


Host evasion and exploitation schemes of Mycobacterium tuberculosis.
Tuberculosis, an ancient disease of mankind, remains one of the major infectious causes of human death. We examine newly discovered facets of tuberculosis pathogenesis and explore the evolution of its causative organism Mycobacterium tuberculosis from soil dweller to human pathogen. M. tuberculosis has coevolved with the human host to evade and exploit host macrophages and other immune cells in multiple ways. Though the host can often clear infection, the organism can cause transmissible disease in enough individuals to sustain itself. Tuberculosis is a near-perfect paradigm of a host-pathogen relationship, and that may be the challenge to the development of new therapies for its eradication.


Mapping of Rice Varieties and Sowing Date Using X-Band SAR Data.
Rice is a major staple food for nearly half of the world's population and has a considerable contribution to the global agricultural economy. While spaceborne Synthetic Aperture Radar (SAR) data have proved to have great potential to provide rice cultivation area, few studies have been performed to provide practical information that meets the user requirements. In rice growing regions where the inter-field crop calendar is not uniform such as in the Mekong Delta in Vietnam, knowledge of the start of season on a field basis, along with the planted rice varieties, is very important for correct field management (timing of irrigation, fertilization, chemical treatment, harvest), and for market assessment of the rice production. The objective of this study is to develop methods using SAR data to retrieve in addition to the rice grown area, the sowing date, and the distinction between long and short cycle varieties. This study makes use of X-band SAR data from COSMO-SkyMed acquired from 19 August to 23 November 2013 covering the Chau Thanh and Thoai Son districts in An Giang province, Viet Nam, characterized by a complex cropping pattern. The SAR data have been analyzed as a function of rice parameters, and the temporal and polarization behaviors of the radar backscatter of different rice varieties have been interpreted physically. New backscatter indicators for the detection of rice paddy area, the estimation of the sowing date, and the mapping of the short cycle and long cycle rice varieties have been developed and assessed. Good accuracy has been found with 92% in rice grown area, 96% on rice long or short cycle, and a root mean square error of 4.3 days in sowing date. The results have been discussed regarding the generality of the methods with respect to the rice cultural practices and the SAR data characteristics.


Analysis of the current applicant pool to vascular surgery: who are they and where do they come from?
There is a manpower crisis in vascular surgery. There may be too few vascular surgeons to meet the demands imposed by the aging of the "Baby-Boom" generation. More than 20% of vascular surgery positions were not filled through the match in 2004 and 2005. The number of vascular surgery training positions has doubled in the past 15 years, based on manpower studies projecting a need for additional vascular surgeons. During the same time period, the number of vascular surgery applicants has remained static. In addition, the proportion of international medical graduates has increased significantly. Furthermore, medical students appear to be selecting "lifestyle-friendly" specialties, such as emergency medicine, radiology, ophthalmology, anesthesiology, and dermatology, with increasing frequency. Approximately 60% of undergraduates in the United States and almost 50% of graduating medical students are currently women. Yet only about 25% of general surgery residents and less than 20% of current vascular surgery trainees are women. Strategies to expand the applicant pool for vascular surgery are needed and discussed in this article.


Brucella endocarditis: clinical, diagnostic, and therapeutic approach.
Brucella endocarditis is an uncommon focal complication of brucellosis. Presented here are 11 cases of Brucella endocarditis, all managed uniformly. The median duration of symptoms prior to diagnosis was 3 months. Five patients (45%) had underlying valvular damage, and in six (55%) endocarditis involved a normal valve. There was a predominance of aortic involvement (82%) and a high incidence of left ventricular failure (91%). Diagnostic suspicion was essential in order to test blood cultures correctly, which in this series were positive in 63% of the patients. Surgical treatment was undertaken in eight patients (72%), all with aortic involvement and left ventricular failure impossible to control with medication. One patient died during the immediate postoperative period. All the other patients received antibiotic therapy for 3 months, with no signs of relapse of the infection or malfunction of the prosthesis during a minimum follow-up period of 24 months.


Evidence for global mobility in the premelting of a polynucleotide from temperature-dependent Raman optical activity.
The backscattered Raman and Raman optical activity (ROA) spectra of poly(rA)-poly(rU) at 20 degrees C and 45 degrees C in buffered aqueous solution between 650 and 1750 cm(-1) are reported. Although the intensity of the majority of the Raman bands increase by varying amounts as the temperature is raised in accordance with the well-known hypochromic effect, the reverse effect is found for the ROA signals which we attribute to thermal accessibility of a greater number of distinct conformations leading to cancellation of ROA signals. The difference ROA spectrum obtained by subtracting the spectrum recorded at 45 degrees C from that recorded at 20 degrees C displays a very similar sign pattern to those at both 20 degrees C and 45 degrees C throughout the spectral region examined. This indicates that the same average structure is maintained in this temperature range and that the thermal fluctuations are correlated through the bases, the glycosidic link, the sugar ring, and the phosphate backbone of both strands. These results indicate that ROA may be a useful new probe of the dynamics of nucleic acid in solution.


ROS1 Kinase Inhibitors for Molecular-Targeted Therapies.
ROS1 is a pivotal transmembrane receptor protein tyrosine kinase which regulates several cellular processes like apoptosis, survival, differentiation, proliferation, cell migration, and transformation. There is increasing evidence supporting that ROS1 plays an important role in different malignancies including glioblastoma, colorectal cancer, gastric adenocarcinoma, inflammatory myofibroblastic tumor, ovarian cancer, angiosarcoma, and non small cell lung cancer; thus, ROS1 has become a potential drug discovery target. ROS1 shares about 49% sequence homology with ALK primary structure; therefore, wide range of ALK kinase inhibitors have shown in vitro inhibitory activity against ROS1 kinase. After Crizotinib approval by FDA for the management of ALK-rearranged lung cancer, ROS1-positive tumors have been focused. Although significant advancements have been achieved in understanding ROS1 function and its signaling pathways plus recent discovery of small molecules modulating ROS1 protein, a vital need of medicinal chemistry efforts is still required to produce selective and potent ROS1 inhibitors as an important therapeutic strategy for different human malignancies. This review focuses on the current knowledge about different scaffolds targeting ROS1 rearrangements, methods to synthesis, and some biological data about the most potent compounds that have delivered various scaffold structures.


Carcinoma of the renal pelvis: a ten-year review.
Twenty-two cases of renal pelvic carcinoma are reviewed, of which nine were squamous cell and 13 were transitional cell carcinomas. No difference in symptoms between the two types was seen except for an increased incidence of a palpable mass and weight loss among patients having the squamous cell variety. Thirteen of the 22 patients have died of renal pelvic carcinoma. Reasons for the low survival rate are discussed. Treatment of transitional cell carcinoma with nephroureterectomy and local lymph node dissection is recommended.


Flexible and Red-Emissive Organic Single-Crystal Microresonator for Efficient Active Waveguides.
We fabricated a flexible and red-emissive microcrystal resonator for highly efficient optical waveguiding. The microfiber crystals of diketopyrrolopyrrole (DPP) used in this work possess a high photoluminescence (PL) quantum efficiency (ΦPL = 0.45) and exhibit a micromechanical deformation shape in the curved state. The crystals show optical fringes in their PL spectra, suggesting the existence of a naturally formed Fabry-Pérot crystal resonator owing to its flat crystal surface. The group refractive index (ng) and Rabi splitting energy (ℏΩ) indicating the coupling strength between excitons and resonator photons are large (ng = 3.7-6.0, ℏΩ = 1.38 eV), suggesting the strong confinement of waveguiding photons. Spatially resolved PL measurements revealed that the PL in a crystal fiber is efficiently waveguided, even in a curved crystal with a very small curvature radius of 11 μm. Strong photon confinement inside a crystal resonator is a plausible origin of efficient optical waveguiding.


Therapeutic effect of adjuvant therapy added to constraint-induced movement therapy in patients with subacute to chronic stroke: a systematic review and meta-analysis.
This review investigated the effectiveness of adjuvant therapy combined with constraint-induced movement therapy (CIMT) in improving the paretic upper limb functionality in adults with stroke sequelae during the subacute to chronic rehabilitation phase. In this systematic review and meta-analysis of randomized controlled trials (RCT), electronic databases, including PubMed, Web of Science, CINAHL, and MEDLINE, were searched. We included RCTs that investigated the outcomes of adjuvant therapy (i.e. other therapies) added to CIMT compared with CIMT alone. Key trial findings were qualitatively synthesized and analyzed. This meta-analysis examined variables, such as mean scores and standard deviations, using the following outcome measures: Fugl-Meyer Assessment (FMA) upper limb items, Action Research Arm Test (ARAT), Amount of Use (AOU) of Motor Activity Log (MAL), and Quality of Movement (QOM) of MAL. Eighteen eligible RCTs were included in the analysis. Adding CIMT to adjunctive therapy significantly improved FMA compared with CIMT alone (mean difference [MD] 4.02, 95% confidence interval [CI] 2.60-5.44; I2 = 85%; 15 studies; 330 participants). Similarly, the ARAT and MAL-AOU scores improved significantly. CIMT combined with several adjunctive therapies effectively improved upper limb function.


Music Training and Education Slow the Deterioration of Music Perception Produced by Presbycusis in the Elderly.
The perception of music depends on the normal function of the peripheral and central auditory system. Aged subjects without hearing loss have altered music perception, including pitch and temporal features. Presbycusis or age-related hearing loss is a frequent condition in elderly people, produced by neurodegenerative processes that affect the cochlear receptor cells and brain circuits involved in auditory perception. Clinically, presbycusis patients have bilateral high-frequency hearing loss and deteriorated speech intelligibility. Music impairments in presbycusis subjects can be attributed to the normal aging processes and to presbycusis neuropathological changes. However, whether presbycusis further impairs music perception remains controversial. Here, we developed a computerized version of the Montreal battery of evaluation of amusia (MBEA) and assessed music perception in 175 Chilean adults aged between 18 and 90 years without hearing complaints and in symptomatic presbycusis patients. We give normative data for MBEA performance in a Latin-American population, showing age and educational effects. In addition, we found that symptomatic presbycusis was the most relevant factor determining global MBEA accuracy in aged subjects. Moreover, we show that melodic impairments in presbycusis individuals were diminished by music training, while the performance in temporal tasks were affected by the educational level and music training. We conclude that music training and education are important factors as they can slow the deterioration of music perception produced by age-related hearing loss.


