Target definition in salvage postoperative radiotherapy for prostate cancer: 18F-fluorocholine PET/CT assessment of local recurrence.
Inadequate clinical target volume (CTV) definition is likely to be a major contributing factor to local recurrence (LR) rate after radiotherapy. Our aims were to identify sites of prostate cancer LR in biochemical recurrence post-prostatectomy using 18F-Fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) and to compare different CTV-delineation guidelines in a cohort of postoperative patients. Thirty-six patients presenting with LR within the prostatic bed on 18F-FCH PET/CT between 10/2011 and 06/2016 were included in this retrospective study. Median PSA at the time of 18F-FCH PET/CT was 2.7 ng/mL (0.8-9.4) and median PSA doubling time was 11 months (3-28). For each patient, the CTVRTOG, CTVFROGG and CTVEORTC following the corresponding guidelines were outlined and compared. Forty-one LR were delineated using a gradient-based method and the percentage of FCH uptake included in each CTV was evaluated. The anastomosis was the most common recurrence site (52.8%), followed by the retrovesical region (31.7%) and the bladder neck (7%). The median SUV max value was 4.8 (2.3-16.1). The percentage of LR entirely included in the CTVRTOG was not significantly different from that included in the CTVFROGG (84% versus 83%, p = .5). Significantly more recurrences were included in the CTVRTOG volume compared to the CTVEORTC (84% versus 68%, p=.006), due to a better coverage of the bladder neck and retrovesical regions. Six out of 10 relapses occurring in the posterior region of the anastomosis were not covered by any of the CTVs. In our study, the CTVRTOG and CTVFROGG ensured the best coverage of LR seen on 18F-FCH PET/CT. When outlining the prostatic fossa, greater coverage of the posterior vesico-urethral region may allow better coverage of potential microscopic disease.


MiR-7 mediates mitochondrial impairment to trigger apoptosis and necroptosis in Rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) is a pediatric cancer with rhabdomyoblastic phenotype and mitochondria act as pivotal regulators of its growth and progression. While miR-7-5p (miR-7) is reported to have a tumor-suppressive role, little is yet known about its antitumor activity in RMS. The effects of miR-7 on RMS were analyzed both in vitro and in vivo. Cell death modalities induced by miR-7 were identified. Influence on mitochondria was evaluated through RNA sequencing data, morphological observation and mitochondrial functional assays, including outer membrane permeability, bioenergetics and redox balance. Dual-luciferase assay and phenotype validation after transient gene silencing were performed to identify miR-7 targets in RMS. MiR-7 executed anti-tumor effect in RMS beyond proliferation inhibition. Morphologic features and molecular characteristics with apoptosis and necroptosis were found in miR-7-transfected RMS cells. Chemical inhibitors of apoptosis and necroptosis were able to prevent miR-7-induced cell death. Further, we identified that mitochondrial impairment mainly contributed to these phenomena and mitochondrial proteins SLC25A37 and TIMM50 were crucial targets for miR-7 to induce cell death in RMS. Our results extended the mechanism of miR-7 antitumor role in rhabdomyosarcoma cancer, and provided potential implications for its therapy.


COVID-19 in long-term care facilities in Frankfurt am Main, Germany: incidence, case reports, and lessons learned.
As of August 30, 2020, the World Health Organisation (WHO) reported 24,822,800 COVID-19 infections world wide. Severe disease and deaths occur especially in older people with chronic illnesses. Residents of nursing homes are considered to be the most vulnerable group. In this paper, the experiences with COVID-19 in nursing homes in Frankfurt will be presented and discussed. Materials and methods: Based on the data of the statutory reporting obligation, the reported COVID-19 cases are presented and incidences are calculated in different age groups and among residents of nursing homes. Outbreaks in various homes are described in detail based on the documentation from the public health department. Results: By August 28, 2020, 2,665 COVID-19 infections were reported in Frankfurt am Main (incidence 351/100,000 inhabitants), including 116 (4.3%) residents of nursing homes (2,416/100,000 residents). Almost half (39%) of all deaths in Frankfurt (n=69; incidence 9.1/100,000) were among nursing home residents (n=27; incidence 558/100,000 nursing home residents), with 22 of them in just one long-term care facility (LTCF). Compared to previous years, the mortality rate in nursing homes did not increase in the first half of 2020. In one home, 75% of residents tested positive for SARS-CoV-2 and 25% died; in two other homes, 6.7% and 14.1% of the residents became infected, and the mortality rate was 0.5% and 1%, resp. In the other 42 homes in the city (3,906 beds), the infection rate remained below 1% and the death rate was 0.1%. Discussion: In many countries, 30-70% of all deaths occur among nursing home residents, including Frankfurt (39%). An increase in overall mortality compared to previous years was not observed in Frankfurt as a whole or in the nursing homes in the city specifically. Due to the measures taken (monitoring of residents and staff, nursing care in protective clothing, prohibition or restriction of visits, physical distancing, isolation of infected people and quarantining of contact persons), only individual cases of COVID-19 illnesses occurred in nursing home residents in most homes and the outbreaks in the three homes could be stopped. We do not recommend regular nontargeted testing in nursing homes, but rather vigilance and the implementation of good hygiene as well as immediate targeted testing if COVID-19 is suspected in residents or staff. In order to mitigate the considerable negative effects of these measures on the residents, a good balance should be sought between infection prevention and the goal of ensuring self-determination and the residents' quality of life.


From Performance to Decision Processes in 33 Years: A History of Organizational Behavior and Human Decision Processes under James C. Naylor.
For the past 33 years, Organizational Behavior and Human Decision Processes has thrived under a single editor. That editor, James C. Naylor, is retiring from his long stewardship. This article chronicles the course of the journal under Jim's direction and marks some of the accomplishments and changes over the past three decades that go to his credit. Copyright 1998 Academic Press.


Multigene model for predicting metastatic prostate cancer using circulating tumor cells by microfluidic magnetophoresis.
We aimed to isolate circulating tumor cells (CTCs) using a microfluidic technique with a novel lateral magnetophoretic microseparator. Prostate cancer-specific gene expressions were evaluated using mRNA from the isolated CTCs. A CTC-based multigene model was then developed for identifying advanced prostate cancer. Peripheral blood samples were obtained from five healthy donors and patients with localized prostate cancer (26 cases), metastatic hormone-sensitive prostate cancer (mHSPC, 10 cases), and metastatic castration-resistant prostate cancer (mCRPC, 28 cases). CTC recovery rate and purity (enriched CTCs/total cells) were evaluated according to cancer stage. The areas under the curves of the six gene expressions were used to evaluate whether multigene models could identify mHSPC or mCRPC. The number of CTCs and their purity increased at more advanced cancer stages. In mHSPC/mCRPC cases, the specimens had an average of 27.5 CTCs/mL blood, which was 4.2 × higher than the isolation rate for localized disease. The CTC purity increased from 2.1% for localized disease to 3.8% for mHSPC and 6.7% for mCRPC, with increased CTC expression of the genes encoding prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and cytokeratin 19 (KRT19). All disease stages exhibited expression of the genes encoding androgen receptor (AR) and epithelial cell adhesion molecule (EpCAM), although expression of the AR-V7 variant was relatively rare. Relative to each gene alone, the multigene model had better accuracy for predicting advanced prostate cancer. Our lateral magnetophoretic microseparator can be used for identifying prostate cancer biomarkers. In addition, CTC-based genetic signatures may guide the early diagnosis of advanced prostate cancer.


Synthesis of some hydroxynaphthazarins and their cardioprotective effects under ischemia-reperfusion in vivo.
A series of hydroxynaphthazarins has been synthesized. Some of them were found in in vivo experiments to be protectors of myocardium under ischemia-reperfusion and to reduce the infarction zone by 50% without any adverse effect. All compounds exhibit a moderate or small toxicity and are active in low doses.


Posterior chamber phakic intraocular lenses to improve visual outcomes in keratoconus patients.
The aim of this review is to summarize the results of using posterior chamber phakic intraocular lenses (pIOLs) to restore quality of vision in keratoconus patients. These pIOLs can correct the refractive errors associated with keratoconus and can also be combined with other surgical techniques to improve the results.


Use of oolong tea extract staining of soft-tissue specimens in low-vacuum scanning electron microscope with a cooling stage.
For direct observation of the surface structures of soft-tissue specimens, we examined rat tracheal tissue in a low-vacuum scanning electron microscope (SEM) equipped with a cooling stage. In specimens fixed with glutaraldehyde and osmium tetroxide, back-scattered electron images of the surface structure could not be clearly observed in the low-vacuum SEM because of the disruption of fine structures and a low signal-to-noise (S/N) ratio. Processing of the specimens in 70% ethanol resulted in marked shrinkage, in contrast to results when processing in 30% ethanol. To overcome these problems, the trachea was initially fixed in 2.5% glutaraldehyde (0.1 M phosphate buffer pH 7.4), treated with a mixture of 0.2% oolong tea extract (OTE) and 2.5% glutaraldehyde, and postfixed in 1% osmium tetroxide. The sample was immersed in 30% ethanol and examined in a chilled SEM at -10 degrees C. The luminal coutour of the tracheal epithelial cells was clearly observed because of the decrease in shrinkage. Cilia of ciliated cells and microvilli of nonciliated cells were also clearly observed. These specimens also showed a high S/N ratio, thus allowing the observation of samples without the need for complete dehydration, critical-point drying, or metal coating. This OTE-incorporated conductive staining method is simple and rapid, and should prove to be highly useful for rapid SEM analyses of biological specimens.


Preparation, characterization, and evaluation (in-vitro, ex-vivo, and in-vivo) of naturosomal nanocarriers for enhanced delivery and therapeutic efficacy of hesperetin.
The present study intends to formulate, characterize and appraise the phospholipid-based nanovesicular system for enhanced delivery of Hesperetin (HT). The quality by design (QbD) approach was employed to prepare Hesperetin naturosomes (HTN) using the solvent evaporation technique and assessed for physicochemical and pharmacological attributes. The FTIR, DSC, and PXRD studies confirmed the successful formation of a vesicular drug-phospholipid complex, while photomicroscopy, SEM, and TEM analysis revealed the morphology of HTN. The functional attributes substantially enhanced the HT's aqueous solubility, drug release, and membrane permeation. The aqueous solubility of HTN was ~10-fold more than that of pure HT. Likewise, the in-vitro dissolution data of HTN showed better competence in releasing the HT (>93%) than the pure HT (~64%) or the physical mixture (~74%). Furthermore, HTN significantly altered HT permeation (>53%) when compared to pure HT (23%) or the physical mixture (28%). The current study showed that naturosomes are a promising way to improve the solubility in water, bioavailability, and therapeutic effectiveness of drugs.


