Natural killer cell activities of patients with breast cancer against different target cells.
Natural killer (NK) cell activity against K 562 erythroleukemic- and MCF-7 breast carcinoma-derived cells was monitored in short-term (3 h/K 562) and long-term (18 h/MCF-7) chromium release tests for 60 patients with untreated primary breast disease. Target cell lysis was the same for patient groups with benign (n = 13) and malignant (n = 47) breast disease (27% versus 36% mean chromium release; target:effector ratio 40:1 for K 562 and 28% versus 40% for MCF-7 cells). NK activity as defined by short-term lysis of K 562 cells did not correlate with MCF-7 cell lysis in long-term assays for the carcinoma patients. This functional heterogeneity of natural cytotoxic activities of breast cancer patients was confirmed by a different age distribution for K 562 and MCF-7 cell lysis and high levels of MCF-7-directed NK activity in the grade I tumor group (56.2%). Our results indicate that measurement of peripheral blood NK activity against a breast carcinoma-derived cell line (MCF-7) defines a disease-related natural cytotoxic activity which correlates better with prognostic tumor parameters (tumor grading) than NK activity as defined by the lysis of K 562 erythroleukemic cells. NK activity testing against breast carcinoma cell lines should be used to monitor natural cytotoxic activities in breast cancer patients and its modulation by different routes of treatment.


Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells.
The mesenchymal phenotype of glioblastoma multiforme (GBM), the most frequent and malignant brain tumor, is associated with the worst prognosis. The epithelial-mesenchymal transition (EMT) is a cell plasticity mechanism involved in GBM malignancy. In this study, we determined 17β-estradiol (E2)-induced EMT by changes in cell morphology, expression of EMT markers, and cell migration and invasion assays in human GBM-derived cell lines. E2 (10 nM) modified the shape and size of GBM cells due to a reorganization of actin filaments. We evaluated EMT markers expression by RT-qPCR, Western blot, and immunofluorescence.We found that E2 upregulated the expression of the mesenchymal markers, vimentin, and N-cadherin. Scratch and transwell assays showed that E2 increased migration and invasion of GBM cells. The estrogen receptor-α (ER-α)-selective agonist 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, 10 nM) affected similarly to E2 in terms of the expression of EMT markers and cell migration, and the treatment with the ER-α antagonist methyl-piperidino-pyrazole (MPP, 1 μM) blocked E2 and PPT effects. ER-β-selective agonist diarylpropionitrile (DNP, 10 nM) and antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazole[1,5-a]pyrimidin-3-yl]phenol (PHTPP, 1 μM) showed no effects on EMT marker expression. These data suggest that E2 induces EMT activation through ER-α in human GBM-derived cells.


Marginal Microleakage and Morphological Characteristics of a Solvent-Free One-Step Self-Etch Adhesive (B1SF).
In recent years, newly developed solvent-free dental adhesives have been introduced. The aim of this study was to evaluate the marginal integrity of a new one-step solvent-free self-etch adhesive and to compare it with a commonly used two-step self-etch adhesive as the gold standard. Class V cavities (2×4×1.5 mm) were prepared on the buccal aspects of 28 human premolars. The cervical margins of the cavity preparations were placed 1 mm apical to the CEJ. Clearfil SE Bond (CSEB) (two-step self-etch adhesive) and Bond 1SF (B1SF) (one-step self-etch adhesive) were applied to the cavities in groups 1 and 2 (n=14), respectively. Then, the specimens were restored with A2 shade of APX composite resin. Each group was evaluated for dye penetration under a stereomicroscope at ×32 after 24 hours and 500 rounds of thermocycling. Statistical analyses were carried out using Mann Whitney test (α=0.05). In addition, in each experimental group, two specimens were prepared for analysis under SEM. There were no significant differences in enamel margin microleakage between the two adhesives used (P=0.24(; whereas, there were significant differences in dentin margin microleakage between CSEB and B1SF (P=0.004). Dentin microleakage of B1SF was higher than that of CSEB. Results showed that the enamel marginal integrity of B1SF as a newly developed one-step solvent-free self-etch adhesive was similar to that of CSEB as a commonly used two-step self-etch; however, dentinal sealing of CSEB was better than that of B1SF.


Baseline correction in parallel thorough QT studies.
In parallel thorough QT (TQT) studies, it has been speculated that either baseline correction should be omitted, under the assumption that it only adds noise to the data, or a time-averaged baseline instead of a time-matched baseline correction should be considered in order to reduce the study variability. This study characterized the assumptions and implications of different baseline correction approaches in parallel TQT studies submitted for regulatory review. 57 parallel TQT studies conducted between 2002 and 2009 in 5591 healthy volunteers were evaluated. Only moxifloxacin and placebo arms, including their baselines, were considered. The options of using no baseline correction, time-averaged baseline correction, and time-matched baseline correction were examined and compared. QTc values exhibited a diurnal pattern, with longer QTc intervals during sleep preserved when correcting for a time-averaged baseline. Post-dose and baseline QTc values were highly correlated (mean ρ = 0.80, range 0.56-0.98 and mean ρ = 0.79, range 0.50-0.96 in the placebo and moxifloxacin groups, respectively). The variability of raw QTc values was substantially larger than that of baseline-adjusted QTc values. The difference in the point estimate of QTc differences between moxifloxacin and placebo differed by up to ± 4 ms between the time-averaged and the time-matched baseline corrections. Statistical tests indicate that assumptions of time-averaged baseline and no baseline correction are not appropriate. Baseline correction in parallel TQT studies leads to more precise QTc estimates. Because of possible inaccuracy introduced by time-averaged baseline correction, the time-matched baseline correction appears to be preferable for a parallel TQT study to both reduce the intrinsic variability due to circadian patterns and obtain more accurate point estimates.


[Phenomenon of remodeling and adjustment the topology of the calcaneus with a solitary cyst--case report].
Solitary cyst is a place of osteolytic bone loss. In this paper presents the biomechanical aspect of the remodeling and adaptation of the topology of the calcaneus suffering from this disease, which leads to the avoidance of pathological fracture.


Pre-eruptive intracoronal resorption in orthodontic patients: A retrospective analysis of 3,143 patients.
The aim of this retrospective study was to analyze the occurrence and characteristics of pre-eruptive intracoronal resorptions in a clinical orthodontic patient population. Patients treated in an orthodontic department (University of Pécs, Pécs, Hungary) were included. Unerupted teeth on panoramic radiographs were analyzed for intracoronal radiolucent lesions. For each patient, the demographic data, jaw localization, number of unerupted teeth with pre-eruptive intracoronal resorption lesions, number of lesions per tooth, size and localization of pre-eruptive intracoronal resorption defects, affected tooth's surface, pulp involvement and ectopic position of the tooth with defects were recorded. In the 3,143 patients investigated, 55 teeth in 49 patients showed pre-eruptive intracoronal resorption lesions (subject incidence: 1.56%). The incidence on unerupted teeth was 0.25%. Pre-eruptive intracoronal resorption was significantly more common in mandibles (43 mandibular vs. 12 maxillary lesions) with an odds ratio of 12.84 (95% Confidence Interval: 5.19-31.74) and no gender differences were found (p = 0.746). The occurrence of pre-eruptive intracoronal resorption was highest in the youngest (7-10 years) mixed dentition status group (p < 0.001). Most of the lesions (44 of 55, or 80.0%) were localized in the dentin, occupying two-third or less of the dentin thickness. Only 12.73% (7/55) of the lesions were not localized on the occlusal surface. Of the lesions, 89.1% (49/55) showed no obvious size increase over an average follow-up of 36.4 ± 8.1 months. Pre-eruptive intracoronal resorption may occur mainly in the mixed dentition stage in orthodontic patients. Careful and attentive radiographic evaluations may facilitate early detection and follow-up of the lesions' possible dimensional changes, especially when resorption influences orthodontic extraction therapy.


Effects of developmental acclimation on adult salinity tolerance in the freshwater-invading copepod Eurytemora affinis.
Invasive species are commonly thought to have broad tolerances that enable them to colonize new habitats, but this assumption has rarely been tested. In particular, the relative importance of acclimation (plasticity) and adaptation for invasion success are poorly understood. This study examined effects of short-term and developmental acclimation on adult salinity tolerance in the copepod Eurytemora affinis. This microcrustacean occurs in estuarine and salt marsh habitats but has invaded freshwater habitats within the past century. Effects of short-term acclimation were determined by comparing adult survival in response to acute versus gradual salinity change to low salinity (fresh water). Effects of developmental acclimation on adult tolerance were determined using a split-brood 4 x 2 factorial experimental design for one brackish-water population from Edgartown Great Pond, Massachusetts. Twenty full-sib clutches were split and reared at four salinities (fresh, 5, 10, and 27 practical salinity units [PSU]). On reaching adulthood, clutches from three of the salinity treatments (no survivors at fresh) were split into low- (fresh) and high- (40 PSU) salinity stress treatments, at which survival was measured for 24 h. Short-term acclimation of adults did not appear to have a long-term affect on low-salinity tolerance, given that gradual transfers to fresh water enhanced survival relative to acute transfers in the short term (after 7 h) but not over a longer period of 8 d. Developmental acclimation had contrasting effects on low- versus high-salinity tolerance. Namely, rearing salinity had a significant effect on tolerance of high-salinity (40 PSU) stress but no significant effect on tolerance of low-salinity (freshwater) stress. In addition, there was a significant effect of clutch on survival under freshwater conditions, indicating a genetic component to low-salinity tolerance but no significant clutch effect in response to high salinity. While developmental acclimation might enhance survival at higher salinities, the minimal effect of acclimation and significant effect of clutch on low-salinity tolerance suggest the importance of natural selection during freshwater invasion events.


Strategies to control hepatitis B: Public policy, epidemiology, vaccine and drugs.
The last 50 years of hepatitis B research has resulted in the development of effective screening assays for surveillance, vaccines for prevention and antiviral drugs that significantly improve patient clinical outcomes. Not surprisingly then, the global epidemiology of hepatitis B virus (HBV) is set to change dramatically over the next decade. For example, the success and the high coverage of universal HBV vaccination and the ageing cohorts of patients with chronic hepatitis B (CHB) will result in reductions of incidence and prevalence of chronic hepatitis, cirrhosis and probably hepatocellular carcinoma. This will be further accelerated by the impressive progress in the treatment outcomes for patients with CHB. In spite of this success, challenges remain, such as planning for the impact of migration from countries with high prevalence rates to those countries with low rates of HBV infection. The recent establishment of the World Health Organisation Global Hepatitis Program with the provision of a framework for global action has become the cornerstone for all countries to now frame their own particular national responses to control hepatitis B. An effective policy framework can prevent new infections, ensure people can access clinical care, and in doing so reduce the burden of infection at an individual, country and regional level. These developments present a real opportunity to reduce the significant, social and economic burden of global hepatitis B, ultimately the critical next steps to render the world hepatitis B free.


