Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic humans.
Plant sterols reduce cholesterol absorption, which leads to a decrease in plasma and LDL-cholesterol concentrations. Plant sterols also lower plasma concentrations of carotenoids and alpha-tocopherol, but the mechanism of action is not yet understood. The aims of this clinical study were to determine whether plant sterols affect the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic men and to compare the effects of plant sterol esters and plant free sterols on cholesterol absorption. Twenty-six normocholesterolemic men completed the double-blind, randomized, crossover study. Subjects consumed daily, for 1 wk, each of the following 3 supplements: a low-fat milk-based beverage alone (control) or the same beverage supplemented with 2.2 g plant sterol equivalents provided as either free sterols or sterol esters. During this 1-wk supplementation period, subjects consumed a standardized diet. Both of the milks enriched with plant sterols induced a similar (60%) decrease in cholesterol absorption. Plant free sterols and plant sterol esters reduced the bioavailability of beta-carotene by approximately 50% and that of alpha-tocopherol by approximately 20%. The reduction in beta-carotene bioavailability was significantly less with plant free sterols than with plant sterol esters. At the limit of significance (P = 0.054) in the area under the curve, the reduction in alpha-tocopherol bioavailability was also less with plant free sterols than with plant sterol esters. Both plant sterols reduced beta-carotene and alpha-tocopherol bioavailability and cholesterol absorption in normocholesterolemic men. However, plant sterol esters reduced the bioavailability of beta-carotene and alpha-tocopherol more than did plant free sterols.


Variable pollen viability and effects of pollen load size on components of seed set in cultivars and feral populations of oilseed rape.
Pollination success is important for crop yield, but may be cultivar dependent. Less is known about which floral traits influence pollination success. Floral traits, e.g. traits related to attraction and reward, can also contribute to gene flow via pollen, the latter being of particular importance in oilseed rape (Brassica napus) where gene flow occurs between plants of crop, volunteer and feral origin as well as related taxa. We investigated the relationship between pollen load size and seed set in winter oilseed rape. We compared variability in pollen-viability traits, flower production (flowers from the main raceme times number of branches) and seed number and weight per siliqua among cultivars and feral populations (growing outside of agricultural fields) under controlled conditions. Both seed number and weight were saturated at relatively low pollen loads in the tested cultivar. Pollen viability and estimated flower production differed among cultivars, indicating that these traits could contribute to yield variability. Seed weight per siliqua, but not pollen traits or flower production, was lower in ferals compared to cultivars. Thus, while the probability of establishment may be reduced in ferals (due to lower seed weight per siliqua) this will not necessarily impact their contribution to gene flow via pollen. In oilseed rape a relatively low pollen load may be sufficient for full seed set in some cultivars, suggesting less dependence on insect pollination for high yield than generally expected. Our results also showed that previously less investigated floral traits, such as pollen viability, pollen tube growth rate and flower number, can differ between cultivars. Studies of these traits may provide targets for increasing crop yield and provide general knowledge about gene flow between cultivated, feral and related wild populations.


The importance of social activity to risk of major depression in older adults.
Several social determinants of health (SDoH) have been associated with the onset of major depressive disorder (MDD). However, prior studies largely focused on individual SDoH and thus less is known about the relative importance (RI) of SDoH variables, especially in older adults. Given that risk factors for MDD may differ across the lifespan, we aimed to identify the SDoH that was most strongly related to newly diagnosed MDD in a cohort of older adults. We used self-reported health-related survey data from 41 174 older adults (50-89 years, median age = 67 years) who participated in the Mayo Clinic Biobank, and linked ICD codes for MDD in the participants' electronic health records. Participants with a history of clinically documented or self-reported MDD prior to survey completion were excluded from analysis (N = 10 938, 27%). We used Cox proportional hazards models with a gradient boosting machine approach to quantify the RI of 30 pre-selected SDoH variables on the risk of future MDD diagnosis. Following biobank enrollment, 2073 older participants were diagnosed with MDD during the follow-up period (median duration = 6.7 years). The most influential SDoH was perceived level of social activity (RI = 0.17). Lower level of social activity was associated with a higher risk of MDD [hazard ratio = 2.27 (95% CI 2.00-2.50) for highest v. lowest level]. Across a range of SDoH variables, perceived level of social activity is most strongly related to MDD in older adults. Monitoring changes in the level of social activity may help identify older adults at an increased risk of MDD.


Family support for stroke: a randomised controlled trial.
Attention is currently focused on family care of stroke survivors, but the effectiveness of support services is unclear. We did a single-blind, randomised, controlled trial to assess the impact of family support on stroke patients and their carers. Patients with acute stroke admitted to hospitals in Oxford, UK, were assigned family support or normal care within 6 weeks of stroke. After 6 months, we assessed, for carers, knowledge about stroke, Frenchay activities index, general health questionnaire-28 scores, caregiver strain index, Dartmouth co-op charts, short form 36 (SF-36), and satisfaction scores, and, for patients, knowledge about stroke and use of services, Barthel index, Rivermead mobility index, Frenchay activities index, London handicap scale, hospital anxiety and depression scales, Dartmouth co-op charts, and satisfaction. 323 patients and 267 carers were followed up. Carers in the intervention group had significantly better Frenchay activities indices (p=0.03), SF-36 scores (energy p=0.02, mental health p=0.004, pain p=0.03, physical function p=0.025, and general health perception p=0.02), quality of life on the Dartmouth co-op chart (p=0.01), and satisfaction with understanding of stroke (82 vs 71%, p=0.04) than those in the control group. Patients' knowledge about stroke, disability, handicap, quality of life, and satisfaction with services and understanding of stroke did not differ between groups. Fewer patients in the intervention group than in the control group saw a physiotherapist after discharge (44 vs 56%, p=0.04), but use of other services was similar. Family support significantly increased social activities and improved quality of life for carers, with no significant effects on patients.


Shape analysis of training data for neural networks in Electrical Impedance Tomography.
Electrical Impedance Tomography (EIT) is a cost-effective and fast way to visualize dielectric properties of the human body, through the injection of alternating currents and measurement of the resulting potential on the bodies surface. However, this comes at the cost of low resolution as EIT is a non-linear ill-posed inverse problem. Recently Deep Learning methods have gained the interest in this field, as they provide a way to mimic non-linear functions. Most of the approaches focus on the structure of the Artificial Neural Networks (ANNs), while only glancing over the used training data. However, the structure of the training data is of great importance, as it needs to be simulated. In this work, we analyze the effect of basic shapes to be included as targets in the training data set. We compared inclusions of ellipsoids, cubes and octahedra as training data for ANNs in terms of reconstruction quality. For that, we used the well-established GREIT figures of merit on laboratory tank measurements. We found that ellipsoids resulted in the best reconstruction quality of EIT images. This shows that the choice of simulation data has an impact on the ANN reconstruction quality.Clinical relevance- This work helps to improve time independent EIT reconstruction, which in turn allows for extraction of time independent features of e.g., the lung.


Donor Endothelial Cell Count Does Not Correlate With Descemet Stripping Automated Endothelial Keratoplasty Transplant Survival After 2 Years of Follow-up.
To analyze the influence of low endothelial cell density (ECD) of donor cornea tissue, donor age, and sex on the transplant survival rate after Descemet stripping automated endothelial keratoplasty (DSAEK). Graft ECD, age, and sex of donors used for DSAEK (n = 1789) during 7 years (2007-2014) in 4 Scandinavian hospitals were assessed for potential association with transplant survival at 2 years of follow-up using a Cox regression model correcting for confounding factors. The data were obtained from The Swedish Cornea Transplant Registry. Transplant failure occurred in 196 patients, with 69 early failures during the first 3 postoperative months, and 127 late secondary failures. Twenty-five of the late secondary failures were due to rejection. Reversible rejections occurred in 67 patients. There was no significant impact of donor age [hazard ratio (HR) 1.0, 95% confidence interval (CI), 0.99-1.02, P = 0.32] or endothelial cell count (HR 1.00, 95% CI, 0.99-1.01, P = 0.3) on the survival rate of DSAEK transplants at 2 years of follow-up. The use of donor grafts with low ECD (<2300 cells/mm) did not influence the survival rate (HR 1.3, 95% CI, 0.76-2.35, P = 0.31). Male donor sex was associated with lower 2-year graft survival (HR 1.5, 95% CI, 1.04-2.28, P = 0.03), but not with rejection events (P = 0.26). Based on data from The Swedish Cornea Transplant Registry, low donor ECD was not detrimental to graft survival, whereas donor sex seemed to influence the outcome at the end of the 2-year follow-up.


Bone mineral density in professional female dancers.
To measure the long term effects of dance training and the contribution of the timing and duration of any menstrual disruption on bone mineral density (BMD). Measurement of BMD in 57 premenopausal, previously professionally dance trained women and the relationship to menstrual and training history. Bone density measurements at lumbar spine and femoral neck by dual energy x-ray absorptiometry. The average Z score for BMD at the lumbar spine in the amenorrhoeic dancers was significantly below that for the normal population. The average Z score for BMD at the femoral neck in the eumenorrhoeic dancers was significantly above that for the normal population. There was a significant difference between the average Z score for BMD at both the lumbar spine and femoral neck between the amenorrhoeic and eumenorrhoeic dancers. Significant negative relationships were found between BMD at the lumbar spine and (1) age at menarche, (2) duration of amenorrhoea, (3) BMD at the femoral neck, and (4) the variable of ideal minus lowest weight, which was independent of amenorrhoea. No significant relationships were found between duration of oral contraceptive pill usage and BMD at either the lumbar spine or the femoral neck in eumenorrhoeic or amenorrhoeic dancers. In order to quantify the effect of a combination of these significant factors, a model of BMD was constructed using multiple regression incorporating the variables duration of amenorrhoea, age at menarche, and ideal minus lowest body weight. In this model R2 was 33.6%, in other words 33.6% of the total variation in the Z score for BMD at the lumbar spine could be accounted for by these factors. Professional female dancers with a history of delayed menarche and amenorrhoea have been identified as another group of premenopausal women potentially at risk of developing osteoporosis because of a decrease in BMD at the lumbar spine. The femoral neck in dancers with a history of amenorrhoea was partially protected from loss of BMD by virtue of being the major weight bearing site in previous dance training, and in eumenorrhoeic dancers BMD was significantly increased at this site.