Rejewski & Enigma.
Alan Turing and Bletchley Park are rightly recognized for their work on breaking the Enigma code. However, this was built on a foundation of work during the 1930s by the Polish cryptographer, Marian Rejewski. Often working alone, and with limited resources, he found ways to break early Enigma code. This article attempts to highlight the man and his invaluable contribution.


Probing new approaches using atmospheric pressure photo ionization for the analysis of brominated flame retardants and their related degradation products by liquid chromatography-mass spectrometry.
Atmospheric pressure photo ionisation has been evaluated for the analysis of brominated flame retardants and their related degradation products by LC-MS. Degradation mixtures obtained from the photochemical degradation of tetrabromobisphenol A and decabromodiphenylether were used as model systems for the assessment of the developed methodology. Negative ion mode gave best results for TBBPA and its degradation compounds. [M - H]- ions were formed without the need of using a doping agent. MS and MS/MS experiments allowed the structural identification of new TBBPA "polymeric" degradation compounds formed by attachment of TBBPA moieties and/or their respective cleavage products. In the case of polybromodiphenylethers, the positive mode provided M*+ ions and gave better results for congeners ranging from mono- to pentabromodiphenylethers whereas for higher bromination degrees, the negative ion mode (providing [M - Br + O]- ions) was best suited. Under both positive and negative ionisation modes, the use of toluene as doping agent gave better results. Liquid chromatography-mass spectrometry by means of atmospheric pressure photo-ionisation was applied to the analysis of aromatic brominated flame retardants and their degradation products. This methodology proved to be particularly useful, for the characterisation and structural identification of some compounds which are not amenable to GC-MS, especially in the case of apolar "polymeric" degradation products of tetrabromobisphenol A investigated in this work.


Immune Phenotypes of Nasopharyngeal Cancer.
Nasopharyngeal cancer (NPC) features intralesional immune cells, but data are lacking on presence/distribution of T-cells and dendritic cells (DCs). Based on intralesional distribution of lymphocytes, a series of NPC biopsies (n = 48) were classified into "inflamed", "excluded", and "deserted" phenotypes. In addition, CD8+ T-cells and CD207+ DCs were quantified. The data were analyzed in relation to Epstein-Barr virus-encoded small RNA (EBER), Epstein-Barr virus (EBV) DNA, and survival. Separately, data on gene expression from a public database were analyzed. 61.7% of NPC lesions were "inflamed", 29.8% were "excluded", and 8.5% were "deserted". While CD8+ cells were present in cancer cell areas and in surrounding stroma, CD207+ cells were observed largely in cancer cell areas. High CD8+ T-cell presence was associated with EBV+ disease, but no such pattern was observed for CD207+ DCs. There was a difference in disease-free survival in favor of "inflamed" over "excluded" NPC. Gene expression analysis revealed differences between NPC and control tissue (e.g., with regard to interferon activity) as well as between subgroups of NPC based on CD8 expression (high vs. low). In conclusion, NPC lesions are heterogeneous with regard to distribution of CD8+ T-cells and CD207+ DCs. NPC can be classified into immune phenotypes that carry prognostic information. CD207+ DCs may represent a target for immunotherapy with potential to facilitate the antigen cross-presentation necessary to execute cytotoxic T-lymphocyte responses.


Crossed cerebellar diaschisis after stroke detected noninvasively by arterial spin-labeling MR imaging.
As a noninvasive perfusion-weighted MRI technique, arterial spin-labeling (ASL) was becoming increasingly used to evaluate cerebral hemodynamics in many studies. The relation between ASL-MRI and crossed cerebellar diaschisis (CCD) was rarely discussed. In this study, the aim of our study was to assess the performance of ASL-MRI in the detection of crossed cerebellar diaschisis after stroke in compared with single-photon emission CT (SPECT). 17 of 51(33.3%) patients revealed CCD phenomenon by the SPECT method. In CCD-positive group, CBFASL of ipsilateral cerebellar were significantly increased compared with contralateral cerebellar (p < 0.0001) while no significant differences (p = 0.063, > 0.001) in the CCD-negative group. Positive correlation was detected between admission National institute of health stroke scale (NIHSS) and asymmetry index of SPECT (AISPECT) (r = 0.351, p = 0.011), AIASL (r = 0.372, p = 0.007); infract volume and AISPECT (r = 0.443, p = 0.001), AIASL (r = 0.426, p = 0.002). Significant correlation was also found between cerebral blood flow of SPECT (CBFSPECT) and CBFASL, AISPECT and AIASL (r = 0.204, p = 0.04; r = 0.467, p = 0.001, respectively). Furthermore, the area under the receiver operating characteristic (ROC) curve value of AIASL was 0.829. CBF derived from ASL-MRI could be valuable for assessment of CCD in supratentorial stroke patients. Additionally, CCD was significantly associated with larger ischemic volume and higher initial NIHSS score.


Egg Overspray with Herbicides and Fungicides Reduces Survival of Red-Legged Partridge Chicks.
Within the environmental risk assessment conducted for pesticide registration in the European Union (EU), avian reproductive toxicity is characterized after exposing adults. However, eggs of ground-nesting species can be exposed when pesticide applications occur during laying or incubation. We simulated environmentally realistic exposure of red-legged partridge (Alectoris rufa) eggs to an herbicide (2,4-D) and a fungicide (tebuconazole) applied to winter cereal crops during the breeding season of most farmland birds. We analyzed the effects on hatching success, offspring survival, and physiology. Exposure by overspray led to greater pesticide accumulation in the eggshell or content than exposure through contact with treated soil (3.1-13.7 times higher, depending on the pesticide and target sample). Egg overspray with tebuconazole significantly increased chick mortality, which was 26% higher than that of controls. 2,4-D caused a similar but a close to significant increase (chick mortality 24% higher than controls). Exposure to either pesticide through contact with treated soils did not affect chick survival but altered some biochemical parameters posthatching. Our experiment shows that egg spraying with pesticides should be considered as a relevant exposure scenario in risk assessment procedures, given its potential to affect the reproductive success of ground-nesting farmland birds.


Under-The-Nose Versus Over-The-Nose Face Mask to Prevent Facial Pressure Sores During Face Mask-Delivered Noninvasive Ventilation for Acute Hypercapnic Respiratory Failure: A Randomized Controlled Trial.
To determine whether an under-the-nose face mask (FM) as the first-line interface strategy reduces the incidence of facial pressure sores with the same clinical improvement as the one obtained by standard over-the-nose face mask-noninvasive ventilation (FM-NIV) in patients with acute hypercapnic respiratory failure (AHRF). A multicenter, prospective randomized controlled study. Two ICUs from two French tertiary hospitals. A total of 108 patients needed NIV for AHRF. participants were randomized (1/1) to receive either the under-the-nose FM (intervention group) or the over-the-nose FM (control group). The primary endpoint was the reduction of facial pressure sores. Secondary endpoints included patients outcome, NIV failure (intubation or death), arterial blood gas improvement, and interface failure (the need to switch to a total face mask). Despite less protective dressings in the intervention group ( n = 4, 5% vs n = 27, 51%; p < 0.001), pressure sores developed less frequently than in the control group ( n = 3, 5% vs n = 39, 74%; p < 0.001). Similar mortality, NIV failure, and arterial blood gas improvement occurred in the two groups. However, under-the-nose FM resulted in a higher interface failure rate than conventional FM ( n = 18, 33% vs n = 5, 9%; p = 0.004), mainly because of excessive unintentional air leaks ( n = 15, 83% vs n = 0, 0%; p < 0.001). In patients with AHRF, under-the-nose FM significantly reduced the incidence of facial pressure sores compared to the most commonly used first-line interface, the standard FM. However, with this new mask, excessive unintentional air leaks more often compelled the attending clinician to switch to another interface to pursue NIV.


The effect of walnut consumption on cardiometabolic profiles of individuals with abnormal glucose homoeostasis: a systematic review and meta-analysis of clinical trials.
Findings on the effect of walnut consumption on cardiometabolic profiles in individuals with abnormal glucose homoeostasis are conflicting. We summarised earlier data in this regard. A systematic literature search of relevant reports published in Medline/PubMed, ISI web of Science, EMBASE, SCOPUS and Google Scholar up to October 2020 was conducted. Randomised trials that enrolled individuals with abnormal glucose homoeostasis in which the main intervention was walnut consumption were included. Abnormal glucose homoeostasis was defined as a spectrum of impaired glucose tolerance or pre-diabetic status that is associated with insulin resistance. Twelve studies were included in systematic review and eight in meta-analysis. No significant effect of walnut consumption on anthropometric measures, including weighted mean difference (WMD: -0·13; 95 % CI -0·64, 0·39 kg), BMI (-0·08; 95 % CI -0·47, 0·32 kg/m2) and waist circumference (0·01; 95 % CI -0·50, 0·52 cm) was observed. Although walnut intake did not influence on lipid profiles (including TAG, total- and HDL-cholesterol levels), individuals in the intervention group tended to have lower levels of LDL-cholesterol than those in the control group (-0·10; 95 % CI -0·20, 0·01 mmol/l; P = 0·06). Other cardiometabolic factors including markers of glycaemic control (fasting blood glucose and HbA1C levels), blood pressure and stimulus-adjusted response measure (a parameter of endothelial function) were not significantly affected. However, walnut consumption resulted in a significant increase in flow-mediated dilation (FMD) (0·93 %; 95 % CI 0·16, 1·71 %). Summarising earlier evidence, we found that walnut consumption might influence FMD and LDL-cholesterol levels in individuals with abnormal glucose homoeostasis. It did not affect other cardiometabolic profiles in these individuals.


A social perspective on resilience: social support and dyadic coping in teacher training.
Stress in teaching and teacher training is a well-known issue and stress management during teacher training may not only be affected by individual coping efforts, but also determined by private and work-related networks the individual is integrated in. In that regard, our article aims firstly to identify sources of social support in the German teacher training system and secondly to analyze interdependencies in dyadic coping interactions based on the Actor-Partner Interdependence Model. On the basis of questionnaire data from 307 German trainees and qualified teachers from vocational and general schools, we found that mentors, partners, fellow trainees, colleagues at school, parents, and good friends were named as the most supportive reference persons during teacher training. In a follow-up survey, data from 49 sources of support were obtained, which could be assigned to the corresponding (trainee) teachers (in the sense of support recipients). These dyads thus form the basis for the analysis of dyadic coping interdependencies. The results of the moderator analyses show, among other things, that support recipients who prefer the coping strategy palliative emotion regulation tend to react rather sensitively to contrary coping strategies of the source of support with regard to their stress symptoms. Social interactions in this respect can represent both protective as well as risk factors. Therefore, a system of complex social interdependencies must be considered when analyzing relational resilience among prospective teachers.


