Visceral Vistas: Basil Hirschowitz and the Birth of Fiberoptic Endoscopy.
Fiberoptic endoscopy was developed at the University of Michigan in the 1950s by gastroenterology fellow Basil Hirschowitz and 2 physicists. Previous methods to visualize the gastrointestinal lumen used rigid instruments that relied on rudimentary optical systems. They were limited in reach and caused patients considerable discomfort. Fiberoptic technology dramatically changed endoscopic practice. The fiberoptic endoscope, or fiberscope, was a flexible instrument that allowed direct inspection of the gastrointestinal lumen. Although many practicing endoscopists initially resisted its adoption, the fiberscope ultimately held sway. Studying the period from the fiberscope's first introduction in the late 1950s to its more widespread acceptance in the late 1960s may help us understand how a new technology makes its way into routine clinical practice.


Social participation: the perspectives of adolescents with cerebral palsy and their mothers.
Social participation is a complex construct, thus different factors may facilitate or restrict engagement. Adolescents with Cerebral Palsy (CP) and their mothers often experience barriers in social participation. Therefore, they are frequently facing challenges in order to engage in meaningful activities, in different contexts. We aimed at exploring the perspectives of mothers and adolescents with CP on their social participation. This is a cross-sectional and exploratory study, with a qualitative design. Seven adolescents with CP, aged from 11 to17 years old and their mothers, participated in a semi-structured interview, in São Paulo, Brazil. Data from interviews were analyzed with the Collective Subject Discourse (CSD) technique. Mothers believed that their parenting practices contribute to the social participation of their children. Mothers revealed concerns about how to support the autonomy of their children and how to help them to establish meaningful and mature relationships. Adolescents with CP reported to engage in a range of social activities, with friends in different contexts, such as restaurants, cinema, concerts, parks and school. They also reported to appreciate social participation and to look for strategies in order to engage. This work can contribute to the understanding of social participation of adolescents with CP, under the perspective of these people and their mothers by allowing them to express their thoughts and voice their fears and limitations. Healthcare providers should adopt a lifespan approach to disabilities and recognize the unique challenges of adolescence in the life of both child and parents.


The influenza pandemic of 1918-1919 in the British Caribbean.
The influenza pandemic swept through the Caribbean during the period October 1918 to March 1919 and resulted in c.100,000 deaths. This article focuses on the British possessions and is based principally on official reports and the local press. It looks at how the virus entered and spread through the region, the possible reasons for variations in levels of morbidity and mortality between islands, popular responses to the infection, and the mainly fruitless official attempts to arrest and deal with the disease. Jamaica was the first island to be affected, and along with Belize and Guyana, suffered most severely. A number of islands, particularly those in the eastern Caribbean, appear to have escaped relatively lightly. Although all sections of the population were vulnerable, the heaviest mortality rates were among the very poor, East Indian immigrant labourers, and native Americans. There was also a high toll among males aged 15-40. Altogether the death rate from influenza in the British Caribbean was c.30,000. In London influenza was added to the official list of British 'imperial diseases', and although it was recognized that poverty provided the conditions for the spread of disease, the resources in the Caribbean were barely used to improve standards of living and nutrition.


The impact of floor space allowance and dietary energy level on finishing pigs, from 65 to 120 kg, on growth performance.
The objective of this experiment was to evaluate the impact of lowering floor space allowance in finishing hogs from 65 to 120 kg when fed high- vs. low-energy diets on growth performance. Eighty-eight mixed-sex pens with 24 ± 1 pigs per pen were randomly assigned by weight in a complete block design to one of eight treatments in a 2 × 4 factorial arrangement with two energy levels: low (LE, 3267 ± 15 kcal/kg) vs. high (HE, 3389 ± 15 kcal/kg) accomplished through fat inclusion; and four floor space allowances: 0.6, 0.63, 0.65, and 0.67 m2/pig. Assigned floor space was accomplished by moveable gates in the rear of the pen which were adjusted at each pig removal until the marketing phase. Pen weight was measured at days 0, 29, and 48, with feed disappearance measured at days 29 and 48 to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (GF). Data were analyzed by pen (SAS 9.4, Cary, NC), as repeated measures, with the fixed effects of floor space allowance, dietary energy level, and the interaction between floor space allowance and energy level. For the overall experiment, decreased floor space had no effect (P > 0.1) on ADG, ADFI, or GF. Energy had a significant effect (P < 0.01) on ADFI (3.17 vs. 3.12 kg for LE and HE, respectively) and GF (0.35 and 0.36 for LE and HE, respectively), and tended to impact (P = 0.08) ADG (1.12 vs. 1.13 kg, for LE and HE, respectively). In conclusion, reducing space allowance from 0.67 m2 down to 0.6 m2 did not affect the growth performance of pigs from 65 to 120 kg. Pigs fed LE consumed more than the HE diets but had generally similar growth and no difference in body weight.


The effect of hormones on endometriosis development.
Endometriosis is a common gynecological condition in which tissue that is histologically similar to the endometrium with glands and/or stroma grows outside the uterine cavity and can lead to pelvic pain, dysmenorrhea and infertility. Many aspects of female reproductive function are strongly influenced by genetic factors and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as endometriosis. The importance of steroid hormones on endometriosis is unquestionable. The disease is most prevalent in women of reproductive age and regresses after menopause and its occurrence before menarche has not been reported. Sex steroids, estrogen and progesterone, are mainly produced in the ovaries and they regulate the growth of endometrial tissue, basically by stimulating and inhibiting cell proliferation, respectively. In addition, estrogen plays an important role in the regulation of cyclic gonadotropin release and in folliculogenesis. Numerous studies have been conducted to demonstrate the interaction of hormone and their receptors with endometriosis with conflict results. Besides, environmental chemicals, known as endocrine disruptors, have the capacity to mimic, block or modulate the endocrine system through the interaction with steroidal receptors. Recently evidences have proposed a putative role for ubiquitous environmental contaminants in the occurrence of endometriosis. Here, we reviewed significant articles regarding the interaction among endometriosis, hormones and genetic polymorphic variants.


THERapy-Related InterACTion (THER-I-ACT) in Rehabilitation-Instrument Development and Inter-Rater Reliability.
Objective: To develop an instrument for the observation of therapeutic communication interactions during rehabilitation sessions and test its inter-rater reliability. Methods: The new instrument THER-I-ACT (THERapy-related Inter-ACTion) has been designed to assess both the frequency and timing of therapeutic interactions in the thematic fields information provision, feedback, other motivational interaction, and bonding. For this inter-rater reliability study, a sample of stroke survivors received arm rehabilitation as either arm ability training, arm basis training, or mirror therapy, or neglect training as individually indicated. Therapy sessions were video-recorded (one for each participant) and therapeutic interactions rated by two independent raters using THER-I-ACT. Results: With regard to the instrument's comprehensiveness to document therapeutic interactions with pre-defined categories the data from 29 sessions suggested almost complete coverage. Inter-rater reliability was very high both for individual categories of therapeutic interaction (frequency and time used for interaction) (intraclass correlation coefficient, ICC 0.91-1.00) and summary scores for the thematic fields of interaction (again for frequency and time used for interaction) (ICC 0.98-1.00). The inter-rater reliability for rating engagement and being focussed for both the therapist and patient was substantial (ICC 0.71 and 0.86). Conclusions: The observational study documented that by use of the newly designed THER-I-ACT various types of therapy-related communication interactions performed by therapists can be assessed with a very high inter-rater reliability. In addition, the thematic fields and categories of therapeutic interaction as defined by the instrument comprehensively covered the type of interaction that occurred in the therapeutic sessions observed.


MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer.
For many patients with breast cancer, symptomatic bone metastases appear after years of latency. How micrometastatic lesions remain dormant and undetectable before initiating colonization is unclear. Here, we describe a mechanism involved in bone metastatic latency of oestrogen receptor-positive (ER+) breast cancer. Using an in vivo genome-wide short hairpin RNA screening, we identified the kinase MSK1 as an important regulator of metastatic dormancy in breast cancer. In patients with ER+ breast cancer, low MSK1 expression associates with early metastasis. We show that MSK1 downregulation impairs the differentiation of breast cancer cells, increasing their bone homing and growth capacities. MSK1 controls the expression of genes required for luminal cell differentiation, including the GATA3 and FOXA1 transcription factors, by modulating their promoter chromatin status. Our results indicate that MSK1 prevents metastatic progression of ER+ breast cancer, suggesting that stratifying patients with breast cancer as high or low risk for early relapse based on MSK1 expression could improve prognosis.


Simultaneous assessment of vasoreactivity using transcranial Doppler ultrasound and cerebral blood flow in healthy subjects.
Blood flow velocities in both middle cerebral arteries and regional cerebral blood flow in their perfusion territories were measured simultaneously in 36 healthy subjects. In 20 subjects, the measurements were first performed under basal conditions and then repeated 15-20 min after an intravenous injection of 1 g of acetazolamide. Reproducibility of simultaneous blood flow and velocity measurements was tested by examining 16 subjects on two occasions under basal conditions with an interval of 20 min. Relatively good reproducibility was found for repeated measurements of velocity and blood flow, being best when side-to-side asymmetry was assessed. The increase in blood flow velocities after acetazolamide was symmetrical (right side, 34.2%; and left side, 35.5%), and the velocity increase was significantly correlated with basal values. The increase in cerebral blood flow was also symmetrical (right side, 29.8%; left side, 30.1%) but not correlated with basal flow values. No significant relationship was found between velocity increase and increase in regional cerebral blood flow. This finding is probably not only due to methodological inaccuracies but may suggest that acetazolamide has an effect on the diameter of the middle cerebral artery or on the magnitude of this artery's perfusion territory. This study supports the use of acetazolamide for assessing cerebral vasoreactivity following the definition of lower limits for velocity and flow increase and for asymmetry of the response.