Relationship between intracellular amino acids and protein synthesis in the extensor digitorum longus muscle of rats.
1. The incorporation into protein, and the accumulation into the free amino acid pools, of radioactive l-leucine and glycine was studied in rat extensor digitorum longus muscle. 2. The tissue was incubated first with (14)C-labelled and then with (3)H-labelled amino acid. 3. The experimental results were consistent with a model based on the premise that the amino acids in protein were incorporated directly from the extracellular pool.


In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes.
CD5 is a 67-kDa T cell surface Ag that can be found physically associated with the CD3-TCR molecular complex. In different experimental models it has been shown to act as a costimulatory receptor for T cell activation. Unexpectedly, studies in CD5-deficient mice suggested a negative role for the CD5 Ag in CD3-TCR signaling in the thymus. In this report we assessed the constitutive interactions of CD5 in freshly isolated human thymocytes with signaling elements of the CD3-TCR complex. We determined that the ZAP-70 protein tyrosine kinase was present in CD5 immunoprecipitates. The two molecules were constitutively tyrosine phosphorylated in a complex also associating with unphosphorylated as well as phosphorylated zeta-chains. Although both p21 and p23 tyrosine-phosphorylated forms of zeta as well as phospho-CD3 epsilon molecules were constitutively present in human thymocytes and could be immunoprecipitated with ZAP-70- or CD3 epsilon-specific Abs, the p21 species of zeta was predominant in CD5 immune complexes. The interaction between CD5 and ZAP-70 was not observed in CD3-negative thymocytes, where the constitutive tyrosine phosphorylation of ZAP-70 was very low. We conclude that CD5 may affect in vivo the signaling capacity of TCRs expressed by human thymocytes by altering the phosphorylation state of CD3 and/or by retaining ZAP-70 with the p21 species of zeta.


[Lymphedema of the upper extremity in patients operated for carcinoma of the breast: clinical experience with coumarinic extract from Melilotus officinalis].
The aim of this clinical study was to verify the therapeutic activity of cumarinic extract of Melilotus officinalis (CEMO) in patients with chronic lymphedema of the upper arm caused by lymphadenectomy for breast cancer. Cumarine, in fact, has antiedemic properties due to macrophagic action that stimulates proteolysis in the tissues affected by chronic lymphedema. In an open clinical study we enrolled 24 patients with chronic upper arm lymphedema due to post-lymphadenectomy of the axilla for breast cancer. 21 patients were eligible to receive 400 mg of CEMO containing 8 mg of cumarine in a sole daily administration for 6 months. We measure the circumference of the upper arm at 3 and 6 months from treatment. We evaluated the symptoms and tolerability through a questionnaire given to the patients at every clinical control. Of the 21 (87.5%) patients eligible, only 14 (66.6%) were treated with CEMO according to protocol. Of these 11 patients (52.3%) had a reduction of the circumference of the affected arm of 5% with respect to base values. Three patients (14.2%) had no change. In 12 patients (57.1%) symptoms improved. As for tolerability: 3 patients (14.2%) had transitory gastrointestinal side-effects. There was worsening of lymphedema and symptoms in 4 patients (19%) that did not receive CEMO and were followed as controls. Three patients (14.2%) were not evaluable because they were lost to follow-up. Cumarinic extract of Melilotus officinalis (CEMO) was effective in reducing lymphedema in 79% of the pts treated for a period of six months. The median reduction of the upper arm circumference was modest (5% with respect to initial values) but statistically significant (p = 0.048). Treatment with CEMO for lymphedema could be associated to the physiotherapy given to these patients such as manual lymph drainage (MLD).


Transport of particles and microorganisms in microfluidic channels using rectified ac electro-osmotic flow.
A new method is demonstrated to transport particles, cells, and other microorganisms using rectified ac electro-osmotic flows in open microchannels. The rectified flow is obtained by synchronous zeta potential modulation with the driving potential in the microchannel. Experiments were conducted to transport both neutral, charged particles, and microorganisms of various sizes. A maximum speed of 50 μm∕s was obtained for 8 μm polystyrene beads, without any electrolysis, using a symmetrical square waveform driving electric field of 5 V∕mm at 10 Hz and a 360 V gate potential with its polarity synchronized with the driving potential (phase lag=0°).


[Childhood tuberculosis. How to diagnose it?].
Tuberculosis is one of the conditions with higher incidence worldwide. Infection occurs when Mycobacterium enters the body, and its progression to disease occurs when immune, nutritional and vaccination status are altered. The diagnosis in children is based on elements such as contact history, tuberculin test, chest radiograph and microbiological finding of the bacillus, so these criteria will help us to make an early diagnosis and treatment, breaking the life cycle of M. tuberculosis, preventing an increase in morbidity and mortality in a community.


BRAF in Melanoma: Pathogenesis, Diagnosis, Inhibition, and Resistance.
Since the initial discovery that a subset of patients with cutaneous melanoma harbor BRAF mutations, substantial research has been focused on determining the pathologic consequences of BRAF mutations, optimizing diagnostic techniques to identify these mutations, and developing therapeutic interventions to inhibit the function of this target in mutation-bearing tumors. Recently, advances have been made which are revolutionizing the standard of care for patients with BRAF mutant melanoma. This paper provides an overview on the pathogenic ramifications of mutant BRAF signaling, the latest molecular testing methods to detect BRAF mutations, and the most recent clinical data of BRAF pathway inhibitors in patients with melanoma and BRAF mutations. Finally, emerging mechanisms of resistance to BRAF inhibitors and ways of overcoming this resistance are discussed.


Efficacy and safety of febuxostat extended release and immediate release in patients with gout and moderate renal impairment: phase II placebo-controlled study.
Febuxostat immediate release (IR), a xanthine oxidase inhibitor, is indicated for the management of hyperuricemia in patients with gout by lowering urate levels. An extended release (XR) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure. The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and moderate renal impairment (estimated glomerular filtrate rate ≥ 30 and < 60 ml/min). This was an exploratory, 3-month, phase II, multicenter, placebo-controlled, double-blind proof-of-concept study. Patients (n = 189) were randomized 1:1:1:1:1 to receive placebo or febuxostat IR 40 mg, XR 40 mg, IR 80 mg, or XR 80 mg once daily. Endpoints included: proportion of patients with serum uric acid (sUA) < 5.0 mg/dl at month 3 (primary endpoint), proportion of patients with sUA < 6.0 mg/dl at month 3, and proportion of patients with ≥ 1 gout flare requiring treatment over 3 months. At month 3, all febuxostat treatment groups were associated with greater proportions of patients achieving sUA < 5.0 mg/dl (p < 0.05 vs placebo). A greater proportion of patients receiving XR 40 mg achieved sUA < 5.0 mg/dl versus those receiving IR 40 mg (p = 0.034); proportions were similar in the IR 80 mg and XR 80 mg groups. Higher proportions of febuxostat-treated patients achieved sUA < 6.0 mg/dl at month 3 (p < 0.05 vs placebo) and experienced ≥ 1 gout flare (significant for all comparisons, except XR 40 mg). Incidences of treatment-related adverse events were low across all treatment groups; the majority were mild or moderate with no apparent trends correlating with IR or XR doses. The most common treatment-emergent adverse event was hypertension. One death (unrelated to the study drug) was reported. These exploratory data demonstrate that febuxostat (XR and IR) formulations were effective and well tolerated in patients with gout and moderate renal impairment. ClinicalTrials.gov, NCT02128490 Registered on 29 April 2014.


Relationship between serum cardiac troponin T level and cardiopulmonary function in stable chronic obstructive pulmonary disease.
High-sensitivity cardiac troponin T (hs-cTnT) in serum is a useful marker of acute myocardial injury, yet information is limited in patients with chronic obstructive pulmonary disease. We aimed to explore the association between hs-cTnT levels and cardiac and pulmonary dysfunction in patients with stable chronic obstructive pulmonary disease and at-risk individuals. We examined community-dwelling adults with/without chronic obstructive pulmonary disease, with a life-long smoking history, current symptoms of dyspnea during exertion, prolonged coughing, and/or sputum. Serum hs-cTnT concentrations were measured, and subjects underwent pulmonary function tests, high-resolution computed tomography of the chest, an echocardiogram, and a 6-minute walking test. Eighty-six stable patients were identified (mean age 65.5 years; predicted forced expiratory volume in 1 second [FEV1% predicted] 75.0%). Their overall mean hs-cTnT level was 0.008 ng/mL. Logarithmically transformed hs-cTnT levels significantly and positively correlated with age, smoking index, serum high-sensitivity C-reactive protein levels, right ventricle systolic pressure, low attenuation area percentage, and brain natriuretic peptide levels (range r=0.231-0.534, P=0.000 to P=0.042). Further, logarithmically transformed hs-cTnT values significantly and negatively correlated with forced vital capacity, FEV1% predicted, diffusion capacity, arterial oxygen tension, and 6-minute walking distance (range r= -0.482 to -0.377, P=0.000 to P=0.002). Multivariate analyses showed that hs-cTnT values varied independently according to the following three parameters: high-sensitivity C-reactive protein levels (B=0.157, β=0.450, t=3.571, P=0.001), age (B=0.008, β=0.352, t=2.789, P=0.009), and right ventricular systolic pressure (B=0.008, β=0.280, t=2.202, P=0.035). Even in patients with stable chronic obstructive pulmonary disease, the serum troponin T concentration was controlled by at least three major factors, ie, systemic inflammation, advancing age, and right cardiac overload.


A cultural values assessment tool.
Faculty members at a small liberal arts college teaching in a course entitled "Contemporary Cultures: China, Guatemala and Nigeria" found that using a cultural values assessment tool strengthened the course. This assessment tool was developed by a faculty member teaching in the course when no standardized tool of this type could be found. Students and faculty involved with this senior core course found the cultural values assessment tool to be effective in introducing the course, in stimulating some critical thinking throughout the course and in concluding the course.


[Forensic significance of anomalies in skull development].
In the course of bone tissue development some genetic disorders such as exostoses and enostoses, may occur. Exostoses and enostoses represent bone tissue hyperplasia that can develop at any part of skeleton. Neurotrauma can cause fatal biological consequences, which is directly associated with skill development abnormalities. This is a case report of a male cadaver 36 years of age. The autopsy revealed massive hemorrhage on the left side of the neck and the right side of the lower jaw. A major fissure of the arterial wall was found on the basilar artery. A bony, wart-like excrescence was found on the clivus of the occipital bone. Coinciding ruptures and consequential bleeding from basilar artery with presence of development abnormalities in the clivus region, suggest that one has to clearly distinguish the result of the injury from anomalies already existing in the skull. The position of the attacker can be determined by concise and objective investigation. This is a case report of an anomaly in bone development: a bony, wart-like excrescence on the right side of the clivus. Due to neurotrauma and consequential sliding of brain structures, the damage of basilar artery and of the bony excrescence occurred, which led to bleeding and fatal outcome.