Silicon attenuates cadmium toxicity in Solanum nigrum L. by reducing cadmium uptake and oxidative stress.
Solanum nigrum L. is considered to be a potential plant for restoring Cd-contaminated soils. Si could enhance plants tolerance to heavy metal; however, the mechanism of Si-mediated alleviation of Cd toxicity in S. nigrum was not clear. Three-week-old S. nigrum seedlings were grown in Hoagland solution containing 0 or 100 μM Cd with or without 1 mM Si for 4 days. The results showed that the Cd concentration both in roots and shoots of Si-supplied plant was significantly reduced, especially in expanding and old leaves. The relative proportion of ethanol-extractable Cd, water-extractable Cd and NaCl-extractable Cd in roots was increased by adding Si, while the root-to-shoot Cd translocation was not decreased. Furthermore, in comparison with single Cd treatment, supplying Si could reduce H₂O₂ accumulation and cell death in roots, and the electrolyte leakage and H₂O₂ concentration in functional leaves. Moreover, the activity of superoxide dismutase (SOD, EC 188.8.131.52), catalase (CAT, EC 184.108.40.206), peroxidase (POD, EC 188.8.131.52) and ascorbate peroxidase (APX, EC 184.108.40.206) in functional leaves was markedly increased by Cd exposure, while the antioxidative enzyme activities in Cd plus Si treatment seedlings were significantly lower than that in Cd treatment alone, this decrease might be attributed to the reduction of Cd concentration and Cd-induced oxidative damages. These results demonstrate that Si-enhanced Cd tolerance in S. nigrum is mainly due to the decrease of Cd uptake in roots and Cd distribution in expanding and old leaves, as well as lowering oxidative stress induced by Cd in plants.


Mouse primary follicles experience slow growth rates after activation and progressive increases that influence the duration of the primary follicle phase†.
There are conflicting estimates of the duration of mouse primary follicle development. An accurate determination is needed for studies examining preantral follicle survival and mathematical modeling of folliculogenesis. Primary follicle granulosa cell proliferation rates are low and variable, which may explain the variation in duration estimates. In the present study, female C57Bl6/J mice were exposed to bromodeoxyuridine for 48 hours, to label the proliferating granulosa cells in a large proportion of primary follicles. The bromodeoxyuridine-containing water was then withdrawn and replaced with drug-free water and the mice were euthanized at 0, 1, 3, 6, 10, or 13 days post-bromodeoxyuridine withdrawal. Granulosa cells were bromodeoxyuridine labeled in 48% of primary follicles at day 0, but this decreased to 5% over the 13-day period, as the labeled primary follicles progressed to the secondary follicle stage. Curve-fitting estimated that the last of the bromodeoxyuridine-labeled primary follicles would progress to the secondary stage by 13.7 days. Mathematical models that assumed constant rates of primary follicle proliferation were fitted to the data, but the observed pattern of bromodeoxyuridine-labeled primary follicle disappearance could not be replicated. The level of immunoreactivity for bromodeoxyuridine and proliferating-cell nuclear antigen in primary follicles revealed follicles with no granulosa cell proliferation during the 48-h bromodeoxyuridine-exposure period had resumed proliferation 1 or 3 days later. Therefore, primary follicle granulosa cells proliferate after follicle activation, but proliferation rates gradually increase as the follicle develops. Prior estimates of primary follicle duration are inaccurate due to the assumption that follicles develop at a constant rate.


Retinitis pigmentosa 2 pathogenic mutants degrade through BAG6/HUWE1 complex.
Retinitis pigmentosa (RP) is the most common inherited retinal degenerative disease which is the major cause of vision loss. X-linked RP patients account for 5%-15% of all inherited RP cases and mutations in RP2 (Retinitis pigmentosa 2) were responsible for about 20% X-linked RP families. A majority of RP2 pathogenic mutations displayed a vulnerable protein stability and degraded rapidly through ubiquitin-proteasome system (UPS). Though the RP2 protein could be readily recovered by proteasome inhibitors, e.g., MG132, their applications for RP2-related RP therapy were limited by their nonspecific characterization. In the present study, we aimed to identify UPS-related factors, such as E3 ligases, which are specifically involved in degradation of RP2 pathogenic mutants. We identified several E3 ligases, such as HUWE1, and the co-chaperon BAG6 specifically interacting with RP2 pathogenic mutants. Knockdown of HUWE1 and BAG6 could partially rescue the reduced protein levels of RP2 mutants. BAG6 is required for recruitment of HUWE1 to ubiquitinate RP2 mutants at the K268 site. The HUWE1 inhibitor BI8622 could restore the levels of RP2 mutant and then the binding to its partner ARL3 in retina cell lines. This study revealed the details of UPS-related degradation of RP2 mutants and possibly provided a potential treatment for RP2-related RP.


Two-Dimensional Culture Systems to Enable Mechanics-Based Assays for Stem Cell-Derived Cardiomyocytes.
Well-controlled 2D cell culture systems advance basic investigations in cell biology and provide innovative platforms for drug development, toxicity testing, and diagnostic assays. These cell culture systems have become more advanced in order to provide and to quantify the appropriate biomechanical and biochemical cues that mimic the milieu of conditions present in vivo. Here we present an innovative 2D cell culture system to investigate human stem cell-derived cardiomyocytes, the muscle cells of the heart responsible for pumping blood throughout the body. We designed our 2D cell culture platform to control intracellular features to produce adult-like cardiomyocyte organization with connectivity and anisotropic conduction comparable to the native heart, and combined it with optical microscopy to quantify cell-cell and cell-substrate mechanical interactions. We show the measurement of forces and displacements that occur within individual cells, between neighboring cells, and between cells and their surrounding matrix. This system has broad potential to expand our understanding of tissue physiology, with particular advantages for the study of the mechanically active heart. Furthermore, this technique should prove valuable in screening potential drugs for efficacy and testing for toxicity.


Acute progesterone feedback on gonadotropin secretion is not demonstrably altered in estradiol-pretreated women with polycystic ovary syndrome.
Women with polycystic ovary syndrome (PCOS) demonstrate gonadotropin-releasing hormone (GnRH) pulse generator resistance to suppression with 7 days of progesterone and estradiol administration. It remains unknown whether such women demonstrate impairments in acute progesterone negative feedback on LH pulse frequency or progesterone positive feedback on gonadotropin release. This was a randomized, double-blind, placebo-controlled crossover study designed to test the hypothesis that acute, progesterone-related suppression of LH pulse frequency and progesterone-related augmentation of gonadotropin release are impaired in PCOS. Twelve normally cycling women and 12 women with PCOS completed study. Volunteers were pretreated with transdermal estradiol (0.2 mg/day) for 3 days and then underwent a frequent blood sampling study (20:00-20:00 h), during which they received micronized progesterone (100 mg) or placebo at 06:00 h. In a second study admission, volunteers received the intervention they did not receive during the first admission, but the protocol was otherwise identical. The primary outcome measures were LH secretory characteristics and circulating gonadotropin concentrations. Exogenous progesterone did not reduce LH pulse frequency in either group. Mean LH, pulsatile LH secretion, LH pulse mass, and mean FSH increased more with progesterone compared to placebo in both groups. Although trends toward less pronounced changes in LH pulse mass and pulsatile LH secretion were observed in the PCOS group, these differences were not statistically significant. In summary, exogenous progesterone did not suppress LH pulse frequency within 12 hours in estradiol-pretreated women, and the positive feedback effect of progesterone on gonadotropin release was not demonstrably impaired in PCOS. NEW & NOTEWORTHY: This study indicated that exogenous progesterone does not reduce LH pulse frequency within 12 h in women with PCOS, but progesterone acutely increased gonadotropin in these women. This study suggested that progesterone-related augmentation of gonadotropin release may be impaired in PCOS compared to normally cycling women, but this finding was not statistically significant.


Lower Urinary Tract Terminology in Daytime Lower Urinary Tract Symptoms in Children: A View of the Pediatric Urologist.
Epidemiological studies have demonstrated rates of lower urinary tract (LUT) symptoms in school-aged children as high as 20%. Symptoms of LUT may have significant social consequences. The diagnosis of LUT symptoms in children is mainly based on the subjective impression, and it is therefore important to translate the clinical impression into a structured LUT terminology. To have a view, as a pediatric urologist and a urologist, of the LUT terminology proposed by the Standardization Committee of the International Children Continence Society. In addition to the known LUT terminology conditions that are mainly functional, we propose to add specific urological malformations due to congenital or acquired urological conditions, leading to LUT symptoms. In addition to the opinion-based statements and practical clinical suggestions, we have added recent literature to support the statements and suggestions. LUT symptoms in children can be from a functional or an anatomical origin. As the diagnosis is often made on the basis of subjective and variable information, experience of the medical caretaker is also important to allow categorization of the condition of the child into a well-structured LUT terminology. Medical caretakers should be aware of possible evidence-based diagnostic tools and be able to follow guidelines and algorithms to come to the correct diagnosis and condition of the child to allow one to distinguish functional from congenital or acquired anatomical LUT conditions. Up to 20% of school-aged children can have wetting problems. Some wetting problems can be temporary, due to the young age, stress, psychological problems, or other associated problems such as bowel dysfunction. However, some wetting problems in children are due to a condition of the kidneys, bladder, or elsewhere in the urinary tract since they were born, and should be well investigated, as in most such situations the LUT problems could be treated surgically.


The Experience of Living with Severe Asthma, Depression and Anxiety: A Qualitative Art-Based Study.
Severe asthma, depression and anxiety often co-exist and increase disease burden. Currently there are no published studies investigating severe asthma and psychological comorbidity using arts-based methodology. We aimed to (i) illustrate the individual experience of adults living with severe asthma, with and without symptoms of depression and/or anxiety and (ii) to explore common characteristics depicted in artworks between those groups. A qualitative arts-based study was conducted. Adults with severe asthma were categorised into two groups according to Hospital Anxiety and Depression Scale scores (<8 on either subscale [SA-D/A] (N=15) or (≥8 on one or both subscales [SA+D/A] (N=15). Art thematic analysis was undertaken using a hybrid approach. The Common-Sense Model of Self-Regulation was used to examine frequencies in artworks. Participants with severe asthma alone and severe asthma with depression/anxiety were of older age (median 67 and 63 years respectively). There was greater asthma QoL impairment in participants with psychological comorbidity than without (4.7 ± 8.3 versus 5.8 ± 0.85, p=<0.01). Analysis of art works identified three themes: (1) "darkness" depicting misery, isolation and sadness; (2) "impacts" describing physical and social consequences; and (3) "resilience" illustrating acceptance and perseverance of living with all three conditions. Art-based research in severe asthma facilitates detailed exploration of intimate and individual experiences. Darkness, impacts and resilience are common themes emerging from artworks. Understanding these experiences may help guide assessment and treatment of psychological comorbidity in the clinic.


