In vitro effectiveness of azithromycin against doxycycline-resistant and -susceptible strains of Rickettsia tsutsugamushi, etiologic agent of scrub typhus.
In an effort to find a potential alternative treatment for scrub typhus, we evaluated the effectiveness of the standard drug doxycycline and the new macrolide azithromycin against a doxycycline-susceptible strain (Karp) and a doxycycline-resistant strain (AFSC-4) of Rickettsia tsutsugamushi. The antibiotics were tested in an in vitro assay system in which infected mouse fibroblast cells (L929) were incubated for 3 days in various concentrations of the drugs. Rickettsial growth was evaluated by direct visual counts of rickettsiae in Giemsastained cells or by flow cytometry. Initial tests were conducted at the concentration of each antibiotic considered to be the upper breakpoint for susceptibility (16 micrograms/ml for doxycycline and 8 micrograms/ml for azithromycin). Growth of both Karp and AFSC-4 was strongly inhibited with both antibiotics, as measured by visual counts, although the percentage of cells infected with AFSC-4 in the presence of doxycycline was three times greater than the percentage of cells infected with Karp but was only 60% as great as the percentage of cells infected with Karp in the presence of azithromycin. Flow cytometry confirmed that rickettsial growth occurred in the absence of antibiotics, but it failed to detect it in the presence of high concentrations of either drug. Visual counts of rickettsial growth at lower concentrations of the antibiotics (0.25 to 0.0078 microgram/ml) showed that the Karp strain was 16 times more susceptible that the AFSC-4 strain to doxycycline. Azithromycin was much more effective than doxycycline against AFSC-4, inhibiting rickettsial growth at 0.0156 microgram/ml to levels below that achieved by 0.25 microgram of doxycycline per ml. Azithromycin was also more effective than doxycycline against the Karp strain, causing greater reductions in the number of rickettsiae per cell at lower concentrations. If in vivo testing confirms the in vitro effectiveness of azithromycin, it may prove to be the drug of choice for the treatment of scrub typhus in children and pregnant women, who should not take doxycycline, and in patients with refractory disease from locations where doxycycline-resistant strains of R. tsutsugamushi have been found. When tested in an in vitro assay system, azithromycin was more effective than doxycycline against doxycycline-susceptible and -resistant strains of R. tsutsugamushi.


Spatial distribution of malignant tissue in gliomas: correlations of 11C-L-methionine positron emission tomography and perfusion- and diffusion-weighted magnetic resonance imaging.
The prognosis of glioma patients is contingent on precise target selection for stereotactic biopsies and the extent of tumor resection. (11)C-L-methionine (MET) positron emission tomography (PET) demonstrates tumor heterogeneity and invasion with high diagnostic accuracy. To compare the spatial tumor distribution delineated by MET PET with that by perfusion- and diffusion-weighted magnetic resonance imaging (MRI), in order to understand the diagnostic value of these MRI methods, when PET is not available. Presurgical MET PET and MRI, including perfusion- and diffusion-weighted MRI, were acquired in 13 patients (7 high-grade gliomas, 6 low-grade gliomas). A quantitative volume of interest analysis was performed to compare the modalities objectively, supplemented by a qualitative evaluation that assessed the clinical applicability. The inaccuracy of conventional MRI was confirmed (area under the curve for predicting voxels with high MET uptake = 0.657), whereas cerebral blood volume (CBV) maps calculated from perfusion data improved accuracy (area under the curve = 0.760). We considered CBV maps diagnostically comparable to MET PET in 5/7 cases of high-grade gliomas, but insufficient in all cases of low-grade gliomas when evaluated subjectively. Cerebral blood flow and apparent diffusion coefficient maps did not contribute to further accuracy. Adding perfusion-weighted MRI to the presurgical protocol can increase the diagnostic accuracy of conventional MRI and is a simple and well-established method compared to MET PET. However, the definition of low-grade gliomas with subtle or no alterations on cerebral blood volume maps remains a diagnostic challenge for stand-alone MRI.


Integrating language information with a hidden Markov model to improve communication rate in the P300 speller.
The P300 speller is a common brain-computer interface (BCI) application designed to communicate language by detecting event related potentials in a subject's electroencephalogram (EEG) signal. Information about the structure of natural language can be valuable for BCI communication systems, but few attempts have been made to incorporate this domain knowledge into the classifier. In this study, we treat BCI communication as a hidden Markov model (HMM) where hidden states are target characters and the EEG signal is the visible output. Using the Viterbi algorithm, language information can be incorporated in classification and errors can be corrected automatically. This method was first evaluated offline on a dataset of 15 healthy subjects who had a significant increase in bit rate from a previously published naïve Bayes approach and an average 32% increase from standard classification with dynamic stopping. An online pilot study of five healthy subjects verified these results as the average bit rate achieved using the HMM method was significantly higher than that using the naïve Bayes and standard methods. These findings strongly support the integration of domain-specific knowledge into BCI classification to improve system performance and accuracy.


Isolates from faba bean and soybean with lowered content of phytic acid and activity of the trypsin inhibitors.
For obtaining protein isolates, water, whey, and waste effluents from a potato processing plant were used as extraction solvents. Isolates obtained on laboratory conditions were subjected to chemical and organoleptic tests. It was shown that proper steering of the processing allowed for obtaining isolates with lower phytic acid content and decreased activity of the trypsin inhibitors, although the efficiency of the process decreased also. Modified processing was more efficient for elimination of the phytic acid from soybean isolates compared to faba bean. It was also shown that isolate neutralization considerably improved their solubility and decreased the activity of trypsin inhibitors.


Timing of events in normal swallowing: a videofluoroscopic study.
Dynamic videofluoroscopic swallow studies were performed on 60 normal adult volunteers to establish normative data for clinically useful timing measures. The relation of swallowing gesture timing to the timing of actual bolus transit was of particular interest because it provides insight into the physiology of larger bolus volume accommodation. Parameters evaluated include the timing of bolus pharyngeal transit, soft palate elevation, aryepiglottic fold elevation and supraglottic closure, arrival of the bolus in the vallecula, hyoid bone displacement onset and duration, arrival of the bolus at the pharyngoesophageal sphincter, maximum pharyngeal constriction, and pharyngoesophageal sphincter opening. These parameters represent events required for normal deglutition, can be used to identify abnormalities in dysphagic patients, and provide a basis for comparison of swallowing performance both within and between patients. In addition, our experience has shown them to be reliably obtained. Other investigators have reported some of the measurements. However, to our knowledge, normative data for timing of aryepiglottic fold elevation, soft palate elevation and closure, and maximum pharyngeal constriction have not been described. Other measures included in the present study may provide alternatives when conventional measures cannot be obtained in selected patients. The relevance and clinical utility of new and alternative measures, in particular, are discussed.


Use of trans sodium crocetinate for sensitizing glioblastoma multiforme to radiation: laboratory investigation.
Adjuvant treatment with radiation (radiation therapy or radiosurgery) is a mainstay of treatment for patients harboring glioblastomas multiforme (GBM). Hypoxic regions within the tumor make cells less sensitive to radiation therapy. Trans sodium crocetinate (TSC) has been shown to increase oxygen diffusion in the brain and elevate the partial brain oxygen level. The goal of this study was to evaluate the radiosensitizing effects of TSC on GBM tumors. A rat C6 glioma model was used, in which C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Following creation of a right frontal tumor, animals were randomized into 1 of 4 groups: 1) TSC alone (animal treated with moderate-dose TSC only); 2) radiation (animals receiving 8 Gy of cranial radiation); 3) radiation and low-dose TSC (animals receiving 8 Gy of radiation and 50 microg/kg of TSC); or 4) radiation and moderate-dose TSC (animals receiving 8 Gy of radiation and 100 microg/kg of TSC). Animals were observed clinically for 60 days or until death. Magnetic resonance (MR) imaging was performed at 2-week intervals on each animal and quantitatively evaluated for tumor response. Immunohistochemical analysis was performed on all brain tumors. Survival differences were also evaluated using the Kaplan-Meier method. On MR imaging, a statistically significant reduction in tumor size was seen in the group receiving moderate-dose TSC and radiation treatment compared with the group receiving radiation treatment alone. The rate of tumor growth was significantly less for the combination of TSC and radiation treatment compared with either modality alone. Median survival times for the TSC-only and the radiation therapy-only groups were 15 and 30 days, respectively. The 60-day median survival times for the groups receiving a combination of either low- or moderate-dose TSC with radiation therapy were statistically improved compared with those for the other treatment groups. Use of TSC improves the extent of GBM tumor regression following radiation therapy and enhances survival. Radiosensitization of hypoxic tumors through increased oxygen diffusion may have clinical utility in patients with GBM tumors but must be explored in a clinical trial.


DNA sequences of human papillomavirus types 11, 16, and 18 in lesions of the uterine cervix in the west of Scotland.
Punch biopsy specimens of the cervix were examined both histologically and for the presence of human papillomavirus (HPV) DNA sequences. The presence of HPV DNA sequences was sought with the Southern blot technique using radioactively labelled HPV-6, 11, 16, and 18 DNA probes, both together and separately. Twenty six biopsy specimens were examined. Histological examination showed cervical intraepithelial neoplasia grade 2 or 3 in 16 specimens, viral changes (koilocytosis) in four, and inflammation or a normal appearance in three. Eleven specimens were negative for HPV DNA sequences, 10 contained HPV-16 DNA, four contained HPV-18 DNA, and one contained both HPV-18 and HPV-11 DNA. Episomal HPV-16 DNA was detected in one case of cervical intraepithelial neoplasia grade 3 and in five cases of cervical intraepithelial neoplasia grade 2/3 with koilocytosis; and episomal HPV-18 DNA was found in two specimens classed as cervical intraepithelial neoplasia grade 2/3, one of which also contained HPV-11 DNA, and in one specimen that showed viral changes alone. Integrated HPV DNA was found in six specimens (four with HPV-16 DNA and two with HPV-18 DNA), including two cases of chronically inflamed cervix with no histological evidence of viral infection or cervical intraepithelial neoplasia. Detection of viral DNA in early lesions may identify patients at risk of malignant progression. This is the first report of HPV-18 DNA in cervical intraepithelial neoplasia in Scotland.