Controllable electrical properties of metal-doped In2O3 nanowires for high-performance enhancement-mode transistors.
In recent years, In(2)O(3) nanowires (NWs) have been widely explored in many technological areas due to their excellent electrical and optical properties; however, most of these devices are based on In(2)O(3) NW field-effect transistors (FETs) operating in the depletion mode, which induces relatively higher power consumption and fancier circuit integration design. Here, n-type enhancement-mode In(2)O(3) NW FETs are successfully fabricated by doping different metal elements (Mg, Al, and Ga) in the NW channels. Importantly, the resulting threshold voltage can be effectively modulated through varying the metal (Mg, Ga, and Al) content in the NWs. A series of scaling effects in the mobility, transconductance, threshold voltage, and source-drain current with respect to the device channel length are also observed. Specifically, a small gate delay time (0.01 ns) and high on-current density (0.9 mA/μm) are obtained at 300 nm channel length. Furthermore, Mg-doped In(2)O(3) NWs are then employed to fabricate NW parallel array FETs with a high saturation current (0.5 mA), on/off ratio (>10(9)), and field-effect mobility (110 cm(2)/V·s), while the subthreshold slope and threshold voltage do not show any significant changes. All of these results indicate the great potency for metal-doped In(2)O(3) NWs used in the low-power, high-performance thin-film transistors.


Defective RNA Particles of Plant Viruses-Origin, Structure and Role in Pathogenesis.
The genomes of RNA viruses may be monopartite or multipartite, and sub-genomic particles such as defective RNAs (D RNAs) or satellite RNAs (satRNAs) can be associated with some of them. D RNAs are small, deletion mutants of a virus that have lost essential functions for independent replication, encapsidation and/or movement. D RNAs are common elements associated with human and animal viruses, and they have been described for numerous plant viruses so far. Over 30 years of studies on D RNAs allow for some general conclusions to be drawn. First, the essential condition for D RNA formation is prolonged passaging of the virus at a high cellular multiplicity of infection (MOI) in one host. Second, recombination plays crucial roles in D RNA formation. Moreover, during virus propagation, D RNAs evolve, and the composition of the particle depends on, e.g., host plant, virus isolate or number of passages. Defective RNAs are often engaged in transient interactions with full-length viruses-they can modulate accumulation, infection dynamics and virulence, and are widely used, i.e., as a tool for research on cis-acting elements crucial for viral replication. Nevertheless, many questions regarding the generation and role of D RNAs in pathogenesis remain open. In this review, we summarise the knowledge about D RNAs of plant viruses obtained so far.


Development of sympathetic ganglionic neurotransmission in the neonatal rat. Pre- and postganglionic nerve response to asphyxia and 2-deoxyglucose.
To determine the time course of development of neurotransmission in the sympathetic ganglion of the rat, pre- and postganglionic activity was recorded from the cervical sympathetic trunk in anesthetized neonatal and mature preparations. Tonic activity and responses to two stimuli, cellular hypoglycemia induced by 2-deoxyglucose and asphyxia, which are known to evoke CNS-mediated sympathetic activation in mature rats were measured. In 2-11-day-old neonates, tonic preganglionic activity recorded from the cervical sympathetic nerve and responses to hypoglycemia and asphyxia were comparable to or greater than that in mature rats. In 17-19-day-old neonates these variables were elevated to twice the adult value. In contrast, tonic postganglionic activity recorded from the internal carotid nerve was barely detectable through 5 days of age and there was no response to hypoglycemia. During asphyxia, maximum postganglionic impulse frequency and total number of impulses discharged were 10-20% of the mature value through the 5th postnatal day and the duration of the postganglionic response was only 25% of the preganglionic response. Tonic postganglionic activity and response to stimuli were equivalent to those in mature rats by the 10th postnatal day. The compound action potential evoked in the postganglionic axons by direct electrical stimulation was comparable in 4-5 and 10-13 day-old rats. In the concluded that functional ganglionic neurotransmission is established in the neonatal rat between the 5th and 10th postnatal day. The relation between biochemical changes associated with maturation of the postganglionic neuron, ganglionic synaptogenisis and neurotransmission is discussed. It is concluded that synaptogenisis and onset of neurotransmission are causally associated with development of CNS regulation of postganglionic activity and end organ response rather than with maturation of the postganglionic neuron and that cholinergic excitation of the postganglionic neuron adequate to evoke action potentials is not essential to initiate maturation of the neuron.


Prevention of lidocaine aerosol-induced bronchoconstriction with intravenous lidocaine.
Lidocaine applied topically provokes bronchoconstriction in persons with hyperreactive airway disease. The authors questioned whether intravenous lidocaine would prevent lidocaine-aerosol induced bronchoconstriction. They compared the effects of lidocaine administered intravenously and by the aerosol route on baseline airway tone, and on the prevention of histamine-induced bronchoconstriction in five Basenji-Greyhound dogs. Dogs were pretreated with either intravenous or aerosol lidocaine followed by histamine aerosol challenge. On separate days, dogs were pretreated with intravenous lidocaine, followed by aerosol lidocaine administration at similar doses. Airway caliber was assessed using high-resolution computed tomography. Data were analyzed by two-way analysis of variance. Serum lidocaine concentrations were obtained. Histamine alone decreased the airway area by 32 +/- 3%. Lidocaine administered intravenously or by the aerosol route significantly inhibited histamine-induced bronchoconstriction. There was no significant difference between the two routes in preventing histamine-induced bronchoconstriction. At the dose that inhibited histamine-induced bronchoconstriction, lidocaine administered by the aerosol route decreased baseline airway area by 27 +/- 3% (P < 0.01), whereas intravenous lidocaine had no effect. Intravenous lidocaine prevented lidocaine aerosol-induced bronchoconstriction, and the combination of intravenous and aerosol lidocaine significantly dilated the airways by 20 +/- 5% (P < 0.01 compared with control). An intravenous bolus of lidocaine prevents the initial bronchoconstriction induced by lidocaine when administered as an aerosol.


Using PET/CT imaging to characterize 18 F-fluorodeoxyglucose utilization in fish.
Fish are becoming an increasingly important research species as investigators seek alternatives to mammalian models. Combined positron emission tomography/computed tomography with ¹⁸F-fluorodeoxyglucose (FDG-PET/CT) is a powerful new technology that has been extensively applied for high-resolution imaging in mammals but not fish. CT scanning provides detailed anatomical three-dimensional imaging. PET scanning detects areas of cellular activity using radio-labelled molecular probes with specific uptake rates appropriate to the tissue involved. FDG-PET is used in oncology because tissues with high glucose uptake, such as neoplasms, are intensely radio-labelled. PET/CT combines the two technologies, so that images acquired from both devices are merged into one superimposed image, thus more precisely correlating metabolic activity with anatomical three-dimensional imaging. Our objective was to determine if fish can be viable replacement animals in cancer studies using this technique by analysing the similarities between fish and humans in glucose uptake in select organs across multiple fish species. Rapid, quantifiable glucose uptake was demonstrated, particularly in brain, kidneys and liver in all imaged fish species. Standard uptake values for glucose uptake in the major organ systems of fish were more similar to those of humans than mice or dogs, indicating that fish may serve as effective alternative animal models using this technology. Applications for this technique in fish may include oncogenesis and metabolism studies as well as screening for environmental carcinogenesis.


Assessing the Effect of Clinical Inertia on Diabetes Outcomes: a Modeling Approach.
There are an increasing number of newer and better therapeutic options in the management of diabetes. However, a large proportion of diabetes patients still experience delays in intensification of treatment to achieve appropriate blood glucose targets-a phenomenon called clinical inertia. Despite the high prevalence of clinical inertia, previous research has not examined its long-term effects on diabetes-related health outcomes and mortality. We sought to examine the impact of clinical inertia on the incidence of diabetes-related complications and death. We also examined how the impact of clinical inertia would vary by the length of treatment delay and population characteristics. We developed an agent-based model of diabetes and its complications. The model was parameterized and validated by data from health surveys, cohort studies, and trials. We studied a simulated cohort of patients with diabetes in San Antonio, TX. We examined 25-year incidences of diabetes-related complications, including retinopathy, neuropathy, nephropathy, and cardiovascular disease. One-year clinical inertia could increase the cumulative incidences of retinopathy, neuropathy, and nephropathy by 7%, 8%, and 18%, respectively. The effects of clinical inertia could be worse for populations who have a longer treatment delay, are aged 65 years or older, or are non-Hispanic whites. Clinical inertia could result in a substantial increase in the incidence of diabetes-related complications and mortality. A validated agent-based model can be used to study the long-term effect of clinical inertia and, thus, inform clinicians and policymakers to design effective interventions.


[Sport and type 1 diabetes].
Physical activity is recognised to be an efficient measure in improving glycemic control in the treatment of type 2 diabetes. This evidence is lacking in type I diabetes but type 1I diabetics benefit from the same advantages like the general population. For many type I diabetics, especially younger patients, sport represents an important modality in the treatment of their disease but also of their quality of life. However, this is often a challenge for the patient as well as for the physician regarding the metabolic consequences (hypo- but also hyperglycemia) which can appear in relation with physical activity. There are existing general recommendations concerning the intake of carbohydrates and the reduction of insulin doses but those have to be adapted individually for each patient and depend significantly on different sports and on the intensity of sport.