Phase I trial of an all-oral combination chemotherapy regimen: topotecan and capecitabine in solid tumor patients.
The objective of this phase I study was to investigate the safety of an all-oral combination chemotherapy regimen: topotecan and capecitabine. Topotecan was administered once a day for 5 consecutive days followed by 2 days of rest and was administered again for 5 consecutive days. The starting dose of topotecan was 0.5 mg/m2/d(-1). Capecitabine was administered concurrently at an oral dose of 1800 mg/m2/d(-1) divided twice daily for 14 concurrent consecutive days. Each cycle of treatment was 21 days. Topotecan pharmacokinetic studies were performed on day 1 of cycles 1 and 2. Nineteen patients with refractory cancer were treated. Dose-limiting toxicity (thrombocytopenia, diarrhea) was observed in 2 of 3 patients at a topotecan dose of 2.0 mg/m2/d(-1). A total of 10 patients were treated at the maximum-tolerated dose of topotecan (1.5 mg/m2/d(-1)) and only 1 treatment-related grade 3 nonhematologic toxic event was demonstrated; however, grade 3 hematologic toxicity was observed in 8 of 10 patients at the maximum-tolerated dose, although no correlated clinical sequela resulted. One patient achieved a partial response and 7 achieved stable disease for 4 months or longer. Measurement of plasma topotecan showed pharmacokinetics consistent with no alteration by capecitabine. In conclusion, we recommend further investigation of oral topotecan (1.5 mg/m2/d(-1)) on days 1 to 5 of each week for 2 weeks in combination with capecitabine (180 mg/m2 twice daily) on days 1 to 14 within a 21-day cycle.


Tic disorders of childhood.
Tic disorders may be classified as simple tics, chronic motor tics or Tourette syndrome, the most severe of the three types. Tourette syndrome is rather uncommon and is often misdiagnosed. Tic disorders of childhood probably have an organic etiology and a genetic component. An increased incidence of obsessive-compulsive behavior, attention deficit disorder and other abnormalities have been reported in Tourette patients. Haloperidol is often useful in controlling severe tic symptoms, while stimulant drugs may worsen the symptoms.


Determination of the time course and extent of neurotoxicity at defined temperatures in cultured neurons using a modified multiwell plate fluorescence scanner.
The cellular and molecular mechanisms of hypoxic/ischemic neurodegeneration are sensitive to numerous factors that modulate the time course and degree of neuronal death. Among such factors is hypothermia, which can dramatically protect neurons from injury. To examine and control for temperature-dependent effects, we developed a technique that provides for a high-throughput, accurate, and reproducible determination of the time course and degree of neurotoxicity in cultured cortical neurons at precisely defined temperatures. We used a fluorescence multiwell plate scanner, modified by us to permit the control of temperature, to perform serial quantitative measurements of propidium iodide (PI) fluorescence in cortical neuronal cultures exposed to excitotoxic insults. In validating this approach, we show that these time course measurements correlate highly with manual counts of PI-stained cells in the same cultures (r = 0.958, p < 0.0001) and with lactate dehydrogenase release (r = 0.964, p < 0.0001). This method represents an efficient approach to mechanistic and quantitative studies of cell death as well as a high-throughput technique for screening new neuroprotective therapies in vitro.


Hair cycle-specific immunolocalization of retinoic acid synthesizing enzymes Aldh1a2 and Aldh1a3 indicate complex regulation.
Retinoic acid has long been known to alter skin and hair growth but an exact mechanism is unclear. This study was performed to examine the sites of endogenous retinoic acid synthesis in the cycling hair follicle to better understand the role retinoic acid plays in this process. Retinal dehydrogenases (Aldh1a1, 2, and 3, formerly Raldh 1, 2, and 3) are the enzymes responsible for the last step in retinoic acid synthesis. Immunohistochemistry was performed on adult C57BL/6J mouse skin sections with antibodies against Aldh1a2 and Aldh1a3. Aldh1a2 expression was seen primarily in the outer root sheath and basal/spinous layer during all stages of the hair cycle, and in the bulge during anagen and early catagen, whereas Aldh1a3 expression was primarily in the dermal papilla, pre-cortex, and hair shaft during mid-late anagen. The expression patterns of these two similar retinoic acid synthesizing enzymes at specific follicular sites suggest that they mediate and are regulated by different epithelial proliferation and differentiation signaling pathways.


Impact of acute chest pain Tc-99m sestamibi myocardial perfusion imaging on clinical management.
Previous studies have demonstrated the high sensitivity and specificity of technetium 99m sestamibi scintigraphy during acute chest pain myocardial perfusion imaging. However, no study has shown that this technique would alter clinical management in practice. One hundred twenty consecutive patients were injected with Tc-99m sestamibi (22 mCi) during pain; single photon emission computed tomography was performed 1 to 6 hours later. The population included inpatients and those who arrived at the emergency department with chest pain deemed to be at intermediate risk for myocardial ischemia. The requesting physician completed a questionnaire before the study, indicating the likelihood of cardiac disease and proposed management had the test not been available. Follow-up management was evaluated from medical records. There was a 34% reduction in total admissions and 59% in planned admissions to the coronary care unit (P <.001). Conversely, 7 patients had discharge cancelled and 17 required coronary care purely because of abnormal acute rest myocardial perfusion imaging results. Coronary angiography was reduced by 40% in a selected subgroup. In our population, acute rest myocardial perfusion imaging reduced total admissions and altered resource utilization. This may result in more appropriate triage of individual patients in the management algorithm, as well as potential cost savings.


Spectroscopic properties in Er3+-doped germanotellurite glasses and glass ceramics for mid-infrared laser materials.
Transparent Er3+-doped germanotellurite glass ceramics (GCs) with variable Te/Ge ratio were prepared by controllable heat-treated process. X-ray diffraction (XRD) and transmission electron microscope (TEM) confirmed the formation of nanocrystals in glass matrix. Raman spectra were used to investigate the evolution of glass structure and photon energy. Fourier transform infrared (FTIR) spectra were introduced to characterize the change of hydroxyl group (OH-) content. Enhanced 2.7 μm emission was achieved from Er3+-doped GCs upon excitation with a 980 nm laser diode (LD), and the influence of GeO2 concentration and heat-treated temperature on the spectroscopic properties were also discussed in detail. It is found that the present Er3+-doped GC possesses large stimulated emission cross section at around 2.7 μm (0.85 × 10-20 cm2). The advantageous spectroscopic characteristics suggest that the obtained GC may be a promising material for mid-infrared fiber lasers.


Hierarchical steepness, counter-aggression, and macaque social style scale.
Nonhuman primates show remarkable variation in several aspects of social structure. One way to characterize this variation in the genus Macaca is through the concept of social style, which is based on the observation that several social traits appear to covary with one another in a linear or at least continuous manner. In practice, macaques are more simply characterized as fitting a four-grade scale in which species range from extremely despotic (grade 1) to extremely tolerant (grade 4). Here, we examine the fit of three core measures of social style-two measures of dominance gradients (hierarchical steepness) and another closely related measure (counter-aggression)-to this scale, controlling for phylogenetic relationships. Although raw scores for both steepness and counter-aggression correlated with social scale in predicted directions, the distributions appeared to vary by measure. Counter-aggression appeared to vary dichotomously with scale, with grade 4 species being distinct from all other grades. Steepness measures appeared more continuous. Species in grades 1 and 4 were distinct from one another on all measures, but those in the intermediate grades varied inconsistently. This confirms previous indications that covariation is more readily observable when comparing species at the extreme ends of the scale than those in intermediate positions. When behavioral measures were mapped onto phylogenetic trees, independent contrasts showed no significant consistent directional changes at nodes below which there were evolutionary changes in scale. Further, contrasts were no greater at these nodes than at neutral nodes. This suggests that correlations with the scale can be attributed largely to species' phylogenetic relationships. This could be due in turn to a structural linkage of social traits based on adaptation to similar ecological conditions in the distant past, or simply to unlinked phylogenetic closeness.


The role of intracellular amyloid beta in Alzheimer's disease.
Extracellular amyloid beta (Abeta) that confers neurotoxicity and modulates synaptic plasticity and memory function has been central to the amyloid hypothesis of Alzheimer's disease (AD) pathology. Like many other misfolded proteins identified in neurodegenerative disorders, Abeta also accumulates inside the AD neurons. This intracellular Abeta affects a variety of cellular physiology from protein degradation, axonal transport, autophagy to apoptosis, further documenting the role of Abeta in AD. Therapeutics targeting intracellular Abeta could be effective treatment for AD.


Pregnancy in heart transplant recipients: management and outcome.
To determine the outcome of pregnancies in cardiac allograft recipients. Thirty women who became pregnant after heart transplantation were identified from cases managed personally, questionnaires sent to all cardiac transplant centers, and review of the literature. Mothers were evaluated for evidence of rejection and for obstetric complications. The infants were observed for congenital abnormalities and perinatal morbidity or mortality. Frequent pregnancy complications included chronic hypertension (48%), preeclampsia (24%), and preterm labor (28%). The rate of cesarean delivery was 32%. Six episodes of rejection required treatment, and three late maternal deaths occurred. Among the 27 live births, 17 infants were born after 36 weeks' gestation and ten were preterm, five were small for gestational age, and four had neonatal complications. There were no congenital anomalies. Pregnancies in heart transplant recipients present management problems similar to those seen in patients with other allografts and should be considered high risk.


