A modular, computer-controlled system for olfactory stimulation in the MRI environment.
Although the cerebral networks involved in sensory perception are of general interest in neuroscience, registration of the effects of olfactory stimulation, especially in a magnetic resonance imaging (MRI) environment, presents particular problems and constraints. This article presents details of a reliable and portable system for olfactory stimulation that is modular in design and based on microcontroller technology. It has the following characteristics: (1) It is under software control; (2) the presentation of olfactory stimulation can be synchronized with respiration; (3) it can be manually controlled; and (4) it is fully compatible with an MRI environment. The principle underlying this system is to direct an odor to the subject's nostrils by switching airflow to different odor diffusers. The characteristics of this system were established using (1) ultraviolet (UV) spectroscopy, to measure its response time, and (2) gas chromatography, to measure the repeatability of odor presentation in terms of gas concentration. A response time of 200 ± 25 ms was obtained for the system, and the standard deviations of the gas concentration delivered during stimulation ranged from 1.5% to 22%, depending on the odor, the airflow, and the dilution of the odor used. Since it is portable, controlled by software, and reliable, on the basis of the results we obtained, this system will lend itself to a wide range of applications in olfactory neuroscience.


UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities without affecting treatment outcome and survival in patients with metastatic colorectal carcinoma.
It is known that the uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1)*28 polymorphism reduces UGT1A1 enzyme activity, which may lead to severe toxicities in patients who receive irinotecan. This study was conducted to assess the influence of this polymorphism on the efficacy and toxicity of irinotecan treatment in Chinese patients with metastatic colorectal carcinoma (CRC). In total, 128 patients with metastatic CRC who had received previous treatment with irinotecan plus 5-fluorouracil/leucovorin were analyzed retrospectively. Genomic DNA samples were obtained from patients' leukocytes, and genotypes were determined by analyzing the sequence of TATA boxes in the UGT1A1 gene. The influence of the UGT1A1*28 polymorphism on toxicity and treatment outcome was analyzed. Approximately 20% of patients were identified with the UGT1A1*28 polymorphism, including 15.6% (n = 20 patients) with the thymine-adenine (TA)6/TA7 genotype and 4.7% (n = 6 patients) with the TA7/TA7 genotype. The remaining 79.7% of patients (n = 102) had wild type TA6/TA6. Marked increases in grade 3 or 4 neutropenia (53.8% vs 4.9%; P < .01), neutropenic fever (38.5% vs 3.9%; P < .01), diarrhea (26.9% vs 5.9%; P < .01), and pretreatment bilirubin level (23.1% vs 8.8%; P = .04) were observed in patients who had the TA6/TA7 or TA7/TA7 genotypes. Patients' pretreatment bilirubin levels correlated well with irinotecan-induced neutropenia (P < .01). It was noted that, although the requirement for irinotecan dose reduction was significantly greater in patients who had this genetic variant (42.3% vs 12.7%; P < .01), it did not affect the response rate to irinotecan-based chemotherapy (42.3% vs 45.1%; P = .80), and it did not significantly affect progression-free survival (10 months vs 11 months; P = .94) or overall survival (19 months vs 18 months; P = .84). The current data suggested that the UGT1A1*28 polymorphism may be a key determinant for predicting irinotecan-induced severe toxicities without affecting treatment outcome for patients with metastatic CRC. Further prospective studies are warranted for using this polymorphism to optimize irinotecan-based chemotherapy.


Defining Benchmark Outcomes for ALPPS.
The aim of this study was to use the concept of benchmarking to establish robust and standardized outcome references after the procedure ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy). The recently developed ALPPS procedure, aiming at removing primarily unresectable liver tumors, has been criticized for safety issues with high variations in the reported morbidity/mortality rates depending on patient, disease, technical characteristics, and center experience. No reference values for relevant outcome parameters are available. Among 1036 patients registered in the international ALPPS registry, 120 (12%) were benchmark cases fulfilling 4 criteria: patients ≤67 years of age, with colorectal metastases, without simultaneous abdominal procedures, and centers having performed ≥30 cases. Benchmark values, defined as the 75th percentile of the median outcome parameters of the centers, were established for 10 clinically relevant domains. The benchmark values were completion of stage 2: ≥96%, postoperative liver failure (ISGLS-criteria) after stage 2: ≤5%, ICU stay after ALPPS stages 1 and 2: ≤1 and ≤2 days, respectively, interstage interval: ≤16 days, hospital stay after ALPPS stage 2: ≤10 days, rates of overall morbidity in combining both stage 1 and 2: ≤65% and for major complications (grade ≥3a): ≤38%, 90-day comprehensive complication index was ≤22, the 30-, 90-day, and 6-month mortality was ≤4%, ≤5%, and 6%, respectively, the overall 1-year, recurrence-free, liver-tumor-free, and extrahepatic disease-free survival was ≥86%, ≥50%, ≥57%, and ≥65%, respectively. This benchmark analysis sets key reference values for ALPPS, indicating similar outcome as other types of major hepatectomies. Benchmark cutoffs offer valid tools not only for comparisons with other procedures, but also to assess higher risk groups of patients or different indications than colorectal metastases.


Epidemiology of central nervous system infections.
The radiologist frequently is asked to contribute to the diagnosis of a patient with central nervous system infections, although radiologic findings usually are nonspecific. The radiologist can consider diagnostic possibilities with more accuracy if the clinician includes accurate demographic and epidemiologic information. This article organizes a broad range of central nervous system infections into demographic and epidemiologic perspective.