Prenatal evaluation and outcome of fetal obstructive uropathies.
Between January 1982 and January 1986, 76 pregnant women between 15 and 40 weeks of gestation were referred because of suspected fetal obstructive urinary tract pathology. A total of 14 high-level (ureter) and 17 low-level (urethral) obstructions were diagnosed. High-level obstructions were at the uretero-pelvic level in 11 and at the uretero-vesical level in 3 cases. Increased amniotic fluid volume was observed in 28 per cent. The survival rate was 86 per cent. In the 17 cases of urethral obstruction, oligohydramnios was present in 70 per cent, associated structural defects in 30 per cent, and abnormal karyotype in 6 per cent. Pregnancy was terminated because of progressive massive hydronephrosis in 41 per cent; intrauterine or neonatal death occurred in 47 per cent, resulting in a survival rate of only 12 per cent.


Fast changes in chemical composition and size distribution of fine particles during the near-field transport of industrial plumes.
Aerosol sampling was performed inside the chimneys and in the close environment of a FeMn alloys manufacturing plant. The number size distributions show a higher abundance of ultrafine aerosols (10-100 nm) inside the plume than upwind of the plant, indicating the emissions of nanoparticles by the industrial process. Individual analysis of particles collected inside the plume shows a high proportion of metal bearing particles (Mn-/Fe-) consisting essentially of internally mixed aluminosilicate and metallic compounds. These particles evolve rapidly (in a few minutes) after emission by adsorption of VOC gas and sulfuric acid emitted by the plant but also by agglomeration with pre-existing particles. At the moment, municipalities require a monitoring of industrial emissions inside the chimneys from manufacturers. However those measures are insufficient to report such rapid changes in chemical composition and thus to evaluate the real impact of industrial plumes in the close environment of plants (when those particles leave the industrial site). Consequently, environmental authorities will have to consider such fast evolutions and then to adapt future regulations on air pollution sources.


Antacids reduce Campylobacter pylori colonization without healing the gastritis in patients with nonulcer dyspepsia and erosive prepyloric changes.
Antral biopsy specimens from 89 consecutive patients with nonulcer dyspepsia and erosive prepyloric changes included in a prospective, randomized, double-blind 4-wk study of the effect of an aluminum-magnesium antacid (120 mmol/day) or pirenzepine (50 mg b.i.d.) vs. placebo were examined histologically. Campylobacter pylori (CP) was found by light microscopy of silver-stained sections in 25 patients (28%). Campylobacter pylori-positive patients were on average older than CP-negative patients (p = 0.02). There was a strong association between CP colonization and acute inflammation (p less than 0.001), both being rare in the absence of chronic inflammation. During treatment with antacids, the density of CP decreased (p less than 0.001) without any improvement of the inflammatory reaction. On the contrary, the number of patients with gastritis tended to increase after antacids as compared with placebo (p less than 0.10). A separate analysis showed no symptomatic effect of the drugs. Thus, neither nonulcer dyspepsia nor erosive prepyloric changes are strongly associated with antral CP colonization or acute inflammation. Aluminum-magnesium antacids may suppress antral CP infection without healing the gastritis or relieving symptoms.


Isolation and characterization of a manganese-containing superoxide dismutase from yeast.
The cyanide-insensitive superoxide dismutase of yeast has been shown to be localized in the mitochondrial matrix. This enzyme has been isolated in good yield from bakers' yeast. Its molecular weight is 96,000. It is a tetramer, being composed of four subunits of equal size. Exposure to sodium dodecyl sulfate at 100 degrees caused dissociation into dimers, while similar treatment but in the presence of 2-mercaptoethanol caused complete dissociation into monomers. This enzyme contains 1 atom of manganese per subunit and its absorption in the visible suggests Mn(III) in the resting enzyme. Ascorbate caused partial bleaching, presumably by reduction to Mn(II). The amino acid composition was determined. This enzyme has activity comparable to that of other previously reported superoxide dismutases and like the chicken mitochondrial and the bacterial enzymes, its rate of reaction with O2 falls as the pH is raised above 7.8. Crystals of high quality were easily prepared.


Relations of prediabetes and type 2 diabetes to the thyroid cancer.
Patients with type 2 diabetes (T2DM) generally experience a higher incidence of cancer. However, the association between T2DM and thyroid cancer is inconclusive. Case-control prospective study, 722 patients were screened for T2DM and prediabetes (PDM) and underwent thyroid ultrasound and biochemical tests. The patients were assigned to groups of PDM (n=55), T2DM (n=79) or a non-diabetes group (NDM) (n=588). Fine needle aspiration biopsy was carried out in 263 patients. Histological examinations were done for 109 patients after surgery, with findings of 52 benign (BS) and 57 malignant tumors (MS). 33 % of patients with T2DM and especially PDM were newly diagnosed by our screening: 6.5 % with T2DM and 72 % with PDM, respectively. The percentage of thyroid cancers did not significantly differ between the groups (χ2 test=0.461; p=0.794). Relevant positive thyroid predictors for T2DM (t-statistic=25.87; p<0.01) and PDM (21.69; p<0.01) contrary to NDM (-26.9; p<0.01) were thyroid volume (4.79; p<0.01), thyroid nodule volume (3.25; p<0.01) and multinodular thyroid gland (4.83; p<0.01), while negative relevant predictors included the occurrence of autoimmune thyroid disease (AITD) (-2.01; p<0.05). In general, we did not observe an increased risk for thyroid cancer in the diabetic and prediabetic groups in comparison to controls, in spite of well-established increased risk for other malignancies. Structural and benign changes such as larger and multinodular thyroid glands, in comparison to autoimmune thyroid disease, are present more often in diabetics.


Long-term outcome of nonsurgical treatment of nontuberculous mycobacterial cervicofacial lymphadenitis in children.
Chronic cervicofacial lymphadenitis in children is often caused by nontuberculous mycobacteria (NTM). Children with NTM infection who were not surgically treated were evaluated for long-term outcome with a follow-up of at least 10 years. Among the 117 nonsurgically treated children, the median age was 46 months (range, 9-155 months), 56 were male (47.9%), and 61 were female (52.1%). Of the overall group, 75 received antibiotic therapy consisting of clarithromycin and rifabutin (64.1%), and for 54, observation (a wait-and-see approach) was chosen (46.2%). In 100 patients, treatment was considered successful (85%), with a median resolution of 24 (range, 11-134) weeks in the antibiotic group compared to 44.5 (range, 18-130) weeks in the wait-and-see group (P < .05). After 6 months, 58 patients in the antibiotic group were successfully treated (77%), whereas 42 patients of the wait-and-see group demonstrated complete resolution after a median observation time of 44.5 weeks (100%). In 10 patients who experienced complete resolution of the lymphadenitis, infection recurrence developed years later (10%). Nonsurgical treatment of NTM infection can be considered an alternative in advanced and surgically challenging cases. However, healing will take months to years, and late recurrences are possible.


Small molecules targeting the interaction between HIV-1 integrase and LEDGF/p75 cofactor.
The search of small molecules as protein-protein interaction inhibitors represents a new attractive strategy to develop anti-HIV-1 agents. We previously reported a computational study that led to the discovery of new inhibitors of the interaction between enzyme HIV-1 integrase (IN) and the nuclear protein lens epithelium growth factor LEDGF/p75.(1) Herein, we describe new findings about the binding site of LEDGF/p75 on IN employing a different computational approach. In this way further structural requirements, helpful to disrupt LEDGF/p75-IN binding, have been identified. The main result of this work was the exploration of a relevant hydrophobic region. So we planned the introduction of suitable and simple chemical modifications on our previously reported 'hit' and the new synthesized compounds were subjected to biological tests. The results obtained demonstrate that the hydrophobic pocket could play a key role in improving inhibitory efficacy thus opening new suggestions to design active ligands.


Presence of doctors and obstetrician/gynecologists for patients with maternal complications in hospitals in six provinces of Indonesia.
To describe doctors' and specialist physicians' availability to manage obstetric complications in hospitals in six provinces of Indonesia. Data from a nonrandomized, quasi-experimental pre-post evaluation study were used to describe the distribution of providers by each cadre of worker and assess the availability of doctors and obstetrician/gynecologists (ob/gyns) for consultations for women experiencing postpartum hemorrhage or pre-eclampsia/eclampsia, disaggregated by hospital type, province, referral status, and by time of day of provider consultation. Among hospitals that should have comprehensive emergency obstetric and newborn care (CEmONC) services available 24 hours a day, 7 days a week, many did not have a doctor available to manage obstetric complications as they presented, despite there being an average of seven ob/gyns and four doctors registered for service across all facilities. Slightly over 50% of obstetric emergency cases admitted with postpartum hemorrhage and severe pre-eclampsia/eclampsia did not receive a consultation from an ob/gyn. Among the patients who received consultations, about 70% received consultations by phone or SMS. Findings from this study indicate that persistent issues of maldistribution of maternal and newborn specialists and high absence rates of both doctors and ob/gyns at CEmONC hospitals during obstetric emergencies undermines Indonesia's efforts to reduce high maternal mortality rates.


Melorheostosis of the hand in a 7-year-old girl.
Melorheostosis of the hand is rare. We report a 7-year-old girl who presented with a contracture of the left hand. Diagnosis was made by conventional radiography and bone scintigraphy. MRI proved to be a very useful tool to visualize the soft-tissue changes. This is especially important when surgical repair is considered.


[Influence of the X-chromosome on finger dermatoglyphic features in the Ukrainian population of Podolye].
Results of twins' and families' investigations of 19 quantitative features of fingertip dermatoglyphic patterns are presented. A conclusion has been drawn that the determinants of most of them have X-linked loci. The data were analysed in the light of the Lyon's hypothesis used in modern methods of interpretation of family correlations. The results revealed some incorrectness of the postulate of the highest connection in sister--sister pairs in the case of X-linked loci. It was ascertained that the distribution of family correlations, according to skin relief quantitative features, depends upon ethnic peculiarities of a sample: the higher the frequency of whorls in the population, the greater the probability of receiving the picture expected to occur in case of X-linked loci.