Regulatory Effects of the Kiss1 Gene in the Testis on Puberty and Reproduction in Hezuo and Landrance Boars.
Kisspeptin, a neuropeptide encoded by the Kiss1 gene, combines with its receptor Kiss1R to regulate the onset of puberty and male fertility by the hypothalamic-pituitary-gonadal axis. However, little is known regarding the expression signatures and molecular functions of Kiss1 in the testis. H&E staining revealed that well-arranged spermatogonia, spermatocytes, round and elongated spermatids, and spermatozoa, were observed in 4-, 6-, and 8-month-old testes compared to 1- and 3-month-old testes of Hezuo pigs; however, these were not observed in Landrance until 6 months. The diameter, perimeter, and cross-sectional area of seminiferous tubules and the perimeter and area of the tubular lumen increased gradually with age in both pigs. Still, Hezuo pigs grew faster than Landrance. The cloning results suggested that the Hezuo pigs' Kiss1 CDS region is 417 bp in length, encodes 138 amino acids, and is highly conserved in the kisspeptin-10 region. qRT-PCR and Western blot indicated that the expression trends of Kiss1 mRNA and protein were essentially identical, with higher expression levels at post-pubertal stages. Immunohistochemistry demonstrated that the Kiss1 protein was mainly located in Leydig cells and post-pubertal spermatogenic cells, ranging from round spermatids to spermatozoa. These studies suggest that Kiss1 is an essential regulator in the onset of puberty and spermatogenesis of boars.


Effect of Maternal Obesity and Preconceptional Weight Loss on Male and Female Offspring Metabolism and Olfactory Performance in Mice.
According to the "developmental origins of health and disease" (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta. We tracked metabolic and olfactory behavioural trajectories of offspring born to control, obese or WL mothers. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD). After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring metabolic phenotypes but had unexpected effects on olfactory performance: a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. Our results confirm the benefits of maternal preconceptional WL for male offspring metabolic health but highlight some possible adverse outcomes on olfactory-based behaviours.


[Early rethoracotomies for diseases and chest traumas].
Rethoracotomies were performed on 34 patients operated for diseases and traumas of the chest, diseases of the esophagus which made up 1.3%. Emergency and reoperations were performed on 14 (46%) patients for ongoing intrapleural bleeding, clotted hemothorax and pulmonary bleeding. Emergency and delayed rethoracotomies were performed on 7 patients for non-hermeticity of the lung and incompetence of the bronchus suture, on 5 patients for incompetence of esophagogastroanastomosis, necrosis of the transplant and gastric wall, 3 patients for chylothorax not-arrested conservatively, 2 patients for gangrene of the residual lung lobe due to disturbed venous outflow. Postoperative complications resulted in death of 12 (37.5%) patients. Causes of lethal outcomes were purulent complications (pleural empyema, mediastinitis, sepsis, polyorganic insufficiency--in 5), massive blood loss with the development of coagulopathy (in 4), pneumonia of the only lung after pulmonectomy (in 2), pulmonary embolism (in 1). In addition, torsion of the residual lung lobe, foreign body in the pleural cavity can be considered as indications for rethoracotomy.


Sex differences in thermal nociception and morphine antinociception in rodents depend on genotype.
It has been appreciated for some time that the sexes can differ in their sensitivity to pain and its inhibition. Both the human and rodent literatures remain quite contentious, with many investigators failing to observe sex differences that others document clearly. Recent data from our laboratory have pointed to an interaction between sex and genotype in rodents, such that sex differences are observed in some strains but not others. However, these studies employed inbred mouse strains and are thus not directly relevant to existing data. We presently examined whether the observation of statistically significant sex differences in nociception and morphine antinociception might depend on the particular outbred rodent population chosen for study. Rats of both sexes and three common outbred strains were obtained from three suppliers (Long Evans, Simonsen; Sprague Dawley, Harlan; Wistar Kyoto, Taconic) and tested for nociceptive sensitivity on the 49 degrees C tail-withdrawal assay, and antinociception following morphine (1-10mg/kg, i.p.). In further studies, three outbred populations of mice (CD-1, Harlan; Swiss Webster, Harlan; Swiss Webster, Simonsen) were bred in our vivarium for several generations and tested for tail-withdrawal sensitivity and morphine antinociception (1-20male, and no significant difference. In a separate study in which the estrous cycle was tracked in female mice, we found evidence for an interaction between genotype and estrous phase relevant to morphine antinociception. However, estrous cyclicity did not explain the observed sex differences. These data are discussed with respect to the existing sex difference and pain literature, and also as they pertain to future investigations of these phenomena.


Development of the UV spectrophotometric method of Olmesartan medoxomil in bulk drug and pharmaceutical formulation and stress degradation studies.
A simple, sensitive, specific, spectrophotometric method was developed for the detection of Olmesartan medoxomil (OLM) in bulk and pharmaceutical formulations. The optimum conditions for the analysis of the drug were established. OLM was subjected to stress degradation under different conditions recommended by the International Conference on Harmonization (ICH). The samples so generated were used for degradation studies using the developed method. The λmax of the OLM was found to be 257 nm. The method exhibited high sensitivity, with linearity, in the 2 to 20 μg/ml range. The lower limit of detection and the limit of quantification were found to be 1.012 μg/ml and 3.036 μg/ml, respectively. All the calibration curves demonstrated a linear relationship between the absorbance and concentration, with the correlation coefficient higher than 0.99. The regression equation of the curve was Y = 0.0579x + 0.0006. The precision of the method was found to be 40.043 ± 0.067 against the label claim of 40 mg. The percentage recovery was found to be 101.32 ± 0.452. The sample solution was stable for up to two hours. Hence, it could be concluded that the proposed method would be suitable for the analysis of OLM in bulk and pharmaceutical formulations.


Ovarian carcinoma: care and survival in a community-based population.
Previous studies of the management and costs of ovarian cancer have been based on data from oncology practices. Such studies may exclude patients who are not candidates for treatment and may not account for costs incurred during diagnosis or primary treatment. The purpose of this study was to describe the epidemiology, management, and costs of care of ovarian cancer in a geographically defined population to better reflect the total spectrum of the disease and its care. We conducted a retrospective review of the medical records of all residents of Olmsted County, Minnesota, who received a first diagnosis of epithelial ovarian carcinoma (including postmortem diagnoses) between 1985 and 1997. Of the 107 women with a new diagnosis of ovarian cacinoma, 42 (39%) had stage I or II tumors at the time of diagnosis. The mean age of the patients at the time of diagnosis was 64.7 years, and 20% were nulliparous. The diagnostic assessment for ovarian carcinoma was initiated by a family physician or internist in 50% of cases and by an obstetrician or gynecologist in 16% of cases. One hundred two patients (95%) underwent surgical treatment, and 80 (75%) received primary chemotherapy. The 5-year survival rate was 88% in those with stage I or II tumors and 17% in those with stage III or IV tumors. The mean charges for secondary care were higher than those for primary care ($36,110 vs $32,367; P < 0.05) in those receiving both types of therapy. Fifty percent of those dying of ovarian cancer received hospice care for a mean of 39.0 days before death. Most assessments leading to a diagnosis of ovarian carcinoma were initiated by primary care physicians. In this community-based population, early-stage and low-grade tumors were common (> or = 30%) and were associated with lower costs of care and higher 5-year survival rates. Total treatment costs for those requiring secondary therapy were approximately twice the costs for those requiring primary treatment only, with approximately 50% of costs associated with inpatient care.


Investigating the Effect of Aging on the Viscosity of Tendon Fascicles and Fibers.
In the current work, we investigate the effect of aging on the viscosity of tendon subunits. To that scope, we make use of experimental relaxation curves of healthy and aged tendon fascicles and fibers, upon which we identify the viscosity parameters characterizing the time-dependent behavior of each tendon subunit. We subsequently combine the obtained results with analytical viscoelastic homogenization analysis methods to extract information on the effective viscous contribution of the embedding matrix substance at the fiber scale. The results suggest that the matrix substance plays a significant role in the relaxation process of the upper tendon subunits both for aged and healthy specimens. What is more, the viscosity coefficients computed for the fibrillar components indicate that aging leads to a viscosity reduction that is statistically significant for both fascicles and fibers. Its impact is more prominent for the lower hierarchical scale of fibers. As such, the reduced stress relaxation capability at the tendon macroscale is to be primarily attributed to the modified viscosity of its inner fibrillar subunits rather than to the matrix substance.


Cognitive-behavioral versus non-directive therapy for preschoolers with severe nighttime fears and sleep-related problems.
To compare the efficacy of a developmentally appropriate cognitive-behavioral therapy protocol for preschoolers with severe nighttime fears and sleep-related problems, with an active control treatment. Ninety children aged four to six years (63% boys) with severe nighttime fears and their parents were randomized to either cognitive-behavioral therapy including parent involved play (CBT-PIP) or to a structurally equivalent non-directive treatment (TEPT; triadic expressive play therapy). Treatment conditions were also equivalent in parent- and child-rated credibility and expectancy, and in therapist-rated compliance. Children and parents were assessed at baseline, during the first intervention week and four weeks after treatment. Measures included actigraphy, daily sleep logs, structured diagnostic interviews and parent questionnaires. Significant reductions were observed in nighttime fears and objectively and subjectively measured sleep disruptions in both intervention groups following treatment. Parent reports indicated more advantageous outcomes for CBT-PIP compared to TEPT, with greater reductions in sleep problems and co-sleeping as well as higher customer satisfaction in the former group. While CBT-PIP showed no significant advantage compared to the active control in reducing fears or in improving objectively measured sleep, it was significantly more beneficial in reducing the adverse behavioral features of nighttime fears.