The reliability and validity of measurements of human dental casts made by an intra-oral 3D scanner, with conventional hand-held digital callipers as the comparison measure.
Intra-oral 3D scanning of dentitions has the potential to provide a fast, accurate and non-invasive method of recording dental information. The aim of this study was to assess the reliability of measurements of human dental casts made using a portable intra-oral 3D scanner appropriate for field use. Two examiners each measured 84 tooth and 26 arch features of 50 sets of upper and lower human dental casts using digital hand-held callipers, and secondly using the measuring tool provided with the Zfx IntraScan intraoral 3D scanner applied to the virtual dental casts. The measurements were repeated at least one week later. Reliability and validity were quantified concurrently by calculation of intra-class correlation coefficients (ICC) and standard errors of measurement (SEM). The measurements of the 110 landmark features of human dental casts made using the intra-oral 3D scanner were virtually indistinguishable from measurements of the same features made using conventional hand-held callipers. The difference of means as a percentage of the average of the measurements by each method ranged between 0.030% and 1.134%. The intermethod SEMs ranged between 0.037% and 0.535%, and the inter-method ICCs ranged between 0.904 and 0.999, for both the upper and the lower arches. The inter-rater SEMs were one-half and the intra-method/rater SEMs were one-third of the inter-method values. This study demonstrates that the Zfx IntraScan intra-oral 3D scanner with its virtual on-screen measuring tool is a reliable and valid method for measuring the key features of dental casts.


The "Wagshurst study": p.Val40Ile transthyretin gene variant causes late-onset cardiomyopathy.
Transthyretin-related amyloidosis (ATTR) is characterized by a wide heterogeneity of genotypes and predominantly neurological and cardiac phenotypes. This study aims to characterize a cohort of patients with the rare transthyretin (TTR) Val20Ile (p.TTRVal40Ile) variant. This study comprises a single-center cohort of 59 individuals subsequently evaluated for TTRVal20Ile variant due to clinical (n = 13) or predictive (n = 46) reasons. All patients were mainly related to Wagshurst, a small village in the South of Germany. Clinical assessment was performed by neurological evaluation, echocardiography, electrocardiography, cardiac biomarkers, cardiac MRI (n = 13), and (99m)Tc-DPD scintigraphy (n = 16). The rare TTRVal20Ile variant was found in 41 patients; evidence of cardiac amyloidosis was present in 22 patients. Evidence of pulmonary involvement was obtained by (99m)Tc-DPD scintigraphy in eight patients. No further organ involvement was observed in any of the patients carrying TTRVal20Ile variant. Correlation of inter-ventricular septum thickness as well as decrease of left ventricular longitudinal contractility with age was observed. Moreover, thickness of inter-ventricular septum correlated with NT-proBNP plasma levels and decrease in mitral annular plane systolic excursion. Cardiac manifestation started during the early sixth life decade indicated by higher left ventricular septum thickness and NT-proBNP plasma levels as compared to patients in fifth decade of life. All patients of the seventh and eighth life decade (n = 10) presented with cardiac amyloidosis. During median follow-up of 26 (0-108) months, eight patients underwent heart transplantation with 1-year mortality rate of 25%. This large cohort of individuals carrying the TTRVal20Ile mutation reveals a predominantly cardiac phenotype with high penetrance and late onset of symptoms. Cardiac manifestation progressed to end-stage heart failure within a few years, finally requiring heart transplantation with promising long-term survival rates.


Interleukin-22 promotes proliferation and reverses LPS-induced apoptosis and steroidogenesis attenuation in human ovarian granulosa cells: implications for polycystic ovary syndrome pathogenesis.
Interleukin 22 (IL-22) plays a role in inflammatory diseases. However, whether IL-22 affects the function of ovarian granulosa cells (GCs) and its relationship with Polycystic Ovary Syndrome (PCOS)remains unclear. We investigated the level of IL-22 in human follicular fluid using ELISA. The expression and localization of the IL-22 receptor 1 (IL-22R1) in GCs were investigated by RT-PCR and immunofluorescence staining, respectively. The proliferation of KGN cells (human GCs line) was assessed by CCK-8 assay and EdU assay after treatment with recombinant human IL-22 (rhIL-22) and lipopolysaccharide (LPS). Apoptosis was assessed using flow cytometry. Apoptotic proteins and steroidogenic genes were detected by western blotting. ELISA's results showed that compared with the control group, PCOS patients showed lower expression of IL-22 in follicular fluid. Immunofluorescence showed that IL-22R1 is expressed and localized in human granulosa cell membranes. IL-22 promoted cell proliferation and reversed LPS-induced inhibition of cell proliferation. IL-22 alone did not affect apoptotic or steroidogenic protein expression, however, it reversed LPS-induced apoptosis via downregulation of Bcl-2, upregulation of Bax and cleaved caspase-3, and restoration of LPS-downregulated StAR, CYP11A1, and CYP19A1 expression. Western blotting confirmed that IL-22 activated the JAK2/STAT3 signaling. IL-22 promotes cell proliferation, inhibits apoptosis, and regulates KGN cell steroidogenesis confronted with LPS, and decreased IL-22 may be involved in the development of PCOS.


Islam, mental health and being a Muslim in the West.
The allegation that, 'Being Muslim means that you cannot be British' is often made. In view of this, we conducted a small survey (n=75) utilising purposive sampling on Muslims residing in the United Kingdom. Participants were recruited in a King's College London Islamic Society event in November 2014 in Guy's Hospital, London. 75/75 (100%) of the participants recruited responded. 69/75 (94%) of respondents either disagreed or strongly disagreed that, 'Being Muslim means that you cannot be British' (75/75 (100%) Muslim participants, 43/75 (57.3%) female participants, 32/75 (42.7%) male participants, mean Age 20.5 years, (Std. Dev. ±2.5)). This paper broadly seeks to answer two related questions. Firstly, 'What is the relationship between Islam and the West?' and secondly, 'What is the relationship between Islam and mental health?' In relation to the former, the rise of radicalization over recent years and the Islamophobia that has ensued have brought Islam and Muslims under intense scrutiny. Hence we feel it is both timely and important to offer a brief background of Islam and its relevance to the Western world. In relation to the latter, for many people religion and mental health are deeply and intimately intertwined. For example, religion can enable a person to develop mental health resilience and Islam has been reported to be a protective factor against suicidal behaviour. We conclude our paper by illustrating how the two questions are interrelated. We do so by offering an autobiographical narrative from a Muslim healthcare professional residing in the UK who developed a mental health problem precipitated by war in the country of his origin. His narrative includes descriptions of the role Islam that played in his recovery as well as his attempts to reconcile seemingly disparate aspects of his identity.


Sustainable Development Goals: Leveraging the Global Agenda for Driving Health Policy Reforms and Achieving Universal Health Coverage in India.
Universal Health Coverage (UHC) is now the critical yardstick for countries to measure and track progress toward the "Sustainable Development Goals (SDGs)." Being a signatory, India has started taking measures to attain the targets laid out within the SDG framework and achieving the UHC. With India's National Health Policy (NHP) - 2017 in place, the policy environment for transforming country's health landscape coincides with that of the global approach toward strengthening of health systems and achieving UHC. It is imperative that for achieving the desired outcomes laid down in the SDGs and NHP-2017, coordinated actions are required including political action for making health an individual's right; effective stewardship from the National Ministry of Health and Family Welfare; reorganization of health-care service delivery implementing a "systems approach;" ensuring financial protection against health-care costs; and enhancing community participation and accountability. Undertaking these steps, imbibing the learning, and dwelling upon global experiences can help the country strongly move forward towards achieving global and national targets, thereby ensuring UHC for all its citizens.


Hemodynamic effects of acute hypoxia and minute amounts of endotoxin in awake swine.
Hemodynamic measurements and arterial blood gases were determined from awake swine (n = 8) during acute hypoxia (12% O2, balance N2 for 5 minutes) and following injection of Escherichia coli endotoxin (4 microgram/kg of body weight) into the pulmonary artery. Comparison of baseline data with these treatments indicated: (1) swine exhibited a marked pulmonary pressor response to acute hypoxia (deltaBPpul = 9 to 12 mm of Hg): (2) injection of minute amounts of endotoxin led to a marked increase of pulmonary arterial blood pressure 10 to 20 minutes following the injection (deltaBPpul = 15 mm of Hg); and (3) the pulmonary pressor response to a 2nd exposure of acute hypoxia was unaffected by the intervening endotoxin injection.


Heart Failure in Patients with Preserved Ejection Fraction: Questions Concerning Clinical Progression.
Over the last two decades, important advances have been made in explaining some pathophysiological aspects of heart failure with preserved ejection fraction (HFpEF) with repercussions for the successful clinical management of the syndrome. Despite these gains, our knowledge for the natural history of clinical progression from the pre-clinical diastolic dysfunction (PDD) until the final clinical stages is significantly limited. The subclinical progression of PDD to the clinical phenotype of HFpEF and the further clinical progression to some more complex clinical models with multi-organ involvement, similar to heart failure with reduced ejection fraction (HFrEF), continue to be poorly understood. Prospective studies are needed to elucidate the natural history of clinical progression in patients with HFpEF and to identify the exact left ventricular remodeling mechanism that underlies this progression.


Impact of prostate weight on perioperative outcomes of robot-assisted laparoscopic prostatectomy with a posterior approach to the seminal vesicle.
To determine the effect of prostate weight on the preoperative and postoperative outcomes of robotic-assisted laparoscopic radical prostatectomy with a posterior approach to the seminal vesicle. This retrospective study examined prospectively collected data on 219 robotic-assisted laparoscopic radical prostatectomies performed from May 2011 to February 2013. Patients were divided into four groups based on pathologic prostate weight: <30 g, 30-49 g, 50-79 g, and ≥80 g. Continence and sexual function were assessed using validated questionnaires. Of the 219 patients, 19, 143, 51, and 6 had prostates weighing <30 g, 30-49 g, 50-79 g, and ≥80 g, respectively. Significant differences were found between the preoperative Gleason scores, total operative times, and robotic times of the groups. Both estimated blood loss and anastomosis time tended to be greater in the higher prostate weight groups, but the differences were not significant. No significant differences were observed in transfusion rate, length of catheterization, complication incidence, or positive surgical margins. The return of urinary function, as determined by questionnaire scores, was not affected by prostate weight. Robotic-assisted laparoscopic radical prostatectomy can be performed safely and with similar perioperative outcomes, regardless of prostate weight. Indeed, oncological outcome, urinary continence, and complications were similar across the prostate weight groups, suggesting that robotic-assisted laparoscopic radical prostatectomy with a posterior approach to the seminal vesicle may be performed effectively on men with large prostates, despite greater surgical times.