Knockdown of long noncoding RNA MIAT attenuates cigarette smoke-induced airway remodeling by downregulating miR-29c-3p-HIF3A axis.
Chronic obstructive pulmonary disease (COPD) is a global public health issue and is defined as persistent airflow limitation. COPD is a major cause of morbidity and mortality worldwide. Long noncoding RNAs are involved in the course of pulmonary diseases. Here, we revealed that a long noncoding RNA called myocardial-infarction-associated transcript (MIAT) is upregulated in lung tissues of cigarette smoke (CS)-exposed mice. Knockdown of MIAT attenuated CS or CS-extract-induced inflammatory processes, epithelial-mesenchymal transition (EMT), and collagen deposition. Moreover, according to bioinformatic analyses and luciferase reporter assays, MIAT binds to microRNA-29c-3p (miR-29c-3p) and upregulates hypoxia-inducible factor 3 alpha (HIF3A), a target gene of miR-29c-3p. When the MIAT-specific short hairpin RNA and an miR-29c-3p inhibitor were cotransfected into cells, the inhibitor reversed the effects of MIAT knockdown on cell proliferation, apoptosis, inflammation, EMT, and collagen deposition. Overall, these results indicate that MIAT participates in CS-induced EMT and airway remodeling in COPD by upregulating miR-29c-3p-HIF3A axis output, thereby offering a novel promising biomarker for the assessment of COPD exacerbation induced by CS exposure.


Age and sex trends in depressive symptoms across middle and older adulthood: Comparison of the Canadian Longitudinal Study on Aging to American and European cohorts.
The literature suggests depressive symptoms differ in a non-linear fashion across adulthood and are more commonly reported in women as compared to men. Whether these trends are observed across countries in population-based cohorts is unclear. Cross-sectional observational study of approximately 138,000 women and men between the ages of 45 and 95 from three population-based cohorts representing Canadian, European, and American populations. Age, gender, educational attainment and annual income were assessed in each cohort. Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale in the US and Canadian cohorts, and by the EURO-D in the European cohort. Across all three cohorts, non-linear age trends and gender differences were observed in the report of depressive symptoms, independent from educational attainment and annual income effects. The non-linear age trends reflected a negative association between depressive symptoms and age during midlife and then a positive association in late life. Females reported greater depressive symptoms than males; however, an interaction between gender and age was also observed in the Canadian and European cohorts. Among Canadians, the gender differences were largest after age 70, whereas among Europeans, gender differences where largest among those approximately aged 60. Limitations include: 1) the cross-sectional nature of the study, resulting in age differences potentially reflecting cohort effects rather than a developmental process; and 2) the use of different depressive symptoms measures across cohorts. Characterization of depressive symptoms over mid and late adulthood in women and men provides insights into potential focal points for intervention and allocation of resources.


History, instrumentation, and techniques of flexible endoscopic laser surgery in horses.
There are clearly a number of applications for which flexible endoscopic laser surgery has become the state of the art in equine surgery, and the Nd:YAG laser seems to be the most versatile instrument for this type of surgery. Nevertheless, it is critical to understand the advantages and disadvantages of each laser technique. For example, the Nd:YAG laser used in a noncontact fashion seems to be superior when ablation of tissue is required such as treatment of upper airway masses. Conversely, contact Nd:YAG laser techniques have proven themselves to be superior when more precise cutting is advantageous such as treatment of epiglottic entrapment. Ultimately, it seems that a range of lasers is necessary to ensure selection of the most appropriate technique, adding significantly to the expense of equipment but improving the outcome for a range of equine diseases.


Preinjury alcohol exposure attenuates the neuroinflammatory response to traumatic brain injury.
Traumatic brain injury (TBI) initiates a neuroinflammatory response that increases the risk of TBI-related mortality. Acute alcohol intoxication at the time of TBI is associated with improved survival. Ethanol is recognized as a systemic immunomodulator that may also impart neuroprotection. The effects of alcohol on TBI-induced neuroinflammation, however, are unknown. We hypothesized that ethanol treatment prior to TBI may provide neuroprotection by diminishing the neuroinflammatory response to injury. Mice underwent gavage with ethanol (EtOH) or water (H2O) prior to TBI. Animals were subjected to blunt TBI or sham injury (Sham). Posttraumatic rapid righting reflex (RRR) and apnea times were assessed. Cerebral and serum samples were analyzed by ELISA for inflammatory cytokine levels. Serum neuron-specific enolase (NSE), a biomarker of injury severity, was also measured. Neurologic recovery from TBI was more rapid in H2O-treated mice compared with EtOH-treated mice. However, EtOH/TBI mice had a 4-fold increase in RRR time compared with EtOH/Sham, whereas H2O/TBI mice had a 15-fold increase in RRR time compared with H2O/Sham. Ethanol intoxication at the time of TBI significantly increased posttraumatic apnea time. Preinjury EtOH treatment was associated with reduced levels of proinflammatory cytokines IL-6, KC, MCP-1, and MIP-1α post TBI. NSE was significantly increased post injury in the H2O/TBI group compared with H2O/Sham but was not significantly reduced by EtOH pretreatment. Alcohol treatment prior to TBI reduces the local neuroinflammatory response to injury. The decreased neurologic and inflammatory impact of TBI in acutely intoxicated patients may be responsible for improved clinical outcomes.


Bronchial carcinoid tumor: demonstration by dynamic inversion recovery turbo-flash MR imaging.
A 38-year-old woman was referred to our hospital following the discovery of a right hilar mass on chest radiograph. Retrospectively, a hilar mass could be seen on a chest X-ray which had been obtained 5 years earlier. A coronal dynamic inversion recovery turbo-FLASH gadolinium-enhanced sequence was performed, demonstrating the right lesion which enhanced during the systemic arterial phase indicating an arterial supply from the bronchial arterial circulation. The surgical and pathological findings were a bronchial carcinoid tumor, with foci of bone formation.


Proteomic analysis of parkin knockout mice: alterations in energy metabolism, protein handling and synaptic function.
Parkin knockout (KO) mice show behavioural and biochemical changes that reproduce some of the presymptomatic aspects of Parkinson's disease, in the absence of neuronal degeneration. To provide insight into the pathogenic mechanisms underlying the preclinical stages of parkin-related parkinsonism, we searched for possible changes in the brain proteome of parkin KO mice by means of fluorescence two-dimensional difference gel electrophoresis and mass spectrometry. We identified 87 proteins that differed in abundance between wild-type and parkin KO mice by at least 45%. A high proportion of these proteins were related to energy metabolism. The levels of several proteins involved in detoxification, stress-related chaperones and components of the ubiquitin-proteasome pathway were also altered. These differences might reflect adaptive mechanisms aimed at compensating for the presence of reactive oxygen species and the accumulation of damaged proteins in parkin KO mice. Furthermore, the up-regulation of several members of the membrane-associated guanylate kinase family of synaptic scaffold proteins and several septins, including the Parkin substrate cell division control related protein 1 (CDCRel-1), may contribute to the abnormalities in neurotransmitter release previously observed in parkin KO mice. This study provides clues into possible compensatory mechanisms that protect dopaminergic neurones from death in parkin KO mice and may help us understand the preclinical deficits observed in parkin-related parkinsonism.


Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS.
The potent neuroprotective activities of neurotrophic factors, including insulin-like growth factor 1 (IGF-1), make them promising candidates for treatment of amyotrophic lateral sclerosis (ALS). In an effort to maximize rate of motor neuron transduction, achieve high levels of spinal IGF-1 and thus enhance therapeutic benefit, we injected an adeno-associated virus 2 (AAV2)-based vector encoding human IGF-1 (CERE-130) into lumbar spinal cord parenchyma of SOD1(G93A) mice. We observed robust and long-term intraspinal IGF-1 expression and partial rescue of lumbar spinal cord motor neurons, as well as sex-specific delayed disease onset, weight loss, decline in hindlimb grip strength and increased animal survival.


Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: A systematic review and meta-analysis.
Immune checkpoint inhibitors (ICIs) rely on the presence of ongoing immune response to exert their antitumor effect. Little is known whether an age-related decline in immune function negatively influences antitumor response and in so doing diminishes the efficacy of ICIs in elderly subjects. We performed a meta-analysis to compare the efficacy of ICIs between younger and older patients. PubMed and the ASCO databases were searched up to September 2015. We included randomized controlled trials (RCTs) of ICIs (ipilimumab, tremelimumab, nivolumab and pembrolizumab) reporting subgroup comparison of overall survival (OS) and/or progression-free survival (PFS) based on age cutoffs. The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. A total of 5265 patients from nine RCTs of ICI were included. When patients are dichotomized into younger and older groups with an age cut-off of 65-70 years, ICIs improved OS in both younger (HR, 0.75; 95% CI, 0.68-0.82) and older (HR, 0.73; 95% CI, 0.62-0.87) groups. An improvement in PFS was observed in younger (HR, 0.58; 95% CI, 0.40-0.84) and older (HR, 0.77; 95% CI, 0.58-1.01) patients. Subgroup analyses according to ICI and tumor type showed a consistent survival benefit in both younger and older groups except for the subgroup of older patients treated in 4 trials of anti-programmed cell death protein-1 (PD-1) monoclonal antibody (HR, 0.86; 95% CI, 0.41-1.83). A benefit in OS with ICIs was significant in both younger and older patients with a cut-off age of 65-70 years.


Protection of the Femoral Trunnion During Acetabular Revision Hip Surgery-A Novel Technique.
Revision of a failed acetabular component in the presence of an intact femoral prosthesis comprises approximately 20% of revision total hip replacements performed by the senior author. During this procedure, the femoral trunnion is at risk of damage because of scratching from retractors, reamers, or other instruments. Scratching can result in mechanically assisted crevice corrosion or adverse local-tissue reaction or trunnionosis leading to implant failure. We have used a variety of techniques for protection of the femoral taper over the last 30 years. We describe our current method of taper protection, using a cut segment of #5 silicon laryngeal airway, which is a simple and effective method.