Septate uterus with left fallopian tube hypoplasia and ipsilateral ovarian agenesis.
To report a combined genital tract anomaly of septate uterus, unilateral fallopian tube hypoplasia, and ipsilateral ovarian agenesis. Case report. Academic tertiary care center. A 24-year-old female. History and physical, pelvic sonogram, hysterosalpingogram, intravenous pyelogram, abdominal and pelvic magnetic resonance imaging, diagnostic laparoscopy, exploratory laparotomy, cuff neosalpingostomy, and uterine septum resection. Recognition of three independent and rare reproductive tract anomalies in the same patient. Restoration of anatomy and subsequent fertility. A careful clinical evaluation with consideration of embryologic origin is essential to the identification and treatment of rare reproductive tract malformations.


Adenine phosphoribosyltransferase deficiency identified by urinary sediment analysis: cellular and molecular confirmation.
Adenine phosphoribosyltransferase deficiency is an autosomal recessive purine enzyme defect that causes urolithiasis and, in severe cases, renal failure. Most homozygotes with this disorder were identified by analyses of excreted or surgically removed urinary stones, but some were identified only because they were family members of symptomatic individuals. We report here the detection of adenine phosphoribosyltransferase deficiency in two cases by routine analysis of urinary sediments. 2,8-Dihydroxyadenine-like spherical crystals were observed in the urinary sediment, and a diagnosis of homozygous adenine phosphoribosyltransferase deficiency was confirmed by cellular and molecular methods. A molecular diagnostic system using the polymerase-chain reaction and single-strand conformational polymorphism analysis proved to be a rapid and sensitive method to identify the APRT*J allele, a common mutant allele among the Japanese people. These methods will facilitate identification of symptomatic and asymptomatic individuals with homozygous adenine phosphoribosyltransferase deficiency.


A population-kinetical approach to RNA formation and degradation in growing and in resting cells.
Labelled RNA was extracted from growing and stationary cultures of the ciliate Tetrahymena and was separated chromatographically into poly(A)- and no poly(A)-containing fractions. A new method was used to derive from the data (cpm/A260, and tD, doubling time of RNA) absolute values of three growth terms which fully describe the population kinetics of RNA molecules: the rates of transcription, decay, and net growth. At all times the messenger RNA (mRNA) content of Tetrahymena was the result of a self-regulating equilibrium between synthesis and decay. The rates of transcription and of degradation of mRNA and ribosomal RNA (rRNA) were found to be controlled independently, but decay was dominant in establishing the growth-specific quantities per cell. In the stationary phase about 94% of all poly(A)-RNA molecules and about 50% of all mRNA molecules were kinetically silent. The remaining portions were transcribed with high rates, but also degraded immediately. During the culture growth cycle the rate of rRNA net growth responded positively to the cellular rRNA content suggesting an autocatalytic effect of rRNA on the rate of its accumulation.


Structure and synthesis of a lipid-containing bacteriophage. An endolysin activity associated with bacteriophage PM2.
Endolysin was induced in Pseudomonas BAL-31 infected with bacteriophage PM2 and was also associated with the purified virion. This enzyme required divalent cations for its activity, Ca2+ being the most effective cation. Endolysin activity in the virion increased up to three-fold upon disruption and the activity could be localized in the viral nucleocapsid. Thus the enzyme is localized within the virion. After purification of the structural proteins of bacteriophage PM2, only the nucleocapsid protein (III) had endolysin activity.


RNAi-mediated silencing of Trichinella spiralis serpin-type serine protease inhibitors results in a reduction in larval infectivity.
Trichinella spiralis serpin-type serine protease inhibitors (TsSPIs) are expressed in adult worms (AW), newborn larvae (NBL) and muscle larvae (ML) of T. spiralis, with the ML stage demonstrating the highest expression level. This study aims to determine TsSPI functions in larval viability and invasion of intestinal epithelial cells in vitro, as well as their development, survival, and fecundity in vivo via RNAi. TsSPI-specific siRNAs and dsRNA were transfected into ML by incubation. The silencing effect of TsSPI transcription and expression was determined using qPCR and western blot, respectively. After incubation in 60 ng/μL dsRNA-TsSPI for 3 days, larval TsSPI mRNA and protein expression levels were reduced by 68.7% and 68.4% (P < 0.05), respectively. dsRNA-mediated silencing of TsSPI significantly impacted larval invasion into intestinal epithelial cells in vitro but did not affect the survival rate of larvae. After challenge with dsRNA-TsSPI-treated ML, mice exhibited a 56.0% reduction in intestinal AW burden and 56.9% reduction in ML burden (P < 0.05), but NBL production of female AW remained the same (P > 0.05). Our results revealed that RNAi-mediated silencing of TsSPI expression in T. spiralis significantly reduced larval infectivity and survival in the host but had no effect on the survival rate and fecundity. Furthermore, TsSPIs have no effect on the growth and reproduction of parasites but may be directly involved in regulating the interaction of T. spiralis and the host. Therefore, TsSPIs are crucial in the process of T. spiralis larval invasion and parasite survival in the host.


A multidimensional model of sexual health and sexual and prevention behavior among adolescent women.
Sexual health refers a state of lifespan well-being related to sexuality. Among young people, sexual health has multiple dimensions, including the positive developmental contributions of sexuality, as well as the acquisition of skills pertinent to avoiding adverse sexual outcomes such as unintended pregnancy and sexually transmitted infections (STIs). Existing efforts to understand sexual health, however, have yet to empirically operationalize a multi-dimensional model of sexual health and to evaluate its association to different sexual/prevention behaviors. Sexual health dimensions and sexual/prevention behaviors were drawn from a larger longitudinal cohort study of sexual relationships among adolescent women (N = 387, 14-17 years). Second order latent variable modeling (AMOS/19.0) evaluated the relationship between sexual health and dimensions and analyzed the effect of sexual health to sexual/prevention outcomes. All first order latent variables were significant indicators of sexual health (β: 0.192 - 0.874, all p < .001). Greater sexual health was significantly associated with sexual abstinence, as well as with more frequent non-coital and vaginal sex, condom use at last sex, a higher proportion of condom-protected events, use of hormonal or other methods of pregnancy control and absence of STI. All models showed good fit. Sexual health is an empirically coherent structure, in which the totality of its dimensions is significantly linked to a wide range of outcomes, including sexual abstinence, condom use and absence of STI. This means that, regardless of a young person's experiences, sexual health is an important construct for promoting positive sexual development and for primary prevention.


Catheter directed embolectomy of right atrial clot in transit-A case series.
In the previous literature, the prevalence of right atrial (RA) clot-in-transit associated with pulmonary embolism is around 4-18% with an associated mortality of 80-100% in untreated cases. Surgical thrombo-embolectomy has been the mainstay of treatment for stable patients but the data for percutaneous thrombo-embolectomy is lacking in the literature. We present a series of three cases of right atrium clot-in-transit treated with catheter-based therapies with Inari FlowTriever® (Inari Medical, Irvine, CA). Our three patients had different clinical profiles and presentations of right atrial clot-in-transit. All of the subjects had contraindications to surgical thrombo-embolectomy and thrombolytic therapy. Catheter based embolectomy using Inari FlowTriever® was successfully performed in all the patients. As the data on this intervention is sparse, our case series highlights successful catheter based thrombo-embolectomies in high-risk individuals with right atrial clot in-transit with or without pulmonary embolism.


Mitochondrial gene mutations in familial non-insulin-dependent diabetes mellitus in Taiwan.
Mitochondrial gene mutations are found to cause certain forms of diabetes mellitus and related syndromes. To study the prevalence of mitochondrial gene mutations in subjects with non-insulin-dependent diabetes mellitus (NIDDM) in Taiwan, 23 pedigrees with multiple siblings affected with NIDDM were consecutively collected from patients living in northern Taiwan. The A-to-G mutation at position 3243 np in the tRNA Leu gene and the mutation at position 8344 were screened by PCR-RFLP methods and confirmed by direct DNA sequence analysis. Among 23 NIDDM pedigrees, one pedigree was found to carry the 3243 np mutation. There was no 8344 np mutation in this series. Clinical features of this pedigree were consistent with mitochondrial disease in terms of maternal transmission, relatively early onset, non-obesity, insulin-requirement and association with hearing impairment. There was no correlation between the degree of heteroplasmy of mitochondrial gene mutation in leukocyte DNA and clinical severity. We conclude that a mitochondrial gene defect is an important genetic factor in familial cases with NIDDM in Taiwan.


Loss of caspase-2 accelerates age-dependent alterations in mitochondrial production of reactive oxygen species.
Mitochondria are known to be a major source and target of oxidative stress. Oxidative stress increases during aging and is suggested to underlie in part the aging process. We have previously documented an increase in endogenous caspase-2 (casp2) activity in hepatocytes obtained from old (28 months) vs. young mice (5 months). More recently, we have shown that casp2 is activated by oxidative stress and is critical for mitochondrial oxidative stress-induced apoptosis. Since casp2 appears integral to mitochondrial oxidative stress-induced apoptosis, in this study we determined whether loss of casp2 altered the production of mitochondrial reactive oxygen radicals (mROS) as a function of age in intact living hepatocytes. To stimulate mitochondrial metabolic activity, we added a mixture of pyruvate and glutamate to hepatocytes while continuously monitoring endogenous mROS production in the presence or absence of rotenone and/or antimycin A. Our data demonstrate that mROS production and neutralization are compromised in hepatocytes of old mice. Interestingly, casp2 deficient hepatocytes from middle age mice (12 months) had similar mROS neutralization kinetics to those of hepatocytes from old WT mice. Rotenone had no effect on mROS metabolism, whereas antimycin A significantly altered mROS production and metabolism in an age-dependent fashion. Our results indicate that: (1) hepatocytes from young and old mice respond differently to dysfunction of the mitochondrial electron transport chain; (2) age-dependent alterations in mROS metabolism are likely regulated by complex III; and (3) absence of casp2 accelerates age-dependent changes in terms of pyruvate/glutamate-induced mROS metabolism.