Primary laryngeal tuberculosis mimicking laryngeal carcinoma: CT scan features.
Laryngeal tuberculosis is a rare disease. It is almost always associated with pulmonary tuberculosis. It occurs generally in adults without BCG vaccination or in cases of the acquired immune deficiency syndrome. On laryngoscopy and imaging, it often simulates laryngeal carcinoma, and confirmation is always histological. We report the case of a 36-year-old man who presented to our hospital with dysphonia and dysphagia. Laryngoscopy revealed a lesion of the left vocal cord and the ventricular strip. CT scan found focal, regular thickening of the left vocal cord, associated with irregular thickening of the posterior laryngeal wall. A biopsy confirmed the diagnosis of tuberculosis.


[MicroRNA-23a knockdown attenuates angiotensin Ⅱ induced hypertrophy in rat H9c2 cells via activating PTEN and AMPK pathway].
Objective: To investigate if microRNA (miR) -23a knockdown could attenuate angiotensin Ⅱ(AngⅡ) induced cardiac hypertrophy by activating phosphatase and tensin homolog deleted on chromosome ten(PTEN) and AMP-activated protein kinase(AMPK) pathway. Methods: Rat H9c2 cells were cultured in DMEM high glucose medium and put in 5% CO(2) incubator at 37 ℃(normal group). After 48 hours of culture, H9c2 cells were stimulated with 10 nmol/L AngⅡ to establish cell hypertrophy model (AngⅡgroup). The H9c2 cells were inoculated in a 6-well cell culture plate and cultured in an incubator at 37 ℃. When the confluence degree of cell growth was about 70%, the cells were transfected with different reagents, and 24 hours after transfection, 10 nmol/L AngⅡ was used to interfere with the cells. The H9c2 cells were divided into different groups according to the reagents, namely AngⅡ+anti-miR group(transfected with miR-23a inhibitor), Ang Ⅱ+NC group(transfected with miR-23a inhibitor negative control), Ang Ⅱ+anti-miR+si-PTEN group(cotransfected with miR-23a inhibitor and PTEN small interference RNA(siRNA)), and AngⅡ+anti-miR+si-NC group(cotransfected with miR-23a inhibitor and PTEN siRNA negative control). The surface area of single cell was measured by Image J software.The mRNA expression levels of α-actin 1 (ACTA1) and β-myosin heavy chain (β-MHC) and miR-23a were detected by quantitative real-time PCR(qRT-PCR). The expression levels of PTEN and AMPK signal pathway related proteins were detected by Western blot. In order to verify whether miR-23a targets PTEN gene, double luciferase reporter gene experiment was performed. The luciferase reporter gene vector recombinant plasmids of wild type pGL-WT-PTEN and mutant pGL-MUT-PTEN were constructed and prepared after normal sequencing. H9c2 cells was inoculated into 24-well cell culture plate and cultured overnight in 37 ℃ incubator. The cells were co-transfected with miR-23a mimic or miR-23a mimic negative control and wild type or mutant reporter gene recombinant plasmid. Forty-eight hours after transfection, firefly luciferase activity and sea kidney luciferase activity were measured, and the ratio of them was recorded as relative luciferase activity. Results: Compared with the normal group, the cell surface area, the mRNA expression levels of ACTA1, β-MHC and miR-23a were significantly higher, while the protein expression levels of PTEN and p-AMPK were significantly lower in the Ang Ⅱ group(all P<0.05). The results of double luciferase reporter gene assay showed that the relative luciferase activity of cells co-transfected with miR-23a mimic and wild-type reporter gene recombinant plasmid was lower than that of miR-23a mimic negative control (P<0.05), and PTEN served as the target gene of miR-23a. In AngⅡ+anti-miR group the mRNA expression levels of miR-23a, ACTA1 and β-MHC were lower, and the cell surface area was smaller, while the protein expression levels of PTEN and p-AMPK were higher than that in AngⅡ group and AngⅡ+NC group(all P<0.05). Compared with AngⅡ+anti-miR group, the cell surface area was bigger, the expression of ACTA1 and β-MHC mRNA was up-regulated, and the protein expression levels of PTEN and p-AMPK were down-regulated in Ang Ⅱ+anti-miR+si-PTEN group(all P<0.05). Conclusion: Inhibition of miR-23a can attenuate Ang Ⅱ-induced hypertrophy in H9c2 cells through targeting PTEN and activating AMPK signaling pathway.


Using the Program Logic Model to Evaluate ¡Cuídate!: A Sexual Health Program for Latino Adolescents in a School-Based Health Center.
Addressing the disparities in pregnancy and sexually transmitted infection (STI) rates for Latino youth in the United States requires an evidence-based approach. Although randomized controlled trials for sexual risk reduction interventions have shown promise in improving short-term outcomes, program sustainability has not been extensively examined in school settings where teens spend time. Latina teen pregnancy rates are nearly twice the national average. Adolescents comprise only 17% of the U.S. population, yet they account for 50% of STIs. ¡Cuídate! is a high-impact sexual health group program endorsed by the Centers for Disease Control and Prevention that has not been replicated in a real-world setting. The program logic model (PLM) was used as the systematic approach to plan, implement, and evaluate a sustainable model of sexual health group programing (¡Cuídate!) in a U.S. high school with a large Latino student population. The PLM provided the framework for the evaluation of outputs, outcome, and impact. A multivariate repeated measures analysis of variance was used as the means to evaluate the participant outcomes immediately postprogram and at 8-12 weeks. ¡Cuídate! was executed within an existing school structure and time constraints, below cost projections, and with high participant retention (95.8%). Three cohorts (N = 24) of female teens demonstrated significant increases in STI or HIV knowledge, self-efficacy, and intention to use condoms (p < .01). Condom use increased postprogram. No participants initiated sexual behavior, nor were there any reported pregnancies or STIs. An evidence-based intervention previously tested in randomized controlled trials can be sustained in a school-based health center with similar results of efficacy. Our success served as a platform for a sustainable program. We continue to extend the impact of the program by delivering ¡Cuídate! in the school setting using a community health worker.


Minimal extrathyroidal extension does not affect survival of well-differentiated thyroid cancer.
Differentiated thyroid cancer (DTC) with minimal extrathyroidal extension (MEE) is classified as stage III regardless of the tumor size. In this study, we aim to examine the effect of MEE on the overall survival and management of this population. A retrospective cohort study was performed, which utilized the National Cancer Database (NCDB), 2004-2012. The study population included patients, aged ≥ 45 years, who underwent surgery for DTC (pT3N0M0) with MEE compared to that in patients with pT2N0M0. A total of 9556 patients were included. These were divided into four groups, 4410 patients with pT2N0M0 (Group 1: T ≤ 4 cm without MEE), 3274 with pT3N0M0 (Group 2: T ≤ 4 cm with MEE), 447 with pT3N0M0 (Group 3: T > 4 cm with MEE) and 1430 patients with pT3N0M0 without MEE (Group 4: T > 4 cm without MEE). Median follow-up time was 46.7 months (interquartile range: 27.8-72.1). Patients in Group 2 (T ≤ 4 cm with MEE) had no significant worse survival compared to patients in Group 1 (T ≤ 4 cm without MEE) (P = 0.85), whereas Groups 3 and 4 (T > 4 cm), both had significantly lower survival (P < 0.001) with no difference between the two groups. Total thyroidectomy was associated with improved overall survival compared to that in lobectomy in Group 4 (T > 4 cm without MEE). Radioiodine utilization was associated with improved survival only with tumors larger than 4 cm with or without MEE. In DTC patients aged older than 45 years of age with tumor size less than 4 cm, MEE has no survival significance. Tumor size is an independent prognostic marker regardless of MEE status. Our data support re-evaluation of the current staging system.


Clinicopathological features of atypical membranous nephropathy with unknown etiology in adult Chinese patients.
Membranous nephropathy is typically classified as idiopathic and secondary, but nowadays the number of atypical membranous nephropathy (aMN) is increasing, many of which cannot determine its etiology in China. In this study, we compared the clinical and pathological characteristics of idiopathic membranous nephropathy (iMN) with aMN with unknown etiology from a single center in China.We retrospectively reviewed the clinical data of 577 patients with iMN and aMN at Peking University People's Hospital from January 2006 to December 2015 over a 10-year period, and analyzed their clinical and pathological characteristics. The level of serum phospholipase A2 receptors (PLA2R) antibody was detected in 106 iMN and 162 aMN patients.There were 278 iMN patients and 299 aMN patients who were included into this study in 3210 cases of renal biopsy during a 10-year period in our hospital. The average age of patients with iMN was significantly older than those with aMN (54.77 ± 13.01 vs 47.13 ± 16.16, P < .001). Around 75 patients (27%) were smokers in iMN patients, and 111 patients (37.1%) in aMN patients (P = .009). The mainly clinical manifestation of these 2 groups was nephrotic syndrome (61.5% in iMN group vs 58.4% in aMN group), but there were more patients accompanied with nephritis syndrome in aMN group than iMN group (17.1% vs 6.1%, P < .001). The immunofluorescence of renal biopsy showed "full house" in aMN group; and IgG subclass of the glomeruli demonstrated IgG4 (90.4%) was commonest in iMN group, but IgG1 (94.6%) in aMN group. 51 (48.1%) patients with iMN were detected positive PLA2R antibody in their serum, and 93 (57.4%) in aMN patients (P = .168). The patients with positive PLA2R antibody had higher positive rate of microscopic hematuria and urinary protein, lower albumin.The aMN patients are younger, higher smoking rate, its main clinical manifestation is nephrotic syndrome, but more of them accompanied with nephritis syndrome than those in iMN patients. Serum PLA2R antibody could not distinguish aMN from iMN. aMN could be a special glomerular disease in China, and need a further research on a larger scale.