A new ECG measure (RSh) for detecting possible sodium channel blockade in vivo in rats.
A new electrocardiographic (ECG) measure for detecting possible sodium channel blocking actions of drugs in anaesthetized rats is described. The conventional measures for sodium channel blockers are increased QRS width and/or P-R prolongation, however, these are limited in their sensitivity. This new measure, RSh, is the height from the peak of the R wave to the bottom of the S wave; it is more sensitive to known sodium channel blocking agents than conventional measures. This was shown by comparing the ECG effects of sodium channel blocking class I antiarrhythmic drugs from the three subclasses lidocaine (Ia), quinidine (Ib), and flecainide (Ic). In each case, RSh increased before changes could be detected in QRS or P-R. With tetrodotoxin and quinacainol, a new class I agent, changes in RSh correlated directly with previously reported changes in dV/dtmax of intracellular potentials recorded in vivo from epicardial cells. Representatives from antiarrhythmic classes II, III, and IV were also tested and only changed RSh when they had known sodium channel blocking properties at high doses. Other physiological maneuvers for altering heart rate, such as changing vagal activity, administration of catecholamines, or direct right atrial pacing, did not alter RSh. Thus RSh is a useful in vivo measure for the detection of possible class I antiarrhythmic actions. It has the advantages of being sensitive, selective, easy to measure, and involving minimal preparation.


Endoscopic Lumbar Decompression.
The most common causes of degenerative narrowing of the spinal canal are disc herniations and spinal canal stenosis. The standard surgical procedure for lumbar spinal canal stenosis today is microsurgical, microscope-assisted decompression. Full-endoscopic decompression is now also technically feasible and more widespread because of the development of surgical access techniques and instruments. The use of the different access technique depends on the anatomic and pathologic inclusion and exclusion criteria. Sufficient decompression can now be achieved using full-endoscopic techniques in a standardized minimally invasive procedure. This article describes the technique for the full-endoscopic decompression of the lumbar spine.


Lateralized hypostasis of the head on post mortem CT (PMCT) scanning of decomposed bodies-a marker for terminal position.
Post-mortem CT (PMCT) scanning was performed on the bodies of two decomposed adult males who had died of natural causes. The bodies both showed changes of marked decomposition with a prominent swelling of tissues on one side of the head compared to the other. A review of police statements confirmed that this matched the positions of the bodies when they were found. Thus, post-mortem hypostasis of putrefactive fluids correlated in both cases with the positions that the bodies had been in when first located. This may be a simple way of identifying or confirming the positions of decomposed bodies after death. It may also assist in indicating whether a body has been moved after putrefactive fluid hypostasis has developed.


Conjugation of soymilk protein and arabinoxylan induced by peroxidase to improve the gel properties of tofu.
Arabinoxylan (AX) can form stable covalent bonds with protein to improve gel properties. We aimed to prepare a conjugate between soymilk protein (SMP) and AX by peroxidase, followed by the addition of transglutaminase (TG) to prepare tofu gels. The conjugate's properties and their effects on the mechanical properties, rheological properties, and microstructure of tofu gels were evaluated. Results revealed that the α-helix content decreased, the β-sheet content increased, and the surface hydrophobicity reduced from 1.60 × 105 to 1.27 × 105. The optimal amount of AX required to improve the properties of tofu gel was 1.0%. The tofu gel showed better hardness (118.44 g), water holding capacity (WHC) (86.17%), and higher storage modulus (G') and loss modulus (G″). Low-Field NMR (LF-NMR) showed that the water was evenly distributed. Scanning electron microscopy (SEM) revealed a denser and more regular three-dimensional gel network.


Single dose of rituximab causing organising pneumonia in a patient with B-cell lymphoproliferative disorder.
Rituximab (RTX) is a monoclonal anti-CD20 antibody used to treat non-Hodgkin's lymphoma. RTX-organising pneumonia (RTX-OP) is a rare complication following treatment with RTX. We report a 49-year-old woman, with CD5-negative B-cell lymphoproliferative disorder who developed high-grade fever, dyspnoea and dry cough 3 days after the first dose of RTX. She responded poorly to antibiotics and antifungal therapy. High-resolution CT (HRCT) of the chest revealed bilateral patchy ground-glass opacities with arcade-like signs suggestive of OP. She was pulsed with intravenous methylprednisolone and RTX was discontinued. She was able to be weaned off the non-invasive ventilation (NIV) support and was discharged with maintenance prednisolone 1 mg/kg and tapered over 6 weeks. A repeated HRCT of the chest at 6 weeks showed a total resolution of OP. This highlights the early occurrence at day 3 of RTX-OP following the first dose of RTX and the complete resolution with steroid therapy.


Emergency department utilization among skin cancer patients: a retrospective study of the national emergency department sample 2013-2015.
Skin cancer-related emergency department (ED) visits are among the most common cancer-related ED visits in the USA. However, ED utilization among skin cancer patients has not been evaluated. To assess overall utilization of EDs among skin cancer patients, reasons for skin cancer-related visits, and factors associated with inpatient admission. This was a retrospective, cross-sectional study of adults with skin cancer presenting to EDs using years 2013-2015 of the Nationwide Emergency Department Sample. In total, 693,835 of the 223,329,909 weighted ED visits were made by patients with skin cancer. Visits among this population were frequently due to age-related comorbidities and skin cancer treatment-specific adverse events. Melanoma accounted for the minority of skin cancer-related visits (27.58%), but over half of subsequent inpatient admissions (51.18%) and was associated with greater odds of inpatient admission compared to keratinocyte carcinoma (OR 1.278, 95% CI 1.264-1.293). Treatment and staging codes were not available, and thus, differences in ED utilization among skin cancer stages and treatment approaches could not be assessed. Ultimately, these findings are important in improving anticipatory outpatient care for patients with skin cancer and in guiding appropriate management of this unique population in the ED.


Study on the antimicrobial effect of silver-containing inner liners in refrigerators.
To investigate the effect of silver-based antimicrobial material incorporated in the inner liners of refrigerators on food safety and quality. In the first stage, the bactericidal effect was tested in the laboratory. Silver-containing samples and control plates were inoculated with different bacterial suspensions and stored at various temperatures. After defined storage periods the bacterial reduction was calculated by comparing viable cell count on reference plates and on silver-containing plates. The reduction caused by the silver-containing material varied between 1.0 and 5.9 log(10) units, depending on bacterial strain, incubation time and temperature. In the second stage, food storage experiments have been carried out. Thus, perishable foods were stored in coated and untreated refrigerators. After certain time periods the products were analysed for their sensorial and microbiological characteristics. A clear drop in viable counts both on the refrigerator wall and on the food was demonstrated using the silver-based antimicrobial material. Silver prevents refrigerators from being a hot spot for contaminants that could be transferred upon contact with food. This study provides original results regarding the antimicrobial activity of silver-containing refrigerator surfaces.


The danger of chlorhexidine in lignocaine gel: A case report of anaphylaxis during urinary catheterisation.
This article describes a case of anaphylaxis secondary to chlorhexidine during urethral catheterisation. Despite little evidence for the use of antiseptic lubricants in preventing catheter-associated urinary tract infections, the distribution and use of such products continues to be widespread. Chlorhexidine-free lubricating gel is widely available and should be used for urological procedures wherever possible.


Iridoids with anti-inflammatory activity from Vitex peduncularis.
A new iridoid, pedunculariside, together with the known iridoid agnuside were isolated from the butanol extract of Vitex peduncularis stem bark. Both pedunculariside and agnuside showed preferential inhibition of COX-2, with IC50 values of 0.15 +/- 0.21 mg/ml and 0.026 +/- 0.015 mg/ml respectively, while having only small inhibitory effects on COX-1. Both compounds did not exhibit cytotoxicity against vero cells.


Troglitazone (Rezulin) and hepatic injury.
Analyze US rates of reported severe liver disease for the oral hypoglycemic agent troglitazone from March 1997 through February 2000 and the possible effects of publicity on reporting. The number of troglitazone reports with liver failure and or hospitalization with jaundice or hyperbilirubinemia, made to the FDA and/or Parke-Davis are used as numerators. The denominators are numbers of patients and person-time estimates of exposure. Additionally, the amount of publicity about troglitazone during its marketing is quantified. Approximately 1.92 million patients were treated with troglitazone from March 1997 through the end of February 2000 resulting in 1.6 million person-years of exposure. Reports of 83 cases of liver failure associated with troglitazone were received (1 in 23,000 patients or 1 in 20,000 person-years). Of the 83 cases, only 49 (59%) were classified by a hepatologist to be 'possibly' or 'probably' attributed to troglitazone. For the first, second, and third years of marketing, rates of reported hepatic failure per 100,000 person years exposure to troglitazone were 8.3, 5.3, and 2.7 respectively. Rates of reported liver disease involving hospitalizations with mention of jaundice and hyperbilirubinemia per 100,000 person-years were 16.0, 6.1, and 3.6 respectively for these years. During the 3-year marketing history of troglitazone, there were 470 lay press and 158 medical literature articles with mentions of hepatotoxicity for the drug. Rates of reported severe liver disease declined substantially during the second and third years of marketing of troglitazone. The decline followed increasingly stringent requirements for liver function test monitoring and may have been due to improved patient selection and management as a result of the widely publicized association between troglitazone and hepatotoxicity.


Cytospora species associated with walnut canker disease in China, with description of a new species C. gigalocus.
Cytospora species associated with canker disease are presently difficult to identify because of lack of ex-types cultures with molecular data, few distinguishable characters, and only Internal transcribed spacer (ITS) sequence data is available for most Cytospora strains in GenBank. We report on Cytospora species from the walnut tree in China. Collections were subjected to morphological and phylogenetic study. The relatedness of species associated with walnut canker were established using combined ITS, nrLSU, β-tubulin, and actin gene sequence data. Cytospora atrocirrhata, Cytospora chrysosperma, Cytospora sacculus, and a new species, Cytospora gigalocus, were identified causing canker disease of walnut. Cytospora gigalocus is formally described and compared with most similar species. Cytospora chrysosperma and C. sacculus have previously been recorded from walnut, whereas C. atrocirrhata is reported as associated with walnut canker for the first time. This is the first study that has established the Cytospora species causing walnut canker in China using a multi-phasic approach. All species are recorded as being associated with walnut canker disease in China for the first time.