Can student tutors act as examiners in an objective structured clinical examination?
The dissemination of objective structured clinical examinations (OSCEs) is hampered by requirements for high levels of staffing and a significantly higher workload compared with multiple-choice examinations. Senior medical students may be able to support faculty staff to assess their peers. The aim of this study is to assess the reliability of student tutors as OSCE examiners and their acceptance by their peers. Using a checklist and a global rating, teaching doctors (TDs) and student tutors (STs) simultaneously assessed students in basic clinical skills at 4 OSCE stations. The inter-rater agreement between TDs and STs was calculated by kappa values and paired t-tests. Students then completed a questionnaire to assess their acceptance of student peer examiners. All 214 Year 3 students at the University of Göttingen Medical School were evaluated in spring 2005. Student tutors gave slightly better average grades than TDs (differences of 0.02-0.20 on a 5-point Likert scale). Inter-rater agreement at the stations ranged from 0.41 to 0.64 for checklist assessment and global ratings; overall inter-rater agreement on the final grade was 0.66. Most students felt that assessment by STs would result in the same grades as assessment by TDs (64%) and that it would be similarly objective (69%). Nearly all students (95%) felt confident that they could evaluate their peers themselves in an OSCE. On the basis of our results, STs can act as examiners in summative OSCEs to assess basic medical skills. The slightly better grades observed are of no practical concern. Students accepted assessment performed by STs.


Taurus: Towards a Unified Force Representation and Universal Solver for Graph Layout.
Over the past few decades, a large number of graph layout techniques have been proposed for visualizing graphs from various domains. In this paper, we present a general framework, Taurus, for unifying popular techniques such as the spring-electrical model, stress model, and maxent-stress model. It is based on a unified force representation, which formulates most existing techniques as a combination of quotient-based forces that combine power functions of graph-theoretical and Euclidean distances. This representation enables us to compare the strengths and weaknesses of existing techniques, while facilitating the development of new methods. Based on this, we propose a new balanced stress model (BSM) that is able to layout graphs in superior quality. In addition, we introduce a universal augmented stochastic gradient descent (SGD) optimizer that efficiently finds proper solutions for all layout techniques. To demonstrate the power of our framework, we conduct a comprehensive evaluation of existing techniques on a large number of synthetic and real graphs. We release an open-source package, which facilitates easy comparison of different graph layout methods for any graph input as well as effectively creating customized graph layout techniques.


Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test.
Escitalopram is a serotonin reuptake inhibitor used in the treatment of depression and anxiety disorders. This study investigated the effect of escitalopram in forced swimming test (FST) and in the tail suspension test (TST) in mice, and tested the hypothesis that the inhibition of NMDA receptors and NO-cGMP synthesis is implicated in its mechanism of action in the FST. Escitalopram administered by i.p. route reduced the immobility time both in the FST (0.3-10 mg/kg) and in the TST (0.1-10 mg/kg). Administration of escitalopram by p.o route (0.3-10 mg/kg) also reduced the immobility time in the FST. The antidepressant-like effect of escitalopram (3mg/kg, p.o.) in the FST was prevented by the pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of 7-nitroindazole (50 mg/kg, i.p., a neuronal nitric oxide synthase inhibitor), methylene blue (20 mg/kg, i.p., an inhibitor of both nitric oxide synthase and soluble guanylate cyclase) or ODQ (30 pmol/site i.c.v., a soluble guanylate cyclase inhibitor) in combination with a subeffective dose of escitalopram (0.1 mg/kg, p.o.) reduced the immobility time in the FST as compared with either drug alone. None of the drugs produced significant effects on the locomotor activity in the open-field test. Altogether, our data suggest that the antidepressant-like effect of escitalopram is dependent on inhibition of either NMDA receptors or NO-cGMP synthesis. The results contribute to the understanding of the mechanisms underlying the antidepressant-like effect of escitalopram and reinforce the role of NMDA receptors and l-arginine-NO-GMP pathway in the mechanism of action of antidepressant agents.


Monitoring patients with acute dyspnoea with a serial focused ultrasound of the heart and the lungs (MODUS): a protocol for a multicentre, randomised, open-label, pragmatic and controlled trial.
Among patients admitted to an emergency department, dyspnoea is one of the most common symptoms. Patients with dyspnoea have high mortality and morbidity. Therefore, novel methods to monitor the patients are warranted. The aim is to investigate whether therapy guided by monitoring patients with acute dyspnoea with serial ultrasound examinations of the heart and the lungs together with standard care can change the severity of dyspnoea compared with treatment guided by standard monitoring alone. The study will be conducted as a multicentre, randomised, pragmatic, open-label and controlled trial where patients admitted with acute dyspnoea to an emergency ward will be randomised into a standard care group and a serial ultrasound group with 103 patients in each. All patients will be examined with an ultrasound of the heart and the lungs upfront. In addition, the patients in the serial ultrasound group will be examined with an ultrasound of the heart and lungs two more times to guide further therapy during the admittance. The primary outcome is a change in dyspnoea on a verbal scale. After discharge, the patients are followed for 1 year to assess the number of readmissions, death and length of hospital stay. The trial is conducted in accordance with the Declaration of Helsinki and approved by The Regional Committee on Health Research Ethics for Region Zealand, Denmark (identifier SJ-744). Data handling agreement with participating centres has been made (identifier REG-056-2019). The General Data Protection Regulation and the Danish Data Protection Act will be respected. The results of the trial will be reported in peer-reviewed scientific journals regardless of the outcomes. NCT04091334.