A gender comparison of motivations for seeking leadership positions among gastroenterologists.
A gender gap exists in leadership positions in gastroenterology. However, individual motivations for seeking leadership positions within the gastroenterology community among men and women have not been explored. The primary aim of this study was to determine whether motivations for pursuing and attaining leadership positions in gastroenterology differ by gender. A 20-question survey was created by the authors and shared with gastroenterologists electronically via a social media group (Facebook) and emails gathered through publicly available society websites and professional and social contacts. Data gathered from the survey included demographics, practice characteristics, presence of spouse or domestic partner, past and present leadership positions, motivations for pursuit of leadership positions, and reasons for lack of desire for a leadership position. The survey was sent to 981 gastroenterologists (679 women, 302 men). The overall response rate was 21.4% (n = 210) (20.9% for women, 22.5% for men). Overall, 41% of respondents (84 of 206) currently hold a leadership position, including more males than females (52% vs 36%, respectively; P = .03). However, among those who completed their training in the past 5 years, more women than men hold a current leadership role (25% vs 6%; P = .11). Other factors associated with currently holding a leadership position included age and years since completion of training, practice type, full-time status, and having a spouse who is not a physician. The positive factors of leadership cited most frequently were (1) ability to effect change, (2) furthering the goals of the organization, and (3) opportunity for career advancement. The negative factors cited most frequently were increased workload and decreased time for personal life. These reported positive and negative factors were similar for male and female respondents. Forty-nine respondents did not desire a leadership position now or in the future. The most common reason cited was lack of interest in the responsibilities, long hours, or stress that accompanies a leadership position (22 of 42, 52%). The second most common reason was that respondents were too busy at home or work to take on the extra responsibilities. A gender gap in gastroenterology leadership exists but is closing. There is fairly equal representation of men and women in leadership positions among those who completed training in the last 5 years. Many gastroenterologists are motivated for a leadership position and at the same time, many qualified individuals do not desire a leadership position because of factors that affect work-life balance. Ongoing efforts to engage motivated individuals into leadership positions and to revise the nature of leadership positions may allow for a larger talent pool from which to recruit.


Protection of jejunal crypts by RH-3 (a preparation of Hippophae rhamnoides) against lethal whole body gamma irradiation.
RH-3, an alcoholic extract of whole berries of Hippopheae rhamnoides, has been demonstrated to provide radioprotective activity in terms of survival of mice against whole body lethal irradiation (10 Gy). It was, therefore, investigated for its mode of action by monitoring crypt survival, cellularity of crypts and villi and the magnitude of apoptosis in the GI tract. Administration of RH-3 before irradiation (-30 min) increased the number of surviving crypts in the jejunum by a factor of 2.02 (p < 0.05) and villi cellularity by 2.5 fold (p < 0.05) in comparison to the irradiated control. RH-3 administration before irradiation also reduced the incidence of apoptotic bodies in the crypts (p < 0.05) in a time dependent manner and increased cellularity in the crypts and villi (84 h post irradiation) as compared to control. Caspase-3 activity was also significantly lower in the mice administered RH-3 before irradiation as compared to irradiated control. This study indicates that reduction in the radiation induced loss of cellularity of crypts and villi and also decrease in frequency of apoptosis could have contributed towards protection of mice treated with RH-3 before irradiation. The cellular and molecular mechanisms of radioprotection by Rh-3 need to be investigated further in detail.


[Calcified coronary artery disease and serum markers].
Severity of coronary artery calcification is closely related to atherosclerotic plaque burden and cardiac event rate. Recent data have suggested that vascular calcification is an actively regulated process similar to the bone formation, and that bone-related factors may be involved in the development of vascular calcification. Non-invasive prediction of calcified coronary artery disease is important using serum bone-related markers. Among them, we focus on matrix Gla protein, osteoprotegerin and fetuin-A as such candidates in this review.


Structural basis for variations in the sensitivity of human decay accelerating factor to phosphatidylinositol-specific phospholipase C cleavage.
Human decay-accelerating factor (DAF) proteins expressed on E and nucleated cells differ in their susceptibility to phosphatidylinositol (PI)-specific phospholipase C (PLC) cleavage/release. To investigate the mechanism of this difference, the glycoinositol-phospholipid anchoring moieties of E DAF, and of HeLa cell, polymorphonuclear cell, and lymphocyte DAF were structurally compared. Labeling of PI-PLC-resistant E DAF with 3-(trifluoromethyl)-3-(m-[125I]-iodophenyl)-diazirine ([125I]TID) and TLC analysis of nitrous acid deamination anchor fragments showed a predominant phospholipid species with less polar migration than the 125I-TID-labeled PI. Gas chromatographic analyses of methanolyzed E protein revealed 2.20 +/- 0.16 mol of fatty acids [16:0, 18:0, 18:1, 20:4, 22:4, and 22:5 (0.76, 0.36, 0.25, 0.15, 0.40, 0.28 mol, respectively)] and 0.86 +/- 0.05 mol of inositol per mol of N-terminal Asp. Gas chromatography-mass spectroscopy demonstrated principally myo-inositol but also variable amounts of the chiro-isomer. Nondenaturing polyacrylamide gel electrophoresis of 14C-radiomethylated E protein revealed that pretreatment with hydroxylamine, a reagent which removes ester-linked lipids, rendered it PI-PLC susceptible. In contrast, parallel analyses of 35S-cys-labeled PI-PLC-sensitive HeLa DAF protein revealed only minor amounts of the hydroxylamine-sensitive phospholipid species. Similar results were obtained with 125I-surface-labeled DAF from polymorphonuclear cells, as well as from unstimulated peripheral blood and anti-CD3-activated lymphocytes. These findings demonstrate that, rather than PI, the E DAF anchor contains an inositol alkylacylglycerol-phospholipid which is heterogeneous with respect to acyl groups and inositol isomers, that an ester-linked substitution in this inositolphospholipid underlies the resistance of E DAF protein to PI-PLC cleavage/release, and that this structural modification is cell-specific.


Present and future role of Mental Illness Advocacy Associations in the management of the mentally ill: realities, needs and hopes at the edge of the third millennium.
The purpose of the present review is the analysis of the development and current status of the Mental Illness Advocacy Movement in the USA and in Europe, as well as of the role such a movement is playing in the management of the mentally ill. Information on the issue has been collected via literature search and several personal inquiries and contacts with different Mental Illness Advocacy Groups in the USA and in Europe. The findings indicate that the Mental Illness Advocacy Movement is very alive and in full growth. Its role in the management of the mentally ill has become more and more important over the years. In several countries, it makes it possible to overcome some of the deficiencies of the National or Private Health Services. Thanks to the actions of the various Mental Illness Advocacy Groups, today, patients and families are more and better informed of their conditions and their rights. In many cases, this results in earlier diagnosis, better compliance and better outcomes. However, despite significant improvement in the status of the mentally ill patient, much still remains to be done. We need an improved dialogue with mental heath providers, public administrators, mental health policy makers, mass media and politicians. The dialogue between primary care team and the specialist must also be improved. A global alliance for action is needed to ensure better and more available services to those who suffer from mental disorders.


Cutaneous Adenoid Cystic Carcinoma with Perineural Invasion Diagnosed in the Foot: A Case Report.
Adenoid cystic carcinoma is a rare, slow-growing neoplasm. It is most commonly located in the salivary glands, affects people older than 55 years of age, and has a predilection for women. These lesions may recur locally but have shown low metastatic potential. We present the unique case of a 71-year-old female with a nonraised hyperpigmented lesion isolated to the right heel. Confusion surrounded the clinical presentation of this dermatologic lesion, and many physicians postulated several differential diagnoses. The purpose of this case report is to bring further awareness to this rare dermatologic variant of adenoid cystic carcinoma, which has been rarely reported in the literature.


The Inhibitory Effect of Eplerenone on Cell Proliferation in the Contralateral Kidneys of Rats with Unilateral Ureteral Obstruction.
The unilateral ureteral obstruction (UUO) model not only induces renal interstitial fibrosis in the obstructed kidney but also induces injury in the contralateral kidney. We hypothesized that activation of the mineralocorticoid receptor (MR) may induce fibrosis in the early stage of UUO. Thirty male Sprague-Dawley rats weighting 200 ± 10 g were used in this study and randomly divided into 3 groups: a UUO group, a UUO and eplerenone group, and a sham group. The contralateral kidney and plasma were harvested for further study 10 days after surgery. The level of plasma aldosterone (869.95 ± 55.851 pg/mL) was significantly higher in the UUO group than that in the sham group (478.581 ± 36.186 pg/mL vs. UUO, p < 0.05). The infiltrated inflammatory cells (F4/80) and deposited collagens were increased significantly in the contralateral kidneys in the UUO group compared to those in the sham group, which were decreased by eplerenone. However, proliferating cell nuclear antigen was increased 2.47 times in the UUO group compared to the sham group in the contralateral kidney (p < 0.01), and those changes are attenuated by eplerenone. The expression of SGK-1 protein and mRNA was upregulated in the contralateral kidney in the UUO group, which is suppressed by eplerenone treatment. NF-κB pathway effecters were also changed markedly in the contralateral kidney in the UUO group and partly reversed by eplerenone. Aldosterone induces inflammatory cell proliferation via the MR/SGK-1 and NF-κB pathways and eventually leads to fibrosis in the contralateral kidney.


ADHD: an integration with pediatric traumatic brain injury.
This review examines the long-standing finding that ADHD is a common sequela of pediatric traumatic brain injury (PTBI) in light of the current conceptualization of ADHD as a dimensional, neuropsychologically heterogeneous disorder. The review contends that this conceptualization established the basis for concluding that frequently occurring symptoms caused by PTBI, such as slow processing speed, emotional dysregulation and disinhibition, are indicative of ADHD. Consequently, it concludes that ADHD following PTBI is even more common than the 30% rate the current literature suggests. It provides recommendations for the assessment and treatment of ADHD associated with PTBI.