Suppression of heterologous immunity by Nematospiroides dubius antigens in vitro.
The direct effect of the soluble antigens in the homogenate of adult Nematospiroides dubius (AH) on spleen cells from uninfected NIH mice was investigated using a Mishell-Dutton culture system. Parasite antigens were shown to reduce the plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in a dose-dependent manner in vitro. A population of suppressor cells was demonstrated in the spleens of infected mice. Furthermore naive spleen cells cultured in the presence of AH gave rise to cells which depressed the PFC response of naive cells when subsequently cultured together in vitro. Treatment of these cell populations with anti-thy 1.2 plus complement did not impair suppressor activity, and it was concluded that cells expressing the T-cell phenotype were not involved.


Recurrence of accessory pathway conduction after successful radiofrequency ablation: histological findings.
The histological findings from a patient with Wolff-Parkinson-White syndrome (right superior paraseptal accessory pathway) who underwent successful radiofrequency ablation and had recurrence of tachycardia one month later in the absence of overt pre-excitation are reported. Histology revealed three small, oval to circular shaped, whitish, smooth areas on the right endocardial surface, the one being situated at the atrial free wall, and the other two being at the ventricular aspect. A very small hole was present in the interventricular component of the membranus septum. The accessory pathway band passed to either side of the small hole albeit disrupted by fibrous tissue in places. These findings indicate that multiple applications may cause penetration of the myocardium, and to achieve success, complete disruption of the pathway at some point along its course is required. Recurrence of retrograde accessory pathway conduction can be explained with the impedance mismatch hypothesis.


The economics of hypertension and stroke.
The prevention of stroke through the control of hypertension is cost-effective economically and medically. A reduced incidence of stroke generates savings to the health service in hospital and surgical costs, and the avoidance of premature mortality means survivors contribute more to the economy as a result of extra working years. In addition to financial benefits, antihypertensive agents can also improve a patient's quality of life. This can be measured with a variety of health profiles or indexes and is often expressed together with life expectancy in quality-adjusted life years. This article examines the benefits produced by the effective control of hypertension, taking data from England and Wales during the past 30 years.


Discovery of thiapyran-pyrimidine derivatives as potential EGFR inhibitors.
A series of novel thiapyran-pyrimidine derivatives (10a-10h, 11a-11g, 12a-12f, 13a-13f, 14a-14f) were synthesized and their antiproliferative activities were tested. Most of the target compounds showed good activity on one or more cancer cell lines but low activity on human normal cell LO2. The most promising compound 13a exhibited the similar IC50 values on A549 and H1975 cell lines to the lead drug Olmutinib, and exhibited excellent activity and selectivity on EGFRT790M/L858R in the kinase experiment. AO and Hoechst33258 staining indicated that 13a could effectively induce H1975 cells apoptosis. Cell cycle and apoptosis analysis suggested that 13a could block cancer cells in G2/M phase and induce into late apoptosis in a manner of concentration-dependent. The structure-activity relationship of 13a was analyzed to explore its mechanism. All the results showed that 13a was a promising EGFR inhibitor.


Application of the Strain Index in multiple task jobs.
Six different methods to calculate the Strain Index (SI) scores for jobs with multiple forces/tasks were developed. Exposure data of 733 subjects from 12 different worksites were used to calculate these SI scores. Results show that using different SI computation methods could result in different SI scores, hence different risk level classifications. However, some simpler methods generated SI scores were comparable to the more complicated composite SI method. Despite differences in the scores between the six different SI computation methods, Spearman rank-order correlation coefficients of 0.61-0.97 were found between the methods. With some confidence, ergonomic practitioners may use simpler methods, depending on their specificity requirement in job evaluations and available resources. Some SI computation methods may tend to over-estimate job risk levels, while others may tend to under-estimate job risk levels, due to different ways used in obtaining the various SI parameters and computations.


Muscimol antagonizes morphine hypermotility without potentiation of analgesia.
Muscimol, a very potent and specific GABA agonist, strongly depressed characteristic morphine-induced locomotor activity. Muscimol induced only a very weak increase in the morphine analgesia measured in the hot plate test which perhaps could be a result of a freezing reaction. No effect on morphine analgesia was observed in the wire grid test. These results indicate that GABA differentially influences morphine stimulation and analgesia.


Activation of masked neural determinants in amphibian eggs and embryos and their release from the inducing tissue.
The neural-archencephalic (forehead) inducing activity of the microsomes and the high speed supernatant from Xenopus laevis ovaries and eggs was tested on gastrula ectoderm of Triturus alpestris. Both fractions have a very small inducing activity which increases considerably after autolysis or treatment with dissociating agents. A comparison with the inducing activity of the high speed supernatant from gastrulae suggests that neural inducing factors are synthesized in the ovary, stored in a masked form and activated, in part, during gastrulation. When the supernatant proteins from eggs and gastrulae were subjected to size-exclusion HPLC the neural inducing activity was eluted in different size classes, suggesting a limited proteolysis of a precursor during early embryogenesis. Further experiments have shown that treatment of the blastoporal lip from early Triturus gastrulae with actinomycin D or cycloheximide which inhibit the synthesis of RNA and protein respectively, diminishes the neural-archencephalic (forehead) inducing activity of the blastoporal lip. Treatment with actinomycin D or cycloheximide followed by ethanol, which, besides other structures, impairs the plasma membrane, does, however, not reduce the inducing activity. This may suggest that components which are needed for the transport of the neuralizing factor are diminished, when the synthesis of mRNA and protein is inhibited. Such components are probably needed for the release of the neuralizing factor from the blastoporal lip, the inducer tissue.


Preindustrial to modern interdecadal variability in coral reef pH.
The oceans are becoming more acidic due to absorption of anthropogenic carbon dioxide from the atmosphere. The impact of ocean acidification on marine ecosystems is unclear, but it will likely depend on species adaptability and the rate of change of seawater pH relative to its natural variability. To constrain the natural variability in reef-water pH, we measured boron isotopic compositions in a approximately 300-year-old massive Porites coral from the southwestern Pacific. Large variations in pH are found over approximately 50-year cycles that covary with the Interdecadal Pacific Oscillation of ocean-atmosphere anomalies, suggesting that natural pH cycles can modulate the impact of ocean acidification on coral reef ecosystems.


General plan of the thalamic projections to the prefrontal cortex in the cat.
This study elucidates the general pattern of the thalamocortical neurons which project to the prefrontal cortex (PfC) in the cat, on the basis of the findings obtained using different retrograde labeling techniques in a large number of animals. The injections of the retrograde tracers covered the whole extent of the PfC, and did not invade gray or white matter outside the intended targets. The labeled neurons formed a vertical paramedian band throughout the rostrocaudal extent of the thalamus. This band was densest at the mediodorsal and ventromedial nuclei regions, encroached upon neurons located more medially and laterally, and largely spared the intralaminar nuclei. There were overlaps between neuron populations projecting to different subdivisions of the PfC, or to the PfC and sectors of the motor, insular, limbic and anterior ectosylvian sulcus cortices. However, these projections to separate cortical subdivisions apparently arise from different neuron clusters, with little collateralization of the axons arising from a single thalamocortical neuron. Only the neurons of the ventromedial nucleus, seem to possess somewhat more widespread terminal axons in the cortex.


Developing a Kinase Chemogenomic Set: Facilitating Investigation into Kinase Biology by Linking Phenotypes to Targets.
Advances in increasingly complex phenotypic screening with lower throughput have necessitated the screening of smaller more highly annotated sets. One such collection of compounds which has been recently assembled is the kinase chemogenomic set. This is a set of curated kinase inhibitors built upon previous iterations, PKIS and PKIS2, and donations from our partners. Each compound in the set has been carefully selected based on selectivity, potency, and kinome coverage. These compounds as a set have been made available to the scientific community, enabling phenotypic screens to identify kinases that drive novel biology. Additionally, the associated data deposited in the public domain have also been used to inform new inhibitor design. Further expansion of this set to complete kinome coverage will allow for a greater understanding of kinase biology and its role in disease.


Negative birefraction of acoustic waves in a sonic crystal.
Optical birefringence and dichroism are classical and important effects originating from two independent polarizations of optical waves in anisotropic crystals. Furthermore, the distinct dispersion relations of transverse electric and transverse magnetic polarized electromagnetic waves in photonic crystals can lead to birefringence more easily. However, it is impossible for acoustic waves in the fluid to show such a birefringence because only the longitudinal mode exists. The emergence of an artificial sonic crystal (SC) has significantly broadened the range of acoustic materials in nature that can give rise to acoustic bandgaps and be used to control the propagation of acoustic waves. Recently, negative refraction has attracted a lot of attention and has been demonstrated in both left-handed materials and photonic crystals. Similar to left-handed materials and photonic crystals, negative refractions have also been found in SCs. Here we report, for the first time, the acoustic negative-birefraction phenomenon in a two-dimensional SC, even with the same frequency and the same 'polarization' state. By means of this feature, double focusing images of a point source have been realized. This birefraction concept may be extended to other periodic systems corresponding to other forms of waves, showing great impacts on both fundamental physics and device applications.


Genetic structure of Aedes albopictus (Diptera: Culicidae) populations in China and relationship with the knockdown resistance mutations.
Mosquito control is needed to prevent dengue fever, which is mainly spread by Aedes albopictus in China. Application of insecticides is one of the main mosquito control methods; however, this approach can fail due to the knockdown resistance (kdr) gene mutation that causes decreased sensitivity to insecticides in Ae. albopictus. The kdr mutation patterns among different regions in China differ significantly. However, the underlying mechanism and factors that influence kdr mutation remain unclear. To explore the potential influence of genetic background on the development of insecticide resistance in Ae. albopictus, we analyzed the genetic structure of Ae. albopictus populations in China and its correlation with major kdr mutations. We collected Ae. albopictus from 17 sites in 11 provinces (municipalities) across China from 2016 to 2021 and extracted the genomic DNA from individual adult mosquitoes. We selected eight microsatellite loci for genotyping, and based on microsatellite scores, we estimated intraspecific genetic diversity, population structure, and effective population size. The association between the intrapopulation genetic variation and F1534 mutation rate was evaluated by the Pearson correlation coefficient. Based on variation analysis of the microsatellite loci of 453 mosquitoes representing 17 populations throughout China, more than 90% of the variation occurred within individuals, whereas only about 9% of the variation occurred among populations, indicating that field populations of Ae. albopictus are highly polymorphic. The northern populations tended to belong to gene pool I (BJFT 60.4%, SXXA 58.4%, SDJN 56.1%, SXYC 46.8%), the eastern populations tended to belong to pool III (SH 49.5%, JZHZ 48.1%), and the southern populations tended to belong to three different gene pools. Moreover, we observed that the greater the fixation index (FST), the lower the wild-type frequency of F1534 of VSGC. The degree of genetic differentiation among Ae. albopictus populations in China was low. These populations were divided into three gene pools, in which the northern and eastern pools are relatively homogeneous, while the southern gene pool is heterogeneous. The possible correlation between its genetic variations and kdr mutations is also noteworthy.