Are influences during pregnancy associated with wheezing phenotypes during the first decade of life?
Recently, attention has focused on possible early life origins for asthma. We sought to identify whether factors present during pregnancy were associated with development of childhood wheezing phenotypes. A whole population birth cohort (n=1456) on the Isle of Wight, UK, was followed through to age 10 y. Where possible, information regarding environmental exposures and events during pregnancy was obtained from the maternity records (n=1238). Children were seen at ages 1, 2, 4 and 10 y, and wheezing symptoms were used to define wheezing phenotypes in the first decade (n=1034). Risk of early-onsetpersistent wheeze (onset in the first 4 y, still present at age 10) was increased by environmental tobacco smoke exposure in pregnancy (OR=2.44; 95% CI: 1.37-4.34) plus maternal asthma (3.57; 1.84-6.94), but reduced by cat ownership (0.30; 0.13-0.62). Early transient wheeze (onset in the first 4 y, but not present at age 10) was increased by environmental tobacco smoke exposure (1.58; 1.02-2.45), male gender (1.68; 1.09-2.60) and low birthweight (3.65; 1.27-10.52). No environmental factors in pregnancy were associated with late-onset persistent wheeze (onset after age 4 y, still present at 10 y). In addition to genetics, maternal exposures during pregnancy show association with childhood and especially early-life wheezing phenotypes.


Influence of medium-chain triglycerides on expansion and rheological properties of extruded corn starch.
Enhancement of product properties of extruded starch based products can be achieved by incorporating health promoting oil into the matrix. In order to achieve a preferably high expansion with a homogeneous pore structure, the expansion mechanisms have to be understood. In our study, we applied a customized twin-screw extruder set up to feed medium-chain triglycerides after complete gelatinization of corn starch, minimizing its effect on the starch gelatinization. Despite the fact, that the addition of up to 3.5% oil showed no influence on the extrusion parameters, we observed a three-fold increase in sectional expansion. Longitudinal expansion was less affected by the oil content. Rheological properties of the gelatinized starch were measured using an inline slit die rheometer. In addition to shear viscosity, we presented a method to determine the Bagley pressure, which reflects the elongational properties of a fluid. We were able to observe an increase in the Bagley pressure from about 25 bar up to 35-37 bar due to the addition of oil.


New insights into the role of fibroblast growth factors in Alzheimer's disease.
Alzheimer's disease (AD), acknowledged as the most common progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. The characteristic pathologic hallmarks of AD-including the deposition of extracellular senile plaques (SP) formation, intracellular neurofibrillary tangles, and synaptic loss, along with prominent vascular dysfunction and cognitive impairment-have been observed in patients. Fibroblast growth factors (FGFs), originally characterized as angiogenic factors, are a large family of signaling molecules that are implicated in a wide range of biological functions in brain development, maintenance and repair, as well as in the pathogenesis of brain-related disorders including AD. Many studies have focused on the implication of FGFs in AD pathophysiology. In this review, we will provide a summary of recent findings regarding the role of FGFs and their receptors in the pathogenesis of AD, and discuss the possible opportunities for targeting these molecules as novel treatment strategies in AD.


Functional interaction between FOXO3a and ATM regulates DNA damage response.
The maintenance of genomic stability in cells is relentlessly challenged by environmental stresses that induce DNA breaks, which activate the DNA-damage pathway mediated by ataxia-telangiectasia mutated (ATM) and its downstream mediators to control damage-induced cell-cycle checkpoints and DNA repair. Here, we show that FOXO3a interacts with ATM to promote phosphorylation of ATM at Ser 1981 and prompting its downstream mediators to form nuclear foci in response to DNA damage. Silencing FOXO3a in cells abrogates the formation of ATM-pS1981 and phospho-histone H2AX foci after DNA damage. Increasing FOXO3a in cells promotes ATM-regulated signalling, the intra-S-phase or G2-M cell-cycle checkpoints, and the repair of damaged DNA, whereas cells lacking FOXO3a did not trigger the DNA-repair mechanism after DNA damage. The carboxy-terminal domain of FOXO3a binds to the FAT domain of ATM, thereby contributing to the activation of ATM. These results suggest that ATM may be regulated directly by FOXO3a in the DNA-damage response.


Signal transducer and activator of transcription 6 (STAT6) and attention-deficit hyperactivity disorder: a speculative hypothesis.
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by hyperactivity, impulsiveness and inattention that begins in childhood. The underlying pathogenesis of this disorder is still unknown, although pharmacological, genetic and neuroimaging studies suggest that dopamine transportation may be implicated in the pathogenesis of ADHD. Signal transducer and activator of transcription 6 (STAT6), similar to other members of the signal transducer and activator of transcription family of proteins, is an important molecule in the induction and regulation of the immune response. Animal studies have demonstrated that STAT6 is highly expressed in the CNS, especially in the developing brain. Recent studies have demonstrated that STAT6-deficient mice exhibit increased locomotor activity and decreased levels of dopamine transporter expression in the striatum, when compared with the wild-type. From these findings, and evidence from other studies, it can be proposed that STAT6 may be implicated in the pathogenesis of ADHD. Several proposals to test this hypothesis are suggested; attempts to prove the STAT6-ADHD hypothesis may provide a new direction that elucidates the pathogenesis of and a treatment for ADHD.


ADHD in Adults: A Systematic Review and Meta-Analysis of Prevalence Studies in Outpatient Psychiatric Clinics.
Systematic review and meta-analysis to estimate the pooled prevalence of ADHD in adult attendees of outpatient mental health clinics and to investigate factors influencing prevalence rates. The following were extracted: demographics, design of the study (screening only or two-phase), scales/criteria for diagnosis of ADHD, number of ADHD, and non-ADHD participants. The pooled prevalence of ADHD from screening studies (n = 9) was 26.7%, (95% CI [17.2-37.4]), ADHD = 1727, No ADHD = 3,578. From studies employing a two-stage design (n = 5), prevalence was 14.61%, CI [10.39-19.41], ADHD = 561, No ADHD = 3,578. Age and gender did not have any significant effect on the estimated prevalence. By contrast exclusion of psychotic disorders lowers prevalence. The screening scale used also influence prevalence rates. Meta-analysis shows high rates of adult ADHD among psychiatric outpatient clinics. Applying DSM-5 criteria increased prevalence rates. More methodologically robust studies, using two-stage design, need to be conducted to help assist in service planning.


Molecular characterization of a novel fusarivirus infecting the edible fungus Auricularia heimuer.
Here, we describe a novel mycovirus, Auricularia heimuer fusarivirus 1 (AhFV1), isolated from the edible fungus Auricularia heimuer strain CCMJ1296. The virus has a single-stranded positive-sense [+ssRNA] genome of 7,127 nucleotides containing two overlapping open reading frames (ORFs) and a poly(A) tail. The large ORF1 encodes a polyprotein of 1,637 amino acids (aa) with conserved RNA-dependent RNA polymerase (RdRp) and DEAD-like helicase superfamily (DEXDc) domains. ORF2 encodes a putative 633-aa protein with unknown function. A BLAST search showed that the nucleotide sequence of the AhFV1 genome is 41.28% identical to that of Sclerotium rolfsii fusarivirus 2 and 40.49% identical to that of Sclerotium rolfsii fusarivirus 1. Phylogenetic analysis based on RdRp and helicase (Hel) sequences indicated that AhFV1 is related to unclassified mycoviruses and other fusariviruses. Our data suggest that AhFV1 should be classified as a member of the newly proposed family "Fusariviridae". This is the second virus and the first full genome sequence of a fusarivirus from A. heimuer.


Targeting of HIV-1 Tat traffic and function by transduction-competent single chain antibodies.
Human immunodeficiency virus type 1-encoded Tat protein is a transactivating factor essentially required for viral replication. Tat binds specifically to the transactivation response RNA stem loop, which is formed at the 5' end of all viral transcripts. The TAR binding motif of Tat also contains a protein transduction domain, PTD that mediates not only nuclear localization of Tat but is also capable of transducing cargo across cellular membranes. In order to target a Tat antagonist directly to the TAR binding site in the nucleus, we engineered a chimeric protein consisting of the Tat-derived PTD fused to the anti-Tat single chain antibody scFvtat1 that binds intracellularly to Tat. Recombinant scFvtat1-PTD(TAT) fusion antibody retained both, anti-Tat specificity and PTD(TAT)-mediated transduction-competence leading to its nuclear accumulation within living cells. Incubation of Jurkat T cells with scFvtat1-PTD(TAT) suppressed Tat-dependent transcription of a HIV-1 reporter gene by >80%. Transfection of a scFvtat1-PTD(TAT) expression plasmid in HEK293 cells resulted in diffuse cytoplasmic and nuclear expression. ScFvtat1-PTD(TAT) did not inhibit HIV-1 Tat translocation to the nucleus, yet showed increased inhibition of 78%, indicating a nuclear site of scFvtat1-PTD(TAT) action. Strikingly, the PTD(TAT) alone showed 55% inhibition in the HIV-1 luciferase reporter assay, indicating competition with HIV-1 Tat binding to the TAR element. The results of this study suggest that Tat traffic can only marginally be affected by anti-Tat antibodies and that effective inhibition of Tat function requires both competition with HIV Tat for TAR binding mediated by PTD(TAT) and steric hindrance mediated by the scFvtat1 moiety.


Preparation and SO2 capture kinetics of a DeSOx coating for the desulfurization of exhaust emission.
Sulfur dioxide (SO2) is an extremely harmful pollutant in diesel engine exhaust fumes, which must be controlled and removed effectively. In order to better integrate desulfurization materials into diesel exhaust systems, a new desulfurization powder coating (DeSOx coating) was prepared. The SO2 capture performance and kinetics of the DeSOx coating were subsequently studied. This study used a fixed-bed reactor to test the DeSOx coating SO2 capture performance and conduct kinetic analysis at various temperatures and gas flows. The analysis obtained the kinetic parameters of the activation energy and Arrhenius constant, with the derived rate control equations, under isothermal conditions. The DeSOx coating and filter which were prepared using metal oxide powders, SiO2 colloidal sol, and additives, exhibited an enhanced SO2 capture performance. In this experiment, an MnO2/SiO2/LiOH coating had the best SO2 removal rate and capture capacity at 400 °C. Under a reaction space velocity of 10700 h-1, the MnO2/SiO2/LiOH coating SO2 removal rate was 100% within the first hour of reaction. Under a reaction space velocity of 32000 h-1, the MnO2/SiO2/LiOH coating SO2 capture capacity was 132.7 mgSO2/gmaterial during the second hour of reaction. The SO2 capture conversion rate of the DeSOx coating and filter follows the second-order kinetic mechanism model. For the MnO2/SiO2/LiOH coating, the Arrhenius equation gives an activation energy of 4952 J/mol and the Arrhenius natural logarithmic constant is 8.969 s-1. For the MnO2/SiO2/LiOH filter, the activation energy of the rate constant is 214 J/mol, and the Arrhenius natural logarithmic constant is 3.744 s-1. Therefore, the desulfurization coating is an effective way to remove SO2 pollutants from diesel exhaust gases.


Palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates at the C-Cl site.
This study described palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates in the Ar-Cl bond. The Pd/SelectPhos system showed excellent chemoselectivity toward the Ar-Cl bond in the presence of the Ar-OTf bond with a broad substrate scope and excellent product yields. The electronic and steric hindrance offered by the -PR2 group of the ligand with the C2-alkyl group was found to be the key factor affecting the reactivity and chemoselectivity of the α-arylation reaction. The chemodivergent approach was also successfully employed in the synthesis of flurbiprofen and its derivatives (e.g., -OMe and -F).


Venatorbacter cucullus gen. nov sp. nov a novel bacterial predator.
A novel Gram-stain negative, aerobic, halotolerant, motile, rod-shaped, predatory bacterium ASxL5T, was isolated from a bovine slurry tank in Nottinghamshire, UK using Campylobacter hyointestinalis as prey. Other Campylobacter species and members of the Enterobacteriaceae were subsequently found to serve as prey. Weak axenic growth on Brain Heart Infusion agar was achieved upon subculture without host cells. The optimal growth conditions were 37 °C, at pH 7. Transmission electron microscopy revealed some highly unusual morphological characteristics related to prey availability. Phylogenetic analyses using 16S rRNA gene sequences showed that the isolate was related to members of the Oceanospirillaceae family but could not be classified clearly as a member of any known genus. Whole genome sequencing of ASxL5T confirmed the relationship to members the Oceanospirillaceae. Database searches revealed that several ASxL5T share 16S rRNA gene sequences with several uncultured bacteria from marine, and terrestrial surface and subsurface water. We propose that strain ASxL5T represents a novel species in a new genus. We propose the name Venatorbacter cucullus gen. nov., sp. nov. with ASxL5T as the type strain.


Biomarker profile of minor physical anomalies in schizophrenia patients.
The aim of this study was to determine the frequency and topographical distribution of minor physical anomalies (MPAs) in schizophrenia patients and control subjects, and the ability of the items of the Waldrop scale to predict the patient-control status. 128 schizophrenic patients (66 men, 62 women) and 103 normal controls (49 men, 54 women) were evaluated for MPAs with a modified version of the Waldrop scale. Compared with controls, schizophrenia patients showed a higher incidence of almost all studied MPAs, differences being statistically significant for 12 items: fine electric hair, abnormal hair whorls, epicanthus, adherent ear-lobes, lower edges of the ears extending backward/upward, malformed ears, asymmetrical ears, high/arched palate, furrowed tongue, smooth/rough spots on the tongue, III toe > or = II toe, big gap between I and II toe. Some anomalies occurred with almost equal frequency in schizophrenic patients and controls, while others were more than 10 times more common in patients (odds ratio: 0.62 - 10.55). The distribution frequency of MPAs in schizophrenia tended to increase in the cranial direction. Nine predictor MPA biomarkers successfully distinguished 81.10% of patients, 81.55% of controls, and 81.30% of all examined subjects. The elevated incidence of MPA biomarkers in schizophrenia patients implies impaired neurodevelopment that increases the risk for the development of schizophrenia. The pattern of changes in the morphological characteristics suggests they may be a random outcome of a general neurodevelopmental defect or may reflect different neurodevelopmental defects that allow better characterization of schizophrenia patients subgroups.


The role of endoscopic ultrasonography in the upper gastrointestinal tract: a review with illustrative cases.
In this article the current applications of endoscopic ultrasound in the upper gastrointestinal tract and its adnexa, as well as the areas of likely development, are reviewed. Illustrative cases are shown from the author's experience. Pitfalls and limitations of the technique are also discussed.


Effect of SK&F 96365 on extracellular Ca2+ -dependent O2- production in neutrophil-like HL-60 cells.
Store-operated Ca2+ entry is referred to a capacitative current activated by Ca2+ -stores depletion in various non-excitable cells. Neutrophil-like HL-60 cells responded to N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLP) by an early O2- production preceded by a [Ca2+]i rise. Cell stimulation in the absence of extracellular Ca2+ resulted in a major reduction of [Ca2+]i rise and O2- production. A purported inhibitor of store-operated Ca2+ entry, SK&F 96365 (1-(beta-(3-(4-methoxy-phenyl)propoxyl)-4-methoxy-phenetyl)- 1H-imidazole hydrochloride), inhibited extracellular Ca2+ -dependent [Ca2+]i rise by 30% but did not alter O2- production. In conclusion, SK&F 96365 did not modify extracellular Ca2+ -dependent O2- production, despite a significant but limited reduction in fMLP-activated membrane Ca2+ fluxes which can be ascribed to store-operated Ca2+ entry. Furthermore, Ca2+ influx is necessary for a full induction and maintenance of the biological response.


Free and conjugated plasma homovanillic acid in schizophrenic patients.
It has recently been suggested that the plasma level of homovanillic acid (HVA) may provide an index of central dopaminergic activity in humans. Clinical studies have shown that in schizophrenic patients, plasma HVA levels increase with the severity of psychopathology. However, these studies only considered the plasma free HVA fraction whereas investigations on conjugated HVA in humans are sparse and results remain controversial. The aim of this study was to measure both plasma free and conjugated HVA in healthy volunteers and drug-free schizophrenic patients. The mean values and the ranges of plasma free HVA in volunteers and patients were similar to those described in the literature. A substantial and significant increase in plasma free HVA was observed in schizophrenic patients compared with normal subjects. In contrast, plasma conjugated HVA was significatively decreased in schizophrenics. The plasma total HVA was nevertheless higher in schizophrenics compared with controls. No significant correlations were observed between plasma HVA levels and the clinical features of schizophrenic patients rated by various psychiatric scales. These findings suggest that there is an imbalance between plasma free and conjugated HVA in schizophrenic patients, who present an increase in total HVA when compared with controls. Paranoid schizophrenic patients, who present mainly positive symptoms, show the most marked plasma free/conjugated HVA imbalance.


Survival after surgery or therapeutic catheterisation for congenital heart disease in children in the United Kingdom: analysis of the central cardiac audit database for 2000-1.
To analyse simple national statistics and survival data collected in the central cardiac audit database after treatment for congenital heart disease and to provide long term comparative statistics for each contributing centre. Prospective, longitudinal, observational, national cohort survival study. UK central cardiac audit database. Survival at 30 days and one year after treatment in the year April 2000-March 2001, assessed by using both volunteered life status and independently validated life status through the Office for National Statistics, using the patient's unique NHS number, or the general register offices of Scotland and Northern Ireland. Institutional results following a group of six benchmark operations and three benchmark catheterisation procedures. Since April 2000 data have been received from all 13 UK tertiary centres performing cardiac surgery or therapeutic cardiac catheterisation in children with congenital heart disease. Altogether 3666 surgical procedures and 1828 therapeutic catheterisations were performed. Central tracking of mortality identified 469 deaths, 194 occurring within 30 days and 275 later. Forty two of the 194 deaths within 30 days were detected by central tracking but not by volunteered data. For surgery overall, survival at 30 days was 94.9%, falling to 91.2% at one year; this effect was most marked for infants. For therapeutic catheterisation survival at 30 days was 99.1%, falling to 98.1% at one year. Survival of individual centres or individual operators did not differ from the national average after benchmark procedures. Independent data validation is essential for accurate survival analysis. One year survival gives a more realistic view of outcome than traditional perioperative mortality. Currently no detectable difference exists in survival between any of the 13 UK tertiary congenital heart disease centres, but confidence intervals for small centres are wide, limiting our power to detect underperformance from analysis of a single year's data. Appropriately resourced, focused national audit is capable of accurate data collection on which nationwide, long term quality control can be based.


Botulinum toxin in tension-type headache.
Despite the controversy regarding specific mechanism of botulinum toxin action in pain relief, clinical results suggest that botulinum toxin type A may be promising treatment options for patients with primary chronic headache. To investigate this, we included sixteen patients with chronic tension-type headache in a prospective double blind, placebo-controlled crossover study and thirty patients in an open-label long-term study. All of the patients showed reduced severity of headache, reduced pericranial muscle tenderness and increased headache-free days during botulinum toxin A treatment. Moreover, constant and cumulative trend of improvement was present during long-term study indicating better quality of life during botulinum toxin treatment. There is need for further placebo-controlled clinical studies to identify the optimal dose, optimal number and place of injection sites as well as optimal injection techniques.


Management of Atraumatic Posterior Interosseous Nerve Palsy.
The posterior interosseous nerve (PIN) is susceptible to a number of traumatic and atraumatic pathologies. In this article, we aim to review our current understanding of the etiology, pathology, diagnosis, treatment options, and published outcomes of atraumatic PIN palsy. In general, the etiology of atraumatic PIN palsy can be divided into mechanical, which is caused by an extrinsic compressive force on the nerve, and nonmechanical, which is caused by an intrinsic inflammatory reaction within the nerve. As per this discussion, there are 3 causes for atraumatic PIN palsy. These are entrapment neuropathy, Parsonage-Turner syndrome, and spontaneous "hourglass" constriction. The typical presentation of atraumatic PIN palsy is a patient with spontaneous onset of weakness of fingers/thumb metacarpophalangeal joints extension. However, the wrist extension is preserved with radial deviation due to preservation of extensor carpi radialis longus/brevis function. Magnetic resonance imaging is the imaging of choice and neurophysiology is indicated in all patients. If there is an obvious structural cause of the nerve palsy, prompt decompression and removal of the causative lesion are recommended to avoid irreversible damage to the nerve/muscles. Otherwise, in general, we would recommend consideration for exploration should there be no sign of recovery after 6 weeks of observation.


Duplication 11q and deletion 5p syndromes due to a reciprocal translocation segregating in four generations.
We report on 2 relatives with duplication 11q and deletion 5p, resulting from an adjacent-1 segregation of a balanced reciprocal translocation 5p15;11q23, segregating in 4 generations of this family. Twelve out of 16 at-risk relatives of inheriting the translocation were shown to be carriers, giving a significant (p less than .05) 3:1 ratio of carriers/noncarriers. The breakpoint on chromosome 11 at q23 is a folate sensitive fragile site into where the proto-oncogene c-ets has been mapped.