[Structural differences between health insurance funds and their impact on health services research: results from the Bertelsmann Health-Care Monitor].
Claims data of health insurance companies are an important database for health services research. We investigated if there are differences in baseline characteristics and prevalence of chronic diseases between members of several health insurance funds in Germany, and if so, whether adjusting for age and sex could explain these differences. 10 representative surveys (conducted between 2004 and 2008) of the 'Bertelsmann Health-Care Monitor' comprising 15 089 participants aged 18 to 79 years were analysed. Our main independent variable was membership in one of 8 health insurance funds. The prevalence of self-reported hypertension, diabetes, atopic diseases, coronary heart disease and heart failure was studied. We first estimated the crude prevalence of chronic diseases stratified by these funds. We further fitted logistic regression models and adjusted for age and sex as well as for further comorbidities and health related factors. Most respondents were insured in the BKK (Betriebskrankenkassen; 20.1%), the AOK (Allgemeinen Ortskrankenkassen; 19.2%) and private health insurances (15.3%). Substantial differences were found according to age, sex, educational level and prevalences of chronic diseases. Stratified by health insurance funds, prevalences ranged between 17.1-29.6% for hypertension, between 3.9-11.4% for diabetes, between 4.3-6.7% for atopic diseases, between 3.4-6.7% for coronary heart disease and between 2.6-5.7% for heart failure. When adjusting for sex and age, estimates for all 5 diseases were significant higher in AOK members compared to privately insured persons (3 diseases within the BAMER and the DAK, accordingly). In total, this was the case for 17 out of 35 comparisons. Even after adjusting for further comorbidities and health related factors 6 out of 35 comparisons showed significant increased estimates compared to privately insured persons. We found considerable differences in the prevalence of chronic diseases between German health insurance funds that remained after controlling for age and sex, and even after adjustment for further health-related variables. Further methodological studies are urgently needed to assess strengths and weaknesses of German claim data.


[2 cases of carcinoid tumor of the testis].
The authors report two cases of carcinoid tumour of the testis in young subjects. One case was isolated and the other was associated with a teratoma. The authors attempt to define this disease on the basis of a review of the literature.


[EFFECT OF Hey1 EXPRESSION ON OSTEOGENIC DIFFERENTIATION AND PROLIFERATION OF C3H10T1/2 CELLS INDUCED BY BONE MORPHOGENETIC PROTEIN 9].
To investigate the effect of Notch signaling pathway important target Hey1 expression on the differentiation and proliferation of C3H10T1/2 cells induced by bone morphogenetic protein 9 (BMP-9). Hey1 lentivirus and Hey1 short hairpin RNA lentivirus were constructed and used to infect C3H10T1/2 cells to change the expression level of Hey1 in C3H10T1/2 cells. C3H10T1/2 cells infected with LV-Blank (empty plasmid) as control. The Hey1 expression levels of different groups were detected by fluorescence microscope, real-time fluorescence quantitative PCR, and Western blot. The C3H10T1/2 cells with different Hey1 expression level were induced by BMP-9 conditioned medium (BMP-9+C3H10T1/2 group, BMP-9+C3H10T1/2-Hey1 group, and BMP-9+C3H10T1/2-shHey1 group); the cells of control groups (C3H10T1/2 group and G3H10T1/2-Blank group) were cultured with normal medium. The mRNA and protein expression levels of osteogenesis related transcription factors (Runx2, osteopontin, and osteocalcin) were detected at 48 hours by real-time fluorescence quantitative PCR and Western blot assay. The cells proliferation and cycles were detected by MTT assay at 4, 5, 6, and 7 days and flow cytometry at 4, 5, and 10 days. The alkaline phosphatase (ALP) activity was analyzed by ELISA and observed by ALP staining at 4 and 7 days. C3H10T1/2 cell lines with different Hey1 expression levels were successfully established. In osteogenesis compared with BMP-9+C3H10T1/2 group, overexpression of Hey1 enhanced the mRNA and protein expressions of transcription factors (Runx2, osteopontin, and osteocalcin), and the expression of osteogenic differentiation marker (ALP) (P < 0.05); however, inhibition of Hey1 expression significantly decreased the above indexes (P < 0.05). In cell proliferation activity compared with BMP-9+C3H10T1/2 group, overexpression of Hey1 increased absorbance (A) value in MTT assay and pecentage of G2+S cells in cytometry assay, but inhibition of Hey1 expression significantly decreased the indexes (P < 0.05). Expression of Hey1 is the important link in the osteogenic differentiation process of C3H10T1/2 cells induced by BMP-9, and plays an important role in the regulation of early cell proliferation.


Carcinoma of pancreas presenting as a decrease in visual acuity.
Recent unilateral decrease in visual acuity of a 72-year-old woman was the background of a comprehensive medical investigation that led to the definitive diagnosis of metastatic pancreatic carcinoma. Visual improvement was achieved after ocular irradiation but the patient died two months later because of bilateral pneumonia and sepsis. Ocular metastasis from advanced carcinoma of various organs is well known and usually is an indicative sign of poor prognosis. Ocular metastases from pancreatic carcinoma are extremely rare, and to the best of our knowledge, it has not been reported previously in English. It should be emphasized that unilateral decrease in visual acuity must be thoroughly investigated.


The Efficacy and The Safety of Ultrasound-guided Ablation Therapy for Treating Papillary Thyroid Microcarcinoma.
The prevalence of papillary thyroid microcarcinoma (PTMC) increases rapidly all around the world, but the management of PTMC hasn't reached a consensus. Recently, ultrasound-guided (US-guided) ablation therapy was introduced as a feasible treatment for low-risk PTMC. The clinical application of US-guided ablation therapy needs doctors' effort to investigate the efficacy and the safety of US-guided ablation in treating PTMC carefully. Although the present evidence showed some limitations, such as short-term study time spans and no randomized control design, in our perspective, US-guided thermal ablation therapy has good short-term efficacy and safety and is a promising PTMC's treatment in future clinical practice.


Epidemiologic inquiry: observational studies.
A major objective of epidemiologic investigation is to determine whether or not an association between an exposure and a condition exists in a human population. The presence of such an association cna be explored using three distinct strategies, the cohort, the case-control, and the cross-sectional approaches. This paper describes each of these research designs and discusses their advantages and disadvantages.


The symmetric-range accuracy under a one-way random model with balanced or unbalanced data.
The symmetric-range accuracy A of a sampler is defined as the fractional range, symmetric about the true concentration, that includes a specified proportion of sampler measurements. In this article, we give an explicit expression for A assuming that the sampler measurements follow a one-way random model so as to capture different components of variability, for example, variabilities among and within different laboratories or variabilities among and within exposed workers. We derive an upper confidence limit for A based on the concept of a 'generalized confidence interval'. A convenient approximation is also provided for computing the upper confidence limit. Both balanced and unbalanced data situations are investigated. Monte Carlo evaluation indicates that the proposed upper confidence limit is satisfactory even for small samples. The statistical procedures are illustrated using an example.


Lack of weight gain with gliclazide treatment for 30 months in type II diabetes.
A long-term follow-up study was carried out in 44 Type II diabetic patients to confirm the lack of effect of gliclazide on body weight as well as its hypoglycaemic efficacy and tolerance. Patients were assessed for up to 51 months. The results showed no overall significant change in body weight, 21 patients gaining weight (mean 3.59 +/- 2.6 kg), 20 patients losing weight (mean 3.39 +/- 2.6 kg) and 3 patients showing no weight change. Satisfactory hypoglycaemic control was achieved in all but 8 patients who were transferred to insulin. Clinical and biochemical tolerance was good.


A privileged intraphagocyte niche is responsible for disseminated infection of Staphylococcus aureus in a zebrafish model.
The innate immune system is the primary defence against the versatile pathogen, Staphylococcus aureus. How this organism is able to avoid immune killing and cause infections is poorly understood. Using an established larval zebrafish infection model, we have shown that overwhelming infection is due to subversion of phagocytes by staphylococci, allowing bacteria to evade killing and found foci of disease. Larval zebrafish coinfected with two S. aureus strains carrying different fluorescent reporter gene fusions (but otherwise isogenic) had bacterial lesions, at the time of host death, containing predominantly one strain. Quantitative data using two marked strains revealed that the strain ratios, during overwhelming infection, were often skewed towards the extremes, with one strain predominating. Infection with passaged bacterial clones revealed the phenomenon not to bedue to adventitious mutations acquired by the pathogen. After infection of the host, all bacteria are internalized by phagocytes and the skewing of population ratios is absolutely dependent on the presence of phagocytes. Mathematical modelling of pathogen population dynamics revealed the data patterns are consistent with the hypothesis that a small number of infected phagocytes serve as an intracellular reservoir for S. aureus, which upon release leads to disseminated infection. Strategies to specifically alter neutrophil/macrophage numbers were used to map the potential subpopulation of phagocytes acting as a pathogen reservoir, revealing neutrophils as the likely 'niche'. Subsequently in a murine sepsis model, S. aureus abscesses in kidneys were also found to be predominantly clonal, therefore likely founded by an individual cell, suggesting a potential mechanism analogous to the zebrafish model with few protected niches. These findings add credence to the argument that S. aureus control regimes should recognize both the intracellular as well as extracellular facets of the S. aureus life cycle.


Bacterial vaginosis.
Bacterial vaginosis (nonspecific vaginitis) is a polymicrobial, superficial vaginal infection caused by an increase in anaerobic organisms and a concomitant decrease in lactobacilli. Gardnerella vaginalis, once thought to be the sole etiologic agent, is probably one of several endogenous members of the vaginal flora that overgrow in women with bacterial vaginosis. Whether the growth of anaerobes or a primary decrease in lactobacilli is the initial pathogenic event remains unclear. Epidemiological studies have revealed that current or previous infections caused by Trichomonas organisms, increased sexual activity, and intrauterine device use are risk factors for this condition. Studies have indicated that bacterial vaginosis, previously thought to be a benign illness, is associated with some morbidity in pregnant women. Symptoms remain unreliable in the diagnosis of bacterial vaginosis. Diagnostic efficacy is best achieved by utilizing clinical signs. Assessment of cure is best accomplished by Gram stain, not clinical criteria. Metronidazole, 500 mg orally for seven days, remains the treatment of choice; however, a 2-g single dose of metronidazole represents a reasonable alternative if cost and compliance issues predominate in a clinical situation. Although a recent study supports the contention that treatment of the male sexual partner of women with bacterial vaginosis is effective, a general recommendation cannot be made with confidence on the issue of sexual partner treatment until other supporting work is done.


Clinical effects of grapefruit juice-nifedipine interaction in a 54-year-old Nigerian: a case report.
Grapefruit juice is known to increase the oral bioavailability of dihydropyridine calcium channel blockers, including nifedipine, by reducing presystemic clearance. The nature and magnitude of this interaction has not been studied in black Africans. Previous studies have reported reduced systemic clearance of nifedipine in this population, suggesting altered risk from the interaction of grapefruit juice and nifedipine. We report a case of a nifedipine-grapefruit juice adverse interaction in a Nigerian to draw attention to the problem and further sensitize practitioners.