Conjugated estrogen reduces transfusion and coagulation factor requirements in orthotopic liver transplantation.
We conducted a prospective, randomized study to determine the efficacy of conjugated estrogen in reducing blood product transfusion during orthotopic liver transplantation (OLT). Patients undergoing OLT were included in the study. Only those having a reaction time of more than 30 mm or 15 min (19 -28 mm) on computed thromboelastography (CTEG) at the beginning of surgery were enrolled in the study. Patients were randomized to receive either conjugated estrogen (CE) or placebo. Every patient received a first dose of CE (100 mg i.v.) (20 mL) or placebo (20 mL of isotonic sodium chloride solution) at the beginning of the procedure and a second dose of CE (100 mg i.v.) or 20 mL of placebo (20 mL of isotonic sodium chloride solution) just after reperfusion of the new graft. The two groups were similar in age, weight, requirement for veno-veno bypass, time on veno-veno bypass, CTEG measurement, and preoperative hemoglobin and platelet values. Blood products were given in relation to hematocrit and coagulation (CTEG) variables, which were measured every hour during the surgery. The amount of transfused blood products did not differ in terms of units of cryoprecipitate, but the intraoperative requirements for red blood cells (6 +/- 3 vs 9 +/- 6 U; P = 0.05), platelets (12 +/- 8 U vs 18 +/- 10 U; P = 0.05) and fresh-frozen plasma (3 +/- 3 U vs 6 +/- 4 U; P = 0.001) was significantly less in the estrogen group than in the control group. We conclude that CE is associated with a significant decrease in use of fresh-frozen plasma, platelets, and red blood cells during OLT. In this study, we prospectively investigated whether i.v. conjugated estrogen could decrease blood product transfusion during orthotopic liver transplantation. Conjugated estrogen-treated patients received less fresh-frozen plasma, red blood cells, and platelets. In this population of patients, conjugated estrogen can be a useful addition in coagulation management during orthotopic liver transplantation.


Hypo-excitability of cortical areas in patients affected by Friedreich ataxia: a TMS study.
The aim of the study was to explore excitability of a motor and a non-motor (visual) area in patients affected by Friedreich ataxia and to correlate neurophysiological data with clinical parameters. Seven patients (3M/4F) and ten healthy controls (5M/5F) participated in the study. The hot-spot for activation of right abductor pollicis brevis was checked by means of a figure-of-eight coil and the motor threshold (MT) on this point was recorded. The phosphene threshold (PT) was measured by means of a focal coil over the occipital cortex as the lower intensity of magnetic stimulation able to induce the perception of phosphenes. The patients showed a significantly higher mean PT (p<.03) and MT values (p<.001) than controls. In all but one patient unable to perceive phosphenes (42% vs. 50% of controls), TMS at 100% intensity did not elicit motor response at rest. The difference in percentage of patients (57.1%) and controls (100%) with motor responses was nearly significant. The size of GAA1 expansion showed significant correlations with PT and MT values. The results of our study showed that FA patients had reduced cortical activation, involving both the motor and the visual cortex. The cortical involvement in these patients seems to be mainly genetically determined. The study provides the first evidence of cortical dysfunction in patients with genetically defined Friedreich ataxia.


Human thioredoxin homodimers: regulation by pH, role of aspartate 60, and crystal structure of the aspartate 60 --> asparagine mutant.
Thioredoxins are a group of ca. 12 kDa redox proteins that mediate numerous cytosolic processes in all cells. Human thioredoxin can be exported out of the cell where it has additional functions including the ability to stimulate cell growth. A recent crystal structure determination of human thioredoxin revealed an inactive dimeric form of the protein covalently linked through a disulfide bond involving Cys 73 from each monomer [Weichsel et al. (1996) Structure 4, 735-751]. In the present study, apparent dissociation constants (Kapp) for the noncovalently linked dimers were determined at various pHs using a novel assay in which preformed dimers, but not monomers, were rapidly linked through oxidation (with diamide) of the Cys 73 disulfide bond, and the relative amounts of monomer and dimer were detected by gel filtration. The values obtained were pH-dependent, varying between 6.1 and 166 microM for the pH range of 3.8-8.0, and were consistent with the titration of a single ionizable group having a pKa of 6.5. A similar value was obtained using gel filtration at pH 3.8 (Kapp = 164 microM), and the crystal structure of the diamide-oxidized protein was determined to be nearly identical to that obtained in the absence of diamide. Asp 60 lies in the dimer interface and was found to be responsible for the pH dependence for dimer formation, and therefore must have a pKa elevated by approximately 2.5 pH units. Mutation of Asp 60 to asparagine abolished nearly all of the pH dependence for dimer formation. The crystal structure of the D60N mutant revealed a dimer nearly identical to the wild type, but, surprisingly, it had the Asn 60 side chain rotated out of the dimer interface and replaced with two water molecules. The values obtained for Kapp suggest human thioredoxin may dimerize in vivo and possible roles for such dimers are discussed.