Biomechanical analysis of blade plate versus locking plate fixation for a proximal humerus fracture: comparison using cadaveric and synthetic humeri.
To compare the mechanical stability of a fixed-angle blade plate with that of a locking plate in a cadaveric proximal humerus fracture-fixation model subjected to cyclic loading. A secondary objective was to evaluate whether the use of synthetic humerus specimens would replicate significant differences found during cadaveric tests. Mechanical evaluation of constructs in bending and torsion. Biomechanical laboratory in an academic medical center. Simulated humeral neck fractures (Orthopaedic Trauma Association (OTA) classification 11A3), in matched-pair cadaveric and synthetic specimens underwent fixation using either a 3.5-mm, 90-degree cannulated LC-Angled Blade Plate or a 3.5-mm LCP Proximal Humerus Locking Plate. Cadaveric specimen constructs were cyclically loaded in bending and torsion; synthetic specimens were tested in torsion. Humeral shaft-bending displacements and angular rotations for respective cyclic bending loads and axial torques were recorded and compared at repeated cyclic intervals to evaluate construct loosening. Locking-plate constructs exhibited significantly less loosening than blade-plate constructs for torsional loading in cadaveric specimens (P = 0.036). The two types of constructs performed similarly for torsional loading in synthetic specimens (P = 0.100). Under cyclic, closed-bending load conditions in which the plates served as tension members, both types of constructs performed similarly in cadaveric specimens (P = 0.079). For simulated humeral neck fractures subjected to cyclic loading, locking-plate constructs demonstrated significantly greater torsional stability and similar bending stability to blade plates in a cadaveric specimen model. In contrast, these same constructs performed similarly with torsional loading when using synthetic humerus specimens. These results indicate potential advantages for locking-plate fixation. They also indicate that the synthetic specimens tested may not be appropriate for evaluating fixation stability in the humeral head, where cancellous bone fixation predominates.


Therapeutic options for sleep-maintenance and sleep-onset insomnia.
Insomnia, defined as difficulty falling asleep, staying asleep, and/or experiencing restorative sleep with associated impairment or significant distress, is a common condition resulting in significant clinical and economic consequences. Many options are available to treat insomnia, to assist with either falling asleep (sleep onset) or maintaining sleep. We searched MEDLINE for articles published between January 1996 and January 2006, evaluated abstracts from recent professional meetings, and contacted the manufacturer of the most recent addition to the pharmacologic armamentarium for insomnia treatment (ramelteon) to gather information. Nonpharmacologic options include stimulus control, sleep hygiene education, sleep restriction, paradoxical intention, relaxation therapy, biofeedback, and cognitive behavioral therapy. Prescription and over-the-counter drug therapies include benzodiazepine and nonbenzodiazepine sedative-hypnotic agents; ramelteon, a melatonin receptor agonist; trazodone; and sedating antihistamines. Herbal and alternative preparations include melatonin and valerian. Before recommending any treatment, clinicians should consider patient-specific criteria such as age, medical history, and other drug use, as well as the underlying cause of the sleep disturbance. All pharmacotherapy should be used with appropriate caution, at minimum effective doses, and for minimum duration of time.


Relationship of biofilm-forming ability of with swimming motility, twitching motility and virulence gene distribution.
To investigate the relationship of biofilm-forming ability of (PA) with swimming motility, twitching motility and virulence gene distribution. A total of 192 clinical isolates of PA were collected consecutively. Microtiter plate method was used to evaluate the ability to form biofilm. The swimming and twitching motilities were detected by plate method. Polymerase chain reaction (PCR) was used to detect virulence genes. Of the 192 PA clinical isolates, 186 (96.9%) showed biofilm-forming ability. Among them, 36 isolates showed weak biofilm-forming ability, 84 exhibited moderate biofilm-forming ability and 66 showed strong biofilm-forming ability. The diameters of the swimming ring for PA with none biofilm-forming ability, weak biofilm-forming ability, moderate biofilm-forming ability, strong biofilm-forming ability were (9.12±6.76), (18.42±7.51), (19.10±4.77) and respectively. The diameters of the twitching ring for PA in above groups were (8.38±1.50), (17.21±7.42), (18.49±5.62) and respectively. The swimming motility and twitching motility of none biofilm-forming ability group were weaker than biofilm-forming ability groups (all <0.05). Among 192 PA strains, 163 were positive (84.9%), 40 were positive (20.8%), 183 were positive (95.3%), and 189 were positive (98.4%). The positive rate of PA virulence gene , and were different in strains with different biofilm-forming abilities (<0.05). The rate of in the strong biofilm-forming ability group was lower than that in the moderate biofilm-forming ability group (=9.293, <0.01) and the weak biofilm-forming ability group (=9.997, <0.01). The rate of in the strong biofilm-forming ability group was higher than that in the weak biofilm-forming ability group (=10.803, <0.01). Most clinical isolates of PA can form biofilm. Swimming and twitching motilities are related to the formation of biofilm, but not significantly related to strength of biofilm-forming ability. The virulence genes of type Ⅲ secretion system for PA may be related to the biofilm-forming ability.


SG2-Type R2R3-MYB Transcription Factor MYB15 Controls Defense-Induced Lignification and Basal Immunity in Arabidopsis.
Lignification of cell wall appositions is a conserved basal defense mechanism in the plant innate immune response. However, the genetic pathway controlling defense-induced lignification remains unknown. Here, we demonstrate the Arabidopsis thaliana SG2-type R2R3-MYB transcription factor MYB15 as a regulator of defense-induced lignification and basal immunity. Loss of MYB15 reduces the content but not the composition of defense-induced lignin, whereas constitutive expression of MYB15 increases lignin content independently of immune activation. Comparative transcriptional and metabolomics analyses implicate MYB15 as necessary for the defense-induced synthesis of guaiacyl lignin and the basal synthesis of the coumarin metabolite scopoletin. MYB15 directly binds to the secondary wall MYB-responsive element consensus sequence, which encompasses the AC elements, to drive lignification. The myb15 and lignin biosynthetic mutants show increased susceptibility to the bacterial pathogen Pseudomonas syringae, consistent with defense-induced lignin having a major role in basal immunity. A scopoletin biosynthetic mutant also shows increased susceptibility independently of immune activation, consistent with a role in preformed defense. Our results support a role for phenylalanine-derived small molecules in preformed and inducible Arabidopsis defense, a role previously dominated by tryptophan-derived small molecules. Understanding the regulatory network linking lignin biosynthesis to plant growth and defense will help lignin engineering efforts to improve the production of biofuels and aromatic industrial products as well as increase disease resistance in energy and agricultural crops.


Endometrial Cancer-Associated FGF18 Expression Is Reduced by Bazedoxifene in Human Endometrial Stromal Cells In Vitro and in Murine Endometrium.
Endometrial cancer develops during exposure to estrogen unopposed by progesterone. Traditional formulations for menopausal hormone therapy include a progestin in women with a uterus. However, progestin exposure increases breast cancer risk in postmenopausal women. Alternatives to progestin include bazedoxifene (BZA), a selective estrogen receptor modulator, which prevents estrogen induced endometrial hyperplasia in clinical trials. Molecular mechanisms responsible for BZA's antiproliferative effect are not fully elucidated. We profiled endometrial adenocarcinoma, hyperplasia, and normal proliferative endometrium for differential expression in genes known to be regulated by estrogens or progesterone. Fibroblast growth factor (FGF)18, a paracrine growth factor promoting epithelial proliferation, was significantly increased in adenocarcinoma. Progesterone represses FGF18 by inducing heart and neural crest derivatives expressed transcript 2 (HAND2) in stromal cells. Notably, we confirmed lower HAND2 mRNA in adenocarcinoma, along with higher FGF tyrosine kinase receptor 2 and E74-like factor 5, collectively promoting FGF18 activity. We hypothesized BZA reduces epithelial proliferation by inhibiting FGF18 synthesis in stromal cells. To determine whether BZA regulates FGF18, we treated primary stromal cells with BZA or vehicle. In vitro, BZA reduced FGF18, but did not affect, HAND2. CD1 female mice received either BZA, conjugated estrogen (CE), or combined BZA/CE for 8 weeks. CE-treated mice had nearly 3-fold higher FGF18 expression. In contrast, BZA-treated mice, alone or with CE, had similar FGF18 as controls. Unexpectedly, BZA, alone or with CE, reduced HAND2 more than 80%, differing from progesterone regulation. Reduction of FGF18 is a potential mechanism by which BZA reduces endometrial proliferation and hyperplasia induced by estrogens. However, BZA works independently of HAND2, revealing a novel mechanism for progestin-free hormone therapy in postmenopausal women.


Gastric H-K-ATPase and acid-resistant surface proteins.
Despite the fact that mucus and bicarbonate are important macroscopic components of the gastric mucosal barrier, severe acidic and peptic conditions surely exist at the apical membrane of gastric glandular cells, and these membranes must have highly specialized adaptations to oppose external insults. Parietal cells abundantly express the heterodimeric, acid-pumping H-K-ATPase in their apical membranes. Its beta-subunit (HKbeta), a glycoprotein with >70% of its mass and all its oligosaccharides on the extracellular side, may play a protective role. Here, we show that the extracellular domain of HKbeta is highly resistant to trypsin in the native state (much more than that of the structurally related Na-K-ATPase beta-subunit) and requires denaturation to expose tryptic sites. Native HKbeta also resists other proteases, such as chymotrypsin and V8 protease, which hydrolyze at hydrophobic and anionic amino acids, respectively. Removal of terminal alpha-anomeric-linked galactose does not appreciably alter tryptic sensitivity of HKbeta. However, full deglycosylation makes HKbeta much more susceptible to all proteases tested, including pepsin at pH <2.0. We propose that 1) intrinsic folding of HKbeta, 2) bonding forces between subunits, and 3) oligosaccharides on HKbeta provide a luminal protein domain that resists gastric lytic conditions. Protein folding that protects susceptible charged amino acids and is maintained by disulfide bonding and hydrophilic oligosaccharides would provide a stable structure in the face of large pH changes. The H-K-ATPase is an obvious model, but other gastric luminally exposed proteins are likely to possess analogous protective specializations.


