Correlation of sidelobe suppression between rugate filters and multilayer mirrors.
We present the study of the correlation between refractive index profiles and the optical response of rugate filters and multilayer mirrors. The conventionally used method in multilayer mirrors for ripple suppression in the passband will be compared with a similar simple method to remove the rugate filter sidelobes without apodization. The resulting layers are compared in performance with a typical quintic matching layer. An example based on silicon oxynitride alloys with refractive indices ranging between 1.47 and 1.83 was designed and deposited.


Psychiatric adverse events during vigabatrin therapy.
To determine the incidence of psychiatric adverse events associated with vigabatrin therapy, we reviewed data from US and non-US double-blind, placebo-controlled trials of vigabatrin as add-on therapy for treatment-refractory partial epilepsy. "Verbatim" terms from investigators' reports had been translated into standard "preferred" terms using an adverse event dictionary. Terms for psychiatric events were then combined into categories for analysis of rates during vigabatrin versus placebo treatment. Compared with placebo, vigabatrin subjects had a higher incidence of events coded as depression (12.1% versus 3.5%, p < 0.001) and psychosis (2.5% versus 0.3%, p = 0.028); there were no significant differences between treatment groups for aggressive reaction, manic symptoms, agitation, emotional lability, anxiety, or suicide attempt. Although depression and psychosis were typically observed during the first 3 months, most studies were 12 to 18 weeks long, so that definitive conclusions could not be reached about timing of events. Psychosis was generally transient and reported to be responsive to reduction or discontinuation of vigabatrin or to neuroleptic treatment. Depression was typically mild. Serious depression, defined as discontinued from the study, hospitalized, or suicide attempt, or coded as psychotic depression, occurred in only 9 of the 49 vigabatrin-treated patients with depression. Vigabatrin use in treatment-refractory partial epilepsy is associated with increased occurrence of depression and of psychosis, although the frequency of psychosis is apparently lower than previously reported. Clinical experience suggests that these adverse events respond to reduction of vigabatrin dose or to counteractive psychotropic treatment.


Association of host cell endoplasmic reticulum and mitochondria with the Toxoplasma gondii parasitophorous vacuole membrane: a high affinity interaction.
The parasitophorous vacuole membrane (PVM) of the obligate intracellular protozoan parasite Toxoplasma gondii forms tight associations with host mitochondria and the endoplasmic reticulum (ER). We have used a combination of morphometric and biochemical approaches to characterize this unique phenomenon, which we term PVM-organelle association. The PVM is separated from associated mitochondria and ER by a mean distance of 12 and 18 nm, respectively. The establishment of PVM-organelle association is dependent on active parasite entry, but does not require parasite viability for its maintenance. Association is not a consequence of spatial constraints imposed on the growing vacuole. Morphometric analysis indicates that the extent of mitochondrial association with the PVM stays constant as the vacuole enlarges, whereas the extent of ER association decreases. Disruption of host cell microtubules partially blocks the establishment but not the maintenance of PVM-mitochondrial association, and has no significant effect on PVM-ER association. PVM-organelle association is maintained following disruption of infected host cells, as assessed by electron microscopy and by sub-cellular fractionation showing co-migration of fixed PVM and organelle markers. Taken together, the data suggest that a high affinity, potentially protein-protein interaction between parasite and organelle components is responsible for PVM-organelle association.


Obesity, confidant support and functional health: cross-sectional evidence from the EPIC-Norfolk cohort.
To investigate the association between body mass index (BMI) and functional health according to age and the support available from a close confidant. A cross-sectional population-based study. A total of 20 921 participants in the European Prospective Investigation into Cancer and Nutrition, aged 41-80 y resident in Norfolk, England. Standardised clinic-based assessment of BMI, self-reported functional health status assessment (according to the anglicised Short Form 36 (SF-36) Health Survey questionnaire) and the availability (and quality) of a close confiding relationship. Self-reported physical functioning declined steadily with increasing age. Obesity (BMI >/=30) was strongly associated with self-reported physical functional health, equivalent to being 11 y older for men and 16 y older for women (after adjustment that included prevalent chronic physical conditions and cigarette smoking). This adverse effect of obesity on physical functional health was found to increase with age for both men and women. Perceived inadequacy of a confiding relationship was associated with reduced physical functional capacity, equivalent to being 4 y older for men and 5 y older for women. For those with markedly inadequate confidant relationships, the impact of obesity on physical functional capacity was approximately constant by age. For those not critical of the adequacy of their confiding relationships, the impact of obesity was least for those younger but rose to equivalent levels as those with markedly inadequate confidant relationships among older participants. The availability of a close confidant relationship (perceived as uncritical and characterised by the absence of shared negative interactions) may delay the impact of obesity in reducing physical functional capacity.


InstantLabs® E. coli O157 Food Safety Kit.
The InstantLabs® E. coli O157 Food Safety Kit was validated against the International Organization for Standardization reference method 16654 for the detection of Escherichia coli O157. The matrixes, raw ground beef, raw beef trim, Romaine lettuce, pasteurized apple juice, and raw ground chicken, were inoculated with appropriate CFU/test portion of E. coli O157 to generate fractional positives (5-15) in 20 inoculated samples. The matrixes were co-inoculated with Salmonella at 2-5 times the level of E. coli O157 to demonstrate the potential for using the same enrichment culture for the detection of multiple organisms. Samples were enriched in prewarmed FASTGRO SE broth at 42±1°C for 10-20 h. All samples were confirmed using the ISO reference method, regardless of initial screen result. The InstantLabs test method performed as well as or better than the reference method for the detection of E. coli O157 in all tested samples. Inclusivity and exclusivity testing revealed no false negatives and no false positives among the 50 E. coli O157 serovars and 30 non-E. coli O157 species examined. Finally, the method was shown to be robust when variations were applied to enrichment time, volume for DNA extraction, and heat block time.


Real-world effectiveness of risankizumab in patients with moderate-to-severe psoriasis using the CorEvitas Psoriasis Registry.
Psoriasis, an inflammatory skin disease, is often treated with biologic therapeutics. To determine the real-world treatment effectiveness of risankizumab, an interleukin-23 inhibitor, in the treatment of moderate-to-severe plaque psoriasis. A retrospective, observational study was conducted using the CorEvitas Psoriasis Registry for eligible adults with a diagnosis of moderate-to-severe psoriasis and persistent use of risankizumab at 12 (±3) months after initiation. Skin clearance measures and patient-reported outcomes were analyzed for the entire study population and by prior biologic treatment. Among 287 patients with persistent risankizumab use at 1 year, most achieved clear or clear/almost clear skin and reported significant reductions in Dermatology Life Quality Index scores, psoriasis symptoms (fatigue, skin pain, and overall itch), and work and activity impairment. The CorEvitas Psoriasis Registry is not necessarily representative of all adults with psoriasis in the United States and Canada and does not measure patient adherence. Patients treated with risankizumab, regardless of prior treatment, achieved high levels of clear and clear/almost clear skin, Dermatology Life Quality Index scores of 0/1, and significant reductions in psoriasis symptoms (fatigue, skin pain, and overall itch) and work and activity impairment 1 year after initiation.


A Space-Refine Paradigm for Automatic Carotid Artery Centerline Extraction in Magnetic Resonance Imaging.
Vessel centerline extraction is essential for carotid stenosis assessment and atherosclerotic plaque identification in clinical diagnosis. Simultaneously, it provides a region of interest identification and boundary initialization for computer-assisted diagnosis tools. In magnetic resonance imaging (MRI) cross-sectional images, the lumen shape and vascular topology result in a challenging task to extract the centerline accurately. To this end, we propose a space-refine framework, which exploits the positional continuity of the carotid artery from frame to frame to extract the carotid artery centerline. The proposed framework consists of a detector and a refinement module. Specifically, the detector roughly extracts the carotid lumen region from the original image. Then, we introduce a refinement module that uses the cascade of regressors from a detector to perform sequence realignment of lumen bounding boxes for each subject. It improves the lumen localization results and further enhances the centerline extraction accuracy. Verified by large carotid artery data, the proposed framework achieves state-of-the-art performance compared to conventional vessel centerline extraction methods or standard convolutional neural network approaches.Clinical relevance- Our proposed framework can be used as an important aid for physicians to quantitatively analyze the carotid artery in clinical practice. It is also used as a new paradigm for extracting the centerline of carotid vessels in computer-assisted tools.


Acute effects of hemodialysis on pulmonary function in patients with end-stage renal disease.
Despite many beneficial effects, hemodialysis may cause pulmonary dysfunction. On the other hand, patients with end-stage renal disease are potentially prone to lung edema and respiratory dysfunction. This study was conducted to evaluate the alterations of pulmonary function indicators after hemodialysis, measured by spirometry. A total of 26 patients on hemodialysis for at least 3 months were studied. They were all older than 18 years old. None of the patients was a current or recent smoker, and none of them had a history of respiratory diseases, current or recent respiratory infections, musculoskeletal disorders, or tuberculosis. All of the patients underwent the spirometry test before and after a 4-hour hemodialysis session, and the forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), vital capacity (VC), and FEV1/FVC ratio were measured. After hemodialysis, the FVC significantly increased (P = .02), while no significant improvement in the FEV1, VC, and FEV1/FVC ratio were observed. Gender was related to the changes in VC, with better results in women (P < .001). There was no association between the changes in spirometry parameters and age, body mass index, cause of kidney failure, type of anion used for hemodialysis, and weight changes. According to our results, pulmonary function, especially the FVC, improves after a session of hemodialysis.


Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma.
Endometrial adenocarcinoma is a common gynaecological cancer, but a comparatively small proportion of patients present with or develop recurrent or advanced disease. Progestogens are widely used, with little evidence of their efficacy. Co-morbidity including obesity and cardiac disease and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents. To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma. The major medical literature databases were searched for all known randomised controlled trials (RCTs), as were trials registers and reference lists of relevant publications. RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded. Data were extracted from the papers by reviewers and authors of included studies contacted for further information. Eleven eligible trials were identified which entered 2288 patients between 1974 and 2000. A meta-analysis of the 6 trials comparing more with less chemotherapy with combination was possible and included 1135 patients. Progression-free survival (PFS) was significantly improved (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI) 0.71 to 0.90, p = 0.004), but there was only a trend toward improved survival (HR = 0.90, 95% CI 0.80 to 1.03). Toxicity was in general higher with the combination chemotherapy regimens. Only one trial showed a significant survival benefit from the addition of paclitaxel to combination chemotherapy, but this was at the expense of increased toxicity. There was insufficient evidence to assess whether there was any benefit from cytotoxic chemotherapy in terms of symptom control or quality of life (QOL) compared with best supportive care. There were no comparative trials of chemotherapy with endocrine therapy The optimum cytotoxic drug regimen for advanced endometrial adenocarcinoma has still to be defined although our review suggests that it may contain paclitaxel or platinum. These mainly North American and European trial populations represent a highly selected subgroup of the 10, 000 women dying annually from this disease. Future trials should include measures of QOL and symptom control in addition to PFS and overall survival (OS). They should should also consider comparison of of endocrine therapy and cytotoxic chemotherapy in patients with no prior drug therapy. Stratification of patients should take into account other prognostic factors including co-morbidity and prior radiation treatment.


Two-dimensional guided mode resonance filters fabricated in a uniform low-index material system.
We demonstrate the fabrication, simulation, and experimental results of a buried, homogeneous narrowband spectral filter with a periodic, hexagonal unit cell of air pockets, encapsulated in a fused silica substrate. The leaky waveguide is formed by depositing SiO(x) on an etched fused silica grating via plasma-enhanced chemical vapor deposition. Design principles of guided mode resonance filters were utilized to achieve a resonance with 60% reflectivity at a wavelength of 1.741 μm. The device demonstrates resonance with FWHM of 6 nm.


Cardioprotective actions of specific thromboxane receptor antagonist in acute myocardial ischemia.
Thromboxane A2 (TxA2) has been implicated as a potential mediator of myocardial damage during acute ischemia. A potent and specific TxA2 receptor antagonist, SQ-29,548 (2 mg/kg bolus + 2 mg/kg/h) was tested in a cat acute coronary ligation model of myocardial ischemia over a 5-h observation period. Those cats given the TxA2 receptor antagonist had a significant reduction in elevated S-T segment from 0.32 to 0.17 mV (p less than 0.01) in contrast to cats given only vehicle which showed a progressive increase in S-T segment elevation over the 5-h course of the experiment. Furthermore, the rise in plasma creatine kinase (CK) activity during myocardial ischemia was significantly attenuated after SQ-29,548 administration (p less than 0.05). This was confirmed by direct myocardial biopsies which demonstrated a reduction in the loss of myocardial CK and nitrogenous compounds from the ischemic region. Because heart rate (HR), mean arterial blood pressure (MABP), and the pressure rate index (PRI) were unaffected by SQ-29,548 administration, its mechanism of protection probably does not occur through reduction of myocardial oxygen demand. Furthermore, specificity of SQ-29,548 for thromboxane/endoperoxide receptors was demonstrated in the isolated cat coronary arteries. These data suggest that SQ-29,548 reduces the damage associated with myocardial ischemia through direct TxA2 receptor antagonism. The data are also consistent with an important role of TxA2 in the pathophysiology of myocardial ischemia.


The pressure-volume relationship in normotensive and permanent essential hypertensive patients.
1. Blood pressure, blood volume and renal blood flow were determined in 101 men; forty-three were normal subjects and fifty-eight were untreated permanent essential hypertensive patients with normal renal function and equilibrated sodium balance. 2. A significant negative pressure-volume relationship was observed overall. The relationship could be expressed as a hyperbola whose slope expressed the reduction in blood volume per unit rise in pressure: the higher the blood pressure, the lower the slope. Thus essential hypertensive subjects have a smaller decrement in blood volume per unit rise in pressure than normal subjects. 3. The relation between change in blood volume and change in pressure was confirmed in each individual by defining for each a ration deltaV/deltaP, statistically identical with the hyperbolic slope dV/dP. The deltaV/deltaP ratio was found to be well correlated with the renal blood flow and the creatinine clearance. No correlation existed between the total blood volume and these two renal parameters. 4. It is concluded that the present study demonstrates a blood volume regulation disturbance in essential hypertension and provides evidence from human studies that a renal defect accompanies high blood pressure.


From ORFeomes to protein interaction maps in viruses.
Although cloned viral ORFeomes are particularly well suited for genome-wide interaction mapping due to the limited size of viral genomes, only a few such studies have been published. Here, we summarize virus interaction mapping projects involving vaccinia virus, hepatitis C virus (HCV), potato virus A (PVA), pea seed-borne mosaic virus (PSbMV), and bacteriophage T7, as well as some projects in progress. The studies reported suggest that virus-specific coding and replication strategies must be taken into account to yield accurate numbers of protein interactions. In particular, the number of false negatives can be significant for RNA viruses expressing precursor polyproteins (because interactions between full-length mature proteins are often not detected due to incorrect processing) and for viruses replicating in the cytoplasm whose transcripts have not been selected for splicing signals. In conclusion, the studies on viral protein interaction maps suggest that cloned pathogen ORFeomes will contribute to a holistic picture of the pathogenesis of infectious diseases and are ideal starting points for new approaches in systems biology. Both viral ORFeome and interaction mapping projects are being documented on our Web site (http://itgmv1.fzk.de/www/itg/uetz/virus/).


Randomised controlled trial of nurse practitioner versus general practitioner care for patients requesting "same day" consultations in primary care.
To ascertain any differences between care from nurse practitioners and that from general practitioners for patients seeking "same day" consultations in primary care. Randomised controlled trial with patients allocated by one of two randomisation schemes (by day or within day). 10 general practices in south Wales and south west England. 1368 patients requesting same day consultations. Patient satisfaction, resolution of symptoms and concerns, care provided (prescriptions, investigations, referrals, recall, and length of consultation), information provided to patients, and patients' intentions for seeking care in the future. Generally patients consulting nurse practitioners were significantly more satisfied with their care, although for adults this difference was not observed in all practices. For children, the mean difference between general and nurse practitioner in percentage satisfaction score was -4.8 (95% confidence interval -6.8 to -2.8), and for adults the differences ranged from -8.8 (-13.6 to -3.9) to 3.8 (-3.3 to 10.8) across the practices. Resolution of symptoms and concerns did not differ between the two groups (odds ratio 1.2 (95% confidence interval 0.8 to 1.8) for symptoms and 1.03 (0.8 to 1.4) for concerns). The number of prescriptions issued, investigations ordered, referrals to secondary care, and reattendances were similar between the two groups. However, patients managed by nurse practitioners reported receiving significantly more information about their illnesses and, in all but one practice, their consultations were significantly longer. This study supports the wider acceptance of the role of nurse practitioners in providing care to patients requesting same day consultations.


[TNF and sepsis].
Recent experiments have demonstrated that TNF plays an important role in the pathogenesis of septic shock. To confirm the involvement of TNF in human septic shock, serum TNF levels were measured in 10 adult patients admitted to the intensive care unit for sepsis with or without shock. Septic shock was corroborated by hemodynamic data (right catheterization, measurement of cardiac output by thermodilution). For TNF measurement, venous blood samples were withdrawn, as soon as possible after the onset of sepsis, into a pyrogen--free tube. Serum TNF levels were determined using a radioimmunoenzymatic assay (IRE Medgenix). During septic shock (n = 7), TNF levels were significantly higher (m = 354 +/- 131 pg/ml) than during sepsis without shock (n = 8; m = 145 +/- 35 pg/ml) (p less than 0.0005). TNF levels were also significantly higher in non-survivors (m = 392 +/- 111 pg/ml) than in survivors (m = 167 +/- 81 pg/ml) (p less than 0.0005). The value of 250 pg/ml seems to be critical: no patient without shock had TNF levels above 250 and all the patients who died early during the first 24 h) had TNF levels above 250. The TNF level is negatively correlated with the platelet count (r = -0.70; p less than 0.05). These data favor a pathophysiological for TNF in human sepsis and septic shock.


Microfluidic encapsulation of enzymes and steroids within solid lipid nanoparticles.
The production of solid lipid nanoparticles (SLNs) is challenging, especially when considering the incorporation of biologics. A novel in-house method of microfluidic production of biologic-encapsulated SLNs is proposed, using a variety of base materials for formulation to help overcome the barriers presented during manufacture and administration. Trypsin is used as a model drug for hydrophilic encapsulation whilst testosterone is employed as a positive non-biologic lipophilic control active pharmaceutical ingredient. Particle sizes obtained ranged from 160 to 320 nm, and a lead formulation has been identified from the combinations assayed, allowing for high encapsulation efficiencies (47-90%, respectively) of both the large hydrophilic and the small hydrophobic active pharmaceutical ingredients (APIs). Drug release profiles were analysed in vitro to provide useful insight into sustained kinetics, providing data towards future in vivo studies, which displayed a slow prolonged release for testosterone and a quicker burst release for trypsin. The study represents a large leap forward in the field of SLN production, especially in the field of difficult-to-encapsulate molecules, and the technique also benefits from being more environmentally sustainable due to the use of microfluidics.


Identifying 5 Common Psychiatric Disorders Associated Chemicals Through Integrative Analysis of Genome-Wide Association Study and Chemical-Gene Interaction Datasets.
Psychiatric disorders are a group of complex psychological syndromes whose etiology remains unknown. Previous study suggested that various chemicals contributed to the development of psychiatric diseases through affecting gene expression. This study aims to systematically explore the potential relationships between 5 major psychiatric disorders and more than 11 000 chemicals. The genome-wide association studies (GWAS) datasets of attention deficiency/hyperactive disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depression disorder (MDD), and schizophrenia (SCZ) were driven from the Psychiatric GWAS Consortium and iPSYCH website. The chemicals related gene sets were obtained from the comparative toxicogenomics database (CTD). First, transcriptome-wide association studies (TWAS) were performed by FUSION to calculate the expression association testing statistics utilizing GWAS summary statistics of the 5 common psychiatric disorders. Chemical-related gene set enrichment analysis (GSEA) was then conducted to explore the relationships between chemicals and each of the psychiatric diseases. We observed several significant correlations between chemicals and each of the psychiatric disorders. We also detected common chemicals between every 4 of the 5 major psychiatric disorders, such as androgen antagonists for ADHD (P value = .0098), ASD (P value = .0330), BD (P value = .0238), and SCZ (P value = .0062), and imipramine for ADHD (P value = .0054), ASD (P value = .0386), MDD (P value = .0438), and SCZ (P value = .0008). Our study results provide new clues for revealing the roles of environmental chemicals in the development of psychiatric disorders.