Prevalence and risk factors for food allergy in older people: protocol for a systematic review.
Studies suggest that the prevalence of food allergy may be increasing worldwide. Results regarding the prevalence and features of adverse food reactions older people have, however, scarcely been analysed in the literature. Thus, the objective of the present systematic review will be to describe the prevalence of food allergy in older individuals, its risk factors, clinical features, as well as the most frequently and commonly involved foods. We will conduct a systematic review and meta-analysis of the incidence, prevalence and risk factors for food allergy in older individuals. We will search international electronic databases including MEDLINE, EMBASE, Cochrane Library, CINAHL, AMED and ISI Web of Science for published, unpublished and ongoing studies from 1980 toJanuary 2019. There will be no restriction on the language or geography of publication. We will use the critical appraisal skills programme quality assessment tool to appraise the methodological quality of included studies. A descriptive summary with data tables will be elaborated, and if deemed clinically relevant and statistically adequate, meta-analysis using random-effects modelling will be carried out, given the expected clinical, methodological and statistical heterogeneity of studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will guide reporting of the systematic review. Since this systematic review will be solely based on published and retrievable literature, no ethics approval will be obtained. This study will allow us to draw up-to-date estimates of the prevalence of adverse food reactions in older individuals, worldwide, besides allowing the identification of its major risk factors, clinical manifestations and predominant foods responsible for such reactions. A multidisciplinary team has been assembled for this systematic review and will participate in relevant dissemination activities, namely reports, publications and presentations. CRD42018102140.


COVID-19 and Work-Family Conflicts in Germany: Risks and Chances Across Gender and Parenthood.
The COVID-19 pandemic has dramatically affected everyone's daily life in one way or another, requiring a re-negotiation of existing strategies for work-life integration, not only for individuals but also within families and partnerships. To contribute to existing knowledge on work-life integration during COVID-19 in Germany, we look at gender and parenthood differences in the experiences of work-to-family (WFC) and family-to-work (FWC) conflicts. By accounting for employees' previous conflict experiences, we were able to reveal the extent to which the current conditions contributed to differences in these conflicts. Moreover, we explored the relevance of demands and resources in the family and work spheres as a way to explain different levels of WFC and FWC across gender and parenthood. Our analyses are based on a sample of 660 employees from a German linked employer-employee panel study and a COVID-19 follow-up survey conducted in late 2020. Results revealed that work-family conflict experiences before the pandemic play an important role in current conflict perceptions. Whereas WFC were more likely to be accentuated during the pandemic, prior FWC experiences may have helped to mitigate conflicts under these new conditions. Work-family conflicts in general have increased during the COVID-19 pandemic, but this finding applied only to conflicts in the family-to-work direction. Although such increases were not limited to parents, they were particularly high in this group. Overall, gender differences in work-family conflicts were absent, but differences were found between mothers and fathers. The need to compensate for a lack of external childcare, as well as having to work from home, increased FWC, especially among fathers. This study suggests that FWC in particular became more important during the pandemic; however, parents were not the only ones who were disadvantaged when it came to work-life integration; childless individuals likewise struggled to balance the demands of work and private life.


Multi-state models for the analysis of time-to-event data.
The experience of a patient in a survival study may be modelled as a process with two states and one possible transition from an "alive" state to a "dead" state. In some studies, however, the "alive" state may be partitioned into two or more intermediate (transient) states, each of which corresponding to a particular stage of the illness. In such studies, multi-state models can be used to model the movement of patients among the various states. In these models issues, of interest include the estimation of progression rates, assessing the effects of individual risk factors, survival rates or prognostic forecasting. In this article, we review modelling approaches for multi-state models, and we focus on the estimation of quantities such as the transition probabilities and survival probabilities. Differences between these approaches are discussed, focussing on possible advantages and disadvantages for each method. We also review the existing software currently available to fit the various models and present new software developed in the form of an R library to analyse such models. Different approaches and software are illustrated using data from the Stanford heart transplant study and data from a study on breast cancer conducted in Galicia, Spain.


Noninvasive continuous intradialytic blood pressure monitoring: the key to improving haemodynamic stability.
Intradialytic hypotension (IDH) occurs in 20% of haemodialysis treatments, leading to end-organ ischaemia, increased morbidity and mortality; and contributing to poor quality of life for patients. Treatment of IDH is reactive since brachial blood pressure (BP) is recorded only intermittently during haemodialysis, making early detection and prediction of hypotension impossible. Noninvasive continuous BP monitoring would allow earlier detection of IDH and thus support the development of methods for its prediction and consequently prevention. Noninvasive continuous BP monitoring is not yet part of routine practice in renal dialysis units, with a small number of devices (e.g. finger cuffs) having occasionally been used in research settings. In use, patients frequently report pain or discomfort at measurement sites. Additionally, these devices can be unreliable in patients with reduced blood flow to the digits, often manifest in dialysis patients. All existing methods are sensitive to patient movement.A new method for continuously estimating BP has been developed by monitoring arterial pressure near the arteriovenous fistula which can be achieved without any extraneous monitoring equipment attached to the patient. Additionally, artificial intelligence-based methods for real-time prediction of IDH are currently emerging. Key monitoring technologies and computational methods are emerging to support the development of real-time IDH prediction.