Comparative efficacy of five different rep-PCR methods to discriminate Escherichia coli populations in aquatic environments.
Development of efficient techniques to discriminate the sources of E. coli in aquatic environments is essential to improve the surveillance of fecal pollution indicators, to develop strategies to identify the sources of fecal contamination, and to implement appropriate management practices to minimize gastrointestinal disease transmission. In this study the robustness of five different rep-PCR methods, such as REP-PCR, ERIC-PCR, ERIC2-PCR, BOX-PCR and (GTG)(5)-PCR were evaluated to discriminate 271 E. coli strains isolated from two watersheds (Lakelse Lake and Okanagan Lake) located in British Columbia, Canada. Cluster analysis of (GTG)(5)-PCR, BOX-PCR, REP-PCR, ERIC-PCR and ERIC2-PCR profiles of 271 E. coli revealed 43 clusters, 35 clusters, 28 clusters, 23 clusters and 14 clusters, respectively. The discriminant analysis of rep-PCR genomic fingerprints of 271 E. coli isolates yielded an average rate of correct classification (watershed-specific) of 86.8%, 82.3%, 78.4%, 72.6% and 55.8% for (GTG)(5)-PCR, BOX-PCR, REP-PCR, ERIC-PCR and ERIC2-PCR, respectively. Based on the results of cluster analysis and discriminant function analysis, (GTG)(5)-PCR was found to be the most robust molecular tool for differentiation of E. coli populations in aquatic environments.


Transcriptional programming during cell wall maturation in the expanding Arabidopsis stem.
Plant cell walls are complex dynamic structures that play a vital role in coordinating the directional growth of plant tissues. The rapid elongation of the inflorescence stem in the model plant Arabidopsis thaliana is accompanied by radical changes in cell wall structure and chemistry, but analysis of the underlying mechanisms and identification of the genes that are involved has been hampered by difficulties in accurately sampling discrete developmental states along the developing stem. By creating stem growth kinematic profiles for individual expanding Arabidopsis stems we have been able to harvest and pool developmentally-matched tissue samples, and to use these for comparative analysis of global transcript profiles at four distinct phases of stem growth: the period of elongation rate increase, the point of maximum growth rate, the point of stem growth cessation and the fully matured stem. The resulting profiles identify numerous genes whose expression is affected as the stem tissues pass through these defined growth transitions, including both novel loci and genes identified in earlier studies. Of particular note is the preponderance of highly active genes associated with secondary cell wall deposition in the region of stem growth cessation, and of genes associated with defence and stress responses in the fully mature stem. The use of growth kinematic profiling to create tissue samples that are accurately positioned along the expansion growth continuum of Arabidopsis inflorescence stems establishes a new standard for transcript profiling analyses of such tissues. The resulting expression profiles identify a substantial number of genes whose expression is correlated for the first time with rapid cell wall extension and subsequent fortification, and thus provide an important new resource for plant biologists interested in gene discovery related to plant biomass accumulation.


Contextualizing black emerging adults' perceptions of neighborhood quality.
The ways in which Black emerging adults perceive and evaluate their neighborhoods may be impacted by a host of social and political factors that interplay with their social identities, the social identities of other urban residents, and their time in the area. Early literature on Black emerging adults' perceived neighborhood quality (PNQ) tended to make comparisons to White people and to focus disproportionately on the perceptions of low-income Black people residing in predominately racial/ethnic minority and underresourced communities. Subsequent work on subjective neighborhood assessment has considered specific features of neighborhoods, such as safety or disorder, but a general sense of the quality of one's neighborhood features is still underexplored. The current study adapts Connerly and Marans' (1985) PNQ model to explore the relations between social identities and locations, neighborhood sociostructural features, time in the area, and PNQ among Black urban-residing emerging adults. Block-wise regression results suggest that education and partner status were associated with PNQ. Perceptions of the percentage of Black neighbors and Census Bureau proportions of residents in the zip code who are poor were also associated with PNQ. Length of residence in the neighborhood was marginally associated with PNQ while length of residence in the city/town was not significantly associated with PNQ. For young Black women, combined household income was marginally associated with PNQ, but neighborhood sociostructural features were the strongest contributors to PNQ. In contrast, education was the only significant contributor to PNQ for young Black men. We discuss the ways that the social positions of young Black residents and their neighbors may impact their experiences and evaluations of urban areas.


Glycosylation influences activity, stability and immobilization of the feruloyl esterase 1a from Myceliophthora thermophila.
Heterologous protein production is widely used in industrial biotechnology. However, using non-native production hosts can lead to enzymes with altered post-translational modifications, such as glycosylation. We have investigated how production in a non-native host affects the physicochemical properties and enzymatic activity of a feruloyl esterase from Myceliophthora thermophila, MtFae1a. The enzyme was produced in two microorganisms that introduce glycosylation (M. thermophila and Pichia pastoris) and in Escherichia coli (non-glycosylated). Mass spectrometric analysis confirmed the presence of glycosylation and revealed differences in the lengths of glycan chains between the enzymes produced in M. thermophila and P. pastoris. The melting temperature and the optimal temperature for activity of the non-glycosylated enzyme were considerably lower than those of the glycosylated enzymes. The three MtFae1a versions also exhibited differences in specific activity and specificity. The catalytic efficiency of the glycosylated enzymes were more than 10 times higher than that of the non-glycosylated one. In biotechnology, immobilization is often used to allow reusing enzyme and was investigated on mesoporous silica particles. We found the binding kinetics and immobilization yield differed between the enzyme versions. The largest differences were observed when comparing enzymes with and without glycosylation, but significant variations were also observed between the two differently glycosylated enzymes. We conclude that the biotechnological value of an enzyme can be optimized for a specific application by carefully selecting the production host.


Occupational asthma caused by nickel sulfate.
A 28-yr-old man developed asthma shortly after being exposed to nickel sulfate (NiSO4) in a metal-plating factory. Recordings of peak expiratory flow rates at work and for an off-work period showed increased variations at work, with best values on weekends. Allergy prick skin tests elicited an immediate reaction with NiSO4 at a concentration of 10 mg/ml. Experimental inhalation challenges with NiSO4 at the same concentration of 10 mg/ml for 60 sec produced a bronchial obstruction typical of an early asthmatic response. A control asthmatic subject with a similar level of sensitivity to histamine failed to react after the same inhalation of NiSO4, which suggests a specific rather than irritant mechanism for the reaction. the patient had evidence of IgE antibody to a NiSO4-human serum albumin antigen. His serum selectively bound 63 Ni, and the test was selectively blocked by nonlabeled nickel sulfate. These results, evaluated together, suggest the development of occupational asthma caused by allergy to NiSO4 in this patient.


Dietary inflammatory index (DII®) and the risk of depression symptoms in adults.
Findings from observational studies investigating the association between Dietary Inflammatory Index (DII®) scores and depression symptoms (DepS) are inconsistent. This study aims to assess the association between energy-adjusted DII (E-DII™) and DepS using the North West Adelaide Health Study (NWAHS) cohort as well as update a previous meta-analysis. A total of 1743 (mean ± SD age: 56.6 ± 13.6 years, 51% female) study participants from NWAHS were included in the cross-sectional study and 859 (mean ± SD age: 58.4 ± 12.1 years, 52.6% female) in the longitudinal analyses. The Center for Epidemiological Studies Depression Scale (CES-D) was used for the measurement of DepS. E-DII scores were calculated from the dietary data collected using a validated food frequency questionnaire (FFQ). Data from two stages [Stage 3 (2008-10) and North West 15 (NW15) (2015)] were used. Log- and negative binomial regression were used to assess the association between quartiles of E-DII and DepS. A recent meta-analysis was updated by including 12 publications (six cross-sectional and six cohort studies) on the association between DII and DepS. In the cross-sectional analysis, a higher E-DII score (i.e., more pro-inflammatory diet) was associated with a 79% increase in odds of reporting DepS [ORQuartile4vs1: 1.79; 95% CI: 1.14-2.81; p = 0.01; p for trend (ptrend) = 0.03]. Males with higher E-DII had a more than two-fold higher odds of DepS (ORQuartile4vs1: 2.27; 95% CI: 1.02-5.06; p = 0.045; ptrend = 0.09). Females with higher E-DII had an 81% increase in odds of DepS (ORQuartile4vs1: 1.81; 95% CI: 1.01-3.26; p = 0.046; ptrend = 0.07). These associations were consistent in the longitudinal analysis. Comparing highest to lowest quintiles of E-DII, the updated meta-analysis showed that a pro-inflammatory diet is associated with a 45% increase in odds of having DepS (OR: 1.45; 95% CI: 1.20-1.74; p < 0.01) with higher odds in females (OR: 1.53; 95% CI: 1.16-2.01; p = 0.01) compared to their male counterparts (OR: 1.29; 95% CI: 0.98-1.69; p = 0.15). The data from the NWAHS and the updated meta-analysis of observational studies provide further evidence that a pro-inflammatory diet is positively associated with increased risk of DepS. These findings support the current recommendation on consuming a less inflammatory diet to improve DepS.


Potential of a gypsum-free composting process of wheat straw for mushroom production.
Wheat straw based composting generates a selective substrate for mushroom production. The first phase of this process requires 5 days, and a reduction in time is wished. Here, we aim at understanding the effect of gypsum on the duration of the first phase and the mechanism behind it. Hereto, the regular process with gypsum addition and the same process without gypsum were studied during a 5-day period. The compost quality was evaluated based on compost lignin composition analysed by py-GC/MS and its degradability by a commercial (hemi-)cellulolytic enzyme cocktail. The composting phase lead to the decrease of the pyrolysis products 4-vinylphenol and 4-vinylguaiacol that can be associated with p-coumarates and ferulates linking xylan and lignin. In the regular compost, the enzymatic conversion reached 32 and 39% for cellulose, and 23 and 32% for xylan after 3 and 5 days, respectively. In absence of gypsum similar values were reached after 2 and 4 days, respectively. Thus, our data show that in absence of gypsum the desired compost quality was reached 20% earlier compared to the control process.