Characterization of the variability and repeatability of gonadotropin-releasing hormone-induced luteinizing hormone responses in dairy cows within a synchronized ovulation protocol.
The primary objective was to determine the variability and repeatability of GnRH-induced LH responses. The secondary objective was to evaluate the associations among plasma LH, FSH, estradiol (E2), and progesterone (P4) concentrations. One hundred lactating Holstein cows (35 primiparous, 65 multiparous) were initially subjected to a presynchronization protocol (d 0, PGF2α; d 3, GnRH) followed 7 d later by Ovsynch (d 10, GnRH; d 17, PGF2α; 56 h later, GnRH) and timed artificial insemination 16 h after the last GnRH. Blood samples were collected immediately before the GnRH injection of presynchronization and the second GnRH of Ovsynch to determine plasma concentrations of LH, FSH, and P4. A second blood sample was collected 2 h after each of the above GnRH injections to determine GnRH-induced LH and FSH concentrations. Plasma concentrations of E2 were also determined in samples collected immediately before the second GnRH of Ovsynch. Cows that (1) had higher LH concentrations at 0 h than at 2 h after GnRH, (2) showed an ongoing spontaneous LH surge, (3) did not respond to GnRH, and (4) had P4 ≥ 0.5 ng/mL at GnRH of presynchronization and the second GnRH of Ovsynch were excluded from the analysis. The variability (coefficient of variation) and repeatability [between animal variance/(within animal variance + between animal variance)] of GnRH-induced LH response were determined from samples collected 2 h after the GnRH of presynchronization and the second GnRH of Ovsynch. The associations among plasma LH, FSH, E2, and P4 were determined at the second GnRH of Ovsynch. Mean (±SEM) LH concentrations before GnRH were 0.5 ± 0.04 and 0.6 ± 0.03 ng/mL, whereas mean LH concentrations 2 h after GnRH were 9.8 ± 1.0 and 12.1 ± 0.8 ng/mL at GnRH of presynchronization and the second GnRH of Ovsynch, respectively. The variability of GnRH-induced LH was 76.1 and 52.1% at GnRH of presynchronization and the second GnRH of Ovsynch, respectively. The repeatability estimate for GnRH-induced LH concentration between GnRH of presynchronization and Ovsynch assessments was 0.10. Plasma concentrations of LH were positively associated with FSH and E2 (r = 0.61 and 0.30, respectively) and negatively associated with P4 (r = -0.46) at the second GnRH of Ovsynch. In summary, GnRH-induced LH responses were highly variable and unrepeatable, and LH concentrations were positively associated with FSH and E2 and negatively associated with P4.


The development of the role of the clinical nurse specialist in the UK.
The modern development of specialist nurses started in the early 1970s. This article provides a brief history of their evolution and in particular outlines some of the key factors in their emergence as a key care provider in health care today. There is a constant threat that their clinical nursing background and key nursing skills will be sacrificed or substituted by a more medical-oriented approach. The future, therefore, is one of striking the right balance between nursing and medicine sub-specialism and holistic patient care.


Expression of the exon 3 skipping form of GLAST, GLAST1a, in brain and retina.
GLAST is a glial glutamate transporter; mRNA for a splice variant, GLAST1a, which lacks exon 3, has previously been identified. To detect GLAST1a protein, we generated antibodies against a peptide sequence encompassing the splice site. We demonstrate by Western blotting and immunocytochemistry the expression of GLAST1a in brains and retinae. Robust immunolabelling was present in the cerebellar Bergmann glia, and weaker labelling was evident in the retinal Müller cells. GLAST1a is differentially targeted to some cellular compartments such as the end feet of the Müller cells. As GLAST1a protein may interfere with the transport of glutamate by normally spliced GLAST, differentially targeted expression of GLAST1a may represent a mechanism for selectively regulating GLAST function in the mammalian nervous system.


Sequencing of cognitive-behavioral treatments for bulimia nervosa.
This study investigated the efficacy of a stepped-care trial of brief group psychoeducation (PE) followed by individual cognitive-behavioral therapy (CBT) in the treatment of bulimia nervosa. Fifty-six subjects first completed PE and were then randomly assigned to either a 16-week trial of CBT (PE + CBT) or to no further treatment follow-up (PE-alone). Compared to PE-alone, PE + CBT produced significantly greater reductions in the specific eating symptoms of binging and purging and significantly higher remission rates that were maintained over a 16-week follow-up. However, there were no differential treatment effects on measures of nonspecific psychopathology. Among PE + CBT subjects, remission in specific eating symptoms was associated with greatest improvements in non-specific psychopathology. The outcome of nonremitted PE + CBT subjects and PE-alone subjects was no different at posttreatment or follow-up. These results provide limited support for offering individual CBT to subjects once they have completed an initial trial of group PE.


Synthesis of N,N-disubstituted 2-aminothiophenes by the cyclization of gem-difluoroalkenes with β-keto thioamides.
A novel and effective method for the construction of highly functionalized aminothiophenes via the cyclization of gem-difluoroalkenes with β-keto tertiary thioamides is described. The reactions proceed smoothly with the assistance of K2CO3 under transition-metal-free conditions, affording a variety of valuable N,N-disubstituted 2-aminothiophenes in moderate to good yields.


Speech rhythms and multiplexed oscillatory sensory coding in the human brain.
Cortical oscillations are likely candidates for segmentation and coding of continuous speech. Here, we monitored continuous speech processing with magnetoencephalography (MEG) to unravel the principles of speech segmentation and coding. We demonstrate that speech entrains the phase of low-frequency (delta, theta) and the amplitude of high-frequency (gamma) oscillations in the auditory cortex. Phase entrainment is stronger in the right and amplitude entrainment is stronger in the left auditory cortex. Furthermore, edges in the speech envelope phase reset auditory cortex oscillations thereby enhancing their entrainment to speech. This mechanism adapts to the changing physical features of the speech envelope and enables efficient, stimulus-specific speech sampling. Finally, we show that within the auditory cortex, coupling between delta, theta, and gamma oscillations increases following speech edges. Importantly, all couplings (i.e., brain-speech and also within the cortex) attenuate for backward-presented speech, suggesting top-down control. We conclude that segmentation and coding of speech relies on a nested hierarchy of entrained cortical oscillations.


Pancreas transplantation.
During the past decade, marked improvement has been made in the field of pancreas transplantation. The best results have been obtained in patients receiving a simultaneous pancreas-kidney transplant using the bladder drainage technique. An overall improvement in the secondary complications of diabetes has been documented in patients receiving successful pancreatic grafts. Pancreatic islet cell transplantation remains largely experimental at this time.


Sequence analyses of cyanobacterial bicarbonate transporters and their homologues.
The primary HCO3- uptake system in the cyanobacterium Synecocystis is the Na+-dependent transporter SbtA. SbtA and its homologues were identified and shown to display a common topology of ten transmembrane segments (TMSs). These proved to have arisen by an intragenic duplication event from an ancestral gene encoding a five TMS protein product. A region of SbtA shows sufficient similarity to 10 TMS ABC-type integral membrane transport proteins to suggest a common origin. Phylogenetic analyses of the SbtA family revealed two clusters of cyanobacterial homologues with all non-cyanobacterial family members outside of these two clusters. The tree topology suggests that SbtA family members display multiple transport functions.


T1 glottic carcinoma involving the anterior commissure.
This study reviews the records of 56 patients with early glottic carcinoma involving the anterior commissure (T1N0M0) who were treated between 1958 and 1988 at Beilinson Medical Center. Five- and 10-year survival rates were 82% and 60%, respectively. Most failures were local (15 patients). In addition, three patients who were treatment failures had neck lesions (regional failure) and one had lung lesions (distant metastases). All 56 patients received irradiation as the only mode of initial treatment. The effectiveness of irradiation for anterior commissure lesions is therefore evaluated. The study supports previous reports suggesting that glottic carcinoma involving the anterior commissure is associated with a high rate of treatment failure.


Epidemiological evaluation of short-form versions of the Child Perception Questionnaire.
The objective of the study was to compare the performance of four short-form versions of the Child Perceptions Questionnaire (CPQ(11-14)) with that of the long-form version in a random population sample of 12- and 13-yr-old children from New Zealand in order to determine which short-form version was the most valid. Children (n = 430, participation rate 74.1%) completed the 37-item CPQ(11-14). Two separate 8- and 16-item short-form versions were previously developed using (a) item impact and (b) regression methods. The four different short-form scales were compared with the full CPQ(11-14) on their construct validity. The children were examined for malocclusion (using the Dental Aesthetic Index) and for dental caries by a single examiner (L.F.P.). All short-form versions revealed substantial variability in overall oral health-related quality of life (OHRQoL). Cronbach's alpha ranged from 0.73 (Regression Short Form [RSF]-8) to 0.86 (RSF-16). For all short-form versions, mean scores were positively associated with self-rated oral health and overall wellbeing; associations with the latter were stronger. All short-form versions detected OHRQoL gradients, as hypothesized, across ascending categories of caries and malocclusion. These findings suggest that the short-form versions of the CPQ(11-14) all show acceptable properties, but that the 16-item versions perform better (and are essentially equivalent); however, the stronger theoretical underpinning of the item-impact-derived 16-item short-form version suggests that it shows the most promise.


Dogslife: a web-based longitudinal study of Labrador Retriever health in the UK.
Dogslife is the first large-scale internet-based longitudinal study of canine health. The study has been designed to examine how environmental and genetic factors influence the health and development of a birth cohort of UK-based pedigree Labrador Retrievers. In the first 12 months of the study 1,407 Kennel Club (KC) registered eligible dogs were recruited, at a mean age of 119 days of age (SD 69 days, range 3 days - 504 days). Recruitment rates varied depending upon the study team's ability to contact owners. Where owners authorised the provision of contact details 8.4% of dogs were recruited compared to 1.3% where no direct contact was possible. The proportion of dogs recruited was higher for owners who transferred the registration of their puppy from the breeder to themselves with the KC, and for owners who were sent an e-mail or postcard requesting participation in the project. Compliance with monthly updates was highly variable. For the 280 dogs that were aged 400 days or more on the 30th June 2011, we estimated between 39% and 45% of owners were still actively involved in the project. Initial evaluation suggests that the cohort is representative of the general population of the KC registered Labrador Retrievers eligible to enrol with the project. Clinical signs of illnesses were reported in 44.3% of Labrador Retrievers registered with Dogslife (median age of first illness 138 days), although only 44.1% of these resulted in a veterinary presentation (median age 316 days). The web-based platform has enabled the recruitment of a representative population of KC registered Labrador Retrievers, providing the first large-scale longitudinal population-based study of dog health. The use of multiple different methods (e-mail, post and telephone) of contact with dog owners was essential to maximise recruitment and retention of the cohort.