Population Structure, Antimicrobial Resistance, and Virulence-Associated Genes in Campylobacter jejuni Isolated From Three Ecological Niches: Gastroenteritis Patients, Broilers, and Wild Birds.
Campylobacter jejuni is the causal agent of the food-borne infection with the highest incidence in Europe. Both poultry and wild birds are a major reservoir. To gain insight into the population structure, virulence potential, and antimicrobial resistance (AMR), a collection of 150 isolates from three different ecological niches (broilers, wild birds, and human patients) was studied. Despite the high genetic diversity found, the population structure defined two distinct clusters, one formed mostly by broiler and human isolates and another one by most wild bird isolates. The ST-21 complex exhibits highest prevalence (in humans and broilers), followed by ST-1275 complex (only in wild birds). The ST-48, -45, and -354 complexes were found in all three niches, but represent only 22 out of 150 studied strains. A higher occurrence of AMR and multidrug resistance was detected among broiler and human isolates. Moreover, significant differences were found in the distribution of certain putative virulence genes. Remarkably, many wild bird strains were negative for either cdtA, cdtB, or cdtC from the canonical strain 81-176, whereas all broiler and human strains were positive. These data suggest that the different variants of the cdt genes might be relevant for the efficient colonization of certain hosts by C. jejuni. Our study contributes to the understanding of the role of the diverse Campylobacter reservoirs in the transmission of campylobacteriosis to humans.


Relative extents of preformation and neoformation in tree shoots: Analysis by a deconvolution method.
Neoformation is the process by which organs not preformed in a bud are developed on a growing shoot, generally after preformation extension. The study of neoformation in trees has been hindered due to methodological reasons. The present report is aimed at assessing the relative importance of preformation and neoformation in the development of shoots of woody species. A deconvolution method was applied to estimate the distribution of the number of neoformed organs for eight data sets corresponding to four Nothofagus species and a Juglans hybrid. The number of preformed organs was higher and less variable than the number of neoformed organs. Neoformation contributed more than preformation to explain full-size differences between shoots developed in different positions within the architecture of each tree species. Differences between the distributions of the numbers of preformed and neoformed organs may be explained by alluding to the duration of differentiation and extension for each of these groups of organs. The deconvolution of distributions is a useful tool for the analysis of neoformation and shoot structure in trees.


Leveraging heterogeneous data from GHS toxicity annotations, molecular and protein target descriptors and Tox21 assay readouts to predict and rationalise acute toxicity.
Despite the increasing knowledge in both the chemical and biological domains the assimilation and exploration of heterogeneous datasets, encoding information about the chemical, bioactivity and phenotypic properties of compounds, remains a challenge due to requirement for overlap between chemicals assayed across the spaces. Here, we have constructed a novel dataset, larger than we have used in prior work, comprising 579 acute oral toxic compounds and 1427 non-toxic compounds derived from regulatory GHS information, along with their corresponding molecular and protein target descriptors and qHTS in vitro assay readouts from the Tox21 project. We found no clear association between the results of a FAFDrugs4 toxicophore screen and the acute oral toxicity classifications for our compound set; and a screen using a subset of the ToxAlerts toxicophores was also of limited utility, with only slight enrichment toward the toxic set (odds ratio of 1.48). We then investigated to what degree toxic and non-toxic compounds could be separated in each of the spaces, to compare their potential contribution to further analyses. Using an LDA projection, we found the largest degree of separation using chemical descriptors (Cohen's d of 1.95) and the lowest degree of separation between toxicity classes using qHTS descriptors (Cohen's d of 0.67). To compare the predictivity of the feature spaces for the toxicity endpoint, we next trained Random Forest (RF) acute oral toxicity classifiers on either molecular, protein target and qHTS descriptors. RFs trained on molecular and protein target descriptors were most predictive, with ROC AUC values of 0.80-0.92 and 0.70-0.85, respectively, across three test sets. RFs trained on both chemical and protein target descriptors combined exhibited similar predictive performance to the single-domain models (ROC AUC of 0.80-0.91). Model interpretability was improved by the inclusion of protein target descriptors, which allow the identification of specific targets (e.g. Retinal dehydrogenase) with literature links to toxic modes of action (e.g. oxidative stress). The dataset compiled in this study has been made available for future application.


Routine thyroid function tests as a case-finding tool.
A comprehensive, multiphasic blood panel was used as a case-finding tool for 738 patients. The thyroid function tests T4 (total thyroxine), rT3U (resin T3 uptake), and FTI (free thyroxine index) were included in this panel. Among the 711 patients found to be clinically euthyroid without known thyroid disorder, 54 had at least one abnormal parameter. Of these patients, four new diagnoses of thyroid dysfunction were made. All four cases had an abnormal T4 and FTI. Two patients had a slightly elevated FTI and normal T4, and have remained clinically euthyroid. All other patients had a normal FTI, and no thyroid dysfunction was noted. This gives FTI in this study a sensitivity of 1.0 and specificity of 0.993, which is camparable to what others have found (1). The prevalence of unsuspected thyroid dysfunction was 0.56 per cent, again comparable to other studies (1-3). It would seem the high sensitivity/specificity of FTI offsets the relatively low prevalence of unsuspected thyroid dysfunction. Since FTI is a sensitive predictor of thyroid dysfunction, consideration should be given to the inclusion of thyroid function studies in existing multiphasic case-finding panels.


The incidence of nerve injury in anterior dislocation of the shoulder and its influence on functional recovery. A prospective clinical and EMG study.
Opinion varies as to the incidence of nerve lesions in anterior dislocation of the shoulder after low-velocity trauma. Most studies are retrospective or do not use EMG. We have investigated the incidence and the clinical consequences of nerve lesions in a prospective study by clinical and electrophysiological examination. Axonal loss was seen in 48% of 77 patients. The axillary nerve was most frequently involved (42%). Although recovery as judged by EMG and muscle strength was almost complete, function of the shoulder was significantly impaired in patients with lesions of the axillary and suprascapular nerves. Unfavourable prognostic factors are increasing age and the presence of a haematoma. It is not necessary to carry out EMG routinely; an adequate programme of physiotherapy is important. In patients with a severe paresis, EMG is essential after three weeks.


Regulation of hemidesmosome dynamics and cell signaling by integrin α6β4.
Hemidesmosomes (HDs) are specialized multiprotein complexes that connect the keratin cytoskeleton of epithelial cells to the extracellular matrix (ECM). In the skin, these complexes provide stable adhesion of basal keratinocytes to the underlying basement membrane. Integrin α6β4 is a receptor for laminins and plays a vital role in mediating cell adhesion by initiating the assembly of HDs. In addition, α6β4 has been implicated in signal transduction events that regulate diverse cellular processes, including proliferation and survival. In this Review, we detail the role of α6β4 in HD assembly and beyond, and we discuss the molecular mechanisms that regulate its function.


Interspinous spacers for lumbar foraminal stenosis: formal trials are justified.
To determine whether preliminary evidence supports X-STOP implants as an effective treatment for lumbar radiculopathy secondary to foraminal stenosis, and if larger formal trials are warranted. Participants had a clinical diagnosis of lumbar radiculopathy supported by MRI findings of foraminal stenosis and relevant nerve root compression. Self-reported disability and pain were measured pre-operation, early and late post-operation using the widely used Oswestry Disablity Index (ODI) and the bodily pain scale of the Medical Outcomes Study 36-item Short Form Health Survey (SF-36BP). The statistical significance (paired samples t test; Wilcoxon signed ranks test), and clinical significance (Cohen's effect size; Standardised response means) of change scores was determined. Fifteen people had X-STOP implants. Data pre- early- and late post-operation were available for ten. Self-reported disability and pain improved substantially by the early post operative measurement. Mean change scores (ODI = 29; SF-36BP = -45), significant at the p < 0.05 but not significant at the p < 0.001, were very large and effect sizes exceeded notably criteria for large clinical improvements (>0.80). Improvements were maintained at 2-3 years. Both scales had floor and ceiling effects implying changes may be underestimated. There were no surgical complications. In this small study, X-STOP appeared safe and effective. It is less invasive than other established surgical procedures, but does not jeopardise other options in the event of failure. Large scale clinical trials are justified but floor and ceiling effects suggest that the ODI and SF-36 may not be the best choice of outcome measures for those studies.


Hepatocyte Growth Factor: A Microenvironmental Resource for Leukemic Cell Growth.
Chronic lymphocytic leukemia (CLL) is characterized by the progressive expansion of B lymphocytes CD5+/CD23+ in peripheral blood, lymph-nodes, and bone marrow. The pivotal role played by the microenvironment in disease pathogenesis has become increasingly clear. We demonstrated that bone marrow stromal cells and trabecular bone cells sustain survival of leukemic B cells through the production of hepatocyte growth factor (HGF). Indeed the trans-membrane kinase receptor for HGF, c-MET, is expressed on CLL cells and STAT3 TYR705 or AKT phosphorylation is induced after HGF/c-MET interaction. We have further observed that c-MET is also highly expressed in a peculiar type of cells of the CLL-microenvironment showing nurturing features for the leukemic clone (nurse-like cells: NLCs). Since HGF treatment drives monocytes toward the M2 phenotype and NLCs exhibit features of tumor associated macrophages of type 2 we suggested that HGF, released either by cells of the microenvironment or leukemic cells, exerts a double effect: i) enhances CLL cells survival and ii) drives differentiation of monocytes-macrophages to an oriented immune suppressive phenotype. We here discuss how paracrine, but also autocrine production of HGF by malignant cells, may favor leukemic clone expansion and resistance to conventional drug treatments in CLL, as well as in other hematological malignancies. Novel therapeutic approaches aimed to block HGF/c-MET interactions are further proposed.