Relevance of proliferative and pro-apoptotic factors in non-small-cell lung cancer for patient survival.
This investigation first set out to analyse which cellular proliferative and apoptotic factors, in addition to the clinical prognostic factors, are most predictive in patients with non-small-cell lung carcinomas (NSCLC). To this purpose, we related the proliferative factors proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin-dependent kinase 2 (cdk2), cdk4 and the proportion of cell cycle phases in NSCLC to the survival times of 150 patients. Additionally, we associated the expressions of Fas, Fas ligand and caspase-3 in NSCLC to patient survival. Immunohistochemistry was used to determine the proteins and flow cytometry to assess the proportion of cell cycle phases. Patients with PCNA-positive carcinomas had significantly shorter survival times than patients with PCNA-negative carcinomas (median survival times: 51 vs 89 weeks). Corresponding results were obtained with the factor cyclin A (64 vs 92 weeks), with the factor cdk2 (76 vs 89 weeks), with the factor cdk4 (62 vs 102 weeks) and with the proportion of S phases (86 vs 121 weeks). Patients with an expression of the apoptotic factors had a more favourable prognosis than patients with negative carcinomas. The median survival times of cancer patients with Fas expression was 86 weeks and of those without Fas expression only 69 weeks. Corresponding results were obtained with the Fas ligand (87 vs 41 weeks) and caspase 3 (87 vs 34 weeks). In order to determine whether a combination of factors can yield improved prognostic information, we investigated all possible combinations of the proliferative and apoptotic factors. Patients with tumours having a high proliferative activity, but which did not express apoptotic factors had the shortest survival times while patients with a low proliferative activity and a high expression of apoptotic factors had the most favourable outcome. A multivariate analysis (Cox model) of the cellular and clinical prognostic factors indicated that stage, lymph node involvement, Fas, PCNA and cyclin A are the most important prognostic factors for the clinical outcome of patients with non-small-cell lung carcinomas.


An appraisal of the sediment yield in western Mediterranean river basins.
The number of studies assessing soil erosion and sediment transport has increased with the aim of achieving sustainable land and water management. Mediterranean rivers have been the object of many of these studies due to their naturally high values of sediment fluxes and a higher vulnerability under future climate scenarios. In this context, we attempt to use empirical relationships to (i) further assess the relation between sediment yield and basin scale and (ii) provide an update on the main drivers controlling sediment yield in these particular river systems. For this purpose, sediment yield data (from reservoir sedimentation surveys and sediment transport records) was collected from >100 locations distributed across the western Mediterranean area, with basin areas ranging from 1 to 100,000km2. Quantile Regression analysis was used to assess the correlation between basin area and sediment yield, while additional basin-scale descriptors were related to sediment yield by means of multiple regression analysis. Results showed the complexity in the relationship between basin scale and sediment yield, with changes in supply conditions with increasing area introducing uncertainties in the correlation. Despite the large scatter, analysis pointed towards the same direction and area appeared to be the main constrain for the maximum value of sediment yield that can be found at a specific basin scale. Results from the multiple regression indicated that variables representing basin's physiography, climate and land use were highly correlated with the basins' sediment yield. Also, a better model performance was obtained when using total sediment yield instead of specific values (per unit area). Validation showed model instability, potentially due to data limitations and the use of catchments with varying characteristics. Overall, despite providing some insights on the correlation between sediment yield and basin-scale characteristics, validation prevented direct extrapolation of the model to other catchments.


Highly polymorphic microsatellite loci in the colonial ascidian Botryllus schlosseri.
Five mircosatellite loci are characterized for the colonial ascidian Botryllus schlosseri. Within one population from Monterey, California, these loci have 3 to 17 alleles, observed heterozygosities from 0.40 to 0.63, expected heterozygosities from 0.52 to 0.84, and an overall paternity exclusion rate (QT) of 0.78. Three of the five loci demonstrated Mendelian patterns of inheritance in laboratory crosses. The size distribution of alleles suggests that most allelic diversity within these loci is generated by single-step and less frequently multistep mutations. However, several alleles may also have been generated by single based insertions or deletions. Mutation rates for the five microsatellite loci are less than 1 x 10(-2) per generation. Because or their highly polymorphic nature, these loci should prove useful for exploring issues of identity, kinship, population structure, and phylogenetics.


Macroscopic Examination of Multiple-Shot Cattle Heads-An Animal Welfare Due Diligence Tool for Abattoirs Using Penetrating Captive Bolt Devices?
Ideally, the application of a penetrating captive bolt device to render cattle immediately unconscious prior to slaughter would be 100% effective. Unfortunately, due to various factors this is not always the case. This paper examined, as an initial proof of concept, 12 bovine heads which had received more than one shot from a penetrating captive bolt, collected from various abattoirs within the United Kingdom. The heads were frozen to facilitate splitting on the medial plane to prevent distortion of soft tissue and each sagittal section was examined macroscopically to ascertain if this method could be used to determine the reasons for repeated stun attempts. In 10 out of 12 heads, shot placement was the determining factor, in one other head it was felt that anatomical variation was the reason and the twelfth head demonstrated signs of gun malfunction as the likely cause. This work provides evidence for a larger trial to facilitate the production of guidance for the abattoir industry, the Animal Welfare Officer and regulators on the examination of heads as part of an investigation of failures of a mechanical stunning system and to provide training material for slaughter staff tasked with effectively stunning cattle.


CMIP Promotes Proliferation and Metastasis in Human Glioma.
Glioma is one of the most common primary malignant brain tumors and the outcomes are generally poor. The intrinsic mechanisms involved in glioma development and progression remain unclear. Further studies are urgent and necessary. In this study, we have proven that CMIP (C-Maf-inducing protein) promotes cell proliferation and metastasis in A172 cells through knockdown of CMIP and in U251 cells through overexpression of CMIP by using MTT assay, cell colony formation assay, cell migration assay, and cell invasion assay. Furthermore, we discovered that CMIP upregulates MDM2, which is involved in the promoting role of CMIP in human glioma cells. For clinical study, 99 glioma tissues and 59 normal tissues were analyzed. CMIP expression was higher in glioma tissues than in normal tissues. In glioma tissues, CMIP is found to correlate positively with tumor grade but no significant correlation is found with patients' age, gender, or Karnofsky performance score (KPS). Moreover, CMIP also correlates with low relapse-free survival (RFS) rate and overall survival (OS) rate in glioma patients. Therefore, CMIP is oncogenic and could be a potential target for human glioma diagnosis and therapy.


Improvements in diabetic albuminuria and podocyte differentiation following Roux-en-Y gastric bypass surgery.
Multiple studies demonstrate an albuminuria-lowering impact of Roux-en-Y gastric bypass surgery, but neither evaluation of its penetrance across different baseline levels of albuminuria nor its association with alterations in podocyte phenotype has previously been reported. We profiled changes in body weight, glycaemic control and urinary albumin excretion following Roux-en-Y gastric bypass surgery in 105 patients with type 2 diabetes, albuminuria of varying degrees of severity and classified as being at moderate or high risk of chronic kidney disease progression according to the Kidney Disease: Improving Global Outcomes 2012 criteria. In parallel pre-clinical studies, the impact of Roux-en-Y gastric bypass surgery on markers of podocyte injury was assessed in the Zucker diabetic fatty rat model of diabetic kidney disease. At 12- to 18-month post-operative follow-up in patients at moderate or high risk of chronic kidney disease, significant reductions in albuminuria were observed across all tertiles of baseline albumin-creatinine ratio, with remission of albuminuria occurring in 78% of patients. Relative to sham-operated control animals, weight loss and improvements in glycaemia following Roux-en-Y gastric bypass surgery in Zucker diabetic fatty rats were paralleled by normalisation of glomerular tuft-size, reductions in podocyte expression of desmin, and preservation of podocyte foot process morphology. Improvements in podocyte differentiation likely underpin the reductions in albuminuria observed following Roux-en-Y gastric bypass surgery.


Benefits of a Psychodynamic Group Therapy (PGT) Model for Treating Veterans With PTSD.
To examine the effectiveness of a treatment model of psychodynamic group therapy (PGT) for combat Veterans with posttraumatic stress disorder (PTSD). A total of 158 male Veterans with PTSD (mean age = 30.09 years) were assigned to 15 treatment groups of 7-13 patients each. PGT was a 1-year therapy, 1.5 hour, once-a-week sessions administered in the following stages: group building activities, differentiation of group members, intimacy building, and termination. Levels of PTSD and depression symptoms, functioning, and hope were assessed at pretreatment baseline, posttreatment, and 12-month follow-up. Multilevel modeling analyses indicate that our group therapy is associated with reductions in PTSD and depressive symptoms at posttreatment, and that these effects were maintained at 12-month follow-up. The results also showed significantly improved patients' functioning by the end of therapy and at the 12-month follow-up point, and that the patients' hope level had increased. The findings show that our model of psychodynamic group therapy is associated with mental improvements in Veterans with PTSD. However, further randomized controlled trials are recommended to establish the advantages of our therapeutic method compared to other modes of therapy.


The importance of the type I interferon system in autoimmunity.
The type I interferon (IFN) system is our main defense against viral infections and consists of a large number of sensors of nucleic acid that can trigger the production of more than 15 different proteins with antiviral and immunostimulatory capacity. There are several observations suggesting an important role for this system in the etiopathogenesis of systemic lupus erythematosus (SLE) and other autoimmune diseases. Among these are the development of autoimmune diseases during IFN-α treatment, a prominent increase in the expression of type I IFN regulated genes (an IFN signature) in a number of rheumatic diseases, the existence of endogenous IFN inducers in SLE patients and a genetic association between autoimmune diseases and gene variants within the type I IFN signalling pathway. Collectively, these observations suggests that inhibition of the type I IFN system could be beneficial in SLE and possible also other autoimmune diseases. Many different therapeutic targets exist and several studies are in progress aiming to block or down-regulate the activated type I IFN system. A number of studies with monoclonal anti-IFN-α antibodies in SLE patients have been reported, and a small study investigating vaccination with an interferon-α-kinoid against IFN-α has been published. Trials targeting the type I IFN receptor are under way, and other possibilities include elimination of the endogenous IFN inducers and inhibition of key molecules in the type I IFN signalling pathway. Results so far show that it is possible to partially suppress the IFN signature, improve several biomarkers and ameliorate clinical manifestations by some of these new treatment strategies.


Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum marianum).
Complete separation, isolation, and structural characterization of four diastereoisomeric flavonolignans, silybins A (1) and B (2), and isosilybins A (3) and B (4) from the seeds of milk thistle (Silybum marianum) were achieved for the first time using a preparative reversed-phase HPLC method. In addition, three other flavonolignans, silychristin (5) isosilychristin (6) and silydianin (7), and a flavonoid, taxifolin (8) were isolated. Structures, including absolute stereochemistries of 1-4, were confirmed using 2D NMR and CD spectroscopy.