Care-seeking behaviors of African American women with breast cancer symptoms.
In this descriptive correlational study, 48 African American women were assessed for delay in care-seeking for breast cancer symptoms by examining: (a) relationships between selected psychosocial variables (fear, denial, utility, and social norm) and delay, (b) relationships between delay and having an identified health provider, affordable health care services, and accessible health-care services, (c) whether denial would mediate the effect of fear on delay, (d) whether utility would moderate the effects of social norm and facilitating conditions on delay, and (e) whether denial was related to escape-avoidance coping. Participants completed mailed questionnaires. Pearson correlation and separate regression analyses showed that denial was associated with increased delay. Confrontive coping, social support, and problem-solving strategies had no relationship with delay. Interventions focusing on denial could help enhance early care seeking.


Novel methicillin resistance gene mecD in clinical Macrococcus caseolyticus strains from bovine and canine sources.
Methicillin-resistant Macrococcus caseolyticus strains from bovine and canine origins were found to carry a novel mecD gene conferring resistance to all classes of β-lactams including anti-MRSA cephalosporins. Association of β-lactam resistance with mecD was demonstrated by gene expression in S. aureus and deletion of the mecD-containing island in M. caseolyticus. The mecD gene was located either on an 18,134-bp M. caseolyticus resistance island (McRImecD-1) or a 16,188-bp McRImecD-2. Both islands were integrated at the 3' end of the rpsI gene, carried the mecD operon (mecD-mecR1m-mecIm), and genes for an integrase of the tyrosine recombinase family and a putative virulence-associated protein (virE). Apart from the mecD operon, that shared 66% overall nucleotide identity with the mecB operon, McRImecD islands were unrelated to any mecB-carrying elements or staphylococcal cassette chromosome mec. Only McRImecD-1 that is delimitated at both ends by direct repeats was capable of circular excision. The recombined excision pattern suggests site-specific activity of the integrase and allowed identification of a putative core attachment site. Detection of rpsI-associated integrases in Bacillus and S. aureus reveals a potential for broad-host range dissemination of the novel methicillin resistance gene mecD.


Toll-like Receptors and Cytokine Modulation by Goat Milk Extracellular Vesicles in a Model of Intestinal Inflammation.
Extracellular vesicles (EVs) are nanometric spherical structures, enclosed in a lipid bilayer membrane and secreted by multiple cell types under specific physiologic and pathologic conditions. Their complex cargo modulates immune cells within an inflammatory microenvironment. Milk is one of the most promising sources of EVs in terms of massive recovery, and milk extracellular vesicles (mEVs) have immunomodulatory and anti-inflammatory effects. The aim of this study was to characterize goat mEVs' immunomodulating activities on Toll-like receptors (TLRs) and related immune genes, including cytokines, using a porcine intestinal epithelial cell line (IPEC-J2) after the establishment of a pro-inflammatory environment. IPEC-J2 was exposed for 2 h to pro-inflammatory stimuli as a model of inflammatory bowel disease (IBD), namely LPS for Crohn's disease (CD) and H2O2 for ulcerative colitis (UC); then, cells were treated with goat mEVs for 48 h. RT-qPCR and ELISA data showed that cell exposure to LPS or H2O2 caused a pro-inflammatory response, with increased gene expression of CXCL8, TNFA, NOS2 and the release of pro-inflammatory cytokines. In the LPS model, the treatment with mEVs after LPS determined the down-regulation of NOS2, MMP9, TLR5, TGFB1, IFNB, IL18 and IL12A gene expressions, as well as lower release of IL-18 in culture supernatants. At the same time, we observed the increased expression of TLR1, TLR2, TLR8 and EBI3. On the contrary, the treatment with mEVs after H2O2 exposure, the model of UC, determined the increased expression of MMP9 alongside the decrease in TGFB1, TLR8 and DEFB1, with a lower release of IL-1Ra in culture supernatants. Overall, our data showed that a 48 h treatment with mEVs after a pro-inflammatory stimulus significantly modulated the expression of several TLRs and cytokines in swine intestinal cells, in association with a decreased inflammation. These results further highlight the immunomodulatory potential of these nanosized structures and suggest their potential application in vivo.


[The effect of membrane channel agonists and antagonists on hemodynamics and vascular tonus].
Compound "C" which was synthesized in Institute of Organic Chemistry NA of Science unite in one molecule remnant of 4-aril-1,4-dihydropyridin kernek cause it as calcium channel block-up property and group of molecule pinacidil which determine if effect as activation potassium channels. This compound cause essential decrease arterial pressure and total periphery resistance of vessels. The decrease this figures of hemodynamic connect with reducing vessels tone. This is proved by substantial decrease contractile activity isolated strips of aorta and portal vein by compound "C". The mechanism reducing tone, as demonstrate investigations on isolated solitary smooth muscle mesenterial arteries, cause with increase potassium current, hyperpolarization of cell's membrane, and with depresses calcium current in L-type Ca(2+) channels.


[Uncommon malformative association (author's transl)].
An uncommon malformative association is presented ((hydrocephalus, bilateral renal hypoplasia, aplasia cutis) associated with neonatal gastrointestinal perforation. The bibliography related with these problems is reviewed, discussing the possible relationship between them. The etiological hypothesis is infective, and pathogenic interpretation is pointed out in this context.


A parent-of-origin effect in two families with retinoblastoma is associated with a distinct splice mutation in the RB1 gene.
We have identified a splice-site mutation (IVS6+1G-->T) in the RB1 gene, in two unrelated families with incomplete-penetrance retinoblastoma. Analysis of RNA from white blood cells showed that this mutation causes skipping of exon 6. Although this deletion results in a frameshift, most carriers of the mutation did not develop retinoblastoma. Interestingly, the relative abundance of the resultant nonsense messenger RNA varies between members of the same family and is either similar to or considerably lower than the transcript level of the normal allele. Moreover, variation of relative transcript levels is associated with both the sex of the parent that transmitted the mutant allele and phenotypic expression: All eight carriers with similar abundance of nonsense and normal transcript have received the mutant allele from their mother, and only one of them has developed retinoblastoma; by contrast, all eight carriers with reduced abundance of the nonsense transcript have received the mutant allele from their father, and all but two them have retinoblastoma. After treatment with cycloheximide, the relative abundance of transcripts from paternally inherited mutant alleles was partly restored, thus indicating that posttranscriptional mechanisms, rather than transcriptional silencing, are responsible for low levels of mutant messenger RNA. Our data suggest that a specific RB1 mutation can be associated with differential penetrance, on the basis of the sex of the transmitting parent.


Recent advances and applications of microspheres and nanoparticles in transarterial chemoembolization for hepatocellular carcinoma.
Transarterial chemoembolization (TACE) is a recommended treatment for patients suffering from intermediate and advanced hepatocellular carcinoma (HCC). As compared to the conventional TACE, drug-eluting bead TACE demonstrates several advantages in terms of survival, treatment response, and adverse effects. The selection of embolic agents is critical to the success of TACE. Many studies have been performed on the modification of the structure, size, homogeneity, biocompatibility, and biodegradability of embolic agents. Continuing efforts are focused on efficient loading of versatile chemotherapeutics, controlled sizes for sufficient occlusion, real-time detection intra- and post-procedure, and multimodality imaging-guided precise treatment. Here, we summarize recent advances and applications of microspheres and nanoparticles in TACE for HCC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.


Screening Tools to Predict the Development of Chronic Low Back Pain: An Integrative Review of the Literature.
To identify and describe available instruments that can be used to screen patients with acute or subacute low back pain for a chronic low back pain trajectory. Integrative literature review. An electronic search of PubMed/MEDLINE, CINAHL, Cochrane Database of Systematic Reviews, and PsychINFO databases took place from May through July of 2014 using systematic search strategies to identify screening instruments developed to identify people at risk of chronic low back pain. After screening for inclusion and exclusion criteria as well as quality indicators, the identified studies were categorized based on whether the instrument measured psychological, clinical, or functional measures to predict chronic low back pain. Initial searches identified 2,274 potential articles. After assessing for duplicates, title, and abstract content, there were 129 remaining articles. Articles were further excluded after analysis of the text, for a total of 42 studies reviewed. Most instruments reviewed were unable to provide evidence of predictive power for developing chronic low back pain. This review identified numerous instruments developed to assess the likelihood of chronic low back pain in acute and subacute low back pain populations. Of the instruments reviewed, the STarT Back Screening Tool and the Örebro Musculoskeletal Pain Questionnaire demonstrated superior predictive power compared with other instruments. Both screening tools offer evidence of validation, translation into different languages and international application, and usage in various health care settings and provide data on predictive power.


Trapping of a Highly Reactive Oxoiron(IV) Complex in the Catalytic Epoxidation of Olefins by Hydrogen Peroxide.
The generation of a nonheme oxoiron(IV) intermediate, [(cyclam)FeIV (O)(CH3 CN)]2+ (2; cyclam=1,4,8,11-tetraazacyclotetradecane), is reported in the reactions of [(cyclam)FeII ]2+ with aqueous hydrogen peroxide (H2 O2 ) or a soluble iodosylbenzene (sPhIO) as a rare example of an oxoiron(IV) species that shows a preference for epoxidation over allylic oxidation in the oxidation of cyclohexene. Complex 2 is kinetically and catalytically competent to perform the epoxidation of olefins with high stereo- and regioselectivity. More importantly, 2 is likely to be the reactive intermediate involved in the catalytic epoxidation of olefins by [(cyclam)FeII ]2+ and H2 O2 . In spite of the predominance of the oxoiron(IV) cores in biology, the present study is a rare example of high-yield isolation and spectroscopic characterization of a catalytically relevant oxoiron(IV) intermediate in chemical oxidation reactions.