[Vertical reflux in lower-limb varicosity: variants, diagnosis, treatment].
Based on thoroughly analysing the findings obtained by ultrasonographic duplex scanning performed on a total of 763 lower limbs in 547 people presenting with various-pattern and different-localization dilatations of the saphenous veins, the author has herein managed to determine that nearly 20% of the examined patients turned out to have no retrograde regurgitation of the blood flow along the vessels concerned, and that in a further 7.3% of the patients, the backward flow of blood appeared to have no communication with the subfascial venous system. To put it otherwise, a vertical reflux in its classical manifestation is not always observed in the presence of the dilated superficial veins of the lower extremities. It turned out that a vertical reflux may be secondary to or result from not only valvular incompetence of the saphenofemoral and saphenopopliteal junctions, which certainly is the case in terms of the perception so deeply rooted in our minds, as a conventionally and rather reasonably considered source of origin, but may also be a consequence of the incompetent venae perforantes of Dodd and those of lateral localization, as well as the communications with the pelvic veins. Amongst the peculiar features encountered herein and worth mentioning was the fact that the vertical reflux could propagate both along the trunk of the great and/or small saphenous veins and along their tributaries only, involving either a part of, or the entire venous vessel all along its length. The obtained findings were later positively reflected in therapeutic decision-making and favourably contributed to carefully assigning and duly delivering appropriate treatment to have eventually consisted in minimally invasive interventions and organ-sparing procedures.


Factors affecting individual foraging specialization and temporal diet stability across the range of a large "generalist" apex predator.
Individual niche specialization (INS) is increasingly recognized as an important component of ecological and evolutionary dynamics. However, most studies that have investigated INS have focused on the effects of niche width and inter- and intraspecific competition on INS in small-bodied species for short time periods, with less attention paid to INS in large-bodied reptilian predators and the effects of available prey types on INS. We investigated the prevalence, causes, and consequences of INS in foraging behaviors across different populations of American alligators (Alligator mississippiensis), the dominant aquatic apex predator across the southeast US, using stomach contents and stable isotopes. Gut contents revealed that, over the short term, although alligator populations occupied wide ranges of the INS spectrum, general patterns were apparent. Alligator populations inhabiting lakes exhibited lower INS than coastal populations, likely driven by variation in habitat type and available prey types. Stable isotopes revealed that over longer time spans alligators exhibited remarkably consistent use of variable mixtures of carbon pools (e.g., marine and freshwater food webs). We conclude that INS in large-bodied reptilian predator populations is likely affected by variation in available prey types and habitat heterogeneity, and that INS should be incorporated into management strategies to efficiently meet intended goals. Also, ecological models, which typically do not consider behavioral variability, should include INS to increase model realism and applicability.


Application of rapid artificial cardiac pacing in thoracic endovascular aortic repair in aged patients.
To compare the safety, efficacy, and impact on stent graft positioning between rapid artificial cardiac pacing (RACP), induced hypotension and sodium nitroprusside (SNP) induced hypotension during thoracic endovascular aortic repair (TEVAR) for Stanford B aortic dissection. One hundred and sixty-eight patients, who were diagnosed with Stanford B aortic dissection and who underwent selective TEVAR in Guangdong General Hospital and the People's Hospital of Baoan District, Shenzhen, People's Republic of China, were enrolled in this study. Patients were randomly divided into a RACP group (n=77) and a SNP group (n=91). During localization and deployment of the stent graft, hypotension was induced by RACP or intravenous SNP, according to randomization. Hemodynamics, landing precision (deviation from planned placement site), duration of procedure, renal function, neurocognitive function, and incidence of endoleaks and paraplegia/hemiplegia were compared. Except for methods of inducing hypotension, TEVAR was performed according to the same protocol in each group. RACP was successfully performed in all patients assigned to the RACP group. Compared with the SNP group, blood pressure was significantly lower (43±5 versus 81±6 mmHg, P=0.003) and the restoration time of blood pressure and the operation duration were significantly shorter (7±2 versus 451±87 seconds, P<0.001; 87±15 versus 106±18 minutes, P<0.001, respectively) in the RACP group. Stent graft localization/deployment was more precise in the RACP group (2±1 versus 5±2 mm, P<0.001). Compared to baseline, there was no significant change after TEVAR in either group in regard to renal function, neurocognitive function, and incidence of endoleaks and paraplegia/hemiplegia. RACP can be safely applied to patients undergoing TEVAR for Stanford B dissection. RACP can shorten the operation duration and facilitate precise graft localization/deployment.


Nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase is phosphorylated in wheat endosperm at serine-404 by an SNF1-related protein kinase allosterically inhibited by ribose-5-phosphate.
Nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase (np-Ga3PDHase) is a cytosolic unconventional glycolytic enzyme of plant cells regulated by phosphorylation in heterotrophic tissues. After interaction with 14-3-3 proteins, the phosphorylated enzyme becomes less active and more sensitive to regulation by adenylates and inorganic pyrophosphate. Here, we acknowledge that in wheat (Triticum aestivum), np-Ga3PDHase is specifically phosphorylated by the SnRK (SNF1-related) protein kinase family. Interestingly, only the kinase present in heterotrophic tissues (endosperm and shoots, but not in leaves) was found active. The specific SnRK partially purified from endosperm exhibited a requirement for Mg(2+) or Mn(2+) (being Ca(2+) independent), having a molecular mass of approximately 200 kD. The kinase also phosphorylated standard peptides SAMS, AMARA, and SP46, as well as endogenous sucrose synthase, results suggesting that it could be a member of the SnRK1 subfamily. Concurrently, the partially purified wheat SnRK was recognized by antibodies raised against a peptide conserved between SnRK1s from sorghum (Sorghum bicolor) and maize (Zea mays) developing seeds. The wheat kinase was allosterically inhibited by ribose-5-phosphate and, to a lesser extent, by fructose-1,6-bisphosphate and 3-phosphoglycerate, while glucose-6-phosphate (the main effector of spinach [Spinacia oleracea] leaves, SnRK1) and trehalose-6-phosphate produced little or no effect. Results support a distinctive allosteric regulation of SnRK1 present in photosynthetic or heterotrophic plant tissues. After in silico analysis, we constructed two np-Ga3PDHase mutants, S404A and S447A, identifying serine-404 as the target of phosphorylation. Results suggest that both np-Ga3PDHase and the specific kinase could be under control, critically affecting the metabolic scenario involving carbohydrates and reducing power partition and storage in heterotrophic plant cells.


Clinical applications of body ventilators.
Interest has been increasing in providing ventilatory support in the home for patients with chronic respiratory failure, mainly with the use of positive pressure ventilation via a chronic tracheostomy. However, body ventilators that assist ventilation by applying intermittent negative or positive pressure to the thorax, abdomen, or airway without requiring an artificial airway, can offer distinct advantages for selected patients over systems requiring a permanent airway. These ventilators include the iron lung, portable lung (Portalung), pneumowrap, chest cuirass, pneumobelt, rocking bed, and positive pressure provided via a face or nose mask. They have successfully stabilized or reversed chronic hypercarbia when used intermittently in patients with slowly progressive chronic respiratory failure due to certain neuromuscular diseases and kyphoscoliosis. How they achieve this stabilization has not been clarified, but reversal of chronic respiratory muscle fatigue following periodic rest probably contributes. These ventilators are generally less effective than positive pressure ventilation through a tracheostomy and should be reserved for patients with relatively stable chronic respiratory failure and intact upper airways. However, they have the advantages of simpler operation and less expense, and they allow maintenance of a normal airway.


Toward a theory of high performance.
What does it mean to be a high-performance company? The process of measuring relative performance across industries and eras, declaring top performers, and finding the common drivers of their success is such a difficult one that it might seem a fool's errand to attempt. In fact, no one did for the first thousand or so years of business history. The question didn't even occur to many scholars until Tom Peters and Bob Waterman released In Search of Excellence in 1982. Twenty-three years later, we've witnessed several more attempts--and, just maybe, we're getting closer to answers. In this reported piece, HBR senior editor Julia Kirby explores why it's so difficult to study high performance and how various research efforts--including those from John Kotter and Jim Heskett; Jim Collins and Jerry Porras; Bill Joyce, Nitin Nohria, and Bruce Roberson; and several others outlined in a summary chart-have attacked the problem. The challenge starts with deciding which companies to study closely. Are the stars the ones with the highest market caps, the ones with the greatest sales growth, or simply the ones that remain standing at the end of the game? (And when's the end of the game?) Each major study differs in how it defines success, which companies it therefore declares to be worthy of emulation, and the patterns of activity and attitude it finds in common among them. Yet, Kirby concludes, as each study's method incrementally solves problems others have faced, we are progressing toward a consensus theory of high performance.


Carotid body: new stimuli and new preparations--invited article.
Beginning with the pioneering work of Heymans and collaborators in the 1930's, investigations into the role of the mammalian carotid body (CB) in the control of ventilation have attracted much attention. Progress for many years was restricted to the whole animal and organ level, resulting in characterization of the stimulus-response characteristics of the CB with its afferent nerve supply during exposure to chemostimuli such as low PO(2) (hypoxia), elevated PCO(2) (hypercapnia), and low pH (acidity). Major advances on the cellular and molecular mechanisms of chemotransduction occurred 20 years ago with the use of freshly-dissociated CB preparations and single cell studies using patch clamp and spectrofluorimetric techniques. This review will focus on more recent advances based on novel preparations including co-cultures of isolated CB receptor clusters and dispersed sensory or autonomic neurons, thin CB tissue slice preparations, and transgenic models. These preparations have contributed significantly, not only to our understanding of the transduction and neurotransmitter mechanisms that operate in the CB during sensory processing, but also to the identification and characterization of novel CB stimuli such as hypoglycemia. Though the complexity of this remarkable organ still belies its tiny size, these recent advances are slowly unraveling the intricacies surrounding its ability to act as a polymodal detector of blood-borne chemicals and to alter its sensitivity to patterned stimuli.