Positron emission tomography/computed tomography and esophageal cancer in the clinical practice: How does it affect the prognosis?
The aim of this study was to assess the diagnostic value of positron emission tomography/computed tomography (PET/CT) in staging of esophageal cancer and to evaluate the prognostic role of metabolic parameters before and after neo-adjuvant treatment. Mono-institutional retrospective study. We retrospectively evaluated 29 patients who underwent PET/CT at initial staging and after neo-adjuvant therapy. Metabolic parameters were calculated: mean, average, maximum standardized uptake value (SUVmax), and total lesion glycolysis (TLG). Diagnostic advantages of PET/CT over conventional imaging (CI) were determined. The relationships between baseline and after-therapy SUVmax and TLG, change in SUV and TLG (reported as ∆) for the primary tumor and prognosis were assessed. Non-parametric statistic (e.g. Wilcoxon test and chi-square test). Twenty-nine patients were eligible for the initial staging. Thirteen patients were incorrectly staged based on CI; PET/CT was able to identify distant lymph nodes in seven patients (59%) and distant metastases in four (31%). The median SUVmax before and after neoadjuvant therapy was 10.38 and 3.53 (P = 0.0005), respectively. Only few semi-quantitative parameters obtained by PET/CT after neoadjuvant therapy seemed to have a prognostic value. TLG and ∆TLG were significantly different between disease-free and died patients (0.49 versus 15.51 and 100% versus 94%, respectively; all P = <0.05). PET/CT is confirmed as being able to detect distant metastases and to avoid unnecessary surgery. Although not routinely reported, post-neoadjuvant TLG and ∆TLG might be considered as useful prognostic parameters and should be further evaluated prospectively.


Video-Assisted Anal Fistula Treatment (VAAFT) for Complex Anal Fistula: A Preliminary Evaluation in China.
BACKGROUND Although many attempts have been made to advance the treatment of complex anal fistula, it continues to be a difficult surgical problem. This study aimed to describe the novel technique of video-assisted anal fistula treatment (VAAFT) and our preliminary experiences using VAAFT with patients with complex anal fistula. MATERIAL AND METHODS From May 2015 to May 2016, 52 patients with complex anal fistula were treated with VAAFT at Yangpu Hospital of Tongji University School of Medicine, and the clinical data of these patients were reviewed. RESULTS VAAFT was performed successfully in all 52 patients. The median operation time was 55 minutes. Internal openings were identified in all cases. 50 cases were closed with sutures, and 2 were closed with staplers. Complications included perianal sepsis in 3 cases and bleeding in another 3 cases. Complete healing without recurrence was achieved in 44 patients (84.6%) after 9 months of follow-up. No fecal incontinence was observed. Furthermore, a significant improvement in Gastrointestinal Quality of Life Index (GIQLI) score was observed from preoperative baseline (mean, 85.5) to 3-month follow-up (mean, 105.4; p<0.001), and this increase was maintained at 9-months follow-up (mean, 109.6; p<0.001). CONCLUSIONS VAAFT is a safe and minimally invasive technique for treating complex anal fistula with preservation of anal sphincter function.


A social empowerment intervention to prevent intimate partner violence against women in a microfinance scheme in Tanzania: findings from the MAISHA cluster randomised controlled trial.
Globally, about 30% of women have experienced physical or sexual violence, or both, from an intimate partner during their lifetime. Associations between poverty and women's increased risk of intimate partner violence have been observed. We therefore aimed to assess the effect of a violence prevention intervention delivered to women participating in a group-based microfinance scheme in Tanzania. We did a cluster randomised controlled trial among women taking part in a microfinance loan scheme in Mwanza city, Tanzania. A microfinance loan group was only enrolled if at least 70% of members consented. We randomly assigned the microfinance groups in blocks of six to receive either the intervention (ie, the intervention arm) or be wait-listed for the intervention after the trial (ie, the control arm). Women in both arms of the trial met weekly for loan repayments. Only those in the intervention arm participated in the ten-session MAISHA intervention that aims to empower women and prevent intimate partner violence. Given the nature of the intervention, it was not possible to mask participants or the research team. The primary outcome was a composite of reported past-year physical or sexual intimate partner violence, or both. Secondary outcome measures were past-year physical, sexual, and emotional intimate partner violence; acceptability and tolerance of intimate partner violence; and attitudes and beliefs related to intimate partner violence. These outcomes were assessed 24 months after the intervention. An intention-to-treat analysis was done, adjusting for age, education, and baseline measure of the respective outcome. The study is registered with ClinicalTrials.gov, number NCT02592252. Between September, 2014, and June, 2015, 66 (65%) of 101 microfinance groups approached in the study area met the trial eligibility criteria and were enrolled, of which 33 (n=544 women) were allocated to the intervention arm and 33 (n=505 women) to the control arm. Overall, 485 (89%) of 544 women in the intervention arm and 434 (86%) of 505 in the control arm completed the outcomes assessment. Among the intervention arm, 112 (23%) of 485 women reported past-year physical or sexual intimate partner violence, or both, compared with 119 (27%) of 434 in the control arm (adjusted odds ratio [aOR] 0·69, 95% CI 0·47-1·01; p=0·056). Women in the intervention arm were less likely to report physical intimate partner violence (aOR 0·64, 95% CI 0·41-0·99; p=0·043) and were less likely to express attitudes accepting of intimate partner violence (0·45, 0·34-0·61; p<0·0001) or beliefs that intimate partner violence is a private matter (0·51, 0·32-0·81; p=0·005) or should be tolerated (0·68, 0·45-1·01; p=0·055). There was no evidence of an effect on reported sexual or emotional intimate partner violence. There were no reports that participation in the trial had led to new episodes of violence or worsening of ongoing violence and abuse. Reported physical or sexual intimate partner violence, or both, was reduced among women who participated in the intervention arm, although the effect was greater for physical intimate partner violence, suggesting that intimate partner violence is preventable in high-risk settings such as Tanzania. Anonymous donor and STRIVE Consortium.


Synthesis of crystalline skutterudite superlattices using the modulated elemental reactant method.
A series of samples ((AB)(x)(CD)(y))(z) were prepared containing both short repeat units (AB and CD) and long repeat units ((AB)(x)(CD)(y)), where the short repeat units were designed to have the composition appropriate to form square M(4)Sb(12) skutterudites (M = Fe, Co, or Ir; square = vacancy, La, or Y). X-ray diffraction and reflectivity were used to follow the evolution of the films from amorphous, layered materials to crystalline skutterudite superlattices as a function of annealing temperature and time. In all cases, the short repeat units interdiffused and crystallized the expected skutterudite, while the long repeat period persisted after annealing. The skutterudites crystallize with random crystallographic orientation with respect to the substrate. The observed splitting of the peaks in the high-angle diffraction data from the IrSb(3)/CoSb(3) sample indicates the formation of a novel superlattice structure with each grain having a random crystallographic orientation of the skutterudite lattice with respect to the superlattice direction.


Translation Rates and Protein Folding.
The mRNA coding sequence defines not only the amino acid sequence of the protein, but also the speed at which the ribosome move along the mRNA while making the protein. The non-uniform local kinetics - denoted as translational rhythm - is similar among mRNAs coding for related protein folds. Deviations from this conserved rhythm can result in protein misfolding. In this review we summarize the experimental evidence demonstrating how local translation rates affect cotranslational protein folding, with the focus on the synonymous codons and patches of charged residues in the nascent peptide as best-studied examples. Alterations in nascent protein conformation due to disturbed translational rhythm can persist off the ribosome, as demonstrated by the effects of synonymous codon variants of several disease-related proteins. Charged amino acid patches in nascent chains also modulate translation and cotranslational protein folding, but can abrogate translation when placed at the N-terminus of the nascent peptide. During cotranslational folding, incomplete nascent chains navigate through a unique conformational landscape in which earlier intermediate states become inaccessible as the nascent peptide grows. Precisely tuned local translation rates, as well as interactions with the ribosome, guide the folding pathway towards the native structure, whereas deviations from the natural translation rhythm may favor pathways leading to trapped misfolded states. Deciphering the 'folding code' of the mRNA will contribute to understanding the diseases caused by protein misfolding and to rational protein design.


[Combination of tricyclic antidepressants and MAOI in the depressions].
This study was aimed at the assessment of therapeutic and side effects of simultaneous administration of tricyclic antidepressants and MAOI. The sample consisted of 122 patients with depressive syndromes, treated at the "Centro de Psicología Médica San Martín de Tours" (period 1970/1973), with Isocarboxazide and Trimiprimine. All patients received both drugs three times a day. The average daily dose was 20 mg of Isocarboxazide together with 125 mg of Trimiprimine. The average treatment was 70 days long. The study lead to the following conclusions: 1. There were no serious side effects. 2. The scarce side effects registered were not very different from those of the other anti-depressants. 3. The therapeutic doses were lower than those required when each drug is used alone. 4. The speed of action was higher than for each drug separately. 5. The overall percentage of improvement in patients was higher than the percentage obtained for each drug alone. 6. The lack of side effects for a theoretically risky combination of drugs is likely to be attributed to the neuroleptic action of Trimipramine.


Leukotriene B4 is the functional ligand binding to and activating the cloned chemoattractant receptor, CMKRL1.
We recently described a novel chemoattractant receptor, provisionally named CMKRL1, which has turned out to be the first cloned leukotriene (LT) receptor. Present binding assays using tritiated LTB4 and isolated membranes from COS-7 cells, transiently transfected with cDNA encoding this receptor, yielded a linear Scatchard plot showing expression of only a single, high-affinity receptor population with a mean Kd of 2.1 nM and Bmax of 17.0 pmoles/mg protein. Sham-transfected cells exhibited no specific binding. LTB4 elicited concentration-dependent increases in intracellular calcium measured with Fura-2 in individual CHO cells stably expressing CMKRL1. No response was seen with sham-transfected control cells, or in calcium-free medium which suggests that calcium mainly originates from extracellular sources. The LTB4-induced cellular calcium increment was blocked in the presence of a monoclonal antibody, raised against a synthetic peptide corresponding to the extracellular tail of CMKRL1 and capable of visualizing the receptor by fluorescence immunocytochemistry. Taken together the analyses show that LTB4 is the endogenous ligand for CMKRL1 which is, thus, identical to the LTB4 receptor, designated BLTR according to the NC-IUPHAR nomenclature.


11C-(R)-PK11195 PET imaging of microglial activation and response to minocycline in zymosan-treated rats.
We sought to advance methodology for studying microglial activation and putative therapeutic downregulation in response to minocycline by means of noninvasive in vivo imaging. A reproducible focal white matter lesion was used to reliably compare treatment conditions. The corpus callosum of female Sprague Dawley rats was injected with zymosan to promote microglial activation as confirmed by hematoxylin and eosin staining, (3)H-PK11195 autoradiography, and CD11b immunohistochemistry. A subset of subjects was treated systemically with minocycline to potentially alter microglial activation. Seven days after zymosan injection, subjects were imaged with PET using the radiotracer (11)C-(R)-PK11195. In vivo binding was evaluated using the distribution volume ratio (DVR) with respect to a reference region. At the lesion site, the observed (11)C-(R)-PK11195 DVR for each treatment was as follows: mean saline DVR ± SD, 1.17 ± 0.05 (n = 5); zymosan-only DVR, 1.96 ± 0.33 (n = 10); and zymosan with minocycline DVR, 1.58 ± 0.12 (n = 9). Therefore, compared with controls, zymosan increased binding (P = 0.0001, 2-tailed t test) and minocycline treatment reduced zymosan-induced binding by 46% (P = 0.004, 2-tailed t test). Zymosan-induced microglial activation and its response to minocycline can be quantitatively imaged in the rat brain using (11)C-(R)-PK11195 PET. The ability to detect a treatment effect in a focal white-matter lesion may be of use in studying therapies for multiple sclerosis (MS).