Analysis of a mathematical model of apoptosis: individual differences and malfunction in programmed cell death.
Apoptosis is an important area of research because of its role in keeping a mature multicellular organism's number of cells constant, hence, ensuring that the organism does not have cell accumulation that may transform into cancer with additional hallmarks. Firstly, we have carried out sensitivity analysis on an existing mathematical mitochondria-dependent apoptosis model to find out which parameters have a role in causing monostable cell survival, which may, in turn, lead to malfunction in apoptosis. We have then generated three base parameter sets that represent healthy cells. These parameter sets were built by changing the sensitive parameters while preserving the bistability. For each base set, we varied the proapoptotic and antiapoptotic production rates, to yield new sets for the cells that have malfunctioning apoptosis. In a hypothetical cell model, we simulated caspase-3 activation by numerically integrating the governing ordinary differential equations of a mitochondria-dependent apoptosis model. These simulations were carried out for four potential treatments, namely: (1) proteasome inhibitor treatment, (2) Bcl-2 inhibitor treatment, (3) IAP inhibitor treatment, (4) Bid-like synthetic peptides treatment. The results suggest that the proteasome inhibitor treatment is the most effective treatment, though it may have severe side effects. For this treatment, the amount of proteasome inhibitor needed for caspase-3 activation may be different for hypothetical cells with a different pro- or anti-apoptotic protein defect. It is also found that caspase-3 can be activated by Bcl-2 inhibitor treatment only in those hypothetical malfunctioning cells with Bax deficiency but not in others. These results are in line with the view that molecular heterogeneity in individuals may be an important factor in determining the individuals' positive or negative responses to treatments.


Energy dependence of HCD on peptide fragmentation: stepped collisional energy finds the sweet spot.
An understanding of the process of peptide fragmentation and what parameters are best to obtain the most useful information is important. This is especially true for large-scale proteomics where data collection and data analysis are most often automated, and manual interpretation of spectra is rare because of the vast amounts of data generated. We show herein that collisional cell peptide fragmentation, in this case higher collisional dissociation (HCD) in the Q Exactive, is significantly affected by the normalized energy applied. Both peptide sequence and energy applied determine what ion fragments are observed. However, by applying a stepped normalized collisional energy scheme and combining ions from low, medium, and high collision energies, we are able to increase the diversity of fragmentation ions generated. Application of stepped collision energy to HEK293T lysate demonstrated a minimal effect on peptide and protein identification in a large-scale proteomics dataset, but improved phospho site localization through increased sequence coverage. Stepped HCD is also beneficial for tandem mass tagged (TMT) experiments, increasing intensity of TMT reporters used for quantitation without adversely effecting peptide identification.


Phosphatidylcholine-coated chest tubes improve drainage after open heart operation.
Occlusion of chest drainage tubes by thrombus is not uncommon after open heart operations. It has been suggested that by coating the tube with phosphatidylcholine (PC), the most prominent phospholipid in the erythrocytes outer membrane, it may be possible to overcome the blood-material interaction responsible for thrombus formation. To test this hypothesis 102 patients (75 males; mean age, 57 +/- 10 years) were randomly allocated to receive either PC-coated or noncoated 32F chest drainage tubes. Preoperative status, type and length of operation, and duration of drainage were similar in the two groups as was postoperative blood loss. Patients receiving PC-coated tubes, however, had less residual blood clot in the tube after removal (0.7 +/- 0.1 versus 3.1 +/- 0.3 g; p < 0.001), a reduced incidence of pericardial effusions (17.6% versus 41.2%; p < 0.01), fewer postoperative supraventricular arrhythmias (2 of 51 versus 10 of 51; p < 0.002), and a shorter hospital stay (8.4 +/- 0.3 versus 9.7 +/- 0.5 days; p < 0.05). Late cardiac tamponade developed in 2 patients in the noncoated group 6 and 10 days postoperatively, which required reexploration. The data show that PC-coated chest drainage tubes are less susceptible to occlusion by thrombus and their use is associated with a significant reduction in postoperative morbidity.


Gastric gastrointestinal stromal tumor with predominant cystic formation diagnosed by endoscopic ultrasound-fine needle aspiration.
A 69-year-old woman who had no symptoms was found to have an intraperitoneal tumor on abdominal ultrasonography in a medical checkup. Thereafter, she was referred to our hospital for a further detailed examination. Contrast-enhanced computed tomography revealed a thin-walled cystic tumor with a diameter of 8 cm and with a hypervascular solid masses in the cystic wall, along with intraperitoneal multiple nodules. The cystic tumor was contiguous with the stomach wall. For solid mass of cystic lesions, endoscopic ultrasound-fine needle aspiration was performed transgastrically with a 25-gauge Franseen needle. Pathologically, the cells in the tumor were spindle shaped with atypical nucleus and were positive for c-kit, CD34, and smooth muscle actin. The tumor was diagnosed as gastrointestinal stromal tumor (GIST). With the diagnosis of gastric GIST with peritoneal dissemination, imatinib chemotherapy was initiated.


Exploring driving behaviour from the perspectives of individuals with chronic pain and health professionals.
Chronic pain affects one in five Australians, and this could impact daily activities such as driving. Driving is a complex task, which requires the cognitive and physical ability to predict, identify, and respond to hazards to avoid crashing. However, research exploring the factors that influence safe driving behaviour for chronic pain individuals is limited. A qualitative study was conducted which involved semi-structured interviews with 23 people who had experienced persistent pain for at least three months and 17 health professionals who had experience working with individuals with chronic pain. The aim of this study was to obtain a deeper understanding of the experiences and challenges that people with chronic pain may have in their day-to-day driving. Participants were also asked about currently available driving assessments and strategies for individuals with chronic pain in the Australian healthcare system. The themes emerging from the interviews highlighted the need for clearer guidelines and educational materials regarding the impact of chronic pain on an individual's ability to drive. These themes included the physical and cognitive challenges resulting from chronic pain, as well as the potential side effects of pain medications. In addition, participants identified a number of self-regulation strategies and driving assessments currently available for monitoring safe driving behaviour in Australia. This study improves our understanding of how chronic pain affects driving behaviour, as reported by individuals experiencing the pain and relevant health professionals. Recommendations for improving the safety of drivers with chronic pain are discussed, including possible technological interventions and better public education.


Tamoxifen-induced increase in cytosol progestin receptor levels in a case of metastatic endometrial cancer.
A patient with endometrial carcinoma metastatic to the groin has had serial cytosol estrogen (ERc) and progestin (PRc) receptor determinations during hormonal therapy. The primary lesion was well differentiated and a left iliac node metastasis had high ERc and borderline PRc levels. PRc levels increased substantially in a subsequently appearing right groin metastasis at three times during the clinical course when the patient was treated with the antiestrogen tamoxifen. The patient had a partial response to the first course of tamoxifen and at one later time briefly had stabilized disease on tamoxifen plus medroxyprogesterone acetate. Tamoxifen with and without progestin should be further evaluated in the treatment of endometrial carcinoma.


United States Experience With a Femoral Neck Retaining Total Hip Arthroplasty Stem: A Retrospective Study With Control Comparison From the Literature.
Femoral neck retaining prostheses have gained popularity in Europe, but the United States has not seen the same trends occurring. Previous reports demonstrate high survivorship for these implants, but to our knowledge, there are no reports examining US data. After institutional review board approval, 824 primary total hip arthroplasties utilizing a femoral neck-retaining prosthesis were examined for femoral component survivorship rates. European studies were systematically reviewed to determine survivorship rates. The data were used to formulate a Kaplan-Meier survivorship curve and compare US data to that of the European studies. European studies demonstrated survivorship rates for all causes of 97.7 and 99.0% for aseptic loosening at an average of 6 years (range, 4.5 to 10). The current study demonstrated an all-cause 94% Kaplan-Meier survivorship estimate at 5 years and when aseptic loosening only was considered, survivorship increased to 99.4% at 5 years and 98.4% at 11 years. This femoral neck-retaining prosthesis demonstrated excellent survivorship that is comparable to the rates seen in European studies as well as the rates of standard and mid-stem prostheses in the United States.


Multimodal Imaging in Dengue-Fever-Associated Maculopathy.
Dengue fever can cause ocular complications that may not be easily identified during a regular eye examination. A high degree of suspicion and multimodal imaging will help characterize the lesions during acute stages of the infection.


Unleashing the power of informatization: How does the "information benefiting people" policy affect green total factor productivity?
Information development is a necessary means for China to achieve technology force and an effective path toward sustainable development. Regarding the "information benefiting people" policy led by the Chinese government as a quasi-experiment of information technology, this study builds an analysis framework for the impact of informatization on green total factor productivity (GTFP). Based on panel data at the Chinese city level from 2006 to 2019, this study further empirically evaluates the mechanism path, heterogeneity, and spatial spillover effects between informatization and GTFP by using a difference-in-difference (DID) model, a mediating model, and a spatial DID model. The results show that (1) the information benefiting people policy contributes considerably to greater GTFP levels in the pilot cities; (2) the policy also promotes the rapid growth of GTFP by fostering the advancement of education, the share of the number of ICT employees, and green technology innovation; (3) the information benefiting people policy raises GTFP in the eastern cities, small cities, and non-old industrial based cities; and (4) the policies lead to a large rise in local GTFP levels, but a decline in GTFP in surrounding cities. This paper offers valuable reference suggestions for the Chinese government to implement informatization-policies to support green development.


Spontaneous white sectored-mutants in Streptomyces hygroscopicus 111-81: characterization and antibiotic productivity.
Spontaneous white mutants from sectors of Streptomyces hygroscopicus 111-81 were isolated. The comparison of morphological, cultural, and biochemical properties of the mutants and ancestor showed the differences in colors of aerial, substrate mycelia, and sporulation. Changes in resistance to antibiotics and sensitivity to lysozyme indicated alterations in cell walls and cell membranes of the mutants. They showed antifungal activity close to that of the parent strain on fermentation medium FM2, with unchanged component composition of the AK-111-81 antibiotic complex. The cells of spontaneous white mutants are characterized with electron-transparent structures, vacuoles, aggregation of ribosomes, intrahyphal growth, and lack of multiple cell septa, which was established by transmission electron microscopy. The appearance of white sectored-mutants in S. hygroscopicus 111-81 is connected with exhausting of nutrients causing the substrate limitation and is a stress response to starvation.