Attitudes of hospital doctors in Wales to use of intravenous fluids and antibiotics in the terminally ill.
Decisions concerning the use of intravenous fluids and antibiotics in terminally ill patients are regularly made by hospital doctors, but there is little record of staff attitudes and current practice in Britain. A questionnaire was therefore distributed to 833 Welsh hospital doctors, citing the case of a hypothetical terminally ill patient and asking questions about medical management. Of the 448 (54%) doctors who replied, 346 (77%) had managed a similar patient recently. Intravenous fluids would be administered by 238 (53%), with 206 of these (87%) resiting the cannula as required and 62 (26%) resorting to a central venous line if there was no alternative. With increasing age and seniority doctors become conservative in their approach. Nearly all claimed that 'ensuring the patient's comfort' was the reason for their decision. Only 72 (16%) would use antibiotics if the patient became pyrexial. The results suggest that British doctors are divided in their approach to the medical management of terminally ill patients and there is a need for greater discussion and training so that all the issues involved are fully appreciated.


Response practices in multilingual interaction with an older Persian woman in a Swedish residential home.
In the present case study, a care encounter between an older multilingual (Farsi/Swedish/English) Persian woman and staff in an ordinary, Swedish residential home is investigated. The woman is perceived as suffering from dementia symptoms, but has not received any formal diagnosis of the disease. More specifically, the study focuses on how the woman's contributions in her mother tongue, Farsi, are responded to by a carer, who is also multilingual and speaks Swedish as a second language (L2), but has a very limited knowledge of Farsi. The data consists of recorded material from a mundane morning activity in the residential home, as the woman is undressed and prepared to go to the shower. The method employed is conversation analysis, and the study addresses the interactional outcome of this type of multilingual encounters, highlighting the way the establishment of mutual understanding is negatively affected by the fact that the participants do not or only to a limited extent share a common language. Analysis of the data shows that most of the woman's contributions in Farsi are responded to in L2-Swedish by the carer, primarily by means of seven different response practices: soothing talk, instrumental talk, minimal responses, explicit expressions of understanding, mitigating talk, questions, and appraisal. The findings are discussed in light of new demands on Swedish (and Western) care- and health care systems to adapt to the increasing number of multilingual, older people, who will become residents in care facilities and attend day centers within the coming years.


CCR5 receptor antagonism inhibits hepatitis C virus (HCV) replication in vitro.
The hepatitis C virus (HCV) is a single-strand RNA virus that infects millions of people worldwide. Recent advances in therapy have led to viral cure using two- and three- drug combinations of direct acting inhibitors of viral replication. CCR5 is a chemokine receptor that is expressed on hepatocytes and represents a key co-receptor for HIV. We evaluated the effect of CCR5 blockade or knockdown on HCV replication in Huh7.5JFH1 cells. Cells were exposed to varying concentrations of maraviroc (CCR5 inhibitor), cenicriviroc (CCR2/CCR5 inhibitor), sofosbuvir (nucleotide polymerase inhibitor), or raltegravir (HIV integrase inhibitor). HCV RNA was detected utilizing two qualitative strand-specific RT-PCR assays. HCV core antigen and NS3 protein was quantified in the supernatant and cell lysate, respectively. siRNA was utilized to knockdown CCR5 gene expression in hepatocytes. Alternatively, anti-CCR5 antibodies were employed to block the receptor. Supernatant levels of HCV RNA (expressed as fold change) were not reduced in the presence of raltegravir but were reduced 8.55-fold and 12.42-fold with cenicriviroc and maraviroc, respectively. Sofosbuvir resulted in a 16.20-fold change in HCV RNA levels. HCV core and NS3 protein production was also reduced in a dose-dependent manner. Two distinct anti-CCR5 antibodies also resulted in a significant reduction in HCV protein expression, as did siRNA knockdown of CCR5 gene expression. These data provide evidence that CCR5 modulation could have a significant effect on HCV replication in an in vitro system. Further evaluation of the role of CCR5 inhibition in clinical settings may be warranted.


Microvesicles as cell-cell messengers in cardiovascular diseases.
Cell-cell communication has proven to be even more complex than previously thought since the discovery that extracellular vesicles serve as containers of biological information on various pathophysiological settings. Extracellular vesicles are classified into exosomes, microvesicles/microparticles, or apoptotic bodies, originating from different subcellular compartments. The cellular machinery controlling their formation and composition, as well as the mechanisms regulating their extracellular release, remain unfortunately much unknown. Extracellular vesicles have been found in plasma, urine, saliva, and inflammatory tissues. Their biomarker potential has raised significant interest in the cardiovascular field because the vesicle composition and microRNA content are specific signatures of cellular activation and injury. More than simply cell dust, extracellular vesicles are capable of transferring biological information to neighboring cells and play an active role in inflammatory diseases, including atherosclerosis and angiogenesis. The molecular interactions regulating these effects involve specific receptor activation, proteolytic enzymes, reactive oxygen species, or delivery of genetic information to target cells. Unraveling their mechanisms of action will likely open new therapeutic avenues.


Impact of the Crystalline Li15Si4 Phase on the Self-Discharge Mechanism of Silicon Negative Electrodes in Organic Electrolytes.
Because of their high specific capacity and rather low operating potential, silicon-based negative electrode materials for lithium-ion batteries have been the subject of extensive research over the past 2 decades. Although the understanding of the (de)lithiation behavior of silicon has significantly increased, several major challenges have not been solved yet, hindering its broad commercial application. One major issue is the low initial Coulombic efficiency and the ever-present self-discharge of silicon electrodes. Self-discharge itself affects the long-term stability of electrochemical storage systems and, additionally, must be taken into consideration for inevitable prelithiation approaches. The impact of the crystalline Li15Si4 phase is of great interest as the phase transformation between crystalline (c) and amorphous (a) phases not only increases the specific surface area but also causes huge polarization. Moreover, there is the possibility for electrochemical over-lithiation toward the Li15+aSi4 phase because of the electron-deficient Li15Si4 phase, which can be highly reactive toward the electrolyte. This poses the question about the impact of the c-Li15Si4 phase on the self-discharge behavior in comparison to its amorphous counterpart. Here, silicon thin films used as model electrodes are lithiated to cut-off potentials of 10 mV and 50 mV versus Li|Li+ (U10mV and U50mV) in order to systematically investigate their self-discharge mechanism via open-circuit potential (UOCP) measurements and to visualize the solid electrolyte interphase (SEI) growth by means of scanning electrochemical microscopy. We show that the c-Li15Si4 phase is formed for the U10mV electrode, while it is not found for the U50mV electrode. In turn, the U50mV electrode displays an almost linear self-discharge behavior, whereas the U10mV electrode reaches a UOCP plateau at ca. 380 mV versus Li|Li+, which is due to the phase transition from c-Li15Si4 to the a-LixSi phase. At this plateau potential, the phase transformation at the Si|electrolyte interface results in an electronically more insulating and more uniform SEI (U10mV electrode), while the U50mV electrode displays a less uniform SEI layer. In summary, the self-discharge mechanism of silicon electrodes and, hence, the irreversible decomposition of the electrolyte and the corresponding SEI formation process heavily depend on the structural nature of the underlying lithium-silicon phase.


Hypothesis: hyperstructures regulate bacterial structure and the cell cycle.
A myriad different constituents or elements (genes, proteins, lipids, ions, small molecules etc.) participate in numerous physico-chemical processes to create bacteria that can adapt to their environments to survive, grow and, via the cell cycle, reproduce. We explore the possibility that it is too difficult to explain cell cycle progression in terms of these elements and that an intermediate level of explanation is needed. This level is that of hyperstructures. A hyperstructure is large, has usually one particular function, and contains many elements. Non-equilibrium, or even dissipative, hyperstructures that, for example, assemble to transport and metabolize nutrients may comprise membrane domains of transporters plus cytoplasmic metabolons plus the genes that encode the hyperstructure's enzymes. The processes involved in the putative formation of hyperstructures include: metabolite-induced changes to protein affinities that result in metabolon formation, lipid-organizing forces that result in lateral and transverse asymmetries, post-translational modifications, equilibration of water structures that may alter distributions of other molecules, transertion, ion currents, emission of electromagnetic radiation and long range mechanical vibrations. Equilibrium hyperstructures may also exist such as topological arrays of DNA in the form of cholesteric liquid crystals. We present here the beginning of a picture of the bacterial cell in which hyperstructures form to maximize efficiency and in which the properties of hyperstructures drive the cell cycle.


Serotonin modulates spike backpropagation and associated [Ca2+]i changes in the apical dendrites of hippocampal CA1 pyramidal neurons.
The effect of serotonin (5-HT) on somatic and dendritic properties was analyzed in pyramidal neurons from the CA1 region in slices from the rat hippocampus. Bath-applied 5-HT (10 microM) hyperpolarized the soma and apical dendrites and caused a conductance increase at both locations. In the dendrites (200-300 microm from the soma) trains of antidromically activated, backpropagating action potentials had lower peak potentials in 5-HT than in normal artificial cerebrospinal fluid. Spike amplitudes were about the same in the two solutions. Similar results were found when the action potentials were evoked synaptically with stimulation in the stratum oriens. In the soma, spike amplitudes increased in 5-HT, with only a small decrease in the peak potential. Calcium concentration measurements, made with bis-fura-2 injected through patch electrodes, showed that the amplitude of the [Ca2+]i changes was reduced at all locations in 5-HT. The reduction of the [Ca2+]i change in the soma was confirmed in slices where cells were loaded with fura-2-AM. The reduction at the soma in 5-HT, where the spike amplitude increased, suggests that the reduction is due primarily to direct modulation of Ca2+ channels. In the dendrites, the reduction is due to a combination of this channel modulation and the lowering of the peak potential of the action potentials.