Hormone replacement therapy in the post-Women's Health Initiative era. Report a a meeting held in Funchal, Madeira, February 24-25, 2003.
Over 24-25 February 2003 in Funchal, Madeira, Novo Nordisk gathered together 25 of the top international hormone replacement therapy (HRT) experts, in order to debate the results of the Women's Health Initiative (WHI) and interpret its possible implications for the future use of HRT. The meeting covered many interesting and controversial areas, addressing the complex and multifaceted issues with insight and realism. Some of the areas covered at the meeting were the use of HRT as a short- or long-term therapy for hot flushes, for general menopausal symptom relief and in osteoporosis prevention; the overall risk-benefit profile and specific breast cancer concerns were also discussed. The WHI data were reviewed and summarized, and, although it was generally agreed that the study was well designed and executed, its relevance to standard hormone therapy for clinical practice must be seriously called into question. The target population used in the WHI is not representative of the target population for whom menopausal HRT is normally considered. It is important to note that randomized controlled trials such as the WHI are really scientific tools for a group of research participants, not a form of individualized medical management. Since their publication, the relevance of the WHI study results for everyday clinical practice has been the subject of controversy. The WHI targeted a group of women who were much older than those normally treated and who had numerous other risk factors. These were not women for whom a practicing clinician would think about initiating hormone therapy with the regimen that was used. Putting a high-risk 70-year-old woman on 0.625 mg conjugated equine estrogens (CEE) plus 2.5 mg medroxyprogesterone acetate would not seem appropriate for any indication. With this in mind, we reviewed statements and guidance that followed the release of the WHI to the media, putting them in context with the actual results. Focusing on data taken out of context and without reference to subject profiles, the media created an emotive wave of uncertainty for patients and physicians, which needs to be addressed through realistic, factual communication. It is clear that hormone therapy is effective for postmenopausal symptoms and osteoporosis prevention. Timing is critical for the initiation of therapy and length of treatment. The individual's unique personal profile must be assessed. This leads to the paradox of osteoporosis prevention: therapy should be long-term, but it is long-term therapy that may increase breast cancer risk. The meeting reviewed the uncertain nature of the risks for breast cancer, although the evidence is becoming stronger that combinations of estrogen and progestogen cause a modest increase in risk after 5 years, while this seems not to be true for estrogen alone. Cardiovascular disease issues were also reviewed and discussed. This is perhaps the most misinterpreted result that came out of the WHI, given the population of women studied. Considering the vascular biology and effects of early interventions, the WHI finding that hormone therapy has no place in primary cardiovascular protection is an unwarranted conclusion. Other issues regarding the risk-benefit profile of HRT for the individual patient were also discussed. Additionally, presenters explored the possibility of class effects against the potential risk factors associated with particular estrogen and progestogen types. It is quite clear that CEE and 17beta-estradiol differ with respect to their source and composition; pharmacokinetic and metabolic data indicate that they differ in their total estrogenic potency, with CEE possessing greater estrogenic potency. Using 17beta-estradiol at the lowest dosage level can provide safe and effective therapy for most indications. The evidence for progestogen differences is even more clear. Medroxyprogesterone acetate and norethisterone acetate have different pharmacokinetic profiles and different activities on steroid receptors. Evidence from preclinical and clinical studies supports the conclusion that these differences result in different pharmacological and clinical effects in favor of norethisterone acetate. Having comprehensively discussed and reviewed all available evidence, a consensus was achieved with regard to appropriate therapy: HRT should be given to women with menopausal complaints to meet their individual needs, taking into account their individual risk profile and the overall therapeutic objectives.


Pouch excision: indications and outcomes.
Restorative proctocolectomy with ileal-pouch anal anastomosis is the procedure of choice for ulcerative colitis. Unfortunately, up to 10% of pouches will fail, requiring either reconstruction or excision. While several series have reported on the aetiology of pouch failure, no study to date has focused on the postoperative complications associated with pouch excision. Patients who had excision of ileoanal reservoir with ileostomy (CPT code 45136) were included. Data abstracted included preoperative, operative and postoperative variables. A Kaplan-Meier curve of pouch survival was performed. In all, 147 patients met the inclusion criteria for the study. The median age of patients was 47 years (73 women), and 132 had a diagnosis of ulcerative colitis at the time of colectomy. The most common indications for pouch excision were sepsis (n = 46; 31%) and Crohn's disease (n = 37; 25%). 84 (57%) patients experienced short-term (< 30 days) postoperative complications, the most common of which was a surgical site infection (n = 32; 21%); 55 (37%) patients had long-term complications (> 30 days) postoperatively, the most common of which was a return to the operating room (n = 19; 13%) largely for perineal wounds. Thirty-day mortality was zero. 4.8%, 47.6%, 65.3% and 84.4% of patients had undergone pouch excision by 1, 5, 10 and 20 years from the time of pouch construction, respectively. Pouch excision has a high rate of both short- and long-term postoperative complications. Patients should be appropriately counselled to set expectations accordingly. In view of these findings we suggest that this operation should ideally be performed at a high volume centre with the availability of a multidisciplinary surgical team.