Croup syndrome: historical perspective.
The management of acute croup syndrome has undergone very interesting changes in the past century. Initially a number of conditions were thought to be synonymous with croup, but with identification of the bacterial and viral etiology these have been separated into different clinical entities: viral croup which is very common and frequently self-limited; bacterial tracheitis, a condition which is infrequently encountered and which may be a complication of viral croup; and epiglottitis or supraglottitis, a disease that has been identified as most frequently due to a specific organism, H. influenzae. The management of the child with airway obstruction has also changed. Before the past decade virtually all children with epiglottitis were treated with tracheotomy and currently very few children are thus treated. Intubation has been showed to be a safe procedure in these cases. There still exists some controversy regarding the treatment of the child with laryngotracheobronchitis. In the vast majority of cases medical management has been successful and in the remainder there is controversy regarding the use of intubation or tracheotomy.


Understanding barriers and enablers to participation in a proposed online lifestyle intervention for older adults with age-related macular degeneration to guide programme implementation.
Age-related macular degeneration (AMD) is a blinding condition associated with depression, loneliness and unhealthy lifestyle behaviours which drives AMD progression. We have proposed the first online lifestyle intervention for AMD, called Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) to promote positive lifestyle changes and reduce loneliness. This qualitative grounded-theory study explored enablers and barriers to future participation in MINGLE for older adults with AMD. Thirty-one participants were interviewed and thematic analysis revealed nine themes. Enablers to participation were: socialising and learning about AMD, motivation to improve health, programme accessibility and structure. Barriers were: lack of time, technology, limited knowledge regarding holistic interventions, vision-related issues, mobility and negative perception of group interactions. These factors must be considered when developing lifestyle interventions for AMD patients to maximise participation. Supporting technology use and raising awareness about benefits of healthy lifestyle behaviours for AMD may help overcome these barriers.


Management of Acetabular Bone Loss in Hip Revision Arthroplasty: Case Series Presentation.
Considering the increase in life expectancy in the general population and the need for a more active lifestyle, total hip arthroplasty has become an absolutely necessary surgical intervention to maintain these desired results. Along with the evolution of medicine and the increase in the quality and performance of the materials used to make prostheses, the number of patients who benefit from total hip replacement is constantly increasing, and proportionally, the number of patients who will require revision arthroplasty is increasing. Before discussing the need for hip arthroplasty revision, it is necessary to carry out a rigorous clinical and imaging examination for differential diagnosis with other pathologies such as low back pain, the presence of bone or soft tissue tumors, arterial occlusions and claudication, or other systemic diseases. One of the biggest challenges for the orthopedic surgeon in planning a hip revision is the compensation of the remaining acetabular bone defect, either as a result of the osteolysis process or following the process of removing the acetabular component, which in some cases can lead to severe bone loss that is difficult to anticipate in the preoperative planning. In this paper, we will present the short-term results of the use of reinforcement cages fixed with screws and cemented retentive acetabular cups in the case of hip revisions with extensive bone loss. The discussions that derive from the presented series of cases are related to the use of reinforcement cages, which are based on the principle of primary stability obtained with the help of screw fixation but whose risk of osteolysis and implant fixation damage is greater than in the case of implants that also associate biological integration at bone level. The use of reinforcement cages together with the retentive acetabular cup in the case of elderly patients with associated comorbidities, a moderate level of physical activity, and severe muscle insufficiency at the hip level as a result of not using the affected pelvic limb is still a viable solution that allows the patient to walk immediately after the surgery, avoiding the risk of dislocation (especially in patients who use the posterolateral approach) and avoiding morbidity induced by prolonged bed rest.


Alterations of the Frank orthogonal scalar leads induced by anaphylactic shock in the rabbit.
The anaphylactic shock of the rabbit is characterized by an acute right ventricular overload, accompanied by severe alterations of cardiac electrogenesis. During shock, the mean QRS vector, as measured from the algebraic sum of the Q, R, and S deflections on the three leads, shifts to the right, inferiorly and anteriorly. An injury current quickly appears. The TQ vector points away from the right ventricle. A progressive depolarization on the right ventricular wall is displayed by suction electrodes and the suppression of right ventricular hypertension by a cross circulation produces an almost immediate disappearance of the injury current. The geneses of these electrical alterations are briefly discussed. The possibility of an anaphylactic reaction at the level of the coronary arterial wall, previously mentioned in the literature, seems unlikely. The role of the haemodynamic changes and of the increased right ventricular blood pool is thought to be predominant.


The Clinical Characteristics of Patients with Chronic Idiopathic Anal Pain.
The aim of this study was to investigate the clinical characteristics, treatment outcomes and psychological distress in patients with chronic idiopathic anal pain. The study was conducted on patients referred to Hangzhou Third Hospital for chronic anal pain from January, 2010 to December, 2014. Patient demographics, clinical history, anorectal physiology, and radiological imaging data were recorded for all patients. The treatment outcome was noted for patients treated and followed up for more than 6 month at the present unit. Ninety-six patients with mean age of 45.1 years (range, 17-82) were studied. Seventy-one patients (74.0%) had functional anorectal pain(FARP). The main complaints were dull, sharp, stabbing, or spasm pain. Among all patients, 34.3% reported that their pain radiated into other locations. Fifty-one patients (53.1%) had bowel dysfunction, while 28.1% patients had urinary dysfunction. The common factors associated with pain relief were day time, lying down and warm water baths; the factors that contributed to aggravated pain were night time, defecation or sitting. 92.7% (89/96) of patients reported symptoms of psychological disturbance. FARP patients exhibited increased depression than non-FARP patients(P<0.05). In addition, female patients were more likely to have depression than male patients (P<0.05). The overall pain treatment success rate was 55.2% (53/96). The pain treatment outcome was better in non-FARP patients than in FARP patients(χ2=3.85, P<0.05). Conclusively, chronic idiopathic anal pain is a complex clinical symptom, involving pelvic floor muscles, the nervous system, endocrine system, and the patients' psychological conditions. Further research is needed to improve diagnosis and treatment for patients with chronic idiopathic anal pain.


Inhibitory effect of aspirin on azoxymethane-induced colon carcinogenesis in F344 rats.
Epidemiologic studies suggest that sustained use of aspirin may reduce the risk of development of and mortality due to colon cancer. Previous preclinical studies have shown that several non-steroidal anti-inflammatory drugs act as potential chemopreventive agents in experimentally induced colon cancer models. The present study was designed to investigate the chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of aspirin administered in the diet on azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. The MTD of aspirin as determined in male F344 rats was 500 p.p.m. Beginning at 5 weeks of age, all animals were randomly divided into various experimental groups (48 rats/group) and fed one of the semipurified diets containing 0, 200 p.p.m. (40% MTD), or 400 ppm (80% MTD) of aspirin. Two weeks later, all animals (36 rats/group) except the vehicle-treated groups (12 rats/group) were administered s.c. injections of AOM at a dose level of 15 mg/kg body wt, once weekly for 2 weeks. All animals were continued on their respective dietary regimen for additional 52 weeks and necropsied. Histopathologic evaluation of colon tumors was performed by routine procedures. Basal levels and ex vivo production of colonic mucosal and tumor prostaglandin E2 (PGE2) were measured in all groups. The results indicate that daily oral administration of 200 and 400 p.p.m. aspirin significantly inhibited the incidence (% animals with tumors) and multiplicity (tumors/animal) of invasive adenocarcinomas of the colon as well as the size of adenocarcinomas. Colonic mucosal and tumor PGE2 levels (basal and ex vivo production) were significantly reduced in animals administered 200 and 400 p.p.m. aspirin. The results of this study support the epidemiologic evidence that ingestion of aspirin inhibits colon carcinogenesis. Although the precise mechanisms of aspirin-induced colon tumor inhibition remain to be determined, it is likely that the effect may be mediated through the modulation of prostaglandin synthesis.


Food intake in rats is unaffected by the profile of dietary essential fatty acids.
Food intake may be differentially responsive to the type of fat in the diet. The present investigation sought to evaluate the energy intake of rats maintained on either a low-fat or a high-fat diet mixed with an oil rich in either linoleic (18:2; n-6; safflower oil) or linolenic (18:3; n-3; flaxseed oil) acid. In Experiment 1, rats (n=28) consumed low-fat versions of either the safflower oil diet or the flaxseed oil diet, each at 9.28% fat (wt/wt). In Experiment 2, different rats (n=28) consumed high-fat versions of these diets, each at 23.6% fat (wt/wt). Within each experiment, the energy intake of rats receiving the safflower oil diet was compared to the energy intake of rats receiving the flaxseed oil diet. Food intake was measured under short-term, long-term and food-deprived conditions. In Experiment 1, short-term energy intakes were not different between the groups, thus demonstrating equal acceptance of the test diets. There were no consistent differences in long-term energy intakes between the safflower group and the flaxseed group. In addition, there were no differences in energy intake under the food-deprivation condition. Results from Experiment 2 paralleled those of Experiment 1. Taken together, the present results suggest that the essential fatty acid profile of the maintenance diet does not influence food intake when nutritive oils are the predominant fatty acid source.