Cimetidine-induced seizures in mice. Antagonism by some GABAergic agents.
The effects of muscimol, aminooxyacetic acid (AOAA), diamino-n-butyric acid (DABA), baclofen, bicuculline, picrotoxin, strychnine, diazepam, phenobarbitone and phenytoin on cimetidine-induced seizures were studied in mice. Cimetidine (400-1000 mg/kg, i.p.) induced dose-dependent tonic convulsion. Muscimol, AOAA and DABA effectively protected mice against cimetidine-induced seizures. Bicuculline and picrotoxin significantly potentiated the seizures induced by cimetidine and effectively antagonized the protective effects of muscimol, AOAA and DABA against the seizures. Diazepam and phenobarbitone significantly protected the mice against cimetidine-induced seizures while phenytoin and strychnine did not significantly alter the seizures. These results indicate that the attenuation of central gamma-aminobutyric acid neurotransmission may underlie cimetidine-induced seizures in mice.


The Prevalent Comorbidome at the Onset of Psoriasis Diagnosis.
Psoriasis (PsO) is currently regarded as a systemic inflammatory disease with a growing burden of post-diagnosis associated comorbidities. To determine the initial burden of comorbiditis we evaluated the comorbidome at PsO onset. In a matched case-control study, we extracted data on 57,228 patients and 125 morbidities from the Clalit Health Services Israeli insurance database. PsO cases were matched with control individuals by sex and age at enrolment. As pre-existing comorbidities, we considered all conditions already present in controls at the same age as the matched PsO case at the time of their diagnosis. To test for differences in the odds of comorbidities between the case and control groups, logistic regression analyses were run to calculate the odds ratio (OR) for each comorbidity, after which the comorbidome was graphically represented. In this study we enrolled 28,614 PsO patients and 28,614 controls with an average age of 45.3 ± 19.6 years. At the time of diagnosis, PsO patients were more likely to be diagnosed with 2-4 comorbidities (28.8% vs 23.8%) and > 5 (19.6% vs 12.9%,). PsO patients' specific comorbidomes evidenced several pathological cores: autoimmune and inflammatory systemic diseases [i.e., hidradenitis suppurativa (OR 3.55, 95% CI 1.88-7.28) or polymyalgia rheumatica (OR 3.01 95% CI 1.96-4.77)], inflammatory bowel diseases [i.e., Crohn's disease (OR 2.99 95% CI 2.20-4.13)], pulmonary inflammatory diseases [i.e., chronic obstructive pulmonary disease (OR 1.81 95% CI 1.61-2.04)], hepatological diseases [i.e., cirrhosis (OR 2.00 95% CI 1.36-3.00)], endocrine diseases [dysthyroidisms (OR 1.82 95% CI 1.30-2.59)], mental disorders [i.e., depression (OR 1.72 95% CI 1.57-1.87)], and cardiovascular diseases (i.e., hypertension (OR 1.47 95% CI 1.41-1.53)]. The PsO-onset comorbidome may help health professionals plan more comprehensive patient management. By screening for these common PsO-linked conditions, early diagnosis and treatment may become more frequent, thus greatly benefiting patients on their medical journey.


Serological assessment of SARS-CoV-2 exposure in northern Sweden by the use of at-home sampling to meet geographical challenges in rural regions.
The current SARS-CoV-2 pandemic has highlighted a need for easy and safe blood sampling in combination with accurate serological methodology. Venipuncture is usually performed by trained staff at health care centers. Long travel distances may introduce a bias of testing towards relatively large communities with close access to health care centers. Rural regions may thus be overlooked. Here, we demonstrate a sensitive method to measure antibodies to the S-protein of SARS-CoV-2. We adapted and optimized this assay for clinical use together with capillary blood sampling to meet the geographical challenges of serosurveillance. Finally, we tested remote at-home capillary blood sampling together with centralized assessment of S-specific IgG in a rural region of northern Scandinavia that encompasses 55,185 sq kilometers. We conclude that serological assessment from capillary blood sampling gives comparable results as analysis of venous blood. Importantly, at-home sampling enabled citizens living in remote rural areas access to centralized and sensitive laboratory antibody tests.


New Paths in Respiratory Sleep Medicine: Consumer Devices, e-Health, and Digital Health Measurements.
Sleep health and tracking sleep with contemporary wearables have become more popular. Sleep disorders, in particular, sleep-disordered breathing, have a higher prevalence than estimated previously. Many patients with apnea and hypopnea events suffer whereas others do not report complaints or show cardiovascular consequences. Assessment with wearables may support efforts to distinguish which type of apnea is related to aging and which to cardiovascular comorbidities. Innovative methods offer smart solutions for problems that are insufficiently addressed. Telemedical concepts help bring patients to sleep medicine expertise at an early stage. To use these methods clinically, they must be certified as medical devices.


Zinc deficiency causes oxidative stress, endoplasmic reticulum stress, apoptosis and inflammation in hepatocytes in grass carp.
A lack of the trace element zinc (Zn) in freshwater environments causes slow growth and malnutrition and affects the normal biological functions of organisms. In this study, a Zn deficiency model of grass carp hepatocytes was established with TPEN. Acetylcysteine (NAC) was used as an inhibitor. TPEN was added to L8824 cell culture medium, and LDH, AST, ALT, and AKP activities were enhanced in a Zn-deficient environment, leading to abnormal hepatopancreas function. Fluorescence microscopy showed an increase in ROS levels, and antioxidant enzyme activity assays revealed that SOD, CAT, GSH-PX, and T-AOC activities were decreased, indicating oxidative stress caused by Zn deficiency. The RT‒PCR results showed that the mRNA expression of GRP78, PERK, EIF2α, ATF4, and Chop was increased due to the addition of TPEN. Calcium kits showed increased Ca2+ levels. The RT‒PCR results showed that the mRNA expression levels of Caspase-12, Caspase-9, Caspase-3, and PARP apoptotic were increased due to the addition of TPEN. RT‒PCR and ELISA showed that the expression levels of interleukin-1β (IL-1β), interleukin-8 (IL-8), tumour necrosis factor (TNF-α), and inducible nitric oxide synthase (iNOS) were increased. This led to the conclusion that Zn deficiency in the freshwater environment caused inflammation and apoptosis in hepatocytes in grass carp. For the first time, apoptosis caused by endoplasmic reticulum stress in grass carp hepatocytes due to Zn deficiency was studied in the context of Ca2+. The present study provided some insight into the adverse effects of Zn deficiency in freshwater environments on fish.


Transfemoral aortic valve implantation of Edwards SAPIEN 3 without predilatation.
The purpose of the present study was to investigate whether transfemoral implantation of the balloon-expandable Edwards SAPIEN 3 device without prior balloon valvuloplasty is feasible. Transcatheter aortic valve implantation (TAVI) without predilatation may be advantageous and is feasible with various transcatheter heart valves. A total of 163 consecutive patients with severe aortic stenosis undergoing transfemoral TAVI were enrolled at two sites. We assessed whether the crossing of the native aortic valve with the prosthesis without prior pre-dilation was feasible and evaluated for procedural success according to VARC-2 criteria. Direct implantation without pre-dilatation was feasible in 154 patients (94.5%), whereas in nine patients predilatation was required due to difficulties while crossing the native aortic valve. Procedural success was achieved in 85.6%. A large proportion of the procedural failures was mainly driven by increased post-procedural gradients ≥20 mm Hg, which almost exclusively concerned the smaller prostheses sizes (23-mm 10/39 (25.6%) vs. 26-mm 5/72 (6.9%) vs. 29-mm 1/52 (1.9%); P < 0.001). Patients in the pre-ballooning group had higher calcium scores of the aortic valve (5,335 [4,421-7,807] vs. 2,893 [1,879-3,993]), more advanced age, higher transvalvular gradients, and smaller aortic valve area. The transfemoral implantation of the balloon-expandable SAPIEN 3 prosthesis without pre-dilatation is feasible in the majority of cases. In the presence of severe aortic valve calcification and critical aortic stenosis, however, predilatation may still be necessary. Furthermore, the significance of increased post-procedural gradients requires further verification. © 2016 Wiley Periodicals, Inc.


Emotional intelligence and clinical skills: preliminary results from a comprehensive clinical performance examination.
The recognition of emotional states in one's self and others, emotional intelligence (EI) may play a key role in patient care. This study examines the relationship between EI and students' clinical skills in a required, comprehensive performance examination (CPX). Prior to taking a 12-station CPX, third-year students in 2003 and 2004 (n=165) completed the Trait Meta-Mood Scale and Davis' Interpersonal Reactivity Index. Dimensional subscales were computed and correlated with selected aspects of students' clinical skills as recorded by standardized patients in each objective structured clinical examination (OSCE)-type encounter. The internal consistencies (alpha) of subtests ranged from .73-.90. Attention to Feelings, Empathic Concern, and Perspective Taking were significantly (p=<or=.05) positively correlated with communication skills, while the latter two were also significantly negatively associated with physical examination skills. Various aspects of EI are modestly implicated in students' clinical skills as assessed by standardized patients in an OSCE.


Hydroformylation of pyrolysis oils to aldehydes and alcohols from polyolefin waste.
Waste plastics are an abundant feedstock for the production of renewable chemicals. Pyrolysis of waste plastics produces pyrolysis oils with high concentrations of olefins (>50 weight %). The traditional petrochemical industry uses several energy-intensive steps to produce olefins from fossil feedstocks such as naphtha, natural gas, and crude oil. In this work, we demonstrate that pyrolysis oil can be used to produce aldehydes through hydroformylation, taking advantage of the olefin functionality. These aldehydes can then be reduced to mono- and dialcohols, oxidized to mono- and dicarboxylic acids, or aminated to mono- and diamines by using homogeneous and heterogeneous catalysis. This route produces high-value oxygenated chemicals from low-value postconsumer recycled polyethylene. We project that the chemicals produced by this route could lower greenhouse gas emissions ~60% compared with their production through petroleum feedstocks.