Retrospective comparison of qualitative and quantitative reverse transcriptase polymerase chain reaction in diagnosing and monitoring the ALL1-AF4 fusion transcript in patients with acute lymphoblastic leukaemia.
We compared quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) to qualitative RT-PCR in determining response to therapy and predicting clinical outcome in 18 retrospectively selected patients with ALL positive for the ALL1-AF4 fusion and with frozen RNA samples collected at diagnosis and during follow-up (96 samples analysed). The ALL1-AF4 junction was detected by qualitative RT-PCR in 18 patients and by Q-RT-PCR in 17 patients (one patient harboured the rare e10-e6 ALL1-AF4 junction, which falls outside of the primer and probe location designed for the Q-RT-PCR). In three of the 12 patients negative to qualitative RT-PCR after induction therapy, a small number of ALL1-AF4 copies was detected by Q-RT-PCR. Thus nine patients were negative and eight positive. Seven of the eight positive patients suffered a relapse, including two of the three patients positive to Q-RT-PCR yet negative to qualitative RT-PCR. Moreover, we found two (5%) discordant results among the 39 follow-up tests of the nine patients who converted to a negative qualitative-quantitative PCR status. The results suggest that qualitative RT-PCR is more appropriate for the routine diagnosis of this genetic alteration. However, Q-RT-PCR is more accurate in assessing the molecular response after induction treatment and could be more useful in clinical decision-making in ALL1-AF4-positive ALL patients.


Characterizing and Identifying the Prevalence of Web-Based Misinformation Relating to Medication for Opioid Use Disorder: Machine Learning Approach.
Expanding access to and use of medication for opioid use disorder (MOUD) is a key component of overdose prevention. An important barrier to the uptake of MOUD is exposure to inaccurate and potentially harmful health misinformation on social media or web-based forums where individuals commonly seek information. There is a significant need to devise computational techniques to describe the prevalence of web-based health misinformation related to MOUD to facilitate mitigation efforts. By adopting a multidisciplinary, mixed methods strategy, this paper aims to present machine learning and natural language analysis approaches to identify the characteristics and prevalence of web-based misinformation related to MOUD to inform future prevention, treatment, and response efforts. The team harnessed public social media posts and comments in the English language from Twitter (6,365,245 posts), YouTube (99,386 posts), Reddit (13,483,419 posts), and Drugs-Forum (5549 posts). Leveraging public health expert annotations on a sample of 2400 of these social media posts that were found to be semantically most similar to a variety of prevailing opioid use disorder-related myths based on representational learning, the team developed a supervised machine learning classifier. This classifier identified whether a post's language promoted one of the leading myths challenging addiction treatment: that the use of agonist therapy for MOUD is simply replacing one drug with another. Platform-level prevalence was calculated thereafter by machine labeling all unannotated posts with the classifier and noting the proportion of myth-indicative posts over all posts. Our results demonstrate promise in identifying social media postings that center on treatment myths about opioid use disorder with an accuracy of 91% and an area under the curve of 0.9, including how these discussions vary across platforms in terms of prevalence and linguistic characteristics, with the lowest prevalence on web-based health communities such as Reddit and Drugs-Forum and the highest on Twitter. Specifically, the prevalence of the stated MOUD myth ranged from 0.4% on web-based health communities to 0.9% on Twitter. This work provides one of the first large-scale assessments of a key MOUD-related myth across multiple social media platforms and highlights the feasibility and importance of ongoing assessment of health misinformation related to addiction treatment.


Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.
Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.


Synaptic organization and ionic basis of on and off channels in mudpuppy retina. III. A model of ganglion cell receptive field organization based on chloride-free experiments.
A chloride-free environment produces selective changes in the retinal network which include a separation of on and off channels. The identification of chloride-sensitive and insensitivie neuronal activity permits identification of some of the connections and intervening polarities of synaptic interactions which are expressed in ganglion cell receptive field organization. These experiments support previous suggestions that surround antagonism is dependent on horizontal cell activity. In addition they suggest a model of the neuronal connections which subserve on-center, off-center, and on-off ganglion cells. Experimental tests of the on-off ganglion cell model favor the idea that this type of ganglion cell receives inhibitory input from amacrine cells and excitatory activation from depolarizing and hyperpolarizing bipolar cells.


Ratiometric Fluorescent Probe for the Detection of Nanomolar Phosgene in Solution and Gaseous Phase: Advancing Crime Detection Applications.
Phosgene, an exceptionally hazardous gas, poses a grave concern for the health and safety of the general public. The present study describes a fluorescent ratiometric probe for phosgene employing 2-(naphthalen-2-yl) benzo[d]oxazol-5-amine (NOA) with an amino group as the recognition site. NOA detects phosgene through the intramolecular charge transfer mechanism. The electron-rich amine group of NOA attacks the electrophilic carbonyl group of phosgene, resulting in a quick response within 20 s. NOA demonstrates a low detection limit of 60 nM while maintaining high selectivity and sensitivity toward phosgene. The final product was isolated and verified by nuclear magnetic resonance spectroscopy. The probe can detect phosgene not just quickly in a solution environment but also in its solid state. The probe's applications in fingerprint imaging and bioimaging are also demonstrated.


The science of mind wandering: empirically navigating the stream of consciousness.
Conscious experience is fluid; it rarely remains on one topic for an extended period without deviation. Its dynamic nature is illustrated by the experience of mind wandering, in which attention switches from a current task to unrelated thoughts and feelings. Studies exploring the phenomenology of mind wandering highlight the importance of its content and relation to meta-cognition in determining its functional outcomes. Examination of the information-processing demands of the mind-wandering state suggests that it involves perceptual decoupling to escape the constraints of the moment, its content arises from episodic and affective processes, and its regulation relies on executive control. Mind wandering also involves a complex balance of costs and benefits: Its association with various kinds of error underlines its cost, whereas its relationship to creativity and future planning suggest its potential value. Although essential to the stream of consciousness, various strategies may minimize the downsides of mind wandering while maintaining its productive aspects.