Insulation of the conduction pathway of muscle transverse tubule calcium channels from the surface charge of bilayer phospholipid.
Functional calcium channels present in purified skeletal muscle transverse tubules were inserted into planar phospholipid bilayers composed of the neutral lipid phosphatidylethanolamine (PE), the negatively charged lipid phosphatidylserine (PS), and mixtures of both. The lengthening of the mean open time and stabilization of single channel fluctuations under constant holding potentials was accomplished by the use of the agonist Bay K8644. It was found that the barium current carried through the channel saturates as a function of the BaCl2 concentration at a maximum current of 0.6 pA (at a holding potential of 0 mV) and a half-saturation value of 40 mM. Under saturation, the slope conductance of the channel is 20 pS at voltages more negative than -50 mV and 13 pS at a holding potential of 0 mV. At barium concentrations above and below the half-saturation point, the open channel currents were independent of the bilayer mole fraction of PS from XPS = 0 (pure PE) to XPS = 1.0 (pure PS). It is shown that in the absence of barium, the calcium channel transports sodium or potassium ions (P Na/PK = 1.4) at saturating rates higher than those for barium alone. The sodium conductance in pure PE bilayers saturates as a function of NaCl concentration, following a curve that can be described as a rectangular hyperbola with a half-saturation value of 200 mM and a maximum conductance of 68 pS (slope conductance at a holding potential of 0 mV). In pure PS bilayers, the sodium conductance is about twice that measured in PE at concentrations below 100 mM NaCl. The maximum channel conductance at high ionic strength is unaffected by the lipid charge. This effect at low ionic strength was analyzed according to J. Bell and C. Miller (1984. Biophysical Journal. 45:279-287) and interpreted as if the conduction pathway of the calcium channel were separated from the bilayer lipid by approximately 20 A. This distance thereby effectively insulates the ion entry to the channel from the bulk of the bilayer lipid surface charge. Current vs. voltage curves measured in NaCl in pure PE and pure PS show that similarly small surface charge effects are present in both inward and outward currents. This suggests that the same conduction insulation is present at both ends of the calcium channel.


Uptake of sevoflurane limited by the presence of cholesterol in the lipid bilayer membrane: a multinuclear nuclear magnetic resonance study.
The effect of cholesterol on the uptake of a fluorinated general anesthetic, sevoflurane (SF, fluoromethyl 2,2,2-trifluoro-1-[trifluoromethyl]ethyl ether) was studied by multinuclear, high-resolution nuclear magnetic resonance (NMR) spectroscopy in combination with a pulsed-field gradient technique. Using large unilamellar vesicles of egg phosphatidylcholine/egg phosphatidylglycerol/cholesterol as model fluid cell membranes, the (19)F and (1)H NMR chemical shifts, longitudinal relaxation times (T1), and diffusion coefficients (D(eff)) were systematically analyzed to quantify the modulation of SF uptake to the lipid membrane by cholesterol. All NMR parameters (chemical shift, T1, and D(eff)) showed that SF uptake is limited by the presence of cholesterol in the membrane. It was found that SF uptake at 40 mol% cholesterol is limited to 50%-60% of the partitioning fraction in the absence of cholesterol in the membrane. This finding is attributed to the loss of motional freedom in the rigid membrane environment, as demonstrated by the gradual slowdown of lipid mobility D(eff) with increase in cholesterol concentration from 0 mol% to 40 mol%.


The morbidity of cardiac nondisease revisited. Is there lingering concern associated with an innocent murmur?
The phenomenon of cardiac nondisease was first reported in 1967 to call attention to the fact that some children were being restricted from their normal activities because their parents believed that they had a heart problem when, in fact, the child's heart was perfectly normal. This influential article and others have suggested that there may be significant morbidity in children who have been found to have innocent cardiac murmurs. Parents of 71 schoolchildren were interviewed 1 to 5 years after their child had been examined by a pediatric cardiologist. Parents were asked about the presence of a family history of heart disease, their recall of the diagnosis and recommendations made by the cardiologist, and their level of satisfaction with the visit to the cardiologist. Parents were extensively questioned for evidence of restriction of the child's activities and for the presence of a belief that their child's murmur was something to still be concerned about. None of the parents reported restricting their child's activity, but 12 (17%) were still concerned about the murmur. A statistically significant relationship between parents reporting being less than "very satisfied" with the visit to the cardiologist and the presence of concern was found (P = .0006 by chi 2, Yates' correction). No other associations were noted. The association with a lower degree of satisfaction suggests that communication issues are relevant to the presence of lingering parental concern. Because the parents of a child with an innocent murmur may consider him or her to be "vulnerable," primary care physicians should follow up with parents of children referred to pediatric cardiologists for evaluation of a murmur so that any potential misunderstandings can be clarified.


Pregnancy complicated by abdominopelvic hydatid disease.
A 22-year-old second gravida presented with asymptomatic abdominal and pelvic hydatid disease at 16 weeks gestation. She opted for conservative management and was treated with oral Albendazole. She underwent elective caesarean along with cyst excision at term as the large pelvic cyst precluded vaginal delivery. A healthy baby girl weighing 2600 g with Apgar of 9, 9 at 1 and 5 min was delivered.


Glycogen determination using periodic acid-schiff: artifact of muscle preparation.
It is common practice for the staining of muscle glycogen with periodic acid-Schiff (PAS) to thaw and dry muscle sections before staining. The goal is to investigate whether this thawing step results in a systematic error that is independent of muscle fiber type and muscle physiological state. Muscle samples from six fasted male subjects were obtained before or after 3 min of high-intensity cycling. Each sample was sectioned; some sections were assessed for muscle fiber composition, and others were either thawed for 20 min or kept frozen before being PAS-stained for glycogen. The response to a 20-min freeze-thaw cycle was also assessed using rested and exercised rats as our experimental model, and the changes in glycogen were measured enzymatically. The inclusion of a 20-min thawing step resulted in a significant reduction (P < 0.05) in the weighted average of the optical density of PAS (ODPAS) staining in both the nonexercised (15 +/- 1.4%) and exercised human muscles (15 +/- 1.3%), with the absolute extent being greater in the nonexercised muscle samples (P < 0.05). Moreover, the observed decrease in ODPAS was greatest in Type IIa fibers for both the nonexercised (P < 0.05) and exercised (P < 0.05) muscle samples. The findings in rats suggest that the muscle damage associated with freeze-thawing is responsible for this stimulation of glycogenolysis. For the quantitative histochemical measurement of glycogen content in skeletal muscle, the common practice of thawing unfixed muscle sections before PAS staining should be abandoned because this causes glycogen breakdown, the extent of which varies across muscle fiber types and prior exercise history.


[Apolipoprotein E deficiency associated with type III hyperlipoproteinemia--analysis of apolipoprotein E].
The patient was a 50-year old male who was found to have a high cholesterol level during a routine health check up at work 5 years before and was examined at Keio University Hospital. Lipoprotein electrophoresis on agarose gel revealed type III hyperlipidemia, and a screening test yielded the following values (mg/dl): total cholesterol, 420; TG, 138; and HDL-cholesterol, 105. Turbidimetric immunoassay showed that the apolipoprotein E (apoE) level was below the limit of detection. Since he was 25 years old, the patient had sometimes noticed xanthomas on his knees and eyelids, and for that reason we made a diagnosis of apoE deficiency associated with type III hyperlipidemia. We tried using SDS-polyacrylamide gel electrophoresis, Western blot, and the protein chip method to detect apoE in this case, but the level was below the limit of detection by the first two methods, and it was so low that it was detected near the sensitivity limit of the protein chip method. Diet therapy, statin therapy, and fibrate therapy have been continued, and the latest data are: total cholesterol, 373; TG, 95; and HDL-cholesterol, 83. No manifestations associated with arteriosclerotic disease other than mild xanthomas have been observed.


[Comparative effectiveness of the anti-inflammatory action of diuretics and butadione in an experiment].
Dichlothiazide and butadione were shown to attenuate equally the development of the rat paw inflammatory edema induced by subplantar dextran administration. Ethacrynic acid produced more pronounced antiedematous effect. Also, ethacrynic acid reduced to the highest degree the damp and dry mass of the inflammatory granuloma. Oxadoline and butadione considerably inhibit the formation of granuloma as well. The combined use of diuretics and butadione did not lead to a mutual potentiation of the antiinflammatory effect in exudative and proliferative inflammation.


Presurgical language fMRI: Mapping of six critical regions.
Language mapping is a key goal in neurosurgical planning. fMRI mapping typically proceeds with a focus on Broca's and Wernicke's areas, although multiple other language-critical areas are now well-known. We evaluated whether clinicians could use a novel approach, including clinician-driven individualized thresholding, to reliably identify six language regions, including Broca's Area, Wernicke's Area (inferior, superior), Exner's Area, Supplementary Speech Area, Angular Gyrus, and Basal Temporal Language Area. We studied 22 epilepsy and tumor patients who received Wada and fMRI (age 36.4[12.5]; Wada language left/right/mixed in 18/3/1). fMRI tasks (two × three tasks) were analyzed by two clinical neuropsychologists who flexibly thresholded and combined these to identify the six regions. The resulting maps were compared to fixed threshold maps. Clinicians generated maps that overlapped significantly, and were highly consistent, when at least one task came from the same set. Cases diverged when clinicians prioritized different language regions or addressed noise differently. Language laterality closely mirrored Wada data (85% accuracy). Activation consistent with all six language regions was consistently identified. In blind review, three external, independent clinicians rated the individualized fMRI language maps as superior to fixed threshold maps; identified the majority of regions significantly more frequently; and judged language laterality to mirror Wada lateralization more often. These data provide initial validation of a novel, clinician-based approach to localizing language cortex. They also demonstrate clinical fMRI is superior when analyzed by an experienced clinician and that when fMRI data is of low quality judgments of laterality are unreliable and should be withheld. Hum Brain Mapp 38:4239-4255, 2017. © 2017 Wiley Periodicals, Inc.


Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells.
Pathogenic Rickettsia species belonging to the spotted fever group are arthropod-borne, obligate intracellular bacteria which exhibit preferential tropism for host microvascular endothelium in the mammalian hosts, resulting in disease manifestations attributed primarily to endothelial damage or dysfunction. Although rickettsiae are known to undergo evolution through genomic reduction, the mechanisms by which these pathogens regulate their transcriptome to ensure survival in tick vectors and maintenance by transovarial/transstadial transmission, in contrast to their ability to cause debilitating infections in human hosts remain unknown. In this study, we compare the expression profiles of rickettsial sRNAome/transcriptome and determine the transcriptional start sites (TSSs) of R. conorii transcripts during in vitro infection of human and tick host cells. We performed deep sequencing on total RNA from Amblyomma americanum AAE2 cells and human microvascular endothelial cells (HMECs) infected with R. conorii. Strand-specific RNA sequencing of R. conorii transcripts revealed the expression 32 small RNAs (Rc_sR's), which were preferentially expressed above the limit of detection during tick cell infection, and confirmed the expression of Rc_sR61, sR71, and sR74 by quantitative RT-PCR. Intriguingly, a total of 305 and 132 R. conorii coding genes were differentially upregulated (> 2-fold) in AAE2 cells and HMECs, respectively. Further, enrichment for primary transcripts by treatment with Terminator 5'-Phosphate-dependent Exonuclease resulted in the identification of 3903 and 2555 transcription start sites (TSSs), including 214 and 181 primary TSSs in R. conorii during the infection to tick and human host cells, respectively. Seventy-five coding genes exhibited different TSSs depending on the host environment. Finally, we also observed differential expression of 6S RNA during host-pathogen and vector-pathogen interactions in vitro, implicating an important role for this noncoding RNA in the regulation of rickettsial transcriptome depending on the supportive host niche. In sum, the findings of this study authenticate the presence of novel Rc_sR's in R. conorii, reveal the first evidence for differential expression of coding transcripts and utilization of alternate transcriptional start sites depending on the host niche, and implicate a role for 6S RNA in the regulation of coding transcriptome during tripartite host-pathogen-vector interactions.


Assessing granular media filtration for the removal of chemical contaminants from wastewater.
Granular media filtration was evaluated for the removal of a suite of chemical contaminants that can be found in wastewater. Laboratory- and pilot-scale sand and granular activated carbon (GAC) filters were trialled for their ability to remove atrazine, estrone (E1), 17α-ethynylestradiol (EE2), N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMOR) and N-nitrosodiethylamine (NDEA). In general, sand filtration was ineffective in removing the contaminants from a tertiary treated wastewater, with the exception of E1 and EE2, where efficient removals were observed after approximately 150 d. Batch degradation experiments confirmed that the removal of E1 was through biological activity, with a pseudo-first-order degradation rate constant of 7.4 × 10(-3) h(-1). GAC filtration was initially able to effectively remove all contaminants; although removals decreased over time due to competition with other organics present in the water. The only exception was atrazine where removal remained consistently high throughout the experiment. Previously unreported differences were observed in the adsorption of the three nitrosamines, with the ease of removal following the trend, NDEA > NMOR > NDMA, consistent with their hydrophobic character. In most instances the removals from the pilot-scale filters were generally in agreement with the laboratory-scale filter, suggesting that there is potential in using laboratory-scale filters as monitoring tools to evaluate the performance of pilot- and possibly full-scale sand and GAC filters at wastewater treatment plants.


Astragaloside IV Improves High-Fat Diet-Induced Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Rats by Regulating Inflammatory Factors Level via TLR4/NF-κB Signaling Pathway.
Objective: Astragaloside IV (AS-IV) is the primary bioactive component purified from Astragalus membranaceus which is one of the traditional Chinese medicines. Research studies found that AS-IV has significant pharmacological effects on focal cerebral ischemia/reperfusion, cardiovascular disease, pulmonary disease, liver cirrhosis, and diabetic nephropathy, but little is known about the effects of AS-IV on nonalcoholic fatty liver disease (NAFLD). In this study, we investigated whether AS-IV has beneficial effects on NAFLD in rats and its potential mechanisms. Methods: Male SD rats were fed with high-fat diet (HFD) for 12 weeks to establish NAFLD rat model, and then, the rats were divided into five groups. The control group rats were fed with normal diet for 12 weeks and then were given normal saline (1.0 ml kg-1 day-1) by intragastric administration for 4 weeks. The model group rats were fed with HFD for 12 weeks and then were given normal saline (1.0 ml kg-1 day-1) by intragastric administration for 4 weeks. The AS-IV-L, AS-IV-M, and AS-IV-H groups were treated with 20, 40, and 80 mg kg-1 day-1 of AS-IV by intragastric administration for 4 weeks and given HFD diet. Then, we detected serum transaminase (ALT, AST), blood lipid (TG, TC), inflammatory cytokines (IL-6, IL-8 and TNF-α), liver histology(NAFLD activity score), TLR4/MyD88 signaling pathway in liver tissue. Results: We found AS-IV significantly reduced serum levels of AST, ALT, TG, TNF-α, IL-6, and IL-8 in NAFLD rats and downregulate the expression of TLR4 mRNA, MyD88 mRNA, NF-κB mRNA, and proteins in liver tissue. Moreover, AS-IV could significantly reduce the NAFLD activity score of NAFLD rat liver. Conclusion: In this study, we demonstrated that AS-IV have a protective effect on NAFLD by inhibiting TNF-α, IL-6 and IL-8 levels and down-regulating TLR4, MyD88 and NF-κB expression in rat liver tissues.


Crystalline metamaterials for topological properties at subwavelength scales.
The exciting discovery of topological condensed matter systems has lately triggered a search for their photonic analogues, motivated by the possibility of robust backscattering-immune light transport. However, topological photonic phases have so far only been observed in photonic crystals and waveguide arrays, which are inherently physically wavelength scaled, hindering their application in compact subwavelength systems. In this letter, we tackle this problem by patterning the deep subwavelength resonant elements of metamaterials onto specific lattices, and create crystalline metamaterials that can develop complex nonlocal properties due to multiple scattering, despite their very subwavelength spatial scale that usually implies to disregard their structure. These spatially dispersive systems can support subwavelength topological phases, as we demonstrate at microwaves by direct field mapping. Our approach gives a straightforward tabletop platform for the study of photonic topological phases, and allows to envision applications benefiting the compactness of metamaterials and the amazing potential of topological insulators.


Increased mean platelet volume and C-reactive protein levels in patients with chronic urticaria with a positive autologous serum skin test.
Activation of the coagulation cascade resulting in thrombin production is a prominent feature of exacerbations in chronic spontaneous urticaria (CU). Autologous serum skin test (ASST) causes wheal-and-flare reactions in 30% to 50% of CU cases. The aim of this study was to evaluate the clinical and laboratory data in patients with CU with positive and negative ASST. To understand the role of platelets in CU, we investigated the relation between CU clinical severity, platelet count and their mean platelet volume (MPV). Clinical and laboratory data were prospectively collected from 373 patients with CU who attended our Allergy and Clinical immunology Clinic during the period 2003 to 2007. The laboratory data were compared with 46 healthy subjects. There were no significant differences in platelet counts between the groups, nevertheless the platelets in ASST-positive CU patients were characterized by a higher MPV (9.12 +/- 1.25 fl), than that in ASST-negative patients (7.95 +/- 1.08 fl; P = 0.039) and control group (7.72 +/- 1.04 fl; P = 0.007). There was a significant positive correlation between CU severity score and MPV in ASST-positive patients (r = 0.44; P < 0.001) but not in ASST-negative patients. Higher levels of C-reactive protein (5.31 +/- 2.74 mg/L) were measured in the ASST-positive CU group compared with the ASST-negative CU group (2.53 +/- 1.27; P = 0.029) and the control group (2.34 +/- 1.38; P = 0.003). CU with positive ASST is characterized with higher clinical severity, increased MPV and C-reactive protein.


A fast minimum variance beamforming method using principal component analysis.
Minimum variance (MV) beamforming has been studied for improving the performance of a diagnostic ultrasound imaging system. However, it is not easy for the MV beamforming to be implemented in a real-time ultrasound imaging system because of the enormous amount of computation time associated with the covariance matrix inversion. In this paper, to address this problem, we propose a new fast MV beamforming method that almost optimally approximates the MV beamforming while reducing the computational complexity greatly through dimensionality reduction using principal component analysis (PCA). The principal components are estimated offline from pre-calculated conventional MV weights. Thus, the proposed method does not directly calculate the MV weights but approximates them by a linear combination of a few selected dominant principal components. The combinational weights are calculated in almost the same way as in MV beamforming, but in the transformed domain of beamformer input signal by the PCA, where the dimension of the transformed covariance matrix is identical to the number of some selected principal component vectors. Both computer simulation and experiment were carried out to verify the effectiveness of the proposed method with echo signals from simulation as well as phantom and in vivo experiments. It is confirmed that our method can reduce the dimension of the covariance matrix down to as low as 2 × 2 while maintaining the good image quality of MV beamforming.


Conjunctival goblet cell secretion stimulated by leukotrienes is reduced by resolvins D1 and E1 to promote resolution of inflammation.
The conjunctiva is a mucous membrane that covers the sclera and lines the inside of the eyelids. Throughout the conjunctiva are goblet cells that secrete mucins to protect the eye. Chronic inflammatory diseases such as allergic conjunctivitis and early dry eye lead to increased goblet cell mucin secretion into tears and ocular surface disease. The purpose of this study was to determine the actions of the inflammatory mediators, the leukotrienes and the proresolution resolvins, on secretion from cultured rat and human conjunctival goblet cells. We found that both cysteinyl leukotriene (CysLT) receptors, CysLT(1) and CysLT(2,) were present in rat conjunctiva and in rat and human cultured conjunctival goblet cells. All leukotrienes LTB(4), LTC(4), LTD(4), and LTE(4), as well as PGD(2), stimulated goblet cell secretion in rat goblet cells. LTD(4) and LTE(4) increased the intracellular Ca(2+) concentration ([Ca(2+)](i)), and LTD(4) activated ERK1/2. The CysLT(1) receptor antagonist MK571 significantly decreased LTD(4)-stimulated rat goblet cell secretion and the increase in [Ca(2+)](i). Resolvins D1 (RvD1) and E1 (RvE1) completely reduced LTD(4)-stimulated goblet cell secretion in cultured rat goblet cells. LTD(4)-induced secretion from human goblet cells was blocked by RvD1. RvD1 and RvE1 prevented LTD(4)- and LTE(4)-stimulated increases in [Ca(2+)](i), as well as LTD(4) activation of ERK1/2. We conclude that cysteinyl leukotrienes stimulate conjunctival goblet cell mucous secretion with LTD(4) using the CysLT(1) receptor. Stimulated secretion is terminated by preventing the increase in [Ca(2+)](i) and activation of ERK1/2 by RvD1 and RvE1.