Experimental study on the atomization characteristics and dust removal efficiency of a fan-shaped nozzle for purifying working environment.
The inadequacy of the existing research in characterizing the atomization performance of the whole atomization field by the local region at nozzle axis hinders the improvement of dust removal performance of a spray system, especially for fan-shaped nozzles with large atomization angle. To solve this inadequacy, 88 measuring points were designed in this study to reveal the spatial distribution characteristics of atomization parameters of a fan-shaped pressure atomization nozzle using a 3D Fiber Phase-Doppler Anemometer. Moreover, the atomization performance and dust removal performance of the whole atomization field under different spray pressures were characterized. The results showed that the spatial distribution of atomization parameters in the axis and radial direction of the nozzle was inhomogeneous. As the axial distance from the nozzle outlet increased, the average droplet size showed a trend of first decreasing and then increasing, the proportion of the droplet of 15-70 μm showed a trend of first increasing and then decreasing, while the average droplet velocity and droplet flux showed a decreasing trend. In addition, the spray orientation was perpendicular to gravity, and the atomization field was parallel to gravity, resulting in a significant difference in the average droplet size between the upper region and the axis. Compared with the upper and lower regions, the atomization effect at the axis was superior, manifested by higher average droplet velocity and droplet flux, indicating that characterizing nozzle atomization performance with atomization parameters at the axis will lead to overestimation. The increase of spray pressure can improve atomization performance and dust removal efficiency to a certain extent, but the improvement effect had a limit. The atomization field can be divided into atomization region, expansion region and contraction region, and the expansion region was considered as an effective dust removal region. These findings provide reference for the design and operation of a spray system.


The place of pelvic osteotomy in the modern era of bladder exstrophy reconstruction.
The place of pelvic osteotomy in reconstructing bladder/cloacal exstrophy has been debated for some time; the experience with 'combined' osteotomy in primary and re-operative exstrophy closure at this institution is presented, with a discussion of the historical and scientific place of osteotomy in managing this condition. Sixty-eight patients had bilateral vertical and transverse iliac osteotomy between 1992 and 2003, and with outcome data available. Of 58 patients with classic exstrophy, eight were newborns, eight were deliberately delayed primary closures, 36 were re-operative after previous failed closure and six were bladder neck reconstructions where the bladder outlet was very wide, such that bony closure was felt necessary for successful bladder neck coaptation. Of 10 patients with cloacal exstrophy, nine were primary closures and one was a re-operative closure. Data were collected relating to age at closure, complications and continence outcome. The mean (range) age (months) was 41 (5-179) for re-operative closures, 12.5 (3-32) for delayed primary closures, 64.1 (38-79) for bladder neck reconstruction, 51.4 (6-165) for cloacal exstrophy closure, and 15 (2-45) days for newborn exstrophy closure. There was a superficial wound infection in two patients, pin-site infection in one, loose pins in two, and two had transient femoral nerve palsy. In two patients the procedure failed and they required further re-operative closure with osteotomy. Sixteen patients are dry urethrally day and night, 12 have had and four are awaiting bladder augmentation, one has a colon conduit, and 35 are awaiting a definitive continence procedure. Osteotomy has a proven track record in the field of exstrophy reconstruction, and the benefit especially in re-operative closure is emphasized by the present results. The surgical morbidity with the 'combined osteotomy' is low, cosmetic results are excellent and the effect on success of closure is clearly advantageous.


The impact of vaginal cone therapy on stress urinary incontinence compared with transobturator tape.
To emphasize the efficiency of vaginal cone (VC) therapy in stress urinary incontinence (SUI) through a comparison with transobturator tape (TOT). A prospective randomized controlled study was conducted at the Etlik Zübeyde Hanım Maternity and Women Hospital during a one year study period. Forty women were allocated into two equal groups; those treated with VCs for a 3 month period, and women who underwent TOT procedures. These women were followed up at 6 weeks and 6 months after the treatments. Subjective cure was assessed using Wagner's Quality of Life Questionnaire. Objective cure was evaluated through a cough stress and pad test results. Maternal demographic features were comparable among groups. We observed improvement in pad weight test among groups when compared with the pretreatment state (p=0.015, p=0.005). Although the subjective cure rate was similar in both groups at the 6th week and 6th month follow up (65% vs. 75%; 75% vs. 80%) (p>0.05), the objective cure rate was significantly higher in the TOT group than in the VC group, as expected (10% vs. 80%; 30% vs. 75%) (p<0.05). The main treatment of SUI is surgery; however, VC could be offered as an alternative treatment for women who refuse surgery, those at high risk for surgery or it could be used temporarily before surgery.


Electronic structure and biological activity of chosen DDT-type insecticides studied by 35Cl-NQR.
A correlation between the electronic structure and biological activity of chosen dichlorodiphenyltrichloroethane (DDT)-type insecticides: 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene, 2,2-bis(4-chlorophenyl)ethanoic acid and 4,4'-dichlorobenzophenone (used in agriculture) has been analysed on the basis of the (35)Cl-nuclear quadrupole resonance (NQR) spectroscopy. The (35)Cl-NQR resonance frequencies measured at 77 K have been correlated with the lethal dose (LD(50)) parameter that characterises the biological activity of these insecticides.


Ectopic ACTH syndrome due to bronchial carcinoid tumour--a case report.
A patient is reported who had Cushing's syndrome and carcinoid tumour of the bronchus. The case illustrates the difficulty in preoperative localization of the ectopic ACTH source and the surgical management of such patients.


Scheduled and unscheduled combination chemotherapy in the treatment of squamous cell lung cancer (cyclophosphamide, adriamycin, vincristine and bleomycin, with and without cis-platinum).
Fifty four patients with squamous cell lung cancer, treated with Cyclophosphamide (750 mg/m2), Adriamycin (50 mg/m2), Vincristine (1.5 mg/m2) and Bleomycin (30 mg) (CAVB) in a 2 day scheduled regime, showed an overall median survival time (MST) of 32 weeks (28 weeks for non-responders and 46.5 weeks for responders--a non-significant difference). The response rate was 24%, the median duration of response being 23 weeks. Bone marrow toxicity was not a major problem. A further 21 patients received the same drugs but in a single bolus (unscheduled regime). Comparison of their results with the 25 patients randomised to the scheduled regime showed no significant difference in MST or toxicity. The addition of Cis-platinum (50 mg/m2) to the unscheduled CAVB regime (CAVBP) in a further 22 patients did not result in an improvement either in survival or response, but added to the toxicity.


Structural biology of human GPCR drugs and endogenous ligands - insights from NMR spectroscopy.
G protein-coupled receptors (GPCRs) represent the largest class of "druggable" proteins in the human genome. For more than a decade, crystal structures and, more recently, cryoEM structures of GPCR complexes have provided unprecedented insight into GPCR drug binding and cell signaling. Nevertheless, structure determination of receptors in complexes with weakly binding molecules or complex polypeptides remains especially challenging, including for hormones, many of which have so far eluded researchers. Nuclear magnetic resonance (NMR) spectroscopy has emerged as a promising approach to determine structures of ligands bound to their receptors and to provide insights into the dynamics of GPCR-bound drugs. The capability to investigate compounds with weak binding affinities has also been leveraged in NMR applications to identify novel lead compounds in drug screening campaigns. We review recent structural biology studies of GPCR ligands by NMR, highlighting new methodologies enabling studies of GPCRs with native sequences and in native-like membrane environments that provide insights into important drugs and endogenous ligands.


Reducing publication bias of prospective clinical trials through trial registration.
Publication bias is the selective publishing of favorable or statistically significant results. This practice, over time, distorts the medical literature by depicting inordinately optimistic outcomes for treatments and interventions. Sources of publication bias include preferential publishing by journals and preferential submission by researchers. Mandatory trial registration, as instituted by the International Committe of Medical Journal Editors (ICMJE), should reduce publication bias by improving the ability to identify all trials pertaining to a specific intervention. Contraception endorses the views of the ICMJE and will now require registration of all prospective trials.


The use of High-Pressure Processing (HPP) to improve the safety and quality of raw coconut (Cocos nucifera L) water.
This research investigated the use of high-pressure processing (HPP) for inactivating vegetative pathogens and spoilage microbiota in fresh unfiltered coconut water (Cocos nucifera L) from nuts obtained from Florida and frozen CW from Brazil with pH >5.0 and storage at 4 °C. Additionally, CW was evaluated to determine if it supported the growth and toxin production of Clostridium botulinum with or without the use of HPP when stored at refrigeration temperatures. Samples of fresh unfiltered CW were inoculated to 5.5 to 6.5 logs/mL with multiple strain cocktails of E. coli O157:H7, Salmonella spp. and Listeria monocytogenes and HPP at 593 MPa for 3 min at 4 °C. HPP and inoculated non-HPP controls were stored at 4 °C for 54 and 75 days for Florida CW and Brazil CW, respectively. Results of analyses showed HPP samples with <1 CFU/mL and no detection (negative/25 mL) with enrichment procedures for the 3 inoculated pathogens for all analyses. The non-HPP control samples did not show growth of the pathogens but a gradual decrease in levels to ca. 3-Logs/mL by day 54 in the fresh Florida CW and similarly in frozen Brazil CW by Day 75. Microbial spoilage of uninoculated samples was evaluated for normal spoilage microbiota through 120 days storage at 4 °C. Microbial counts remained at ca. 2-logs with no detectable signs of spoilage for HPP samples through 120 d. The non-HPP control samples spoiled within 2 weeks of storage at 4 °C with gas production, cloudiness, and off-odors. To evaluate if CW supports the growth and toxin production of C. botulinum, samples of unfiltered and filtered (0.2 μm) CW were inoculated with either proteolytic or non-proteolytic C. botulinum spores at 2 log CFU/mL that were processed at 593 MPa for 3 min and stored at 4 °C and 10 °C for 45 days. Inoculated positive and non-inoculated negative controls were prepared and stored as the HPP treated and non-HPP samples. No growth of C. botulinum or toxin production was detected in either the unfiltered or filtered CW regardless if products were HPP treated or not. All inoculated samples with C. botulinum spores were enriched at Day-45 in PYGS media to determine the viability of the inoculated spores at the end of shelf-life and screened for C. botulinum toxins. In all samples, C. botulinum toxin Types A, B and E were detected indicating spores were viable throughout the storage. Type F toxin was not detected possibly due to inherent conditions in the samples that may affected toxin screening.