Protozoa as a cause of recurrent abdominal pain in children.
The aim of this study was to investigate whether protozoa can be identified as a cause of recurrent abdominal pain (RAP), and whether protozoan infections can be recognized by a specific clinical presentation. For 2 years, all patients (ages 4-16 years) fulfilling the Apley criteria of RAP referred to secondary care were prospectively evaluated for protozoa (Giardia lamblia, Dientamoeba fragilis, Blastocystis hominis) and treated if positive. Re-examination followed at least 10 days after treatment. Disappearance of pain with eradication and a pain-free follow-up of at least 6 months were considered to be indicative of a causal relation with RAP. The predictive value of the characteristics of the pain for protozoan infections was calculated. Of 220 included patients (92 boys, mean age 8.8 years), 215 brought a stool sample; 73 (34%) carried parasites, 10 of whom had 2 parasites, 2 had 3 parasites. Sixty-five patients were treated. Twenty-five (11%) were pain-free after eradication (21 had D fragilis, 8 B hominis, 4 G lamblia), of whom 11 had another infection (2) or constipation (9) as second diagnosis for the pain. Five had recurrence of infection with D fragilis and were again pain-free with eradication. Patients with protozoa as cause of their pain did not show differences with respect to their presentation when compared with patients with an asymptomatic infection and patients without protozoa. Protozoa were found as the cause of pain in 6% to 11% of children with RAP. These patients did not show a characteristic presentation when compared with patients with other causes of abdominal pain.


Three-Dimensional Lesion Phenotyping and Physiologic Characterization Inform Remyelination Ability in Multiple Sclerosis.
Multiple sclerosis (MS) clinical management is based upon lesion characterization from 2-dimensional (2D) magnetic resonance imaging (MRI) views. Such views fail to convey the lesion-phenotype (ie, shape and surface texture) complexity, underlying metabolic alterations, and remyelination potential. We utilized a 3-dimensional (3D) lesion phenotyping approach coupled with imaging to study physiologic profiles within and around MS lesions and their impacts on lesion phenotypes. Lesions were identified in 3T T2 -FLAIR images and segmented using geodesic active contouring. A calibrated fMRI sequence permitted measurement of cerebral blood flow (CBF), blood-oxygen-level-dependent signal (BOLD), and cerebral metabolic rate of oxygen (CMRO2 ). These metrics were measured within lesions and surrounding tissue in concentric layers exact to the 3D-lesion shape. BOLD slope was calculated as BOLD changes from a lesion to its surrounding perimeters. White matter integrity was measured using diffusion kurtosis imaging. Associations between these metrics and 3D-lesion phenotypes were studied. One hundred nine lesions from 23 MS patients were analyzed. We identified a noninvasive biomarker, BOLD slope, to metabolically characterize lesions. Positive BOLD slope lesions were metabolically active with higher CMRO2 and CBF compared to negative BOLD slope or inactive lesions. Metabolically active lesions with more intact white matter integrity had more symmetrical shapes and more complex surface textures compared to inactive lesions with less intact white matter integrity. The association of lesion phenotypes with their metabolic signatures suggests the prospect for translation of such data to clinical management by providing information related to metabolic activity, lesion age, and risk for disease reactivation and self-repair. Our findings also provide a platform for disease surveillance and outcome quantification involving myelin repair therapeutics.


Development of a reservoir-type transdermal enantioselective-controlled delivery system for racemic propranolol using a molecularly imprinted polymer composite membrane.
The aims of this study were to develop a transdermal patch for selective controlled delivery of the active S-enantiomer from racemic propranolol, and to evaluate its performance in vivo using Wistar rats. A molecularly imprinted polymer (MIP) thin-layer composited cellulose membrane with selectivity for S-propranolol was employed as the enantioselective-controlled release system. The effect of gel reservoir (poloxamer and chitosan) on enantioselective delivery was investigated. The chitosan gel allowed excellent selectivity for delivery of the S-propranolol enantiomer, whilst the more rheologically structured poloxamer gel formulation provided no selective release of S-propranolol. The chitosan gel exhibited high flux and had the ability to enantioselective deliver S-propranolol across excised rat skin. The results from confocal laser scanning microscopy study, carried out with the R- and S-propranolol enantiomers labeled with a 1-pyrenebutyric acid probe as fluorescent markers, suggested that the MIP composite membrane selectively regulated the release of the recognised S-enantiomer via a facilitated transport pathway through complex formation with the selective receptor sites, while the release of the R-enantiomer was via a non-selective route. The reservoir patch for enantiomer-controlled delivery of propranolol was therefore fabricated by incorporating the chitosan gel formulation containing racemic propranolol hydrochloride into the MIP composite membrane laminated backing. These patch devices were shown to exhibit the significant stereoselectivity uptake of propranolol when attached to the skin, using pharmacokinetic studies in rats. S-Propranolol enantiomer plasma concentration profiles for the transdermal patch in the in vivo study were comparable to data for the gel formulations that were applied directly to skin, and containing a single S-enantiomer of propranolol. The results demonstrate that the transdermal patch based on the MIP composite membrane-controlled release system may have potential in the enantioselective-controlled delivery of the S-isomer of racemic propranolol.