Antibacterial activity and mode of action of tert-butylhydroquinone (TBHQ) and its oxidation product, tert-butylbenzoquinone (TBBQ).
The antioxidant tert-butylhydroquinone (TBHQ) is a food additive reported to have antibacterial activity, and may therefore have application in the healthcare setting. This study sought to characterize the antibacterial activity and mode of action of TBHQ and its oxidation product, tert-butylbenzoquinone (TBBQ). The stability of TBHQ/TBBQ was studied in buffer. Susceptibility testing was performed by broth microdilution, and killing and lytic activity were evaluated by viable counting and culture turbidity measurements. Mode of action studies included following the incorporation of radiolabelled precursors into macromolecules. The effect of TBHQ/TBBQ upon bacterial and mammalian membranes was assessed using the BacLight(TM) assay and by monitoring the haemolysis of equine erythrocytes. TBHQ underwent oxidation in solution to form TBBQ. When oxidation was prevented, TBHQ lacked useful antibacterial activity, indicating that TBBQ is responsible for the antibacterial activity attributed to TBHQ. TBBQ demonstrated activity against Staphylococcus aureus SH1000 (MIC 8 mg/L) and against a panel of clinical S. aureus isolates (MIC90 16 mg/L). TBBQ at 4× MIC caused a >4 log10 drop in cell viability within 6 h without lysis, and eradicated staphylococcal biofilms at 8× MIC. TBBQ did not display preferential inhibition of any single macromolecular synthetic pathway, but caused loss of staphylococcal membrane integrity without haemolytic activity. TBBQ is responsible for the antibacterial activity previously ascribed to TBHQ. TBBQ prompts loss of staphylococcal membrane integrity; it is rapidly and extensively bactericidal, but is non-lytic. In view of the potent and selective bactericidal activity of TBBQ, this compound warrants further investigation as a candidate antistaphylococcal agent.


Utilizing Zebrafish Visual Behaviors in Drug Screening for Retinal Degeneration.
Zebrafish are a popular vertebrate model in drug discovery. They produce a large number of small and rapidly-developing embryos. These embryos display rich visual-behaviors that can be used to screen drugs for treating retinal degeneration (RD). RD comprises blinding diseases such as Retinitis Pigmentosa, which affects 1 in 4000 people. This disease has no definitive cure, emphasizing an urgency to identify new drugs. In this review, we will discuss advantages, challenges, and research developments in using zebrafish behaviors to screen drugs in vivo. We will specifically discuss a visual-motor response that can potentially expedite discovery of new RD drugs.


Pathogenesis of high-altitude pulmonary edema: inflammation is not an etiologic factor.
The pathogenesis of high-altitude pulmonary edema (HAPE) is considered an altered permeability of the alveolar-capillary barrier secondary to intense pulmonary vasoconstriction and high capillary pressure, but previous bronchoalveolar lavage (BAL) findings in well-established HAPE are also consistent with inflammatory etiologic characteristics. To determine whether inflammation is a primary event in HAPE and to define the temporal sequence of events in HAPE. Case study from July through August 1999 of 10 subjects with susceptibility to HAPE and 6 subjects resistant to HAPE, all of whom are nonprofessional alpinists with previous mountaineering experience above 3000 m. Pulmonary artery pressure measurements and BAL findings at low altitude (490 m) and shortly before or at the onset of HAPE at an altitude of 4559 m. Subjects who were HAPE susceptible had higher mean (SD) pulmonary artery systolic blood pressures at 4559 m compared with HAPE-resistant subjects (66 vs 37 mm Hg; P =.004). Despite development of HAPE in the majority of HAPE-susceptible subjects, there were no differences in BAL fluid total leukocyte counts between resistant and susceptible subjects or between counts taken at low and high altitudes. Subjects who developed HAPE had BAL fluid with high concentrations of plasma-derived proteins and erythrocytes, but there was no increase in plasma concentrations of surfactant protein A and Clara cell protein. The chest radiograph score was 12.7 for the 3 HAPE-susceptible subjects who developed HAPE before BAL was performed; they were lavaged within 3 to 5 hours. The remainder of the HAPE-susceptible group was lavaged before edema was apparent on radiographs. However, 6 subjects from the HAPE-susceptible group who developed HAPE on the following day had a score on bronchoscopy of 1.5, which increased to 4.6, reflective of mild pulmonary edema. In HAPE cases, there were no elevations in a number of proinflammatory cytokines and eicosanoid and nitric oxide metabolites. Early HAPE is characterized by high pulmonary artery pressures that lead to a protein-rich and mildly hemorrhagic edema, with normal levels of leukocytes, cytokines, and eicosanoids. HAPE is a form of hydrostatic pulmonary edema with altered alveolar-capillary permeability.


Adrenal Hemangioma Definite Diagnosis on CT, MRI, and FDG PET in a Patient With Primary Lung Cancer.
Distinguishing adrenal incidentalomas (5% of all abdominal CT scans) from metastasis is a frequent diagnostic challenge in primary malignancies with a propensity for adrenal spread, such as lung cancer. Adrenal myelolipoma and adenoma can be definitively characterized as benign by demonstrating gross and microscopic fat, respectively, on CT and MRI and an absence of abnormal uptake on PET. Unfortunately, adrenal sampling is frequently necessary in indeterminate cases for adequate staging of extra-adrenal primary malignancy. We present a lung cancer case in which definite characterization of a rare adrenal hemangioma with CT, PET, and MRI avoided unnecessary adrenal sampling.


Vascularised composite allotransplants: Transplant of upper extremities and face.
Transplantation of solid organs and bone marrow has become a highly acceptable and often the only available clinical solution in many situations. It has been practiced across the globe for quite a long time since the first kidney transplant in 1954. Transplantation of tissues other than these, which was termed composite tissue allotransplantation and currently as vascularised composite allotransplantation (VCA) is gaining acceptance as a solution for complex reconstructive problems. This involves the transfer of multiple types of tissue such as bone, muscle, nerve, skin and blood vessels. The advantage of these over the conventional reconstructive methods is its ability to give aesthetically and functionally superior equal composite substitute to the missing or deformed part. The composite tissues transplanted commonly include the upper extremities, face and abdominal wall. Among these, hand transplants were the first to be done and have been carried out more than any other VCA. This article reviews the current scenario of VCA especially of the hand and face, in the light of experience of the two bilateral hand transplants done recently in India.


Effect of p-chlorophenoxyisobutyrate (CPIB) fed to rats on hepatic biosynthesis and catabolism of ubiquinone.
The effect of p-chlorophenoxyisobutyrate (CPIB) feeding on cholesterol and ubiquinone metabolism in rats was investigated. The results obtained from acetate-1-(14)C and mevalonate-2-(14)C incorporation studies both in vivo and in vitro confirm the results of other workers that CPIB feeding caused a metabolic block in the conversion of acetate to mevalonate, thereby inhibiting over-all steroidogenesis. Liver ubiquinone synthesis was inhibited in CPIB-fed rats, but a block in the catabolism of the ubiquinone resulted in accumulation of ubiquinone in CPIB-fed animals.


A Case-Based Review of the Management of Penetrating Brain Trauma.
Principles of penetrating head trauma management were established by Harvey Cushing in relation to the management of penetrating brain injuries of World War One. Cushing radically debrided the scalp and skull and aggressively irrigated wound tracks to remove foreign bodies. He would then obtain water-tight closure. Cushing significantly decreased infection rates which reportedly limited the major cause of mortality due to penetrating head injuries. Many advances have been made by contributions from World War Two, Korean War, Vietnam War, and Iran/Iraq conflicts. Early radical decompression, with conservative debridement and duraplasty applied to blast-induced penetrating injuries during Operation Iraqi Freedom, has resulted in increased survivability and neurological improvement. Each advance in the management of these injuries is based upon more effectively addressing one or more components of Matson's tenets. This case series reviews the successful management of three patients that presented to a level I trauma center with a penetrating head injury from high-velocity projectiles. Management principles of each patient begin with a proper patient assessment, application of Matson's tenets from the time of injury, and airway control. Surgical management is based upon adherence to Grahm's Guidelines which emphasize criteria centered upon post-resuscitative Glasgow Coma Scale score and appropriate imaging. This case series suggests that proper patient evaluation, adherence to Matson's tenets and to Grahm's Guidelines, and appropriate patient selection for operative management leads to improved survival of patients with penetrating head trauma from high-velocity projectiles.


The renin-angiotensin system in nonmammalian vertebrates.
The most primitive components of the RAS appeared early in the phylogenetic history of vertebrate animals. It is probable that renin granules were present in the kidneys of ancestral chordates before divergence in the evolution of actinopterygian fish and tetrapods occurred. Granulated juxtaglomerular cells similar to the renin-containing cells of the mammalian nephron are found in most extant vertebrate species although not in agnathan and elasmobranch fish. A macula densa occurs in amphibians, birds and mammals; and an extraglomerular mesangium, only in birds and mammals. Renin-like activity and angiotensin-like pressor material have been demonstrated in all classes of vertebrates. The amino acid sequences of native ANG I have been determined for representative species of teleost fish, amphibian, reptile and bird. These peptides differ from mammalian angiotensins at positions 1, 5 and 9. The RAS appears to be involved in osmoregulation, ionoregulation and the control of blood circulation. Prolonged hypovolemic hypotension or sodium depletion increases renin levels. Angiotensins elicit drinking and stimulate transepithelial ion transport. However, direct steroidogenic and antidiuretic hormone-releasing activities, which would promote mineral and fluid conservation, have not been demonstrated unambiguously in nonmammalian vertebrates. ANG II raises blood pressure by direct vasoconstrictor action on arteriolar muscles in some animals, but perhaps more generally by acting on the nervous system and adrenal paraneurons. In birds the hormone also has a hypotensive effect. ANG II stimulates the SNS in agnathans, elasmobranchs, teleosts, amphibians, reptiles, birds and mammals. Thus, modulation of sympathetic activity may be one of the most primitive and conservative functions of the RAS. For this reason, nonmammalian vertebrates are valuable models for studying the neurogenic actions of angiotensin II relevant to hypertensive disease.


The management of fulminant meningitis in the intensive care unit.
Fulminant meningitis requires aggressive management in an intensive care unit setting. The pathophysiology of the various factors that damage the central nervous system in this disease have been reviewed, as well as the management of the many complications of this serious, often devastating, infection. The etiologic agents according to age group have been discussed, and recommendations for empiric therapy have been made.