Olive oil polyphenols suppress the TGF-α-induced migration of hepatocellular carcinoma cells.
Oleuropein and 3-hydroxytyrosol (3-HT) are natural polyphenols present in olive oil that are known to exhibit potent anti-oxidant activities and exert protective effects against a number of human diseases. In the liver, olive oil polyphenols have been demonstrated to prevent hepatocellular carcinoma (HCC) cell growth. However, little is known about their effects against HCC cell migration. Therefore, the present study investigated whether or not oleuropein and 3-HT were involved in the suppression of transforming growth factor-α (TGF-α)-induced migration of human HCC cells using human HCC-derived HuH7 cells. The TGF-α-induced migration of HuH7 cells was significantly and dose-dependently suppressed by oleuropein and 3-HT. This study group demonstrated previously that the TGF-α-induced activation of AKT and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) were involved in HuH7 cell migration. In addition to these protein kinases, the present study examined the involvement of TGF-α-induced activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and Rho kinase in HuH7 cell migration. TGF-α-induced HuH7 cell migration was decreased by SB203580, a p38 MAPK inhibitor, and Y27632, a Rho kinase inhibitor. However, PD98059, an inhibitor of the upstream kinase activating ERK, did not suppress the TGF-α-induced migration of HuH7 cells. Although AKT, SAPK/JNK, p38 MAPK and Rho kinase pathways were suggested to be involved in the TGF-α-induced migration of HuH7 cells, 10-30 µM 3-HT did not exhibit any suppressive effect on the TGF-α-stimulated activities of these kinases. The results of the present study suggest that olive oil polyphenols suppressed the TGF-α-induced migration of HCC cells.


CCAAT/enhancer-binding proteins: structure, function and regulation.
CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that all contain a highly conserved, basic-leucine zipper domain at the C-terminus that is involved in dimerization and DNA binding. At least six members of the family have been isolated and characterized to date (C/EBP alpha[bond]C/EBP zeta), with further diversity produced by the generation of different sized polypeptides, predominantly by differential use of translation initiation sites, and extensive protein-protein interactions both within the family and with other transcription factors. The function of the C/EBPs has recently been investigated by a number of approaches, including studies on mice that lack specific members, and has identified pivotal roles of the family in the control of cellular proliferation and differentiation, metabolism, inflammation and numerous other responses, particularly in hepatocytes, adipocytes and haematopoietic cells. The expression of the C/EBPs is regulated at multiple levels during several physiological and pathophysiological conditions through the action of a range of factors, including hormones, mitogens, cytokines, nutrients and certain toxins. The mechanisms through which the C/EBP members are regulated during such conditions have also been the focus of several recent studies and have revealed an immense complexity with the potential existence of cell/tissue- and species-specific differences. This review deals with the structure, biological function and the regulation of the C/EBP family.


mTORC1 Activation in Osteoclasts Prevents Bone Loss in a Mouse Model of Osteoporosis.
The mechanistic/mammalian target of rapamycin (mTOR) is widely implicated in the pathogenesis of various diseases, including cancer, obesity, and cardiovascular disease. Bone homeostasis is maintained by the actions of bone-resorbing osteoclasts and bone-forming osteoblasts. An imbalance in the sophisticated regulation of osteoclasts and osteoblasts leads to the pathogenesis as well as etiology of certain metabolic bone diseases, including osteoporosis and osteopetrosis. Here, we identified mTOR complex 1 (mTORC1) as a pivotal mediator in the regulation of bone resorption and bone homeostasis under pathological conditions through its expression in osteoclasts. The activity of mTORC1, which was indicated by the phosphorylation level of its downstream target p70S6 kinase, was reduced during osteoclast differentiation, in accordance with the upregulation of Hamartin (encoded by tuberous sclerosis complex 1 [Tsc1]), a negative regulator of mTORC1. Receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclastogenesis was impaired in Tsc1-deficient bone marrow macrophages. By contrast, osteoclastogenesis was markedly enhanced by Raptor deficiency but was unaffected by Rictor deficiency. The deletion of Tsc1 in osteoclast lineage cells in mice prevented bone resorption and bone loss in a RANKL-induced mouse model of osteoporosis, although neither bone volume nor osteoclastic parameter was markedly altered in these knockout mice under physiological conditions. Therefore, these findings suggest that mTORC1 is a key potential target for the treatment of bone diseases.


An evaluation of the Australian Sentinel Practice Research Network (ASPREN) surveillance for influenza-like illness.
The Australian Sentinel Practice Research Network (ASPREN) is a national network of general practitioners (GPs) who collect and report data on selected conditions, including influenza-like illness (ILI). The Australian Government Department of Health and Ageing initiated an evaluation of ASPREN, aiming to assess its potential to contribute to surveillance of emerging infectious diseases including pandemic influenza. System attributes and utility for decision-making were elucidated from stakeholder surveys. ASPREN ILI data for 2002 to 2004 were compared with ILI data from South Australia and New South Wales. In 2004, 50 GPs participated in the ASPREN surveillance, with proportionately more in New South Wales (30%) and South Australia (30%) than in other states. The majority (78%) of GPs were in metropolitan practices. Compliance with the manual data collection system was not optimal, nor consistent by state. ASPREN ILI data compared favourably with that of other surveillance systems. No formal structures were in place by which to assess data trends, provide alerts or initiate public health action. To maximise the contribution to biosecurity surveillance, ASPREN would require targeted GP recruitment to achieve geographic representativeness; exploration of alternative technologies for data collection and reporting; provision of committed resources adequate for system operation; and negotiation with state-based public health reference laboratories to provide laboratory support. The main potential of ASPREN is to permit rapid dissemination of a syndromic case definition and acquisition of nationwide community level clinical presentation data. These evaluation findings will be used to inform redevelopment of ASPREN as part of the Biosecurity Surveillance System project.


The usefulness of prostate specific antigen density as a screening method for prostatic carcinoma.
Prostate specific antigen (PSA) has been used extensively for monitoring the progression of prostatic cancer since its discovery in 1979. Unfortunately the measurement of PSA in serum is not sufficiently specific for early detection of prostatic carcinoma (CaP) as it is secreted by normal as well as hyperplastic or cancerous prostatic tissue. As serum PSA is the reflection of the number of prostatic epithelial cells, a small cancerous prostate gland having increased number of cells per unit volume leaks more PSA in serum than a benign, large gland. Thus the concept of PSA density (PSAD) has been proposed (the quotient of serum PSA divided by the volume of prostate in cubic centimeter) as an indicator for prostatic malignancy. In the present study pre-operative PSAD values of 65 cases of prostatic diseases were calculated [54 cases of benign prostatic hyperplasia (BPH) and 11 cases of C3P]. Serum PSA was measured by enzyme linked immunosorbent assay (ELISA) method and the prostatic volume was measured by transrectal ultrasonography (TRUS). Although 8 cases of BPH (14.8%) had raised PSA level, abnormal PSAD (0.1 or above) was noted in only 3 cases. All cases having PSAD value above 0.2 had carcinoma. The PSAD value above 0.1 in cases of CaP was found to be significant (p<0.001). By using PSAD as screening test the sensitivity increased from 85.1% to 94.4% and positive predictive value increased from 55.5% to 75%, compared to the detection of carcinoma by measuring PSA alone. The present study concludes that PSAD is more useful for prediction of CaP and the need of prostatic biopsy for early detection.


Asymmetric frontal cortical activity and negative affective responses to ostracism.
Ostracism arouses negative affect. However, little is known about variables that influence the intensity of these negative affective responses. Two studies fill this void by incorporating work on approach- and withdrawal-related emotional states and their associated cortical activations. Study 1 found that following ostracism anger related directly to relative left frontal cortical activation. Study 2 used unilateral hand contractions to manipulate frontal cortical activity prior to an ostracizing event. Right-hand contractions, compared to left-hand contractions, caused greater relative left frontal cortical activation during the hand contractions as well as ostracism. Also, right-hand contractions caused more self-reported anger in response to being ostracized. Within-condition correlations revealed patterns of associations between ostracism-induced frontal asymmetry and emotive responses to ostracism consistent with Study 1. Taken together, these results suggest that asymmetrical frontal cortical activity is related to angry responses to ostracism, with greater relative left frontal cortical activity being associated with increased anger.


Wollastonite to hinder growth of Aspergillus niger fungus on cotton textile.
Effects of Aspergillus niger was investigated on the strength of cotton textile specimens impregnated with nano-wollastonite, and then compared with normal specimens. Cotton strips were cut and prepared in warp and wept directions according to the standard specifications ASTM D-5035. Results showed that incubation of A. niger on specimens for three months resulted in a significant decrease in tensile stress as well as weight mass change in both directions. Impregnating specimens with NW ameliorated the negative effects of fungal attack on tensile stress to a considerable extent. Moreover, weight change was significantly decreased. It is concluded that NW positively protect cotton textile against A. nigra; the ultimate NW-content should be studied in complimentary studies.


The Invasive Management of Pain: Diagnosis and New Treatment Options.
Both the diagnosis and treatment of pain are evolving, especially in interventional approaches. Diagnosis of low back pain combines old and new methodologies, in particular, it involves an expanded role for ultrasound. While low back pain is a common complaint, there are many etiologies to the condition which must be explored before a final diagnosis can be made and treatment planned. Tumors and infections are rarely involved in low back pain but should be ruled out in the initial phase itself since failing to address them early can have devastating consequences. Some invasive treatments seem promising in the management of low back pain. Treating musculoskeletal pain with regenerative medicine, such as platelet-rich plasma, holds great promise. Autologous blood products are safe and may help stimulate the body's own responses for regeneration. The so-called "orthobiologics" play a role in sports medicine and the treatment of musculoskeletal pain. Neuromodulation, especially spinal cord stimulation, is undergoing a renaissance with new waveforms, devices, and a greater albeit incomplete understanding of its mechanisms of action. Spinal cord stimulation is not a first-line therapy and not all patients or all back problems respond to this treatment. Nevertheless, the therapy can be safe, effective, and cost-effective with appropriate patient selection. Radiofrequency ablation of nerves in the form of neurotomy can be effective in reducing the pain of osteoarthritis. These procedures, including the newer cooled radiofrequency neurotomy, can restore function, reduce pain, and may potentially have an opioid-sparing effect. Technical expertise in nerve and anatomy is needed for the use of this technique. This review article aims to provide updated information on some invasive intervention techniques in pain management.