The relevance of hippocampal subfield integrity and clock drawing test performance for the diagnosis of Alzheimer's disease and mild cognitive impairment.
The clock drawing test (CDT) is one of the worldwide most used screening tests for Alzheimer's disease (AD). MRI studies have identified temporo-parietal regions being involved in CDT impairment. However, the contributions of specific hippocampal subfields and adjacent extrahippocampal structures to CDT performance in AD and mild cognitive impairment (MCI) have not been investigated so far. It is unclear whether morphological alterations or CDT score, or a combination of both, are able to predict AD. 38 AD patients, 38 MCI individuals and 31 healthy controls underwent neuropsychological assessment and MRI at 3 Tesla. FreeSurfer 5.3 was used to perform hippocampal parcellation. We used a collection of statistical methods to better understand the relationship between CDT and hippocampal formation. We also tested the clinical feasibility of this relationship when predicting AD. Impaired CDT performance in AD was associated with widespread atrophy of the cornu ammonis, presubiculum, and subiculum, whereas MCI subjects showed CDT-related alterations of the CA4-dentate gyrus and subiculum. CDT correlates in AD and MCI showed regional and quantitative overlap. Importantly, CDT score was the best predictor of AD. Our findings lend support for an involvement of different hippocampal subfields in impaired CDT performance in AD and MCI. CDT seems to be more efficient than subfield imaging for predicting AD.


Transient elastography to assess liver stiffness in patients with inflammatory bowel disease.
Liver injury during inflammatory bowel disease (IBD) is primarily diagnosed by liver biopsy, which has a small but serious risk of severe complications. The aim of this study was to assess liver stiffness, and subsequently the prevalence and associations of liver fibrosis in IBD patients with thiopurine therapy and other clinical factors, by using transient elastography (TE). In this prospective, international two-center study, included IBD-patients underwent TE measurements. Laboratory results and medication reports, radiology results and historical liver biopsy results were extracted from the patient charts. Transient elastography results of 168 patients were presented. Moderate and severe fibrosis were detected in 4% (7/168) and 1% (1/168) of the cohort, respectively. Factors contributing to lower liver stiffness were female gender and (historical) exposure to azathioprine. Further, there was a statistical trend towards lower liver stiffness in patients using thiopurines overall (4.7 vs. 5.2kPa, p=0.07). Liver stiffness correlated positively with waist circumference, liver enzyme tests, hemoglobin and 6-methylmercaptopurine concentration and negatively with platelet count. Exposure to thiopurine therapy was not associated with higher liver stiffness, although no clinical difference in severity of fibrosis was detected. Further research should robustly determine the accuracy of TE as an evaluation of liver fibrosis in IBD patients.


Mutations in the second extracellular region of connexin 43 prevent localization to the plasma membrane, but do not affect its ability to suppress cell growth.
Connexin 43 (Cx43), the most widely expressed gap junction protein, has a role in regulation of cell growth. In this study, we demonstrate that the point mutations F199L, R202E, and E205R in the second extracellular region of Cx43 prevent localization of the mutant proteins to the plasma membrane. The mutants were aberrantly localized in the cytoplasm if expressed in HeLa cells, which lack Cx43. Coexpression with wild-type Cx43 promoted localization of the F199L and R202E mutant proteins to the plasma membrane. By dye transfer assay, we showed that gap junctional intercellular communication (GJC) is decreased in cells expressing the mutants, compared to Cx43 wild-type-expressing cells. However, the F199L mutant does not appear to have a dominant-negative effect on GJC. Despite the loss of GJC, the ability of the F199L Cx43 mutant to inhibit growth of either Cx43-/- cells or two cancer cell lines, HeLa and C6 glioma cells, was similar to that of the wild-type Cx43. In addition, we showed that both R202E and E205R Cx43 mutant expressions cause growth retardation of HeLa cells. Therefore, the point mutations in the second extracellular region of Cx43 do not affect the ability of the mutant proteins in vitro to suppress cell growth, although they prevent localization to the plasma membrane. The results support the concept that regulation of cell growth by Cx43 does not necessarily require GJC and suggest that the growth-suppressive properties of Cx43 may be independent of the second extracellular loop.


Being pragmatic about syntactic bootstrapping.
Words have meanings vastly undetermined by the contexts in which they occur. Their acquisition therefore presents formidable problems of induction. Lila Gleitman and colleagues have advocated for one part of a solution: indirect evidence for a word's meaning may come from its syntactic distribution, via syntactic bootstrapping. But while formal theories argue for principled links between meaning and syntax, actual syntactic evidence about meaning is noisy and highly abstract. This paper examines the role that syntactic bootstrapping can play in learning modal and attitude verb meanings, for which the physical context is especially uninformative. I argue that abstract syntactic classifications are useful to the child, but that something further is both necessary and available. I examine how pragmatic and syntactic cues can combine in mutually constraining ways to help learners infer attitude meanings, but need to be supplemented by semantic information from the lexical context in the case of modals.


A quantitative technique for assessing the change in severity over time in psoriatic lesions using computer aided image analysis.
Psoriasis is a chronic skin disease affecting an estimated 125 million people worldwide. One of the key problems in the management of this condition is the objective measurement of lesion severity over time. Currently, severity is scored by clinicians using visual protocols leading to intra and inter observer variability that makes measurement of treatment efficacy subjective. In this paper, an automatic computer aided image analysis system is proposed that quantitatively assess the changes of erythema and scaling severity of psoriatic lesions in long-term treatment. The algorithm proposed in this paper works on 2D digital images by selecting features that can be used to accurately segment erythema and scaling in psoriasis lesions and assess their changes in severity, according to the popular psoriasis area and severity index (PASI). The algorithms are validated by developing linear models that correlate well with changes in severity scores given by dermatologists. To the best of our knowledge, no such computer assisted method for psoriasis severity assessment in a long-term treatment exists.


Patient educational media preferences for information about irritable bowel syndrome (IBS).
To identify the educational media preferences of patients with irritable bowel syndrome (IBS). The IBS-Patient Education Questionnaire (PEQ) was administered to a national sample of IBS patients. Frequencies of item endorsements were compared and meaningful clinical differences were used to identify differences among subgroups. 1,242 patients completed the survey, mean age 39.3 years, 85% female, IBS duration 6.9 years, 79% had seen an MD for IBS within 6 months, and 92.6% used the web for medical information. The most desired source of education was "my doctor" (68%), followed by Internet (62%) and brochure (45%). Notably, patients favored an increase in use of media in the future (past vs. future): doctor (43 vs. 68%); Internet (36 vs. 62%); and brochures (26 vs. 45%). IBS patients expect more education than they have received. Understanding IBS patients' learning preferences can be highly valuable in the development or implementation of educational interventions.


Molecular cloning and expression analysis of the complementary deoxyribonucleic acid for chicken inhibin/activin beta(B) subunit.
Inhibins and activins are dimeric peptide hormones that play an integral role in the intraovarian regulation of folliculogenesis. The domestic hen, with its well-defined follicular hierarchy, provides a unique model in which to study the role of these hormones in follicular development. In the present study, the complete coding sequence and deduced amino acid sequence for the chicken inhibin/activin beta(B) subunit has been determined from cDNA clones isolated from a chicken ovarian granulosa cell library. This beta(B)-subunit cDNA predicts a precursor protein of 392 amino acids containing the mature C-terminal 115 amino acid beta(B) subunit. When compared to the beta(B) subunit isolated from a variety of species, the chicken cDNA clone showed high nucleotide identity in the full-length coding region (>70%) and in the mature coding region (>80%). In addition, the deduced amino acid sequence of chicken beta(B) subunit showed greater than 95% identity compared to other species in the mature peptide region. Expression of the beta(B)-subunit mRNA was detected by reverse transcription-polymerase chain reaction in both gonadal and extragonadal tissues. Northern blot analysis detected expression in the gonadal tissues only, specifically in the granulosa tissue from the F3-F5 follicles, small yellow follicles (SYF), large white follicles, and immature and mature rooster testes. A major transcript of approximately 4.1 kilobases (kb) and three minor transcripts of approximately 8.4 kb, 6.5 kb, and 1.7 kb were detected in the SYF granulosa samples. To examine the expression pattern of the beta(B) subunit around the stage of follicle selection, the SYF granulosa was subdivided into two groups: 6-8 mm and 9-12 mm. Quantification of RNA expression (n = 3) showed that expression of the beta(B) subunit was maximal in the 6-8 mm SYF. Activin B, as well as other intraovarian signals, may regulate early follicle selection and/or development in the chicken.


An experimentally induced osteoarthritis model in horses performed on both metacarpophalangeal and metatarsophalangeal joints: Technical, clinical, imaging, biochemical, macroscopic and microscopic characterization.
Osteoarthritis is a common cause of pain and economic loss in both humans and horses. The horse is recognized as a suitable model for human osteoarthritis, because the thickness, structure, and mechanical properties of equine articular cartilage are highly comparable to those of humans. Although a number of equine experimental osteoarthritis models have been described in the literature, these cases generally involve the induction of osteoarthritis in just one joint of each animal. This approach necessitates the involvement of large numbers of horses to obtain reliable data and thus limits the use of this animal model, for both economic and ethical reasons. This study adapts an established equine model of post-traumatic osteoarthritis to induce osteoarthritis-associated lesions in all 4 fetlock joints of the same horse in order to reduce the number of animals involved and avoid individual variability, thus obtaining a more reliable method to evaluate treatment efficacy in future studies. The objectives are to assess the feasibility of the procedure, evaluate variability of the lesions according to interindividual and operated-limb position and describe the spontaneous evolution of osteoarthritis-associated pathological changes over a twelve-week period. The procedure was well tolerated by all 8 experimental horses and successfully induced mild osteoarthritis-associated changes in the four fetlock joints of each horse. Observations were carried out using clinical, radiographic, ultrasonographic, and magnetic resonance imaging methods as well as biochemical analyses of synovial fluid and postmortem microscopic and macroscopic evaluations of the joints. No significant differences were found in the progression of osteoarthritis-associated changes between horses or between the different limbs, with the exception of higher synovial effusion in hind fetlocks compared to front fetlocks and higher radiographic scores for left fetlocks compared to the right. This model thus appears to be a reliable means to evaluate the efficacy of new treatments in horses, and may be of interest for translational studies in human medicine.


Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant.
Antibody responses against the SARS-CoV-2 Spike protein correlate with protection against COVID-19. Serum neutralizing antibodies appear early after symptom onset following SARS-CoV-2 infection and can last for several months. Similarly, the messenger RNA vaccine, mRNA-1273, generates serum neutralizing antibodies that are detected through at least day 119. However, the recent emergence of the B.1.1.7 variant has raised significant concerns about the breadth of these neutralizing antibody responses. In this study, we used a live virus neutralization assay to compare the neutralization potency of sera from infected and vaccinated individuals against a panel of SARS-CoV-2 variants, including SARS-CoV-2 B.1.1.7. We found that both infection- and vaccine-induced antibodies were effective at neutralizing the SARS-CoV-2 B.1.1.7 variant. These findings support the notion that in the context of the UK variant, vaccine-induced immunity can provide protection against COVID-19. As additional SARS-CoV-2 viral variants continue to emerge, it is crucial to monitor their impact on neutralizing antibody responses following infection and vaccination.


Cerebral hemodynamic effects of pentobarbital coma in head-injured patients.
The purpose of this study was to examine the changes in cerebral hemodynamics of head-injured patients undergoing barbiturate treatment of refractory intracranial hypertension. Cerebral blood flow (CBF) and metabolism variables were measured in 67 severely head-injured patients at the following times: before the loading dose of pentobarbital; after the loading dose of pentobarbital (average pentobarbital level 28.1+/-8.3 microg/mL); and 3 days later, when the peak pentobarbital level averaged 42.5+/-17.2 microg/mL. Intracranial pressure (ICP) and mean arterial blood pressure (MAP) were decreased by the loading dose of pentobarbital by an average of 12 and 9 mm Hg, respectively. Cerebral perfusion pressure (CPP) was unchanged when the entire group was analyzed together. CBF, cerebral oxygen consumption (CMR(O)2), and arteriovenous oxygen difference (AVD(O)2) were significantly decreased after the loading dose of pentobarbital, by 20%, 31%, and 11%, respectively. The average cerebrovascular resistance (CVR) was increased by 20%. The change in CMR(O)2 with the loading dose of pentobarbital was closely related to the pretreatment value (n = 67, r2 = 0.65, p < .001). Thirty (45%) of the patients had a "good ICP response," with a reduction in ICP from 34+/-9 to 15+/-5 mm Hg after the initial loading dose of pentobarbital. Twenty-seven (40%) of the patients had a "partial ICP response," with ICP decreasing but still remaining above 20 mm Hg after the loading dose of pentobarbital. In the remaining 10 patients, ICP did not change or even increased after pentobarbital. In the 30 patients with a good ICP response, pretreatment CMR(O)2 and AVD(O)2 were greater before administration of pentobarbital, and CMR(O)2 and AVD(O)2 decreased more with the loading dose of pentobarbital, than in the patients with partial or no ICP response. The outcome was significantly better in the patients with a good or partial ICP response to pentobarbital, with 21% of these patients having a good recovery or moderate disability at 3 months after injury, compared with 100% persistent vegetative state or death in the nonresponders. In summary, barbiturate coma can be a useful treatment modality for acutely reducing ICP in selected patients. Patients with overwhelmingly severe injuries are not likely to benefit, partly because their CMR(O)2 is already markedly reduced by the injury and partly because their outcome is already predetermined by the injury. Patients with systemic hypotension are not likely to have a good response because hypotension limits the amount of barbiturates that can be given.


Effect of Knee Joint Angle and Contraction Intensity on Hamstrings Coactivation.
This study investigated the effect of knee joint angle and contraction intensity on the coactivation of the hamstring muscles (when acting as antagonists to the quadriceps) in young and older individuals of both sexes. A total of 25 young (24 ± 2.6 yr) and 26 older (70 ± 2.5 yr) healthy men and women participated. Maximal voluntary isometric contraction of the knee extensors and flexors was assessed at two knee joint angles (90° and 60°, 0° = full extension). At each angle, participants performed submaximal contractions of the knee extensors (20%, 50%, and 80% maximal voluntary isometric contraction), whereas surface EMG was simultaneously acquired from the vastus lateralis and biceps femoris muscles to assess the level (EMG root-mean-square) of agonist activation and antagonist coactivation. Subcutaneous adipose tissue in the areas corresponding to surface EMG electrode placements was measured via ultrasonography. The contractions performed at 90° knee flexion demonstrated higher levels of antagonist coactivation (all P < 0.01) and agonist activation (all P < 0.01) as a function of contraction intensity compared with the 60° knee flexion. Furthermore, after controlling for subcutaneous adipose tissue, older participants exhibited a higher level of antagonist coactivation at 60° knee flexion compared with young participants (P < 0.05). The results of the present study suggest that 1) the antagonist coactivation is dependent on knee joint angle and contraction intensity and 2) subcutaneous adipose tissue may affect the measured coactivation level likely because of a cross-talk effect. Antagonist coactivation may play a protective role in stabilizing the knee joint and maintaining constant motor output.


Photoreactivation of ultraviolet radiation-induced pyrimidine dimers in neonatal BALB/c mouse skin.
The numbers of ultraviolet light (UV)-induced pyrimidine dimers in the DNA of neonatal BALB/c mouse skin were measured by assessing the sensitivity of the DNA to Micrococcus luteus UV endonuclease. Irradiation of neonatal BALB/c mice with FS40 sunlamps caused a dose-dependent induction of endonuclease-sensitive sites (pyrimidine dimers) in DNA extracted from back skin. Exposure of these UV-irradiated neonatal mice to photoreactivating (PR) light ("cool white" fluorescent lamp and incandescent lamp) caused a reduction in the number of pyrimidine dimers in the DNA, as revealed by a shift in low-molecular-weight DNA to high-molecular-weight DNA. In contrast, DNA profiles of the skin of either UV-irradiated mice or UV-irradiated mice kept in the dark for the same duration as those exposed to PR light did not show a loss of UV-induced endonuclease-sensitive sites. Furthermore, reversing the order of treatment, i.e., administering PR light first and then UV, did not produce a reduction in pyrimidine dimers. These results demonstrate that PR or UV-induced pyrimidine dimers occurs in neonatal BALB/c mouse skin. The optimal wavelength range for in vivo PR appears to be in the visible region of the spectrum (greater than 400 nm). Although dimer formation could be detected in both dermis and epidermis, PR occurred only in the dermis. Furthermore, the PR phenomenon could not be detected in the skin of adult mice from the same inbred strain.


Intra- and inter-rater reliability of movement and palpation tests in patients with neck pain: A systematic review.
Neck pain is common and often becomes chronic. Various clinical tests of the cervical spine are used to direct and evaluate treatment. This systematic review aimed to identify studies examining the intra- and/or interrater reliability of tests used in clinical examination of patients with neck pain. A database search up to April 2016 was conducted in PubMed, CINAHL, and AMED. The Quality Appraisal of Reliability Studies Checklist (QAREL) was used to assess risk of bias. Eleven studies were included, comprising tests of active and passive movement and pain evaluating participants with ongoing neck pain. One study was assessed with a low risk of bias, three with medium risk, while the rest were assessed with high risk of bias. The results showed differing reliabilities for the included tests ranging from poor to almost perfect. In conclusion, active movement and pain for pain or mobility overall presented acceptable to very good reliability (Kappa >0.40); while passive intervertebral tests had lower Kappa values, suggesting poor reliability. It may be a coincidence that the studies indicating very good reliability tended to be of higher quality (low to moderate risk of bias), while studies finding poor reliability tended to be of lower quality (high risk of bias). Regardless, the current recommendation from this review would suggest the clinical use of tests with acceptable reliability and avoiding the use of tests that have been shown to not be reliable. Finally, it is critical that all future reliability studies are of higher quality with low risk of bias.


Diversion of flux toward sesquiterpene production in Saccharomyces cerevisiae by fusion of host and heterologous enzymes.
The ability to transfer metabolic pathways from the natural producer organisms to the well-characterized cell factory Saccharomyces cerevisiae is well documented. However, as many secondary metabolites are produced by collaborating enzymes assembled in complexes, metabolite production in yeast may be limited by the inability of the heterologous enzymes to collaborate with the native yeast enzymes. This may cause loss of intermediates by diffusion or degradation or due to conversion of the intermediate through competitive pathways. To bypass this problem, we have pursued a strategy in which key enzymes in the pathway are expressed as a physical fusion. As a model system, we have constructed several fusion protein variants in which farnesyl diphosphate synthase (FPPS) of yeast has been coupled to patchoulol synthase (PTS) of plant origin (Pogostemon cablin). Expression of the fusion proteins in S. cerevisiae increased the production of patchoulol, the main sesquiterpene produced by PTS, up to 2-fold. Moreover, we have demonstrated that the fusion strategy can be used in combination with traditional metabolic engineering to further increase the production of patchoulol. This simple test case of synthetic biology demonstrates that engineering the spatial organization of metabolic enzymes around a branch point has great potential for diverting flux toward a desired product.


Is partial thickness excision in TAMIS without defect suture safe for benign rectal lesions?
One of the minimally invasive methods used in the surgical treatment of large-based polypoid lesions located in the rectum is transanal minimally invasive surgery (TAMIS). This method, which relieves patients from the severe morbidities of invasive surgical procedures, is performed in both malign (T1-T2) and benign lesions. Difficulty of suturation after TAMIS emerges as the most important factor to prolong the procedure. We aimed to analyse the efficacy of TAMIS procedure with partial thickness resection without suturation. This was a retrospective study. The study was conducted in a Turkish Education and Research Hospital in 2016. Data of 10 patients who diagnosed with benign rectal masses were included in the study. Patients who were suspected for muscularis propria invasion and lymph node positivity in magnetic resonance imaging preoperatively excluded from the study. All lesions were resected with TAMIS and the mucosal defects were not closed in any patients. Demographic features, lesion's distances to anal verge, excised lesion's size, histopathological report, operation times, duration of hospital stay and complications were recorded RESULTS: Six male and 4 female patients were treated. The mean distance to the anal werge of the lesions was 8.5 (5-12) cm. The longest diameters of the lesions ranged from 1-4 cm in length. All the patients were discharged the day after the surgery. Operation times were found to be 46.1 ± 5 min (30-70). Histopathological examinations of the removed lesions revealed villous adenomas in 3 patients, villous adenoma and Tis adenocarcinoma in 5 patients, villous adenoma and T1 adenocarcinoma in 1 patient and neuroendocrine tumor in 1 patient. There were no early complications such as bleeding, and late complications such as perforation, anal incontinence or anorectal dysfunction in any patient. No evidence of recurrence was found in any of the patients under control rectosigmoidoscopy and pelvic MRI examinations. Partial thickness resection of rectal benign lesions by TAMIS method is safe. After resection some surgeons suggest to close the defect by suture or stapler. In our study resection without closure of the defect is found safe and feasible with limited patient prejudice. Rectal benign lesions, Transanal partial thickness excision.