Mediastinal 99mTc-Methylene Diphosphonate Accumulation in a Patient With Primary Mediastinal Soft Tissue Giant Cell Tumor.
Soft tissue giant cell tumor (GCT) is rare. It usually involves the extremities. We report the case of a 37-year-old woman who was suspected of having mediastinal tumor on radiograph. Thoracic CT revealed the tumor had extensive calcification and invaded the adjacent vertebrae and spinal canal. It intensively accumulated Tc-methylene diphosphonate on bone scan. The tumor showed hypointensity on T1-weighted and mixed intensity on T2-weighted fat-saturated sagittal images. Finally, a soft tissue GCT was confirmed by pathology. The case cautions us soft tissue GCT should be in the differential diagnosis spectrum in a calcified posterior mediastinal mass with Tc-methylene diphosphonate accumulation.


Analysis of a mutant p53 protein arising in a medulloblastoma from a mouse transgenic for the JC virus early region.
JC virus (JCV) is a polyomavirus that causes progressive multifocal leukoencephalopathy (PML) in humans and is highly oncogenic in experimental animals. Transgenic mice with JCV T-antigen develop cerebellar tumors, which resemble human medulloblastomas, containing two distinct cell subpopulations, T-antigen positive and negative. In T-negative clones, a novel mutant p53 was detected (p53(mt)). We have compared p53(mt) to wild-type p53 (p53wt) in p53-null cells. p53(mt) had lost the transcriptional transactivation activity of p53(wt), and unlike p53(wt), partially localized to the cytoplasm. Unlike mutant p53 from many human cancers, p53(mt) did not show a gain of function or a dominant negative phenotype. Adenovirus expressing p53(wt) but not p53(mt) inhibited cell growth and induced apoptosis of p53-null cells. During the course of tumor evolution of the JCV T-antigen mouse medulloblastoma, a mutation occurred that inactivated p53 allowing tumor progression even in the absence of continued T-antigen expression.


Addressing uncertain assumptions in DNA evidence evaluation.
Evidential value of DNA mixtures is typically expressed by a likelihood ratio. However, selecting appropriate propositions can be contentious, because assumptions may need to be made around, for example, the contribution of a complainant's profile, or relatedness between contributors. A choice made one way or another disregards any uncertainty that may be present about such an assumption. To address this, a complex proposition that considers multiple sub-propositions with different assumptions may be more appropriate. While the use of complex propositions has been advocated in the literature, the uptake in casework has been limited. We provide a mathematical framework for evaluating DNA evidence given complex propositions and discuss its implementation in the DBLR™ software. The software simultaneously handles multiple mixed samples, reference profiles and relationships as described by a pedigree, which unlocks a variety of applications. We provide several examples to illustrate how complex propositions can efficiently evaluate DNA evidence. The addition of this feature to DBLR™ provides a tool to approach the long-accepted, but often impractical suggestion that propositions should be exhaustive within a case context.


High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS.
Hyperuricemia (HUA) as a metabolic disease is closely associated with metabolic disorders. The etiology and pathogenesis of HUA are not fully understood, so there is no radical cure so far. Metabolomics, a specialized study of endogenous small molecule substances, has become a powerful tool for metabolic pathway analysis of selected differential metabolites, which is helpful for initially revealing possible development mechanisms of various human diseases. Twenty HUA patients and 20 healthy individuals participated in the experiment, and ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was employed to investigate serum samples to find differential metabolites. The statistical techniques used were principal component analysis and orthogonal partial least-squares discriminant analysis. The differences in metabolomics results of samples after pretreatment with different solvents were compared, 38, 20, 26, 28, 33, 50, and 40 potential differential metabolites were found, respectively, in HUA patient samples, and each group involved different metabolic pathways. Repetitive metabolites were removed, 138 differential metabolites in HUA serum were integrated for analysis, and the human body was affected by 7 metabolic pathways of glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and α-linolenic acid metabolism. In this work, the metabolomics approach based on UPLC-Q-TOF/MS was employed to investigate serum metabolic changes in HUA patients, 138 potential differential metabolites related to HUA were identified, which provided associations of lipids, amino acids, fatty acids, organic acids, and nucleosides profiles of HUA individuals. Metabolic pathways involved in glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and a-linolenic acid metabolism shed light on the understanding of the etiology and pathogenesis process of HUA.


Weighted patterns as a tool for improving the Hopfield model.
We generalize the standard Hopfield model to the case when a weight is assigned to each input pattern. The weight can be interpreted as the frequency of the pattern occurrence at the input of the network. In the framework of the statistical physics approach we obtain the saddle-point equation allowing us to examine the memory of the network. In the case of unequal weights our model does not lead to the catastrophic destruction of the memory due to its overfilling (that is typical for the standard Hopfield model). The real memory consists only of the patterns with weights exceeding a critical value that is determined by the weights distribution. We obtain the algorithm allowing us to find this critical value for an arbitrary distribution of the weights, and analyze in detail some particular weights distributions. It is shown that the memory decreases as compared to the case of the standard Hopfield model. However, in our model the network can learn online without the catastrophic destruction of the memory.


Describing Trajectories of Homeless Service Use in Hawai'i Using Latent Class Growth Analysis.
The State of Hawai'i, like many other areas across the United States, has large numbers of individuals and families experiencing homelessness, many of whom seek support through statewide shelters and services. This study explored the diversity of ways in which individuals and families moved through Hawai'i's homeless service system. Using administrative data, a cohort of new service users was tracked across time to trace the developmental trajectories of their homeless service use. The sample consisted of adults who had entered the service system for the first time in the fiscal year (FY) of 2010 (N = 4655). These individuals were then tracked through the end of FY 2014, as they used emergency shelter, transitional shelter, and outreach services. A latent class growth analysis was conducted and identified four distinct patterns of service use: low service use (n = 3966, 85.2%); typical transitional shelter use (n = 452, 9.7%); atypical transitional use (n = 127, 2.7%), and potential chronic service use (n = 110, 2.4%). Multinomial logistic regression models were then used to determine if select demographic, family, background experience (e.g., education, employment), or health variables were associated with class membership. The distinct profiles for class membership are discussed.


Subclinical hypothyroidism and lipid abnormalities in older women attending a vascular disease prevention clinic: effect of thyroid replacement therapy.
The authors evaluated the frequency and type of lipid disorders associated with subclinical hypothyroidism (SH) in older women referred to their university vascular disease prevention clinic. They also assessed the results of thyroid replacement therapy. Fasting serum lipid profiles and thyroid function tests were measured in 333 apparently healthy women (mean age: 71.8 +/- 7 years). These women were divided into 3 groups: group I: 60-69 years old (n = 132); group II: 70-79 years old (n = 153); group III: 80-89 years old (n = 48). SH was defined as a serum thyrotropin concentration higher than 3.20 mlU/mL with a normal free thyroxine concentration. The prevalence of SH was 7.5%. Thyrotropin was higher than 3.20 mU/mL in 25 women; 7 (5.3%), 14 (9.2%), and 4 (8.3%) in groups I, II, and III, respectively. Low-density lipoprotein cholesterol (LDL-C) concentrations were higher in the women with SH (p = 0.037). The mean values of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, lipoprotein (a) (Lp[a]), apolipoprotein A-I (apo AI) apolipoprotein B100 (apo B) and apo B/apo A ratio were higher and triglycerides (TG) were lower, compared with those with normal levels of thyrotropin. However, none of these differences reached significance. Restoration of euthyroid status (thyroxine: 50-100 microg/day) in 17 SH women significantly improved TC (p = 0.017), LDL-C (p = 0.014), TC/HDL-C (p = 0.05), LDL-C/HDL-C (p = 0.03), apo B (p = 0.013), and Lp(a) (p = 0.0005) values. SH is relatively common in older women attending a vascular disease prevention clinic. Thyroid hormone replacement therapy significantly improved serum lipids. In particular, the reduction in LDL-C and Lp(a) concentrations may be of clinical benefit.


DFT Studies of the Photocatalytic Properties of MoS2-Doped Boron Nitride Nanotubes for Hydrogen Production.
This study investigated the photocatalytic properties of MoS2-doped boron nitride nanotubes (BNNTs) for overall water splitting using popular density functional theory (DFT). Calculations of the structural, mechanical, electronic, and optical properties of the investigated systems were performed using both the generalized gradient approximation and the GW quasi-particle correction methods. In our calculations, it was observed that only (10, 10) and (12, 12) single-walled BNNTs (SWBNNTs) turned out to be stable toward MoS2 doping. Electronic property calculations revealed metallic behavior of (10, 10)-MoS2-doped SWBNNTs, while the band gap of (12, 12) SWBNNT was narrowed to 2.5 eV after MoS2 doping, which is within the obtained band gaps for other photocatalysts. Hence, MoS2 influences the conduction band of pure BNNT and improves its photocatalytic properties. The water-splitting photocatalytic behavior is found in (12, 12) MoS2-doped SWBNNT, which showed higher water oxidation (OH-/O2) and reduction (H+/H2) potentials. In addition, optical spectral calculations showed that MoS2-doped SWBNNT had an optical absorption edge of 2.6 eV and a higher absorption in the visible region. All of the studied properties confirmed MoS2-doped SWBNNT as a better candidate for next-generation photocatalysts for hydrogen evolution through the overall water-splitting process.


[Intervention in situations of psychic crisis: challenges and suggestions of a prehospital care staff].
A qualitative and descriptive research, aimed at knowing how the pre-hospital care professionals perceive the interventions towards people in mental crisis. The study was developed in Santa Catarina with four teams of basic life support units of the Department of Mobile Emergency Care, during April to June 2011. The Collective Subject Discourse was used as the method of analysis. Two themes emerged: Awareness of the difficulties in meeting a person in mental crisis and Suggestions in the search for a closer attention to the person in mental crisis. The difficulties mentioned were related to the lack of training and a local to forward the patients, suggesting a better training and systematization of care. We conclude that it is necessary to invest in the educational process, based on new care strategies guided by the principles of SUS and of the psychosocial paradigm, and revisit the strategy of protocols as guidelines and not as standardizing systems.