Prognostic and predictive value of YKL-40 in stage IIB-III melanoma.
This study investigates the prognostic and predictive value of YKL-40 in stage IIB-III melanoma patients who were randomized to adjuvant interferon α-2b (IFN) or observation. Serum YKL-40 was determined postoperatively in patients from the Nordic IFN Trial (n=602), EORTC 18952 (n=246), and EORTC 18991 (n=386) (EORTC, European Organisation for Research and Treatment of Cancer). YKL-40 protein expression was determined in 300 tissue sections of primary melanoma or lymph node metastases from 204 Danish patients from the Nordic IFN Trial. Multivariate Cox analysis (including sex, age, stage, ulceration, YKL-40) showed that elevated baseline YKL-40 level was associated with shorter overall survival (OS) in observation groups from the Nordic IFN Trial and EORTC 18952 [hazard ratio (HR)=1.33; 95% confidence interval (CI) 1.01-1.74; P=0.04], but not in the interferon groups (1-year IFN: HR=0.97; 95% CI 0.76-1.25; P=0.83; 2-years IFN: HR=1.06; 95% CI 0.83-1.34; P=0.64). During follow-up, increases in YKL-40 were significantly associated with shorter OS, but not with recurrence-free survival in univariate analysis. YKL-40 expression was stronger in tumor-associated macrophages than melanoma cells in primary melanoma. High YKL-40 expression in macrophages in lymph node metastases was associated with shorter OS in the observation group (HR=2.76; 95% CI: 1.13-6.76, P=0.02), but not in the interferon-treated groups. YKL-40 was an independent prognostic biomarker of OS in melanoma patients stage IIB-III. High serum YKL-40 in poor-prognosis patients may originate from macrophages in the tumor microenvironment and the melanoma cells. Furthermore, we hypothesize that elevated serum YKL-40 after surgery may predict the efficacy of adjuvant IFN treatment.


SPEDEN: reconstructing single particles from their diffraction patterns.
SPEDEN is a computer program that reconstructs the electron density of single particles from their X-ray diffraction patterns, using a single-particle adaptation of the holographic method in crystallography [Szöke, Szöke & Somoza (1997). Acta Cryst. A53, 291-313]. The method, like its parent, is unique because it does not rely on 'back' transformation from the diffraction pattern into real space and on interpolation within measured data. It is designed to deal successfully with sparse, irregular, incomplete and noisy data. It is also designed to use prior information for ensuring sensible results and for reliable convergence. This article describes the theoretical basis for the reconstruction algorithm, its implementation, and quantitative results of tests on synthetic and experimentally obtained data. The program could be used for determining the structures of radiation-tolerant samples and, eventually, of large biological molecular structures without the need for crystallization.


The Tomita collection of medaka pigmentation mutants as a resource for understanding neural crest cell development.
All body pigment cells in vertebrates are derived from the neural crest. In fish the neural crest can generate up to six different types of pigment cells, as well as various non-pigmented derivatives. In mouse and zebrafish, extensive collections of pigmentation mutants have enabled dissection of many aspects of pigment cell development, including fate specification, survival, proliferation and differentiation. A collection of spontaneous mutations collected from wild medaka (Oryzias latipes) populations and maintained at Nagoya University includes more than 40 pigmentation mutations. The descriptions of their adult phenotypes have been previously published by Tomita and colleagues (summarised in Medaka (Killifish) Biology and Strains, 1975), but the embryonic phenotypes have not been systematically described. Here we examine these embryonic phenotypes, paying particular attention to the likely defect in pigment cell development in each, and comparing the spectrum of defects to those in the zebrafish and mouse collections. Many phenotypes parallel those of identified zebrafish mutants, although pigment cell death phenotypes are largely absent, presumably due to the different selective pressures under which the mutants were isolated. We have identified mutant phenotypes that may represent the Mitf/Kit pathway of melanophore specification and survival. We use in situ hybridisation with available markers to confirm a key prediction of this hypothesis. We also highlight a set of novel phenotypes not seen in the zebrafish collection. These mutants will be a valuable resource for pigment cell and neural crest studies and will strongly complement the mutant collections in other vertebrates.


Association of Group B Streptococcus colonization and bovine exposure: a prospective cross-sectional cohort study.
While Group B Streptococcus (GBS) human colonization and infection has long been suspected as originating from cows, several investigators have suggested that ongoing interspecies GBS transmission is unlikely due to genotyping data demonstrating that human and bovine-derived GBS strains represent mostly distinct populations. The possibility of ongoing transmission between humans and their livestock has not been systematically examined. To examine ongoing interspecies transmission, we conducted a prospective cross-sectional cohort study of 68 families and their livestock. Stool specimens were collected from 154 people and 115 livestock; GBS was detected in 19 (12.3%) humans and 2 (1.7%) animals (bovine and sheep). Application of multilocus sequence typing (MLST) identified 8 sequence types (STs or clones), with STs 1 and 23 predominating. There were 11 families in which two members submitted stools and at least one had GBS colonization. In 3 of these families, both members (consisting of couples) were colonized, yielding a co-colonization rate of 27% (95% CI: 7%-61%). Two of these couples had strains with identical MLST, capsule (cps) genotype, susceptibility, and RAPD profiles. One couple co-colonized with ST-1 (cps5) strains also had a bovine colonized with the identical strain type. On multivariate analysis of questionnaire data, cattle exposure was a predictor of GBS colonization, with each unit increase in days of cattle exposure increasing the odds of colonization by 20% (P = 0.02). These results support interspecies transmission with additional evidence for transmission provided by the epidemiological association with cattle exposure. Although GBS uncommonly colonizes livestock stools, increased frequency of cattle exposure was significantly associated with human colonization and one couple shared the same GBS strains as their bovine suggesting intraspecies transmission. These results set the framework for GBS as a possible zoonotic infection, which has significant public health implications.


Quality of Reduction of Displaced Intra-articular Calcaneal Fractures Using a Sinus Tarsi Versus Extensile Lateral Approach.
To evaluate the difference in the quality of fracture reduction between the sinus tarsi approach (STA) and extensile lateral approach (ELA) using postoperative Computed Tomography (CT) scans in displaced intra-articular calcaneal fractures (DIACFs). Retrospective. Level 1 and level 2 academic centers. Consecutive patients undergoing operative fixation of DIACFs with postoperative CT scans and standard radiographs. Patients were identified based on Current Procedural Terminology code and chart review. All operative calcaneal fractures treated between 2012 and 2018 by fellowship-trained orthopaedic trauma surgeons were evaluated. Those with both postoperative CT scans and radiographs were included. Exclusion criteria included extra-articular fractures, malunions, percutaneous fixation, ORIF and primary fusion, and those patients without a postoperative CT scan. The Sanders classification was used. Cases were divided into 2 groups based on ELA versus STA. Bohler angle and Gissane angle were evaluated on plain radiographs. CT reduction quality grading included articular step off/gap within the posterior facet, and varus angulation of the tuberosity: CT reduction grading included: excellent (E): no gap, no step, and no angulation; good (G): <1 mm step, <5 mm gap, and/or <5° of angulation, fair (F): 1-3 mm step, 5-10 mm gap, and/or 5-15° angulation; and poor (P): >3 mm step, >10 mm gap, and/or >15° angulation. Seventy-seven patients with 83 fractures were included. Average age was 42 years (range, 18-74 years), with 57 men. Four fractures were open. There were 37 Sanders II and 46 Sanders III fractures; 36 fractures were fixed using the STA, whereas 47 used the ELA. Average days to surgery were 5 for STA and 14 for ELA (P < 0.001). A normal Bohler angle was achieved more often with the ELA (91.5%) than with STA (77.8%) (P < 0.001). There was no difference by approach for Gissane angle (P = 0.5). ELA had better overall reduction quality (P = 0.02). For Sanders II, there was no difference in reduction quality with STA versus ELA (P = 0.51). For Sanders III, ELA trended toward better reduction quality (P = 0.06). The ELA had a better overall reduction of Bohler angle on plain radiographs and of the posterior facet and tuberosity on postoperative CT scans. For Sanders type II DIACFs, there was no difference between STA and ELA. Importantly, for Sanders III DIACFs, ELA trended toward better reduction quality. In addition to fracture reduction, surgeon learning curve, early wound complications, and long-term outcomes must be considered in future studies comparing the ELA and STA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Movement ability of rye terminal neocentromeres.
Rye terminal neocentromeres were analyzed in various aspects. Plants with and without neocentromeres were crossed to determine the possible genetic control on their formation. The segregation obtained in our work is consistent with the hypothesis of two trans-acting genes determining neocentric activity in such a way that individuals with no neocentromeres at all would carry all non-activating alleles, whereas one activating allele might permit the activation of a few neocentromeres. Individuals with four activating alleles would show the maximum frequency of neocentromeres per cell. Anti-tubulin immunolabelling was used to visualize the interaction between the neocentromeres and the microtubules. In most cases an end-on interaction between neocentromeres and microtubules was observed, but a few neocentromeres were observed free of them. Spikes were irradiated at early meiosis to determine whether acentric fragments carrying subtelomeric heterochromatin were able to behave as neocentromeres. In no case were acentric fragments observed to form an extension polewards as they did in whole chromosomes. Broken chromosomes joined by a thin thread of chromatin to the centromeric region


Buspirone, Parkinson's disease, and the locus ceruleus.
Buspirone is a novel anxiolytic whose pharmacological profile differs from that of the benzodiazepines and includes dopaminergic agonist effects. Because of these properties, buspirone's usefulness in the management of idiopathic Parkinson's disease was evaluated in a controlled study of 16 outpatients with stage I-IV disease. At doses of 10 to 60 mg/day, no significant group or individual effects could be discerned on standardized disability, dyskinesia, anxiety, or depression scales. At high dose levels (100 mg/day) however, there was a significant worsening of disability ratings and a decrease in dyskinesia scores; anxiety ratings were also significantly increased. The results indicate that buspirone is well tolerated by parkinsonian patients at conventional antianxiety doses of 10 to 40 mg. Clinical effects of high dose treatment, on the other hand, resemble those associated with a reduction in central dopamine mediated synaptic function. Since buspirone reportedly produces dose-dependent stimulation of norepinephrine containing neurons in the locus ceruleus and behavioral symptoms of such activation were observed, these clinical observations support the concept that central noradrenergic stimulation can adversely affect parkinsonian symptoms.