[Use of vasopressin in the treatment of acute hemorrhagic lesions of the stomach. Our experience].
Since bleeding from acute lesions of the gastric mucosa can cease spontaneously and the mortality rate of emergency surgery is high, conservative treatment is always preferable. Satisfactory results were obtained with continuous infusions of vasopressin in low doses (0.2 U/kg/hr for 8 hours) so that this treatment appears a valid alternative to more recent techniques (somatostatin).


Metformin inhibits lung cancer cells proliferation through repressing microRNA-222.
Metformin, which is commonly used as an oral anti-hyperglycemic agent of the biguanide family, may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including lung cancer, remains unknown. MiR-222 induces cell growth and cell cycle progression via direct targeting of p27, p57 and PTEN in cancer cells. In the present study, we used A549 and NCI-H358 human lung cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment reduced expression of miR-222 in these cells (p < 0.05). As a result, protein abundance of p27, p57 and PTEN were increased in cells exposed to metformin. Therefore, these data provide novel evidence for a mechanism that may contribute to the anti-neoplastic effects of metformin suggested by recent population studies and justifying further work to explore potential roles for it in lung cancer treatment.


Information extraction from FN plots of tungsten microemitters.
Tungsten based microemitter tips have been prepared both clean and coated with dielectric materials. For clean tungsten tips, apex radii have been varied ranging from 25 to 500 nm. These tips were manufactured by electrochemical etching a 0.1 mm diameter high purity (99.95%) tungsten wire at the meniscus of two molar NaOH solution. Composite micro-emitters considered here are consisting of a tungsten core coated with different dielectric materials-such as magnesium oxide (MgO), sodium hydroxide (NaOH), tetracyanoethylene (TCNE), and zinc oxide (ZnO). It is worthwhile noting here, that the rather unconventional NaOH coating has shown several interesting properties. Various properties of these emitters were measured including current-voltage (IV) characteristics and the physical shape of the tips. A conventional field emission microscope (FEM) with a tip (cathode)-screen (anode) separation standardized at 10 mm was used to electrically characterize the electron emitters. The system was evacuated down to a base pressure of ∼10(-8) mbar when baked at up to ∼180 °C overnight. This allowed measurements of typical field electron emission (FE) characteristics, namely the IV characteristics and the emission images on a conductive phosphorus screen (the anode). Mechanical characterization has been performed through a FEI scanning electron microscope (SEM). Within this work, the mentioned experimental results are connected to the theory for analyzing Fowler-Nordheim (FN) plots. We compared and evaluated the data extracted from clean tungsten tips of different radii and determined deviations between the results of different extraction methods applied. In particular, we derived the apex radii of several clean and coated tungsten tips by both SEM imaging and analyzing FN plots. The aim of this analysis is to support the ongoing discussion on recently developed improvements of the theory for analyzing FN plots related to metal field electron emitters, which in particular introduces a new form of intercept correction factors. The results derived demonstrate the applicability of the applied method on needle shaped - i.e. non planar - emitters as well as its limits.


A Cyclometalated Iridium (III) Complex as a Microtubule Probe for Correlative Super-Resolution Fluorescence and Electron Microscopy.
The visualization of microtubules by combining optical and electron microscopy techniques provides valuable information to understand correlated intracellular activities. However, the lack of appropriate probes to bridge both microscopic resolutions restricts the areas and structures that can be comprehended within such highly assembled structures. Here, a versatile cyclometalated iridium (III) complex is designed that achieves synchronous fluorescence-electron microscopy correlation. The selective insertion of the probe into a microtubule triggers remarkable fluorescence enhancement and promising electron contrast. The long-life, highly photostable probe allows live-cell super-resolution imaging of tubulin localization and motion with a resolution of ≈30 nm. Furthermore, correlative light-electron microscopy and energy-filtered transmission electron microscopy reveal the well-associated optical and electron signal at a high specificity, with an interspace of ≈41 Å of microtubule monomer in cells.


[Follow-up studies and results of dorsal stabilization of unstable spinal fractures].
Temporary dorsal plate spondylodesis with transpedunclar screwing has proved successful in the therapy of recent unstable injuries to the spine. This method allows a considerable reconstruction and stabilization of the vertebral body as well as an early mobilization of the patient. The mobility of the spine will not be essentially reduced if the spondylodesis plates are removed early, i.e. six to nine months after their insertion.


Potential links between neurological disease and Tako-Tsubo cardiomyopathy: a literature review.
Tako-Tsubo cardiomyopathy (TTC), is defined as a fully reversible acute deterioration of left-ventricular (LV) function, which is mainly found in women after an episode of emotional or physical stress (e.g. psychosocial stress, sepsis, surgery). The underlying mechanisms remain unclear. There is evidence suggesting a possible link between neurological disease and TTC. The pathophysiology of the several neurologic diseases has been reviewed searching for possible mechanisms that could lead to TTC in these patients.


Comparative incidence of cancer in HIV-AIDS patients and transplant recipients.
Studies have found a relationship between decreased immunity and increased incidence of cancer. A systematic review of observational studies evaluating the incidence of cancer in both organ recipients and people with HIV/AIDS compared with the general population. Eligible studies were searched up to March 2011 in the following databases: Pubmed, Embase, Scielo, Cancerlit and Google scholar. In this study, the standardized incidence ratios (SIR) of cancer in people with HIV/AIDS and of organ transplant recipients were compared with those found among the general population. Twenty-five studies of transplant and HIV-associated cancer risk, involving 866776 people with HIV/AIDS or organ recipients and 21260 new cases of cancer, were included. The risk for the development of new cancer cases was higher among people with HIV/AIDS (SIR=4, IC95% 3.78-4.24) and who received organs (SIR=3.28, IC95% 3.06-3.52) when compared with the general population. Similar SIR in both immunocompromised populations suggests that the weakened immune system is responsible for the increased risk of new cases of cancer among these groups. Research investments are needed to develop effective cancer prevention strategies in these populations.


Impact of Transcatheter Device Closure of Atrial Septal Defect on Atrial Arrhythmias Propensity in Young Adults.
Atrial septal defect (ASD) is a condition that requires early intervention because of the consequences over the right-side heart. Chronic atrial stretching promotes atrial conduction delay and the imbalance of the conduction homogeneity, which lead to the propensity to atrial arrhythmias (AA). We aim to evaluate the impact of transcatheter closure of ASD on atrial vulnerability markers leading to late AA in young adults. We conducted a prospective, longitudinal study in one hundred patients (mean age 25.2 ± 5.4 years) who underwent transcatheter closure of ASD at Cardiocentro Pediátrico William Soler. P-wave maximum (Pmax) and P-wave dispersion (Pd) were analyzed from 12-lead electrocardiogram. Left-side and right-side intraatrial and interatrial electromechanical delay (EMD) were measured with tissue Doppler imaging. Both electrocardiographic and echocardiographic analyses were performed during the study period. Compared to baseline, there was a significant reduction in P max (p ≤ 0.001) and Pd (p ≤ 0.001) after 3 months of procedure. All atrial electromechanical coupling parameters significantly reduced at 6 months of ASD closure and tend to remain at lower values till the last evaluation. Over 9.2 ± 1.6 years of follow-up, 15 subjects (15%) developed AA, of which intraatrial reentrant tachycardia (66.6%) became the main rhythm disturbance. Intra-right atrial EMD ≥ 16 ms (HR 4.08, 95% CI 1.15-14.56; p = 0.03) and Pd 45 ms (HR 1.66, 95% CI 1.06-2.59; p = 0.02) were identified as predictors of late AA. Transcatheter device closure of ASD in young adults promotes a significant reduction of electrocardiographic and echocardiographic markers of AA vulnerability, which persist during the long-term follow-up. Nevertheless, Pd and interatrial EMD were identified as independent risk factors of AA.


ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal.
One of the major problems related with anticancer chemotherapy is resistance against anticancer drugs. The ATP-binding cassette (ABC) transporters are a family of transporter proteins that are responsible for drug resistance and a low bioavailability of drugs by pumping a variety of drugs out cells at the expense of ATP hydrolysis. One strategy for reversal of the resistance of tumor cells expressing ABC transporters is combined use of anticancer drugs with chemosensitizers. In this review, the physiological functions and structures of ABC transporters, and the development of chemosensitizers are described focusing on well-known proteins including P-glycoprotein, multidrug resistance associated protein, and breast cancer resistance protein.


Modulation of human ovarian tumor cell sensitivity to N-(phosphonacetyl)-L-aspartate (PALA) by liposome drug carriers.
Carrier-based formulations of cytotoxic agents may be highly efficacious for intracavitary therapy of malignancies which reside in or metastasize to the peritoneal cavity. N-(Phosphonacetyl)-L-aspartic acid (PALA) is a transition-state inhibitor of aspartate transcarbamylase which has shown enhanced activity against several cell lines upon encapsulation in liposomes. We have examined the growth inhibitory effects of PALA-containing liposome formulations against four human ovarian cancer cell lines (Ovcar-3, Hey-1b, A90, and A121a) that have significantly different growth characteristics. With the optimal liposome formulation defined in the present studies, the potency of encapsulated PALA was 22- to 570-fold greater than that of free PALA, depending on the cell line. Control liposomes containing buffer, rather than PALA, did not inhibit cell growth. Fluorescence studies of liposome-cell interaction suggest that high liposome negative surface charge density and high phase transition temperature increase both cellular association and retention of liposome contents. Briefer exposure of tumor cells to treatment accentuates the advantage of liposome formulations; on Hey-1b cells, the cytostatic effect of 1-hr exposure to PALA-liposomes is 900-fold greater than is the equivalent exposure to free PALA. The considerable increase in in vitro potency of PALA-liposome formulations, coupled with potential pharmacokinetic advantages in vivo (i.e., intraperitoneal retention of liposome-associated drug versus rapid clearance of free PALA), suggests the possibility of enhanced antitumor activity of liposome-encapsulated PALA for both single-agent and combination chemotherapy.


Studies on the microcytotoxicity test. II. The uptake of amino acids ([3H]leucine or [75Se]methionine) but not nucleosides ([3H]thymidine or [125I]IUdR) or 51CrO24-provides a direct and quantitative measure of target cell survival in the presence of lymphoid cells.
We have studied the suitability of various commonly used radioactive materials for the direct post-labeling of adherent rat target cells in long-term cytotoxicity tests. The use of nucleosides at high concentration avoids the necessity of adding fluorodeoxyuridine to enhance nucleoside uptake by target cells, and reduces the degree of non-specific inhibition of nucleoside uptake caused by products released from effector lymphoid cells. However, when [125I]iododeoxyuridine was used for labelling, such inhibition was not completely avoided even at very high nucleoside concentration, necessitating the washing of target cells prior to labelling. Similarly, without prewashing, the uptake of 51CrO24-ions frequently failed to correlate well with the numbers of surviving target cells as assessed by cell counting. On the other hand, radiolabelled amino acids, when present at semi-saturating concentrations, were taken up quantitatively by target cells under all conditions tested. Furthermore, in comparison to [125I]iododeoxyuridine, radioactive amino acids showed little if any toxicity to target cells. The use of the gamma-emitting amino acid analogue, [75Se]selenomethionine, is particularly recommended.