Emotion regulation and decision making under risk and uncertainty.
It is well established that emotion plays a key role in human social and economic decision making. The recent literature on emotion regulation (ER), however, highlights that humans typically make efforts to control emotion experiences. This leaves open the possibility that decision effects previously attributed to acute emotion may be a consequence of acute ER strategies such as cognitive reappraisal and expressive suppression. In Study 1, we manipulated ER of laboratory-induced fear and disgust, and found that the cognitive reappraisal of these negative emotions promotes risky decisions (reduces risk aversion) in the Balloon Analogue Risk Task and is associated with increased performance in the prehunch/hunch period of the Iowa Gambling Task. In Study 2, we found that naturally occurring negative emotions also increase risk aversion in Balloon Analogue Risk Task, but the incidental use of cognitive reappraisal of emotions impedes this effect. We offer evidence that the increased effectiveness of cognitive reappraisal in reducing the experience of emotions underlies its beneficial effects on decision making.


Pathophysiology and Current Clinical Management of Preeclampsia.
Preeclampsia is characterized by blood pressure greater than 140/90 mmHg in the second half of pregnancy. This disease is a major contributor to preterm and low birth weight babies. The early delivery of the baby, which becomes necessary for maintaining maternal well-being, makes preeclampsia the leading cause for preterm labor and infant mortality and morbidity. Currently, there is no cure for this pregnancy disorder. The current clinical management of PE is hydralazine with labetalol and magnesium sulfate to slow disease progression and prevent maternal seizure, and hopefully prolong the pregnancy. This review will highlight factors implicated in the pathophysiology of preeclampsia and current treatments for the management of this disease.


Laboratory surveillance for wild and vaccine-derived polioviruses--worldwide, January 2006-June 2007.
The Global Polio Laboratory Network (GPLN) was established after announcement of the 1988 World Health Assembly resolution to eradicate poliomyelitis. Operating in all six World Health Organization (WHO) regions, the network currently has 146 laboratories that test stool specimens from acute flaccid paralysis (AFP) patients for polioviruses. The virologic data provided by GPLN underpin the global polio eradication initiative, guiding decisions regarding where targeted immunization activities should be conducted, based on confirmed wild or vaccine-derived poliovirus circulation. The data also are used to monitor progress toward polio eradication by documenting the genetic diversity and transmission links of viral isolates. This report updates previous reports and describes GPLN performance and initiatives during January 2006-June 2007.


Mandibular plasmacytoma of jaw - a case report.
The plasma cell neoplasm may present as Extramedullary Plasmacytoma (EMP) in soft tissues in bone as a Solitary Plasmacytoma of bone (SPB) or as a part of multi focal disseminated disease Multiple Myeloma (MM). The majority of 80% occurs in head and neck region. In our case, a 62-year-old male patient presented with a non tender swelling of short duration. The swelling was noted obliterating the vestibular depth in right lower mandibular region. The radiological features were non specific.


Urodynamic implications of benign prostatic hyperplasia.
By the age of 60, about 70% of men have developed benign prostatic hyperplasia (BPH), and 85%-95% of these have symptomatic dysfunction of the lower urinary tract, 10%-20% undergoing prostatectomy. Although transurethral resection of the prostate is generally considered to be a safe and effective surgical procedure, it has recently been shown that immediate surgery, as opposed to a wait-and-see strategy, leads to a 1-month reduction in life expectancy. In 10%-15% of the patients who undergo surgery, the postoperative result is unsatisfactory as symptoms persist. Between 4% and 40% of patients undergoing prostatectomy become impotent. A urodynamic study with a scope extending beyond that of the standard urological examination is therefore needed to help reduce the number of treatment failures. The value of preoperative cystometry is questionable, since preoperative documentation of detrusor instability has no bearing on the postoperative result. Measurement of urinary flow, in contrast, is of predictive value in BPH, patients in whom the maximum urinary flow before surgery is more than 15 ml/s having significantly worse results of surgery than those with a maximum urinary flow of less than 15 ml/s before surgery. Further data relevant to the prognosis are yielded by pressure-flow investigations, which allow a quantitative estimate of the degree of obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)


Single-Band 2-nm-Line-Width Plasmon Resonance in a Strongly Coupled Au Nanorod.
This paper reports a dramatic reduction in plasmon resonance line width of a single Au nanorod by coupling it to a whispering gallery cavity of a silica microfiber. With fiber diameter below 6 μm, strong coupling between the nanorod and the cavity occurs, leading to evident mode splitting and spectral narrowing. Using a 1.46-μm-diameter microfiber, we obtained single-band 2-nm-line-width plasmon resonance in an Au nanorod around a 655-nm-wavelength, with a quality factor up to 330 and extinction ratio of 30 dB. Compared to an uncoupled Au nanorod, the strongly coupled nanorod offers a 30-fold enhancement in the peak intensity of plasmonic resonant scattering.


Abeta42, presenilins, and Alzheimer's disease.
The significance of amyloid beta protein, especially those ending at the 42nd residue (Abeta42), in the pathogenesis of familial Alzheimer's disease (FAD) linked to the mutations of presenilins, was examined by transfection studies using cultured cells and immunohistochemical analysis of autopsied brains. The levels of Abeta42 secreted from cells transfected with mutant presenilins linked to FAD, as well as the Abeta42 burden in the cortices of patients with presenilin mutation were elevated. Thus, mutations in presenilin genes may enhance the production and deposition of Abeta42 in the brains, thereby leading to Alzheimer's disease.


Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients.
Cerebrovascular disease is an independent risk factor for dementia that may also be synergistic with Alzheimer's disease. In recent years attention has switched from cerebral infarcts to microvascular disease as the primary cause of cerebrovascular cognitive decline, with damage to the white matter the primary mechanism. Uncertainties remain regarding the risks posed by different types vascular threat, the extent to which cerebrovascular damage occurs in middle age, and whether relatively "normal" amounts of white matter damage are accompanied by meaningful degrees of cognitive decline. We explored these issues via laboratory, cardiovascular, cognitive, and magnetic resonance imaging (MRI) data in 67 middle-aged cognitively normal offspring of dementia patients. The sample was enriched for vascular risk. Plasma insulin, 24-h systolic blood pressure, body mass index, age, and % small dense LDL cholesterol were the strongest correlates of MRI white matter hyperintensity (WMH) volume. With shared variance controlled for, 24 h systolic BP, plasma insulin, and age remained as significant predictors of WMH volume. An interaction variable (24 h BP * insulin) did not improve the prediction of WMH. WMH volume correlated negatively with cognition. No evidence for an ApoE ε4 effect emerged for either WMH or cognition. Hypertension and hyperinsulinemia appear to pose independent, consequential threats to the cerebral small vessel vasculature in middle age, reflected in the presence of areas of WMH on MRI scans. Our data show that even modest WMH volumes in middle age are associated with cognitive decrement, underscoring the importance of aggressive treatment and lifestyle modifications to address vascular risk throughout adulthood.


Pulmonary endarteritis and subsequent pulmonary embolism associated with clinically silent patent ductus arteriosus.
A 49-year-old man without heart murmur was admitted with fever because of bacteremia following a tooth extraction. Antibiotics rapidly alleviated the fever; however, a small nodule in the pulmonary artery was identified on computed tomography (CT). When the patient experienced chest discomfort with fever, CT demonstrated the absence of the nodule and the appearance of an abnormal lung opacity, and echocardiography showed turbulent retrograde flow in the pulmonary artery. We had the rare opportunity to follow a case of pulmonary bacterial endarteritis and subsequent pulmonary embolism with clinically silent patent ductus arteriosus (PDA) that was confirmed by 3-dimensional CT.


High fat diet-induced TGF-β/Gbb signaling provokes insulin resistance through the tribbles expression.
Hyperglycemia, hyperlipidemia, and insulin resistance are hallmarks of obesity-induced type 2 diabetes, which is often caused by a high-fat diet (HFD). However, the molecular mechanisms underlying HFD-induced insulin resistance have not been elucidated in detail. In this study, we established a Drosophila model to investigate the molecular mechanisms of HFD-induced diabetes. HFD model flies recapitulate mammalian diabetic phenotypes including elevated triglyceride and circulating glucose levels, as well as insulin resistance. Expression of glass bottom boat (gbb), a Drosophila homolog of mammalian transforming growth factor-β (TGF-β), is elevated under HFD conditions. Furthermore, overexpression of gbb in the fat body produced obese and insulin-resistant phenotypes similar to those of HFD-fed flies, whereas inhibition of Gbb signaling significantly ameliorated HFD-induced metabolic phenotypes. We also discovered that tribbles, a negative regulator of AKT, is a target gene of Gbb signaling in the fat body. Overexpression of tribbles in flies in the fat body phenocopied the metabolic defects associated with HFD conditions or Gbb overexpression, whereas tribbles knockdown rescued these metabolic phenotypes. These results indicate that HFD-induced TGF-β/Gbb signaling provokes insulin resistance by increasing tribbles expression.


Multiple primary malignant neoplasms in breast cancer patients in Israel.
The data of an epidemiologic study of multiple primary malignant neoplasms in breast cancer patients in Israel are presented. During the 18-year period of the study 12,302 cases of breast carcinoma were diagnosed, and, of these, 984 patients (8%) had multiple primary malignant tumors. Forty-seven of these patients developed two multiple primary cancers. A significantly higher than expected incidence of second primary cancers occurred at the following five sites: the opposite breast, salivary glands, uterine corpus, ovary, and thyroid. Cancers of the stomach and gallbladder were fewer than expected. Treatment of the breast cancer by irradiation was associated with an increased risk of subsequent cancers of lung and hematopoietic system. The prognosis was mainly influenced by the site and malignancy of the second primary cancer. The incidence of multiple primary malignancies justifies a high level of alertness to this possibility in the follow-up of breast cancer patients.