Exploring factors behind pregnant women's quality of life in Iran: a qualitative study.
Pregnancy-related physiologic and psychosocial alterations can impact on the body and cause symptoms which may affect quality of life. Since qualitative studies can provide more in-depth understanding of quality of life and its determining factors, this study was conducted with the aim of exploring factors affecting pregnant women's quality of life. A qualitative descriptive study with conventional content analysis approach was made using the conventional content analysis approach on a purposeful sample of sixteen pregnant Iranian women in Hamadan, Iran from May 2015 to December 2015. Sampling was continued until data saturation. Data were collected through in-depth semi-structured personal interviews, and were analyzed using the conventional content analysis approach. Data analysis resulted in three main categories, namely, the effects of pregnancy on different aspects of health (including psychological disorders, impaired interactions, disturbances in doing daily activities, disturbed body image, alterations in sexual relationships, physical disorders, and alterations in dietary habits and treatment regimens), pregnancy-related concerns (regarding the gender of the fetus, financial problems, childbirth, health, and the future), and coping with pregnancy (through strategies such as spirituality, positive attitude toward pregnancy, distraction and imagination, and support). This study showed that different factors can affect pregnant women's quality of life. Nonetheless, prenatal care services are mainly focused on pregnancy-related physical problems, and other aspects of care are usually taken for granted. Consequently, healthcare professionals need to pay greater attention to pregnant women's quality of life and its contributing factors.


Challenges of Racism and Health Equity in Medicine.
The racial/ethnic populations in the United States, in general, have less access to quality health care and behavioral healthcare services than the Caucasian population. They face barriers to access health care access, and experience higher rates of chronic diseases and complications with heart disease, diabetes, cancer, HIV, and obesity. Increasing the number of racial/ethnic physicians is one way to build trust, provide patient-centered and cultural quality care, and attract racial/ethnic patients to healthcare services. However, the inherent structural racism of medicine and implicit bias of physicians makes this challenging. In this collection of stories from racial/ethnic physicians, trainees, and other health care providers, authors focus on the trauma they have experienced with racist patients and colleagues during their careers, yet discuss how what they have learned is important for medical education for other healthcare providers like them.


Breaking bad news: doctors' skills in communicating with patients.
Breaking bad news is one of doctors' duties and it requires them to have some skills, given that this situation is difficult and distressful for patients and their families. Moreover, it is also an uncomfortable condition for doctors. The aim of this study was to evaluate doctors' capacity to break bad news, ascertain which specialties are best prepared for doing this and assess the importance of including this topic within undergraduate courses. Observational cross-sectional quantitative study conducted at a university hospital in Belo Horizonte (MG), Brazil. This study used a questionnaire based on the SPIKES protocol, which was answered by 121 doctors at this university hospital. This questionnaire investigated their attitudes, posture, behavior and fears relating to breaking bad news. The majority of the doctors did not have problems regarding the concept of bad news. Nevertheless, their abilities diverged depending on the stage of the protocol and on their specialty and length of time since graduation. Generally, doctors who had graduated more than ten years before this survey felt more comfortable and confident, and thus transmitted the bad news in a better conducted manner. Much needs to be improved regarding this technique. Therefore, inclusion of this topic in undergraduate courses is necessary and proposals should be put forward and verified.


[Prophylactic splenectomy for splenic vein thrombosis in patients undergoing resection for chronic pancreatitis].
Chronic pancreatitis (CP) is the leading cause of splenic vein thrombosis (SVT). SVT occurs in about 15 % of patients with CP. The risk of variceal bleeding in SVT is approximately 10 %. Splenectomy is indicated in symptomatic SVT but its role in asymptomatic SVT is discussed controversially. Aim of our study was to evaluate the outcome of splenectomy performed during pancreatic resection in patients with CP and asymptomatic SVT. 33 of 198 patients undergoing resection for CP underwent concomitant prophylactic splenectomy for asymptomatic SVT. Perioperative data were compared in the groups of patients with or without splenectomy. Follow-up was complete in 84 % (average 31 months). Median operative time, postoperative morbidity, reoperation rate and mortality were not different in patients with or without splenectomy. The median number of blood units transfused was higher in patients with prophylactic splenectomy (6 vs 4 units; p < 0.01). One complication of splenectomy (postoperative bleeding) occurred (3 %). During follow-up no variceal bleeding, no episode of postsplenectomy sepsis or thrombosis due to temporary thrombocytosis occurred. Complications of prophylactic splenectomy are rare and less frequent than reported episodes of variceal bleeding. In the presence of asymptomatic SVT splenectomy should be considered during pancreatic resection to facilitate surgery and to avoid further variceal bleeding.


Breast cancer detection epoch.
The Action and Planning Committee on Breast Cancer Control was formed in 1970 by the American Cancer Society, based on their earlier successful experience with early-detection programs for uterine cancer. The original intention was to support 12 centers for 2 years, but with the passage of the Conquest of Cancer Act in 1971, and the consequent availability of more funds for cancer programs, the American Cancer Society and the National Cancer Institute decided jointly to expand the program to 27 Breast Cancer Detection Demonstration Project Centers, with 280,000 women participating, who would be examined annually for 5 years. Data from the examinations, which included history, physical examination, mammogram, and thermogram, were subjected to a continuing computer analysis. The thermogram was deleted after the second year. Although patients were randomly selected, there was an almost identical number of subjects in two age groups--35-49 years and 50-75 years. The results of the study are presented, and the importance of the program's efforts at breast self-examination education as contained in the program's original protocol, is discussed.


Capsular polysaccharides secreted by building façade colonisers: characterisation and adsorption to surfaces.
Exopolymers secreted by algal and cyanobacterial strains isolated from building façades were imaged by microscopy techniques. They were extracted and characterised to investigate their possible contribution to interactions with solid surfaces. The polymers were polysaccharides, with anionic and hydrophobic properties varying between the various strains. Capsular polysaccharides extracted from a strain of Klebsormidium flaccidum adsorbed in higher amounts on hydrophobic than on hydrophilic surfaces. These results tend to confirm the hypothesis that exopolymers are important in the colonisation process of microorganisms to surfaces.


The Relationship Between Enlistment Body Mass Index and the Development of Obstructive Sleep Apnea in the U.S. Military.
The incidence of obstructive sleep apnea (OSA) in the military has risen dramatically. OSA is considered "service connected" and compensable by the Veterans Administration. The association between body mass index (BMI) (kg/m(2)) measured at initial enlistment and development of OSA has yet to be assessed. Data were obtained from the Defense Medical Surveillance System, the Armed Forces Health Surveillance Center, U.S. Department of Defense, Silver Spring, Maryland (inclusive dates:1993-2012; release date: December 2013). A study population of 550,000 randomly-selected active duty enlisted personnel was followed retrospectively from January 1, 2008, through December 31, 2012, or until diagnosis with OSA, separation from the military, or death occurred. The main exposure of interest was BMI recorded at time of enlistment. Adjusted hazard ratios for enlistment BMI were calculated using BMI of 23 to 23.9 as reference. Exponentially increasing risk for OSA was observed as BMI increased. The heaviest individuals (BMI > 35) were at the highest risk (hazard ratio: 3.93; 95% confidence interval [CI]: 3.35-4.62) for developing OSA. Enlistment BMI's role in developing OSA may be valuable in designing screening tools and preventive interventions in higher-risk groups, as well as prompt further consideration in the realm of military enlistment policy.


[Functional preservation in rectal cancer surgery].
Improvement in the cancer eradication and prevention of pelvic organ dysfunction are the most important strategy in rectal cancer surgery. More than 90% of rectal cancer in my experiences received APR resection before 1962. However, after 1963 anal function preserving operations were adopted 45% or more of rectal cancer. Pull-through was adopted at the beginning, however, anterior resection took the place of this procedure after 1969. When the suture instruments were applied to rectal surgery in 1984, 65% of patients were treated by instrumental end-to end reconstruction. Cancers, which have depth invasion a1, are treated enough with 2 cm length of distal stump, while cancers further depth invasion need 3 cm or more distal stump. Dysuria and male sexual impotence are caused by intrapelvic nerve injuries during surgery. Dysuria was found in 49% and impotence in 38% following conventional surgery. The incidence of dysuria and impotence, however, increased to 67% and 97% by extended dissection, respectively. To prevent these deteriorations, the pelvic node dissection should be limited to do for the locally advanced cases. Nerve preserving operation was performed for cancer with flat sm and slight invasion into pm layer, and the incidence of dysuria and impotence was decreased to 15% and 21%, respectively.


Spillover benefits from the world's largest fully protected MPA.
Previous research has cast doubt on the potential for marine protected areas (MPAs) to provide refuge and fishery spillover benefits for migratory species as most MPAs are small relative to the geographic range of these species. We test for evidence of spillover benefits accruing from the world's largest fully protected MPA, Papahānaumokuākea Marine National Monument. Using species-specific data collected by independent fishery observers, we examine changes in catch rates for individual vessels near to and far from the MPA before and after its expansion in 2016. We find evidence of spillover benefits for yellowfin (Thunnus albacares) and bigeye tuna (Thunnus obesus).


Enhancement of antigen-specific humoral and cell-mediated immunity by electric footshock stress in rats.
The effect of footshock stress on the induction phase of sensitization to keyhole limpet hemocyanin (KLH) introduced intraperitoneally was studied in adult male Sprague-Dawley rats. Rats were shocked at Days -1, 0, 1, and 3 relative to sensitization with 50 micrograms KLH and 14 days later were intradermally injected with 25 micrograms KLH or were noninjected. Anti-KLH IgG levels were measured in serum by ELISA and were enhanced in stressed versus control rats shocked on Days 0 or 1; splenocyte proliferation to KLH in vitro was also found to be enhanced in shocked rats compared to that in nonshocked rats. Skin at the challenge sites was removed and histologically examined for infiltrate density. There was an increased infiltrate in animals shocked on Days 0 or 1 in comparison to nonshocked controls. The increased humoral and cell-mediated anti-KLH immunity in stressed rats is evidence for enhanced immune function by exposure to footshock proximal to the induction phase of the immune response. The possibility of a generalized increase in immune function in stressed rats is doubtful since splenocyte proliferation to the T-cell mitogens concanavalin A (Con A) and phytohemagglutinin and the B-cell mitogen lipopolysaccharide showed no alteration between control and stressed rats at the time of sacrifice.


Nursing leadership collaboration for rehabilitation of polytrauma patients.
This article describes a variety of nursing issues that emerged over a 3-year period on polytrauma rehabilitation nursing units and the leadership roles and strategies that were used to meet the rehabilitation needs of newly injured servicemembers who served in Operation Enduring Freedom (OEF) in Afghanistan and Operation Iraqi Freedom (OIF). Nursing's leadership responsibilities focus on three primary areas: patient advocacy, family centeredness, and advocacy for staff Collaboration among the four national polytrauma rehabilitation centers (PRCs) run by the U.S. Department of Veterans Affairs has enhanced the skill set for nursing staff members. These rehabilitation nurses possess the strong skills necessary to assess complex patient cases involving blast injuries, as well as strengthened interpersonal competencies in family dynamics, family education, and team function.