MR imaging of treated prostate cancer.
Many management options are available to patients with newly diagnosed prostate cancer. Magnetic resonance (MR) imaging plays an important role in initial staging of prostate cancer, but it also aids in tumor detection when there is clinical or biochemical suspicion of residual or recurrent disease after treatment. The purpose of this review is to describe the normal appearances of the prostatic region after different kinds of treatment for prostate cancer and to discuss how these appearances differ from those of recurrent and residual disease. Several MR imaging techniques used in evaluating patients with prostate cancer are described, including conventional MR imaging sequences (mainly T1- and T2-weighted sequences), MR spectroscopic imaging, diffusion-weighted imaging, and dynamic contrast agent-enhanced MR imaging. Clinical considerations, together with the different approaches for interpreting serum prostate-specific antigen values in the posttreatment setting, are also presented. All forms of treatment alter the MR imaging features of the prostatic region to a greater or lesser extent, and it is important to be able to recognize expected posttreatment appearances and distinguish them from the features of recurrent or residual cancer to aid subsequent clinical management.


Less Complex Contact Lens Required for a Patient With Keratoconus After Topography-Guided Photorefractive Keratectomy.
In this report, we discuss contact lens (CL) fitting in a patient with a history of keratoconus (KC), before and after undergoing topography-guided photorefractive keratectomy (TG PRK). Before TG PRK, the patient failed multiple CL modalities and reported difficulty with his habitual CLs and inadequate spectacle-corrected visual acuity to perform his activities of daily living. In this case, a collaborative, comprehensive approach to visual management in a patient with KC was used, and after TG PRK was performed to improve his corneal contour and symmetry, our patient was fit with a standard soft CL and additionally had improved spectacle-corrected visual acuity.


The role of the cerebellum in adaptation: ALE meta-analyses on sensory feedback error.
It is widely accepted that unexpected sensory consequences of self-action engage the cerebellum. However, we currently lack consensus on where in the cerebellum, we find fine-grained differentiation to unexpected sensory feedback. This may result from methodological diversity in task-based human neuroimaging studies that experimentally alter the quality of self-generated sensory feedback. We gathered existing studies that manipulated sensory feedback using a variety of methodological approaches and performed activation likelihood estimation (ALE) meta-analyses. Only half of these studies reported cerebellar activation with considerable variation in spatial location. Consequently, ALE analyses did not reveal significantly increased likelihood of activation in the cerebellum despite the broad scientific consensus of the cerebellum's involvement. In light of the high degree of methodological variability in published studies, we tested for statistical dependence between methodological factors that varied across the published studies. Experiments that elicited an adaptive response to continuously altered sensory feedback more frequently reported activation in the cerebellum than those experiments that did not induce adaptation. These findings may explain the surprisingly low rate of significant cerebellar activation across brain imaging studies investigating unexpected sensory feedback. Furthermore, limitations of functional magnetic resonance imaging to probe the cerebellum could play a role as climbing fiber activity associated with feedback error processing may not be captured by it. We provide methodological recommendations that may guide future studies.


Carnivore-caused livestock mortality in Trans-Himalaya.
The loss of livestock to wild predators is an important livelihood concern among Trans-Himalayan pastoralists. Because of the remoteness and inaccessibility of the region, few studies have been carried out to quantify livestock depredation by wild predators. In the present study, we assessed the intensity of livestock depredation by snow leopard Uncia uncia, Tibetan wolf Canis lupus chanku, and Eurasian lynx Lynx l. isabellina in three villages, namely Gya, Rumtse, and Sasoma, within the proposed Gya-Miru Wildlife Sanctuary in Ladakh, India. The three villages reported losses of 295 animals to these carnivores during a period of 2.5 years ending in early 2003, which represents an annual loss rate of 2.9% of their livestock holdings. The Tibetan wolf was the most important predator, accounting for 60% of the total livestock loss because of predation, followed by snow leopard (38%) and lynx (2%). Domestic goat was the major victim (32%), followed by sheep (30%), yak (15%), and horse (13%). Wolves killed horses significantly more and goats less than would be expected from their relative abundance. Snow leopards also killed horses significantly more than expected, whereas they killed other livestock types in proportion to their abundance. The three villages combined incurred an estimated annual monetary loss of approximately $USD 12,120 amounting to approximately $USD 190/household/y. This relatively high total annual loss occurred primarily because of depredation of the most valuable livestock types such as yak and horse. Conservation actions should initially attempt to target decrease of predation on these large and valuable livestock species.


Treatment of tinea pedis with econazole nitrate cream.
This study investigated the clinical effectiveness and the long-term relapse rate of the topical imidazole, econazole nitrate, in the treatment of tinea pedis. Econazole nitrate cream was applied by twenty-two patients with tinea pedis for twenty-eight consecutive days. Therapy was then discontinued and patients were evaluated to determine the long-term relapse rate. Nineteen (86 percent) of the twenty-two patients were considered cured at the end of twenty-eight days of treatment. At the follow-up examinations, 74 percent of the group considered to be clinically cured at the end of therapy remained clear for one month, 84 percent for two months, and 63 percent for three months after stopping active treatment. These data demonstrate that econazole nitrate is a highly effective topical agent in the treatment of tinea pedis and that clinical and mycologic cures in almost two thirds of the patients last for at least three months.


Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor.
Aquaporin-4 (AQP4) water channel-specific IgG distinguishes neuromyelitis optica (NMO) from multiple sclerosis and causes characteristic immunopathology in which central nervous system (CNS) demyelination is secondary. Early events initiating the pathophysiological outcomes of IgG binding to astrocytic AQP4 are poorly understood. CNS lesions reflect events documented in vitro following IgG interaction with AQP4: AQP4 internalization, attenuated glutamate uptake, intramyelinic edema, interleukin-6 release, complement activation, inflammatory cell recruitment, and demyelination. Here, we demonstrate that AQP4 internalization requires AQP4-bound IgG to engage an astrocytic Fcγ receptor (FcγR). IgG-lacking Fc redistributes AQP4 within the plasma membrane and induces interleukin-6 release. However, AQP4 endocytosis requires an activating FcγR's gamma subunit and involves astrocytic membrane loss of an inhibitory FcγR, CD32B. Interaction of the IgG-AQP4 complex with FcγRs triggers coendocytosis of the excitatory amino acid transporter 2 (EAAT2). Requirement of FcγR engagement for internalization of two astrocytic membrane proteins critical to CNS homeostasis identifies a complement-independent, upstream target for potential early therapeutic intervention in NMO.


Titres of naturally occurring alloantibodies against feline blood group antigens in Turkish Van cats.
Seventy-eight Turkish Van cats were examined for alloantibody titres, of which 42.3 per cent had type A blood and 57.7 per cent had type B blood. No type AB cats were found. All type B cats (n = 45) showed gross evidence of agglutinating anti-A antibody, with titres ranging from 2 to 256. Sixty-seven per cent of type B cats had anti-A antibody in their plasma, with titres ranging from 8 to 32. However, 13 per cent of type B cats had plasma alloantibody titres of less than 8 and 20 per cent had titres that were higher than 32. A total of 33 type A cats were also tested for anti-B alloantibody titres in their plasma. Among the type A plasma, gross agglutination at titres of 2 and greater than 2 were determined in 24 per cent and 36 per cent of samples, respectively. Microscopic agglutination was seen in an additional 18 per cent of plasma samples. There was no significant association between gender and plasma alloantibody titres of cats (P > 0.05).


Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression.
Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker β-amyloid (Aβ). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aβ accumulation. Here, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aβ correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aβ relationship followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aβ accumulation may involve Homer1 activity in the cortical regions, where harbor Aβ deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.


Bone mineral status in prepubertal children with cystic fibrosis.
To determine whether osteopenia is evident in prepubertal children with cystic fibrosis (CF) and, if so, whether it is caused by a deficiency in bone formation or increased bone resorption. With the use of a prospective case control study design, we investigated 11 prepubertal children with CF between the ages of 8 and 12 years old and a non-CF control group matched by weight and sex. Bone density at the radius, ulnar, trochanter, femoral neck, and lumbar spine, biochemical markers of bone metabolism, calcium, vitamin D metabolites, and intact parathyroid hormone were measured in all subjects. Comparisons between the 2 groups were performed with Wilcoxon matched pairs and Fisher exact tests. Intake of total calories, calcium, phosphorus, and vitamin D was significantly greater in the CF group than in the control group. Serum 25(OH)vitamin D levels were significantly lower in the CF group: median 22 ng/mL for the CF group and 39 ng/mL for the control group (P =.02). 1,25(OH)(2) vitamin D levels were borderline or low in 7 subjects in the CF group and 2 members of the control group (P =.08, Fisher exact test). Intact parathyroid hormone levels were higher than the upper limit of normal in 4 subjects of the CF group and 1 member of the control group. Despite these biochemical abnormalities, we found no evidence of bone mineral deficiency in the CF group. Prepubertal children with CF do not have bone mineral deficit compared with a weight- and sex-matched control group; however, their lower vitamin D levels may portend problems with bone mineralization during adolescence and adulthood.


Skin infections in Australian Aboriginal children: a narrative review.
Impetigo, scabies, cellulitis and abscesses are common in Australian Aboriginal children. These conditions adversely affect wellbeing and are associated with serious long term sequelae, including invasive infection and post-infectious complications, such as acute post-streptococcal glomerulonephritis and acute rheumatic fever, which occurs at the highest documented rates in the world in remote Aboriginal communities. Observational research in remote communities in northern Australia has demonstrated a high concurrent burden of scabies and impetigo and their post-infectious complications. Few data are available for other Australian states, especially for urban Aboriginal children; however, nationwide hospital data indicate that the disparity between Aboriginal and non-Aboriginal children in skin infection prevalence also exists in urban settings. The Australian National Healthy Skin Guideline summarises evidence-based treatment of impetigo, scabies and fungal infections in high burden settings such as remote Aboriginal communities. It recommends systemic antibiotics for children with impetigo, and either topical permethrin or oral ivermectin (second line) for the individual and their contacts as equally efficacious treatments for scabies. β-Lactams are the treatment of choice and trimethoprim-sulfamethoxazole and clindamycin are effective alternatives for treatment of paediatric cellulitis. Abscesses require incision and drainage and a 5-day course of trimethoprim-sulfamethoxazole or clindamycin. Addressing normalisation of skin infections and the social determinants of skin health are key challenges for the clinician. Research is underway on community-wide skin health programs and the role for mass drug administration which will guide future management of these common, treatable diseases.