Comparison of two different techniques for brachial plexus block: infraclavicular versus axillary technique.
Brachial plexus block via the axillary approach is problematic in patients with limited arm mobility. In such cases, the infraclavicular approach may be a valuable alternative. The purpose of our study was to compare axillary and infraclavicular techniques for brachial plexus block in patients undergoing arm or forearm surgery. After institutional approval and informed consent were obtained, 30 patients (ASA physical status I or II) scheduled for forearm and hand surgery under brachial plexus anesthesia were included in the study. Patients were randomly allocated into two groups. Brachial plexus block was performed via the axillary approach in the Group A patients and via the infraclavicular approach in the Group I patients using a peripheral nerve stimulator. All blocks were performed with a total dose of 40 ml 0.375% bupivacaine. In each nerve territory (radial, ulnar, median, and musculocutaneous), the mean values of the degree and the duration of the sensory block and motor block were not significantly different between the two groups (P > 0.05). Inadvertent vessel puncture was significantly more frequent in the axillary approach (P < 0.05). Brachial plexus block performed via the infraclavicular approach is as safe and effective as the axillary approach. Infraclavicular approach may be preferred to the axillary approach when the upper arm mobility is impaired or not desired.


Laryngeal mask airways in ear, nose, and throat procedures.
The use of laryngeal mask airway (LMA) and its variants in ear, nose, and throat procedures have been extensively described in case reports, retrospective reviews, and randomized clinical trials. The LMA has developed a considerable following because of its lack of tracheal stimulation, which can be a considerable advantage in ear, nose, and throat (ENT) procedures. The incidence of coughing on emergence has been shown to be lower with the LMA than with the endotracheal tube (ETT). Although other approaches to smooth emergence have been described, few would argue that it is as easy to achieve a smooth emergence with an ETT as with an LMA. Although patients certainly exist for whom the LMA is contraindicated, many will experience better results with the LMA because of the features delineated in this article.


Relationship between symptoms and health-related quality of life in chronic lung disease.
The authors studied the relationship between patient self-reported symptoms and responses to a general measure of health-related quality of life [Short Form 36 (SF-36)] for 102 patients who had chronic lung disease [forced expiratory volume in one second (FEV1) < 70%]. The primary diagnoses were chronic bronchitis, emphysema, and asthma; the mean age was 62 years, and 46% were women. Based upon Medical Research Council (MRC) symptom scores, the patients' disease severity was classified as mild (21%), moderate (22%), or severe (57%). The SF-36 scores differed significantly between disease severity groups in domains of health perception, physical functioning, physical role, and energy. The SF-36 physical functioning and Oxygen Cost Diagram scores correlated well (r = 0.78). The authors conclude that SF-36 is a useful and valid measure of general health status in patients with chronic lung disorders.


Somatic complaints as a mediator in the association between body mass index and quality of life in children and adolescents.
Children and adolescents with overweight are known to have lower Quality of Life (QoL) compared to peers with a normal weight. QoL is a broad concept and is associated with many factors. A better understanding of the factors associated with QoL in children and adolescents and their impact on the association between overweight/obesity and QoL, may help to develop and improve interventions that lead to an improvement in QoL in children/adolescents with a high body mass index (BMI > 25). This study investigated the possible mediating effects of somatic complaints and general practitioner consultations in the association between overweight/obesity and QoL in children and adolescents. For the current study, cross-sectional data were used from a longitudinal study, the DOERAK cohort, collected from general practitioners' medical files and through questionnaires. This cohort included 2-18 year olds with normal weight and overweight. Uni- and multivariate regression analyses were performed to gain more insight into variables associated with QoL. Mediation analyses were performed to investigate the possible mediating effects of somatic complaints and GP consultations in the association between overweight/obesity and QoL in children. In the total sample of 733 participants aged 2-18 years, participants with normal weight had a significantly higher QoL (83.64, SD10.65) compared to participants with overweight (78.61, SD14.34) and obesity (76.90, SD13.63) at baseline. The multivariate analyses showed that a lower socio-economic status (SES), higher BMIz, and the presence of somatic complaints are associated with a lower QoL. The mediation analysis showed a significant effect of the indirect pathway of BMIz on QoL through somatic complaints (β = - 0.46, 95% CI[- 0.90, - 0.06]). BMIz has a direct impact on QoL in children and adolescents. Somatic complaints seem to mediate the effect of BMIz on QoL.


Deciphering aggregates, prefibrillar oligomers and protofibrils of cytochrome c.
Aggregation of protein into insoluble intracellular complexes and inclusion bodies underlies the pathogenesis of human neurodegenerative diseases. Importance of cytochrome c (cyt c) arises from its involvement in apoptosis, sequence homology and for studying molecular evolution. A systemic investigation of polyethylene glycol (PEG) and trifluoroethanol (TFE) on the conformational stability of cyt c as a model hemeprotein was made using multi-methodological approach. Cyt c exists as molten globule (MG) at 60% PEG-400 and 40% TFE as confirmed by far-UV CD, attenuated total reflection Fourier transform infrared spectroscopy, Trp environment, 8-anilino-1-naphthalene-sulfonic acid (ANS) binding and blue shift in the soret band. Q-band splitting in MG states specifies conformational changes in the hydrophobic heme-binding pocket. Aggregates were detected at 90% PEG-400 and 50% TFE as confirmed by increase thioflavin T and ANS fluorescence and shift in Congo red absorbance. Detection of prefibrils and protofibrils at 90% PEG-400 and 50% TFE was possible after 72-h incubation. Single cell gel electrophoresis of prefibrils and protofibrils showed DNA damage confirming their toxicity and potential health hazards. Scanning electron microscopy and XRD analysis confirmed prefibrillar oligomers and protofibrils of cyt c.


Isolation of peste des petits ruminants virus from the Sudan.
Based on clinical signs, the presence of a rinderpest related antigen and the ability of rinderpest immune serum to prevent virus isolation, rinderpest was diagnosed in two outbreaks in goats in central Sudan during 1971 and 1972. Two viruses isolated from these goats have been re-examined both serologically and by the inoculation of experimental cattle, sheep and goats. Each is now considered to represent the virus of peste des petits ruminants, thereby extending the geographical range of this agent.


Can protection motivation theory predict protective behavior against ticks?
Cases of reported tick-borne diseases in humans have increased over the past decades. Strategies informing the public about ticks, their associated diseases, and preventive measures are often highlighted as important in limiting pathogen transfer and disease. However, knowledge about the motivation for people to apply preventative measures is sparse. The aim was to examine if Protection Motivation Theory, a model of disease prevention and health promotion, can predict the use of protective measures against ticks. Ordinal logistic regression and Chi-square tests were used on data from a cross-sectional survey with respondents from Denmark, Norway, and Sweden (n = 2658). We examined the effect of (1) the perceived seriousness of tick bites, Lyme borreliosis (LB), and tick-borne encephalitis (TBE), and (2) the perceived probability of getting a tick bite, Lyme borreliosis, and tick-borne encephalitis on protection against ticks. Finally, we examined if there was an association between the use of a protective measure and the perceived efficacy of that measure. The perceived seriousness of a tick bite and LB significantly predict who is more likely to apply protective measures for all three countries combined. The perceived seriousness of TBE did not significantly predict the level of adoption of protective measures applied by respondents. The perceived likelihood of getting a tick bite within the next 12 months and the perceived likelihood of getting LB if bitten by a tick significantly predicted the application of protective measures. However, the increases in the likelihood of protection were very small. The application of a certain type of protection was always correlated with the perceived efficacy of the same protective measure. Some variables of PMT may be used to predict the level of adoption of protection applied against ticks and tick-borne diseases. We found that the perceived seriousness of a tick bite and LB significantly predict the level of adoption protection. The perceived likelihood of getting a tick bite or LB also significantly predicted the level of adoption of protection, although the change was very small. The results regarding TBE were less clear. Lastly, there was an association between applying a protective measure and the perceived efficacy of the same measure.


Early marijuana initiation: The link between prenatal marijuana exposure, early childhood behavior, and negative adult roles.
We investigated the associations among gestational factors including prenatal marijuana exposure (PME), child behavior at age 3, early age of onset of marijuana use (EAOM, <15years), and adult roles at 22years. Participants were drawn from the Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of prenatal substance exposure in offspring who have been studied for over 22years since the prenatal phase. Data from the prenatal, birth, 3-, and 22-year phases (N=608) were used in the present study. Age of onset of offspring substance use was determined based on data from the 14-, 16-, and 22-year phases. The subjects were of lower socioeconomic status, 43% were Caucasian and the remaining were African-American, and 48% were males. Early childhood behavior was significantly (p<0.05) related to EAOM after controlling for PME, birth and childhood environmental risk factors, and Conduct Disorder. EAOM was significantly associated with negative adult roles including increased risk of being arrested (p<0.001), lower educational attainment (p<0.001), having a child without being married (p<0.05), and unemployment at 22years (p<0.001). The correlations between PME and negative adult roles and between early childhood behavior and negative adult roles were also statistically significant. Pathway analysis demonstrated that EAOM significantly mediated the associations between PME and fulfillment of adult roles and between early childhood behavior and adult roles. There are a number of intervention points that could be targeted that would have a long-term impact on lowering the probability of EAOM and less success in adult roles.


Rostral ventral medullary surface activity during hypercapnic challenges in awake and anesthetized goats.
Regions within the rostral ventral medullary surface (RVMS) play an important role in cardiorespiratory responses to CO2 during anesthesia. Activity within a RVMS area, in which local cooling elicited marked ventilatory and blood pressure reductions, was measured as 660 nm scattered light changes in 5 goats following 5% CO2 challenges during waking and anesthetic states. During wakefulness, hypercapnia elicited a substantial, short latency transient (1-1.5 min) activity increase, followed by a sustained decrease. Stimulus cessation elicited a large and rapid off-transient activity increase which persisted for approximately 20 min. In contrast, during halothane anesthesia, the initial activation was absent, and the later activity decline and off-response were much reduced. We conclude that biphasic RVMS activity responses emerge to CO2 stimulation, and are state-dependent.