Transfer of ciprofloxacin, ofloxacin and levofloxacin across the perfused human placenta in vitro.
To investigate the transfer of therapeutically important fluoroquinolones: ciprofloxacin, ofloxacin and levofloxacin, through the isolated perfused human placenta, from the maternal to the fetal compartment. Isolated placental cotyledons from normal human term placentae were dually perfused with M199 medium enriched with 3g/l bovine serum albumin and 1g/l glucose. Perfusion rates were 12 and 6 ml/min in the maternal and fetal circulation, respectively. Maternal and fetal closed circulation was used to evaluate steady-state concentrations and transplacental gradient formation. Eighteen placentae were used in our study: six for each experiment with ciprofloxacin, ofloxacin and levofloxacin were added to the maternal circulation. Samples were collected from the maternal and fetal compartments. Antipyrine was used as a reference drug that crosses the placenta by simple diffusion. The concentrations of ciprofloxacin, ofloxacin, levofloxacin and antipyrine were measured by specific HPLC (high performance liquid chromatography) methods. Results are presented as mean+/-S.D. In all the placentae, ciprofloxacin, ofloxacin, levofloxacin crossed the placenta from the maternal to the fetal compartment. The mean transplacental transfer percent of ciprofloxacin was 3.2+/-0.7% and the transplacental transfer index, the ratio of transplacental transfer between ciprofloxacin and antipyrine was 0.34+/-0.12. The mean transplacental transfer percent of ofloxacin was 3.7+/-2.4% and the transplacental transfer index was 0.33+/-0.3. The mean transplacental transfer percent of levofloxacin was 3.9+/-1.5% and the transplacental transfer index was 0.34+/-0.2. Only a small fraction of ciprofloxacin, ofloxacin and levofloxacin passed from the maternal to the fetal compartment. This fraction is significantly smaller compared to antipyrine. This may indicate that there is a barrier to the transport of fluoroquinolones in human placenta.


Reconstitution of HuR-Inhibited CUGBP1 Expression Protects Cardiomyocytes from Acute Myocardial Infarction-Induced Injury.
Myocardial infarction (MI) is one of the leading causes of death in elderly people. Expanding the knowledge of the molecular mechanisms underlying MI is of profound importance to developing a cure for MI. The CUGBP- and ETR-3-like factor (CELF) proteins, a family of RNA-binding proteins, play key roles in RNA metabolism. To determine the functions and molecular mechanisms of CELF proteins in MI, an animal model of acute myocardial infarction (AMI) was used in our study. We found that the CUG triplet repeat RNA-binding protein 1 (CUGBP1)/CELF1 expression levels were decreased in AMI-injured hearts, and further studies showed that two highly conserved adenylate-uridylate-rich (AU-rich) elements in the 3'UTR of CUGBP1 were responsible for the decreased CUGBP1 expression. Upon AMI, human antigen R (HuR) was relocated to the cytoplasm from the nucleus and interacted with these AU-rich elements to affect the expression of CUGBP1. Reintroduction of CUGBP1 via gene delivery by recombinant adenovirus improved cardiac function in AMI mice. Our studies also indicated that CUGBP1 protected cardiomyocytes from ischemia-induced injury through the promotion of angiogenesis and inhibition of apoptosis by regulating the vascular endothelial growth factor-A gene. Innovation and Conclusion: Our studies indicate a role for CUGBP1 in cardiac disease and reveal a novel MI post-transcriptional gene regulatory mechanism. The reconstitution of CUGBP1 could be developed as a potential therapeutic option for the management of MI. Antioxid. Redox Signal. 27, 1013-1026.


[Accidents and accident mortality in Denmark--a comparison with Scandinavia and Europe].
As the development in mean age of the population and life expectancy has been less favourable in Denmark than in the rest of Western Europe, the Ministry of Health decided to investigate statistics for the period, 1972-1990, for the main areas where Danish life expectancy was poorer. A sharp increase in the incidence of accidental poisoning with medical drugs and alcohol during the period was found to be a factor contributing to the poorer Danish statistics during the period. In the subcategory, death after a fall, there was an increase in incidence among the elderly, but the loss of life-years remained constant. The subcategory, fatal road accidents, manifested a marked reduction in incidence, despite the increase in traffic density during the period, and there was a reduction in the loss of life-years. Thus, in the category, accidental deaths, the increase in the incidence of accidental poisonings would appear to be the only factor contributing to the poorer development in mean age and life expectancy in Denmark.


Photophysics and photochemistry of cis- and trans-hydroquinone, catechol and their ammonia clusters: a theoretical study.
Excited state hydrogen transfer in hydroquinone- and catechol-ammonia clusters has been extensively investigated by high level ab initio methods. The potential energy profiles of the title systems at different electronic states have been determined at the MP2/CC2 levels of theory. It has been predicted that double hydrogen transfer (DHT) takes place as the main consequence of photoexcited tetra-ammoniated systems. Consequently, the DHT processes lead the excited systems to the (1)πσ*-S0 conical intersections, which is responsible for the ultrafast non-radiative relaxation of UV-excited clusters to their ground states. Moreover, according to our calculated results, the single hydrogen detachment or hydrogen transfer process essentially governs the relaxation dynamics of smaller sized clustered systems (mono- and di-ammoniated).


[Aims and realizations in the manufacture of articulators].
The various designs of the most familiar articulators are described. Also the different concepts important to comprehending the stomatognathic functions are discussed. Their impact on the designs of various articulators are shown. The purpose of this study is not to given a complete review of the history and development of different articulators, rather, the purpose is to present the application of various stomatognathic philosophies to the design of various articulators.


Presence of Functional Neurotrophin TrkB Receptors in the Rat Superior Cervical Ganglion.
Sympathetic neurons express the neurotrophin receptors TrkA, p75NTR, and a non-functional truncated TrkB isoform (TrkB-Tc), but are not thought to express a functional full-length TrkB receptor (TrkB-Fl). We, and others, have demonstrated that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) modulate synaptic transmission and synaptic plasticity in neurons of the superior cervical ganglion (SCG) of the rat. To clarify whether TrkB is expressed in sympathetic ganglia and contributes to the effects of BDNF upon sympathetic function, we characterized the presence and activity of the neurotrophin receptors expressed in the adult SCG compared with their presence in neonatal and cultured sympathetic neurons. Here, we expand our previous study regarding the immunodetection of neurotrophin receptors. Immunohistochemical analysis revealed that 19% of adult ganglionic neurons expressed TrkB-Fl immunoreactivity (IR), 82% expressed TrkA-IR, and 51% expressed p75NTR-IR; TrkB-Tc would be expressed in 36% of neurons. In addition, using Western-blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses, we confirmed the expression of TrkB-Fl and TrkB-Tc protein and mRNA transcripts in adult SCG. Neonatal neurons expressed significantly more TrkA-IR and TrkB-Fl-IR than p75NTR-IR. Finally, the application of neurotrophin, and high frequency stimulation, induced the activation of Trk receptors and the downstream PI3-kinase (phosphatidyl inositol-3-kinase) signaling pathway, thus evoking the phosphorylation of Trk and Akt. These results demonstrate that SCG neurons express functional TrkA and TrkB-Fl receptors, which may contribute to the differential modulation of synaptic transmission and long-term synaptic plasticity.


Some recent developments in the chemical synthesis of inorganic nanotubes.
Inorganic nanotubes have been a subject of intensive research in the past decade. We recently developed a number of synthetic strategies for generating nanotubes from inorganic materials that do not have a layered structure. It is the intention of this contribution to provide a brief account of these research activities.


First experience of cadaveric renal transplantation in Sri Lanka
To analyse the outcome of 50 consecutive cadaveric renal transplants performed in Sri Lanka. This was a single-centre longitudinal cohort study conducted in the Nephrology and Kidney Transplant Unit, Teaching Hospital Kandy, Sri Lanka. Records of 50 Sri Lankan cadaveric renal transplant recipients from 7th December 2004 to 1st September 2013 were reviewed and categorized according to early graft function, cold ischaemia time and the duration of dialysis before surgery. Out of the 50 patients, twenty one (42%) had immediate graft function (IGF), 26 (52%) delayed graft function (DGF), and 2 (4%) primary non function (PNF). The average cold ischaemia time (CIT) was 8.8 hours. Out of 23 patients who died during the study period, 19 (82.6%) died although they had a functioning graft. Infection was the commonest cause of death (n=15; 65.2%). Rejection occurred in four (17.4%). Patient survival was 77.3% at one year, 63.0% at three years and 46% at five years. Graft survival was 93.2% at one year, 88.9% at 3 years and 84.6% at 5 years when death with a functioning graft was censored. Univariate analysis revealed that neither CIT nor duration of dialysis before transplant affected patient survival. There was no significant difference in patient survival between DGF and IGF. The events occurring in the early period following renal transplantation do not have a significant impact on long term graft outcome or patient survival. Infection is the commonest cause of death after renal transplantation and efforts should be directed to understand and prevent this complication.


Population-Specific Responses to Interspecific Competition in the Gut Microbiota of Two Atlantic Salmon (Salmo salar) Populations.
The gut microbial community in vertebrates plays a role in nutrient digestion and absorption, development of intestine and immune systems, resistance to infection, regulation of bone mass and even host behavior and can thus impact host fitness. Atlantic salmon (Salmo salar) reintroduction efforts into Lake Ontario, Canada, have been unsuccessful, likely due to competition with non-native salmonids. In this study, we explored interspecific competition effects on the gut microbiota of two Atlantic salmon populations (LaHave and Sebago) resulting from four non-native salmonids. After 10 months of rearing in semi-natural stream tanks under six interspecific competition treatments, we characterized the gut microbiota of 178 Atlantic salmon by parallel sequencing the 16S rRNA gene. We found 3978 bacterial OTUs across all samples. Microbiota alpha diversity and abundance of 27 OTUs significantly differed between the two populations. Interspecific competition reduced relative abundance of potential beneficial bacteria (six genera of lactic acid bacteria) as well as 13 OTUs, but only in the LaHave population, indicating population-specific competition effects. The pattern of gut microbiota response to interspecific competition may reflect local adaptation of the host-microbiota interactions and can be used to select candidate populations for improved species reintroduction success.