Immunopotentiating and immunotherapeutic effects of thymic hormones and factors with special emphasis on thymic humoral factor THF-gamma2.
The essential role played by the thymus in the development of the immune response was well documented in many publications. These findings prompted a long series of studies devised to define the factors produced and secreted by thymus cells, which are involved in the development and nature of immunological responsiveness. First experiments done with crude thymus extracts were followed by isolation of purified products and finally by chemical characterization and synthesis of immunologically active thymus-derived peptides. In this article we review the various thymic hormones and factors described, that is, thymosin fractions 5, the thymosins, prothymosin alpha, thymulin (FTS-Zn), thymopoietin, thymostimulin (TP-1), Thymic humoral factor (THF), and THF-gamma2. Studies demonstrating the activity of the various thymic factors in increasing the immunocompetence potential in both in vitro and in vivo conditions are discussed. The immunostimulatory potential of thymic factors was also investigated in experimental models where beneficial therapeutic effects were sought in a situation of immunological malfunction. The last part of the review is dedicated to clinical trials with thymic factors that revealed improvement in the immunocompetence potential in cases of immunodeficiencies, viral infections, and cancer and its correlation with therapeutic effectiveness. It seems that more research is required in order to better define conditions for the use of thymic factors in immunotherapy.


Novel Sp family-like transcription factors are present in adult insect cells and are involved in transcription from the polyhedrin gene initiator promoter.
We earlier documented the involvement of a cellular factor, polyhedrin (polh) promoter-binding protein, in transcription from the Autographa californica nuclear polyhedrosis virus polh gene promoter. Sequences upstream of the polh promoter were found to influence polh promoter-driven transcription. Analysis of one such region, which could partially compensate for the mutated polh promoter and also activate transcription from the wild-type promoter, revealed a sequence (AcSp) containing a CACCC motif and a loose GC box resembling the binding motifs of the transcription factor Sp1. AcSp and the consensus Sp1 sequence (cSp) specifically bound factor(s) in HeLa and Spodoptera frugiperda (Sf9) insect cell nuclear extracts to generate identical binding patterns, indicating the similar nature of the factor(s) interacting with these sequences. The AcSp and cSp oligonucleotides enhanced in vivo expression of a polh promoter-driven luciferase gene. In vivo mopping of these factor(s) significantly reduced transcription from the polh promoter. Recombinant viruses carrying deletions in the upstream AcSp sequence confirmed the requirement of these factor(s) in polh promoter-driven transcription in the viral context. We demonstrate for the first time DNA-protein interactions involving novel members of the Sp family of proteins in adult insect cells and their involvement in transcription from the polh promoter.


Prinzmetal's angina with documented coronary artery spasm. Treatment and follow-up.
Eighteen patients with Prinzmetal's angina were studied angiographically and 17 were followed for an average of 27 months. The were 12 men and six women, with a mean age of 46.3 years. The mean duration of symptoms before clinical diagnosis was 4.1 weeks. Four had had a previous myocardial infarction. Six patients had spontaneous cardiac arrests within 48 hours of diagnosis and hospital admission. At coronary arteriography, 10 patients had significant coronary artery disease; two of these had coronary artery spasm. The remaining eight patients had normal cornary arteries with significant coronary artery spasm at arteriography. Angiographic mitral valve prolapse was found in eight patients; seven of these had inferior ST segment elevation with pain. Six of the 10 patients with significant coronary artery disease had aortocoronary bypasses performed with good results. Ten of the remaining 11 patients who were treated medically had their symptoms controlled with oral isosorbide dinitrate alone or in combination with propranolol, nifedipine or perhexiline but propranolol may have an adverse effect. Though the initial clinical course in untreated patients was unfavourable, progress after starting treatment was good, with no further cardiac arrests, myocardial infarctions, or deaths.


High blood pressure and colorectal cancer mortality in a 29-year follow-up of the Japanese general population: NIPPON DATA80.
Onco-hypertension has been proposed, although associations of high blood pressure (BP) with cancer risk remain inconsistent. We examined associations of high BP with risk of mortality from stomach, lung, colorectal, liver, and pancreatic cancers independent of possible confounders in an analysis that excluded deaths within the first 5 years of follow-up to consider the reverse causality. In a prospective cohort representative of the general Japanese population (1980-2009), we studied 8088 participants (mean age, 48.2 years; 56.0% women) without clinical cardiovascular disease or antihypertensive medication at baseline. Fine-Gray competing risks regression was used to estimate hazard ratios for 10 mmHg higher BP adjusted for confounders including smoking, alcohol-drinking, obesity, and diabetes mellitus. During 29-year follow-up, 159 (2.0%), 159 (2.0%), 89 (1.1%), 86 (1.1%), and 68 (0.8%) participants died from stomach, lung, colorectal, liver, and pancreatic cancers, respectively. We observed a positive association of high BP with risk of colorectal cancer mortality but not with mortality risks from any other cancers. The association with colorectal cancer mortality for systolic and diastolic BP was evident in those aged 30-49 years (hazard ratios 1.43 [95% confidence interval, 1.22-1.67] and 1.86 [1.32-2.62], respectively) but not in those aged 50-59 years and ≥60 years (P for age interaction <0.01 for systolic and diastolic BP). The associations with colorectal cancer mortality were similar in the analyses stratified by smoking, alcohol-drinking, obesity, and diabetic status. In conclusion, high BP among young to middle-aged adults was independently associated with risk of colorectal cancer mortality later in life.


Prioritizing vulnerable children: why should we address inequity?
Children and young people from vulnerable population groups, including Indigenous Australians, those in out of home care, those with disabilities and those from refugee families, have difficulties in accessing health services and are at high risk of adverse outcomes, driving population health inequity. Although heterogeneous, these groups face common disadvantage and shared challenges in health service utilization. This study aims to analyse the demographics of vulnerable child populations in NSW, the rationale for focussing on their health needs and strategies for addressing population health inequity. A literature review was undertaken on vulnerable child populations and successful strategies for improving their health outcomes. NSW data on vulnerable children were collated. Vulnerable children in NSW are estimated to comprise 10-20% of the childhood population. Efforts to improve their health and well-being can be justified based on child rights, a focus on equity and effectiveness of care, public opinion and the evidence base supporting such interventions. Targeted (subpopulation specific) interventions and delivery of universally applied (population wide) strategies that disproportionately benefit vulnerable populations have been shown to be effective in reducing healthcare disparities. Most available information relates to specific vulnerable population groups. However, some effective strategies and key principles are broadly applicable to the vulnerable child population as a whole. Vulnerable children should be a key focus of healthcare interventions if inequities are to be addressed.


Gene expression profile of zebrafish exposed to hypoxia during development.
Understanding how vertebrates respond to hypoxia can have important clinical implications. Fish have evolved the ability to survive long exposure to low oxygen levels. However, little is known about the specific changes in gene expression that result from hypoxia. In this study we used a zebrafish cDNA microarray to examine the expression of >4,500 genes in zebrafish embryos exposed to 24 h of hypoxia during development. We tested the hypotheses that hypoxia changes gene expression profile of the zebrafish embryos and that these changes can be reverted by reexposure to a normoxic (20.8% O(2)) environment. Our data were consistent with both of these hypotheses: indicating that zebrafish embryos undergo adaptive changes in gene expression in response to hypoxia. Our study provides a striking genetic portrait of the zebrafish embryos' adaptive responses to hypoxic stress and demonstrates the utility of the microarray technology as a tool for analyzing complex developmental processes in the zebrafish.


Emotion in languaging: languaging as affective, adaptive, and flexible behavior in social interaction.
This article argues for a view on languaging as inherently affective. Informed by recent ecological tendencies within cognitive science and distributed language studies a distinction between first order languaging (language as whole-body sense making) and second order language (language as system like constraints) is put forward. Contrary to common assumptions within linguistics and communication studies separating language-as-a-system from language use (resulting in separations between language vs. body-language and verbal vs. non-verbal communication etc.) the first/second order distinction sees language as emanating from behavior making it possible to view emotion and affect as integral parts languaging behavior. Likewise, emotion and affect are studied, not as inner mental states, but as processes of organism-environment interactions. Based on video recordings of interaction between (1) children with special needs, and (2) couple in therapy and the therapist patterns of reciprocal influences between interactants are examined. Through analyzes of affective stance and patterns of inter-affectivity it is exemplified how language and emotion should not be seen as separate phenomena combined in language use, but rather as completely intertwined phenomena in languaging behavior constrained by second order patterns.


A novel class of inhibitors for human steroid 5 alpha-reductase: phenoxybenzoic acid derivatives. I.
In a search for novel nonsteroidal inhibitors of human prostatic 5 alpha-reductase, we found a new series of phenoxybenzoic acid derivatives to be potent human prostatic 5 alpha-reductase inhibitors. Among them, 4-(biphenyl-4-yloxy)benzoic acid derivatives (2n, YM-31758), 2o and 2s showed more potent inhibitory activities than finasteride with IC50 values of 0.87, 0.67 and 0.56 nM, respectively. The optimized structures for the phenoxybenzoic acid derivatives 2d-2i were calculated by molecular modeling analysis, and the favorable distance between the carbon of the carboxyl group and the centroid of the phenyl group (benzene ring C) was found to be in the 9-11 A range.


[Effects of sodium molybdate on guinea pig atria contractility].
Sodium molybdate (Mo) 10-1000 mumol/L markedly reduced the contratile force of left atria isolated from guinea pig. Mo 100 mumol/L obviously reduced the heart rates in right atria, markedly prolonged the functional refractory period from 185 +/- 12 to 245 +/- 4 ms and inhibited the resting potentiation. Mo 100 and 300 mumol/L reduced the frequency-dependent positive staircase phenomenon. However, verapamil 25 mumol/L reversed the frequency-dependent positive staircase phenomenon to negative one. The mechanism can be explained by the effect on Ca2+ movement in the heart atrium.