Development and application of an ELISA for the detection of duck antibodies against Riemerella anatipestifer antigens in egg yolk of vaccinees and in serum of their offspring.
A direct and an indirect antibody enzyme-linked immunosorbent assay for duck yolk IgY and duck serum IgY was developed and tested on egg yolk and serum of ducks vaccinated with Riemerella anatipestifer (Ra). Tests were performed either with primary antibodies labelled with horseradish peroxidase or with alkaline phosphatase-labelled secondary antibodies reacting with specifically bound rabbit anti-duck IgY antibodies, respectively. Ra-specific IgYs in egg yolk from three ducks increased rapidly at day 8 after the first of two vaccinations. In two ducks, the IgY titre persisted on a high plateau for 3 months. The concentration of Ra-specific IgYs in the serum of the progeny of vaccinees decreased between day 3 and day 10 after hatching. The fraction of total IgYs decreased less but also significantly. It was shown that antibodies were vertically transmitted and therefore protect offspring against Ra infection at least during the first week after hatching. The test design with anti-IgY rabbit antibodies is further suitable to detect other specific antibodies if respective antigens were fixed on solid phases.


Mice lacking dopamine D2 and D3 receptors have spatial working memory deficits.
Mice deficient for dopamine D(2) and D(3) receptors exhibit blunted c-fos responses to D(1) agonist stimulation. Stereologic cell counting revealed decreased numbers of medial prefrontal cortex neurons that express Fos immunoreactivity in all layers, particularly in the prelimbic and anterior cingulate subregions. Pretreatment of these mutants with a single, low dose of methamphetamine (METH) led to a sustained increase in the number of neurons that express Fos immunoreactivity in response to a D(1) agonist challenge, which was most significant in prelimbic and anterior cingulate subregions. The increased c-fos responses reached wild-type-like levels in METH-pretreated D(2) mutants but remained submaximal in METH-pretreated D(3) mutants. Additional studies tested the performance of wild type and mutants in a delayed alternation test, a cognitive task critically dependent on optimal activation of prefrontal cortical D(1) receptors by synaptically released dopamine. Both D(2) and D(3) mutants exhibited deficits in their spatial working memory, with increasing impairments at increasing delays. Whereas METH pretreatment rescued the spatial working memory of D(2) mutants, it had no effect on D(3) mutants. These data suggest that the sustained improvement of spatial working memory in METH-pretreated D(2) mutants is attributable to D(1) receptor-mediated mechanisms.


Relationship between first dorsal sacral foramen and lumbar facet joint connecting line in South Korea populations: Retrospective study.
The first sacral nerve root block (S1 nerve root block) is a practical procedure for patients with radiating lower back pain. In general, S1 nerve root block is performed under x-ray fluoroscopy. It is necessary to adjust the position of the patient and angle of fluoroscopy to properly visualize the first dorsal sacral foramen (dorsal S1 foramen). The purpose of this study was to analyze the location of dorsal S1 foramen and lumbar facet joint in S1 nerve root block.A total of 388 patients undergoing x-ray fluoroscopy-guided S1 nerve root block in the prone position were examined. X-ray fluoroscopy was fixed at the corresponding location of facet joint of L4-5 and L5-S1. The relationship of the connecting line vertical to L5-S1 facet joint and upper margin sacrum was evaluated. The surface anatomical relationships between dorsal S1 foramen and lumbar facet joint were assessed.Based on the localization of dorsal S1 foramen, the line drawn from point to upper margin sacrum passed through the dorsal S1 foramen in all cases. The horizontal distance from the spinous process to the dorsal S1 foramen was 25.9 ± 3.0 mm for men and 26.2 ± 1.4 mm for women. The horizontal distance from the between posterior superioriliac spine to the dorsal S1 foramen was 26.2 ± 2.7 mm for men and 26.8 ± 1.7 mm for women. The vertical distance from the upper margin of sacrum to dorsal S1 foramen to the dorsal S1 foramen was 45.6 ± 6.5 mm for men and 43.8 ± 6.0 mm for women.The connecting line vertical to L5-S1 facet joint and upper margin sacrum is located on the same line from the dorsal S1 foramen. For difficult cases of locating dorsal S1 foramen, the lumbar facet joint can assist in predicting the vertical location of the dorsal S1 foramen.


A novel excision selection method for isolation of antibodies binding antigens expressed specifically by rare cells in tissue sections.
There is a growing appreciation of single cell technologies to provide increased biological insight and allow development of improved therapeutics. The central dogma explains why single cell technologies is further advanced in studies targeting nucleic acids compared to proteins, as nucleic acid amplification makes experimental detection possible. Here we describe a novel method for single round phage display selection of antibody fragments from genetic libraries targeting antigens expressed by rare cells in tissue sections. We present and discuss the results of two selections of antibodies recognizing antigens expressed by perivascular cells surrounding capillaries located in a human brain section; with the aim of identifying biomarkers expressed by pericytes. The area targeted for selection was identified by a known biomarker and morphological appearance, however in situ hybridizations to nucleic acids can also be used for the identification of target cells. The antibody selections were performed directly on the tissue sections followed by excision of the target cells using a glass capillary attached to micromanipulation equipment. Antibodies bound to the target cells were characterized using ELISA, immunocytochemistry and immunohistochemistry. The described method will provide a valuable tool for the discovery of novel biomarkers on rare cells in all types of tissues.


Infarct Topography and Detection of Atrial Fibrillation in Cryptogenic Stroke: Results from CRYSTAL AF.
Insertable cardiac monitors (ICM) have been shown to detect atrial fibrillation (AF) at a higher rate than routine monitoring methods in patients with cryptogenic stroke (CS). However, it is unknown whether there are topographic patterns of brain infarction in patients with CS that are particularly associated with underlying AF. If such patterns exist, these could be used to help decide whether or not CS patients would benefit from long-term monitoring with an ICM. In this retrospective analysis, a neuro-radiologist blinded to clinical details reviewed brain images from 212 patients with CS who were enrolled in the ICM arm of the CRYptogenic STroke And underLying AF (CRYSTAL AF) trial. Kaplan-Meier estimates were used to describe rates of AF detection at 12 months in patients with and without pre-specified imaging characteristics. Hazard ratios (HRs), 95% confidence intervals (CIs), and p values were calculated using Cox regression. We did not find any pattern of acute brain infarction that was significantly associated with AF detection after CS. However, the presence of chronic brain infarctions (15.8 vs. 7.0%, HR 2.84, 95% CI 1.13-7.15, p = 0.02) or leukoaraiosis (18.2 vs. 7.9%, HR 2.94, 95% CI 1.28-6.71, p < 0.01) was associated with AF detection. There was a borderline significant association of AF detection with the presence of chronic territorial (defined as within the territory of a first or second degree branch of the circle of Willis) infarcts (20.9 vs. 10.0%, HR 2.37, 95% CI 0.98-5.72, p = 0.05). We found no evidence for an association between brain infarction pattern and AF detection using an ICM in patients with CS, although patients with coexisting chronic, as well as acute, brain infarcts had a higher rate of AF detection. Acute brain infarction topography does not reliably predict or exclude detection of underlying AF in patients with CS and should not be used to select patients for ICM after cryptogenic stroke.


Currently Used Biologic Agents in the Management of Behcet's Syndrome.
Behcet's s yndrome (BS) is a multisystem vasculitis with frequent mucocutaneous, joint, eye and visceral organ involvement. From early 2000s, biologic drugs have been increasingly used in the management of BS, enabling rapid and complete remission in most cases with critical organ involvement. Despite the current experience with steroids and traditional immunosuppressives, biologics are exceptionally promising for treatment of resistant cases. Among the biologics used in BS, TNF-alpha antagonists are the oldest and their efficacy has been proven in recalcitrant ocular, vascular, gastrointestinal and neurologic involvements. These drugs have significantly reduced morbidity and mortality in BS and they have an acceptable safety profile. Tocilizumab, an IL6 receptor antibody, has been shown to be effective in BS patients with neurologic involvement and amyloidosis, and IL1β antagonists such as anakinra, canakinumab, gevokizumab were effective in the management of ocular involvement. Studies investigating the efficacy of daclizumab, IL2 receptor antibody, and secukinumab, IL17 monoclonal antibody, in the management of BS with eye involvement failed to demonstrate significant clinical improvement and both studies were halted. A monoclonal vascular endothelial growth factor antagonist, bevacizumab, was shown to be effective in BS-related macular edema. Alemtuzumab and ustekinumab are among other biologics which were effective in controlling disease symptoms. In this review, we discuss the efficacy and safety of various recently developed biologic agents targeting different pathways involved in the pathogenesis of BS.


Dental School Faculty Attitudes Toward Dental Therapy: A Four-Year Follow-Up.
This study is a follow-up to a 2010 study at one U.S. dental school that found faculty attitudes toward the dental therapy model were mixed and there was a clear divide in attitudes between faculty members who were full-time educators and part-timers who also practiced outside the educational institution. The aim of this study was to determine faculty attitudes toward and perceptions of the dental therapy model at the same school four years after implementation of the dental therapy program. The identical questionnaire used in 2010 was used in this survey conducted from November 2013 to January 2014. All 254 full-time and part-time faculty members were invited to participate; responses were received from 75 faculty members, for a 30% response rate. Four years after the initial survey, the respondents showed greater acceptance of dental therapists and of dental therapy as a mechanism for addressing access to care problems. A majority of the respondents reported feeling a personal responsibility to ensuring the dental therapy model succeeded (52%); indicated being comfortable having a dental therapist provide care for their patients (60%); and agreed that the ability to delegate work to a dental therapist would make a dentist's job more satisfying (54%). Faculty members who also worked in a private practice viewed the role of dental therapists in private practice more favorably in 2014 than in 2010. This study provides insight into how attitudes of educators toward a new profession evolve over time. The faculty appeared to be undergoing a reorientation on the topic of dental therapy. This transition in point of view may have been facilitated by factors such as continued exposure to the new professionals, information sharing, and time.