[Production on alkaline protease by Bacillus subtilis NRRL 3411].
The aim of this work was to study the influence of medium composition and the effect of the operative conditions on alkaline protease production. Several nitrogen sources (in amount of 10 g/l) were tested and compared with bacto peptone Difco: Casein was the best. The addition of "Tween 80" 0,5% resulted in a marked increase in yields of the alkaline protease. The maximum alkaline protease production (3.342.290 UAPAM/g) was achieved using the following medium: Lactose 20 g/l; casein 10 g/l; NaCl 1,5 g/l; MgSO4.7H2O 0,15 g/l; CaCl2.2H2O 0,06 g/l; MnCl2.4H2O 0,01 g/l; "Tween 80" 5,0 g/l; EDTA 1,5 X 10(-4)M; KH2PO4 1,5 g/l; K2H PO4 1,5 g/l; Na2SO4 1,5 g/l. It was found that a volumetric relation of 0,1 ml, vol. of medium/vol. of flask at 25 degrees C of temperature was the best process condition.


The Black Esophagus.
Acute esophageal necrosis (AEN), commonly referred to as black esophagus, is a rare clinical condition resulting from a combination of ischemic insult and thromboembolic injury to the esophagus. It is characterized by the circumferential black appearance of the esophagus. The risk factors for the development of AEN include coronary artery disease (CAD), diabetes mellitus, hypertension, malignancy, and alcohol use disorder. The treatment is directed at correcting the underlying medical conditions, supportive measures, and gastric acid suppression. We present the case of a 60-year-old female with multiple medical comorbidities who was detected to have a black esophagus during the evaluation of anemia.


[The distinctive features of EMG-activity in early age children with movement disorders].
The purpose of this work was the study of neuromuscular characteristics of healthy infants and infants with movement disorders by method of surface electromyography. 76 children at the age from 6 months till 3 years participated in the investigation: 61 with movement disorders (13--with ataxic form of cerebral palsy (CP), 48--with spastic form of CP) and 15 without movement disorders. Passive flexing and extending of knee and hip joints was conducted to the child in a recumbent position, EMG activity of the basic muscles groups of a hip and a shin was recorded. Characteristic properties of electromyographic activity were assessed with wavelet transform and subsequent analysis of obtained time dependencies. As a result of work the parameters connected with diagnosis of infants with movement disorders were revealed.


Stress-induced birefringence control in optical planar waveguides.
For what is to our knowledge the first time, the thermal-stress formula in analytical form is derived for the core layer in an optical planar waveguide by the thin-film approximation, which is based on a closed-form solution in multilayered isotropic structures off the edges. This formula indicates that elastic, thermal, and structural parameters can affect the magnitude of the stress. Using the formula, one can remove thermal stress and hence stress-induced birefringence by proper waveguide design.


Modification of potassium channel kinetics by histidine-specific reagents.
We have examined the actions of histidine-specific reagents on potassium channels in squid giant axons. External application of 20-500 microM diethylpyrocarbonate (DEP) slowed the opening of potassium channels with little or no effect on closing rates. Sodium channels were not affected by these low external concentrations of DEP. Internal application of up to 2 mM DEP had no effect on potassium channel kinetics. Steady-state potassium channel currents were reduced in an apparently voltage-dependent manner by external treatment with this reagent. The shape of the instantaneous current-voltage relation was not altered. The voltage-dependent probability of channel opening was shifted toward more positive membrane potentials, thus accounting for the apparent voltage-dependent reduction of steady-state current. Histidine-specific photo-oxidation catalyzed by rose bengal produced alterations in potassium channel properties similar to those observed with DEP. The rate of action of DEP was consistent with a single kinetic class of histidine residues. In contrast to the effects on ionic currents, potassium channel gating currents were not modified by treatment with DEP. These results suggest the existence of a histidyl group (or groups) on the external surface of potassium channels important for a weakly voltage-dependent conformational transition. These effects can be reproduced by a simple kinetic model of potassium channels.


Review of the current literature as a preparatory tool for the trauma content of the Orthopaedic in-Training Examination.
Currently, the only standardized evaluation of trauma knowledge throughout orthopedic training is found in the Orthopaedic In-Training Examination, which is administered annually to all residents by the American Academy of Orthopaedic Surgeons. Our goals were to assess the Orthopaedic In-Training Examination to (1) determine the content of the trauma questions, (2) identify the content of the 3 most frequently referenced journals on the answer keys, and (3) evaluate the correlation between those contents.We reviewed the trauma-related Orthopaedic In-Training Examination questions and answer keys for 2002 through 2007. Content for test questions and cited literature was assessed with the same criteria: (1) category type, (2) anatomic location, (3) orthopedic focus, and (4) treatment type. For each of the 3 most frequently referenced journals, we weighted content by dividing the number of times it was referenced by the number of its trauma-related articles. We then compared the journal data individually and collectively to the data from the Orthopaedic In-Training Examination trauma questions. A chi-square analysis with Yates correction was used to determine differences. Questions and literature were similar in the most frequently addressed items in each of the 4 areas: category type (taxonomy 3, treatment), 52.4% and 60.7%, respectively; anatomic location (femur), 23.3% and 27.7%, respectively; orthopedic focus (fracture), 51.0% and 56.5%, respectively; and treatment type (multiple/nonspecific), 39.0% and 35.4%, respectively.The content correlation found between the questions and literature supports the idea that reviewing current literature may help prepare for the trauma content on the Orthopaedic In-Training Examination.


Activity of cells in area 17 of the cat in absence of input from layer a of lateral geniculate nucleus.
1. Injections of 4 mM cobaltous chloride were used to block synaptic transmission in layer A of the lateral geniculate nucleus (LGN) without blocking fibers of passage going to or arising from other layers. 2. Selective inactivation of geniculate layer A virtually abolished all visual activity in cortical layers 4ab, 4c, and 6. Under these conditions, the stimulus-evoked response, orientation selectivity, and direction selectivity of cells in layers 2 and 3 were not seriously affected. In layer 5, the effects of the block were more variable, with special complex cells least affected and simple cells most affected. 3. Since the organization of complex receptive fields and the maintenance of normal orientation selectivity in supragranular layers survive disruption of major interlaminar interactions, it appears that much of the functional architecture of cat striate cortex does not depend on the integrity of the column. 4. These results support the idea that each layer of the LGN is a functional unit with a unique pattern of access to the various layers of visual cortex.


Evaluation and surgical treatment of high-grade isthmic dysplastic spondylolisthesis.
In children and young adults who seek medical treatment for high-grade isthmic dysplastic spondylolisthesis, common clinical symptoms are referable to the lumbosacral spine and/or the lower extremities. Pain in the lumbosacral spine may be secondary to altered lumbosacral alignment and biomechanics. It also may be caused by malalignment of the entire spinal-pelvic axis as a result of anterior sagittal imbalance. Lower extremity radiculopathies involving the L5 nerve root(s) may be present, and in severe forms of spondylolisthesis crisis, marked entrapment of the cauda equina at L5-S1 may occur. High-grade isthmic dysplastic spondylolisthesis are treated surgically and should include appropriate central and foraminal decompressions at the L5-S1 level, followed by lumbosacral fusion. Partial reduction aiming at improving the slip angle (lumbosacral kyphosis) is more beneficial and provides less risk to the L5 nerve roots than complete reduction of the translational component of the slip. Solid anterior and posterior spinal fusion at L5-S1 appears to provide the best long-term results.


Newer insecticides and scabicides.
Experimental and clinical data show that taking thiamine chloride internally protects against flea bites. Application of DDT powder to the breeding places of fleas controls infestation. Clinical data appear to show that the use of an ointment containing gamma isomer hexachlorocyclohexane is an effective and pleasant means of treating scabies.


The effect of foliar application of Ascophyllum nodosum (L.) Le Jol. seaweed extract on biochemical traits related to abiotic stresses in pistachio (Pistacia vera L. cv. Kaleh-Ghoochi).
Due to the important economic role of pistachio (Pistacia vera L.) the cultivation of this valuable crop has been extended. Various abiotic stresses harm the growth and performance of pistachio. Seaweed extract containing various substances such as pseudo-hormones that stimulate growth, nutritional elements, and anti-stress substances can cause more resistance to abiotic stresses, and increase the quantity and the quality of the fruit. The present study was conducted to evaluate the effect of foliar application of Ascophyllum nodosum (L.) Le Jol. seaweed extract on some biochemical traits related to abiotic stress in Pistacia vera L. cv. Kaleh-Ghoochi. The first factor of foliar spraying treatment included A. nodosum seaweed extract at four levels (0, 1, 2, and 3 g/L), and the second factor was the time of spraying solution which was done at three times (1- at the beginning of pistachio kernel growth period at the end of June, 2- at the stage of full kernel development at the end of August, and 3- Spraying in both late June and August). The results showed that all investigated traits were significant under the treatment of seaweed extract compared with the control. The seaweed extract concentrations had a significant effect on all traits except soluble carbohydrates, but the time of consumption of seaweed extract on soluble carbohydrates, protein, peroxidase, ascorbate peroxidase, and superoxide dismutase enzymes was significant, while had no significant effect on the rest of the traits. According to the interaction effect of time and concentration of consumption of seaweed extract, the highest values of the biochemical characters were as follows: total phenol content: 168.30 mg CAE/g DW, flavonoid content: mg CE/g DW, catalase: 12.66 µmol APX min- 1 mg- 1 protein, superoxide dismutase: 231.4 µmol APX min- 1 mg- 1 protein, and ascorbate peroxidase: 39.53 µmol APX min- 1 mg- 1 protein. Based on the results of this study, it seems that it is possible to use fertilizers containing A. nodosum seaweed extract with a concentration of 3 g/L in August to increase the tolerance of the pistachio cultivar "Kaleh-Ghoochi" to abiotic stresses.