The Québec BCG Vaccination Registry (1956-1992): assessing data quality and linkage with administrative health databases.
Vaccination registries have undoubtedly proven useful for estimating vaccination coverage as well as examining vaccine safety and effectiveness. However, their use for population health research is often limited. The Bacillus Calmette-Guérin (BCG) Vaccination Registry for the Canadian province of Québec comprises some 4 million vaccination records (1926-1992). This registry represents a unique opportunity to study potential associations between BCG vaccination and various health outcomes. So far, such studies have been hampered by the absence of a computerized version of the registry. We determined the completeness and accuracy of the recently computerized BCG Vaccination Registry, as well as examined its linkability with demographic and administrative medical databases. Two systematically selected verification samples, each representing ~0.1% of the registry, were used to ascertain accuracy and completeness of the electronic BCG Vaccination Registry. Agreement between the paper [listings (n = 4,987 records) and vaccination certificates (n = 4,709 records)] and electronic formats was determined along several nominal and BCG-related variables. Linkage feasibility with the Birth Registry (probabilistic approach) and provincial Healthcare Registration File (deterministic approach) was examined using nominal identifiers for a random sample of 3,500 individuals born from 1961 to 1974 and BCG vaccinated between 1970 and 1974. Exact agreement was observed for 99.6% and 81.5% of records upon comparing, respectively, the paper listings and vaccination certificates to their corresponding computerized records. The proportion of successful linkage was 77% with the Birth Registry, 70% with the Healthcare Registration File, 57% with both, and varied by birth year. Computerization of this Registry yielded excellent results. The registry was complete and accurate, and linkage with administrative databases was highly feasible. This study represents the first step towards assembling large scale population-based epidemiological studies which will enable filling important knowledge gaps on the potential health effects of early life non-specific stimulation of the immune function, as resulting from BCG vaccination.


Core-spun carbon nanotube yarn supercapacitors for wearable electronic textiles.
Linear (fiber or yarn) supercapacitors have demonstrated remarkable cyclic electrochemical performance as power source for wearable electronic textiles. The challenges are, first, to scale up the linear supercapacitors to a length that is suitable for textile manufacturing while their electrochemical performance is maintained or preferably further improved and, second, to develop practical, continuous production technology for these linear supercapacitors. Here, we present a core/sheath structured carbon nanotube yarn architecture and a method for one-step continuous spinning of the core/sheath yarn that can be made into long linear supercapacitors. In the core/sheath structured yarn, the carbon nanotubes form a thin surface layer around a highly conductive metal filament core, which serves as current collector so that charges produced on the active materials along the length of the supercapacitor are transported efficiently, resulting in significant improvement in electrochemical performance and scale up of the supercapacitor length. The long, strong, and flexible threadlike supercapacitor is suitable for production of large-size fabrics for wearable electronic applications.


CCK, carbachol, and bombesin activate distinct PLC-beta isoenzymes via Gq/11 in rat pancreatic acinar membranes.
Four different isoforms of phospholipase C-beta (PLC-beta 1-4) have been discovered, raising the important question of whether a distinct receptor activates a single PLC-beta isoenzyme or a subset of PLC-beta isoenzymes. The present study was designed to investigate activation of PLC-beta isoenzymes by three different PLC-activating agonists that bind to different receptor entities, i.e., cholecystokinin octapeptide (CCK-8), bombesin, and carbachol in rat pancreatic acinar membranes. PLC activity was measured using exogenous [3H]phosphatidylinositol 4,5-bisphosphate as substrate. Western blot analysis of pancreatic acinar membranes revealed the presence of PLC-beta 1, -beta 3, -gamma 1, and -delta 1, but not of PLC-beta 2, -beta 4, -gamma 2, and -delta 2. Preincubation of the membranes with anti-PLC-beta 1 or -beta 3 antibody reduced agonist-induced activation of PLC. The order of sensitivity toward inhibition by anti-PLC-beta 1 antibody was CCK-8 > bombesin > carbachol. An opposite order of sensitivity was found for inhibition of PLC activity by anti-PLC-beta 3 antibody (carbachol > bombesin > CCK-8). Anti-PLC-beta 2, -beta 4, -gamma 1, -gamma 2, -delta 1, and -delta 2 antibodies had no effect. Preincubation of the membranes with an antibody raised against the COOH terminus of the alpha-subunit of Gq/11 proteins inhibited PLC activity in response to all three different receptor agonists to a similar extent, whereas anti-Gi alpha 1-2 and anti-Gi alpha 3 antibodies had no effect. In conclusion, the data of the present study indicate that CCK-8 and carbachol activate PLC-beta 1 and PLC-beta 3, respectively, whereas bombesin activates both PLC-beta 1 and PLC-beta 3. Activation of PLC-beta by these receptor agonists is mediated by Gq/11.


Suggested guidelines for validation of real-time PCR assays in veterinary diagnostic laboratories.
This consensus document presents the suggested guidelines developed by the Laboratory Technology Committee (LTC) of the American Association of Veterinary Laboratory Diagnosticians (AAVLD) for development, validation, and modification (methods comparability) of real-time PCR (rtPCR) assays. These suggested guidelines are presented with reference to the World Organisation for Animal Health (OIE) guidelines for validation of nucleic acid detection assays used in veterinary diagnostic laboratories. Additionally, our proposed practices are compared to the guidelines from the Foods Program Regulatory Subdivision of the U.S. Food and Drug Administration (FDA) and from the American Society for Veterinary Clinical Pathology (ASVCP). The LTC suggestions are closely aligned with those from the OIE and comply with version 2021-01 of the AAVLD Requirements for an Accredited Veterinary Medical Diagnostic Laboratory, although some LTC recommendations are more stringent and extend beyond the AAVLD requirements. LTC suggested guidelines are substantially different than the guidelines recently published by the U.S. FDA for validation and modification of regulated tests used for detection of pathogens in pet food and animal-derived products, such as dairy. Veterinary diagnostic laboratories that perform assays from the FDA Bacteriological Analytical Method (BAM) manual must be aware of the different standard.


Knowledge of risk factors, beliefs and practices of female healthcare professionals towards breast cancer, Morocco.
Breast cancer is the most common cancer affecting women in Morocco. Screening for early detection has led to reduction in mortality from the disease. It is known that female healthcare professionals have greater influence on women's positive perception of breast cancer and motivation to practice screening methods for early detection of the disease. This study aims to investigate knowledge of breast cancer risk factors, beliefs about treatment and practice of screening methods among a cohort of female healthcare professionals in Morocco. A cross-sectional study was conducted using a self-administered questionnaire to assess the knowledge of breast cancer risk factors, beliefs about treatment and practice of screening methods among 136 female doctors and nurses working in the university hospital of Rabat, Morocco. Stratified random sampling method was employed. Chi square test, analysis of variance and Mantel-Haenszel test were performed in data analysis using SPSS v19.0. Female doctors were the only professional group that had satisfactory knowledge of risk factors while the nurses had an unsatisfactory knowledge with a mean score of 43%. A half of participants believed that that herbal therapy can cure breast cancer. 75% practice breast self-examination once a month and only 15% have ever had a mammogram. Age, profession and beliefs were not significantly associated with rate of BSE in this study; however this rate is influenced by knowledge of breast cancer risk factors. Results from this study suggest the need for continuing medical education programs aimed at improving knowledge of breast cancer among the nurses.


Identification and nucleotide sequence of the thymidine kinase gene of Shope fibroma virus.
The thymidine kinase (TK) gene of Shope fibroma virus (SFV), a tumorigenic leporipoxvirus, was localized within the viral genome with degenerate oligonucleotide probes. These probes were constructed to two regions of high sequence conservation between the vaccinia virus TK gene and those of several known eucaryotic cellular TK genes, including human, mouse, hamster, and chicken TK genes. The oligonucleotide probes initially localized the SFV TK gene 50 kilobases (kb) from the right terminus of the 160-kb SFV genome within the 9.5-kb BamHI-HindIII fragment E. Fine-mapping analysis indicated that the TK gene was within a 1.2-kb AvaI-HaeIII fragment, and DNA sequencing of this region revealed an open reading frame capable of encoding a polypeptide of 176 amino acids possessing considerable homology to the TK genes of the vaccinia, variola, and monkeypox orthopoxviruses and also to a variety of cellular TK genes. Homology matrix analysis and homology scores suggest that the SFV TK gene has diverged significantly from its counterpart members in the orthopoxvirus genus. Nevertheless, the presence of conserved upstream open reading frames on the 5' side of all of the poxvirus TK genes indicates a similarity of functional organization between the orthopoxviruses and leporipoxviruses. These data suggest a common ancestral origin for at least some of the unique internal regions of the leporipoxviruses and orthopoxviruses as exemplified by SFV and vaccinia virus, respectively.


The Effects of Acupressure on Pain Severity in Female Nurses with Chronic Low Back Pain.
Low back pain causes physical and psychological impacts among nurses. This study aimed to investigate the effects of acupressure on the severity of pain in chronic low back pain in female nurses. This study is a single-blinded randomized clinical trial conducted among 50 nurses suffering from chronic low back pain. After simple sampling, participants were randomly assigned into acupressure and sham groups using lottery method (25 patients in each group). In the experimental group, the intervention was performed by the researcher three times a week throughout a 3-week period. The sham group received placebo interventions. Data was collected through VAS questionnaire before, immediately after, 2 weeks, and 4 weeks after performing intervention. Data analysis was conducted using SPSS version 18 using descriptive and inferential statistical methods. There was no significant difference in the mean pain severity scores in the pre-interventions phase between the groups (P = 0.63), however, a significant difference was observed Immediately, 2 weeks, and 4 weeks after performing intervention. Further, the mean pain severity scores in intervention group significantly decreased compared to the sham group (P = 0.000). Acupressure on specific points was proved to reduce pain. Thus, acupressure can be used as nonmedicament, inexpensive, and without side effects treatment in reducing pain.