The management of acute pain in children.
Children cannot always articulate the level of pain they are experiencing, and need to be assessed carefully. The final article in this three-part series discusses a number of pain assessment tools available to help nurses caring for children in pain.


Global taxation of electronic nicotine and non-nicotine delivery systems: a cross-country evaluation.
Taxation is a key component of tobacco products' regulation given its proven effectiveness to generate revenue and achieve public health goals. The diversity of the market for e-cigarettes (electronic nicotine delivery systems and electronic non-nicotine delivery systems, ENDS/ENNDS) complicates comparative analyses per unit, thus challenging efforts to assess countries' excise tax burdens for e-cigarettes. Further complicating taxes on e-cigarettes is the necessity to balance two public health priorities: (1) deterring initiation among people who have never smoked, and (2) supporting cessation efforts among people currently smoking or who previously smoked. This study evaluates and compares excise tax burdens and tax system characteristics of e-cigarettes across 54 countries. To determine countries' excise tax burdens per millilitre of e-liquid, we collect a unique database of tax characteristics and prices in countries where ENDS/ENNDS are currently sold. We calculate the excise tax per millilitre of e-liquid and convert e-liquid prices to a comparable price per millilitre across countries. Thirty countries employ a specific excise system, 10 apply an ad valorem system, 9 apply a tiered specific system, 1 applies a tiered ad valorem system and 4 apply a mixed tax system. The excise tax burden is highest in Belarus (87.2%, specific), Norway (81.2%, tiered specific) and Egypt (74.7%, mixed), and lowest in Costa Rica (7.4%, ad valorem), Paraguay (2.9%, ad valorem) and Croatia (0%, specific). The advantages of one tax system over another are context specific. Tax burdens tend to be much larger in countries that use a specific tax than in countries that use a value-based (ad valorem) tax.


Schistosoma mansoni infection is associated with quantitative and qualitative modifications of the mammalian intestinal microbiota.
In spite of the extensive contribution of intestinal pathology to the pathophysiology of schistosomiasis, little is known of the impact of schistosome infection on the composition of the gut microbiota of its mammalian host. Here, we characterised the fluctuations in the composition of the gut microbial flora of the small and large intestine, as well as the changes in abundance of individual microbial species, of mice experimentally infected with Schistosoma mansoni with the goal of identifying microbial taxa with potential roles in the pathophysiology of infection and disease. Bioinformatic analyses of bacterial 16S rRNA gene data revealed an overall reduction in gut microbial alpha diversity, alongside a significant increase in microbial beta diversity characterised by expanded populations of Akkermansia muciniphila (phylum Verrucomicrobia) and lactobacilli, in the gut microbiota of S. mansoni-infected mice when compared to uninfected control animals. These data support a role of the mammalian gut microbiota in the pathogenesis of hepato-intestinal schistosomiasis and serves as a foundation for the design of mechanistic studies to unravel the complex relationships amongst parasitic helminths, gut microbiota, pathophysiology of infection and host immunity.


[2 site-specific endonucleases of the cyanobacterium Nostoc linckia].
Two restrictases Nli387/7 I and Nli387/7 II have been isolated from cyanobacterium Nostoc linckia using chromatography on phosphocellulose, "Mono Q" column, and heparin sepharose 4B. The preparations are described by the method of electrophoresis in polyacrylamide gel under denaturing conditions. Catalytic properties of restrictases are determined: optimal pH of the action--9.0--9.5, optimal concentration of Na+--5 mM, that of Mg2+--6 mM, optimal temperature--37 degrees C. The isolated enzymes are isoschizomers of restrictases avaI and AvaII. The point of cutting is determined for enzyme Nli387/7 I. It is shown that restrictase Nli387/7 I is a false isoschizomer Ava I.


Improvement in Overground Walking After Treadmill-Based Gait Training in a Child With Agenesis of the Corpus Callosum.
Agenesis of the corpus callosum (ACC) is a rare congenital brain defect that produces a wide variety of cognitive and motor impairments. Literature regarding the response of pediatric populations with ACC to physical rehabilitation is scarce. Treadmill-based gait training (TT) has been shown to improve walking ability in some pediatric populations but has not been investigated in children with ACC. The purpose of this study was to investigate the effect of a novel treadmill intervention paradigm on the gait parameters of a child with ACC. A single-participant design with 2 phases was used. The settings were the participant's home and the laboratory. The participant was a 13-year-old girl who had ACC and cortical visual impairment and who ambulated independently using a reverse walker for household and short community distances. A home-based TT intervention (2 phases of 3 months of training over 6 months) was implemented, and a laboratory-based gait analysis was conducted at 4 time points: baseline, after each of the 2 training phases, and 3 months after the cessation of training. The intervention consisted of weekly bouts of TT. Phase I incorporated forward, backward, and incline walking for 15 minutes each; in phase II, this protocol was continued, but short-burst interval training for 10 minutes was added. Data collected at each laboratory visit included spatiotemporal parameters and kinematics (joint angles) during overground and treadmill walking. After both phases of training, increased step length, decreased step width, and foot progression angle and decreased variability of most spatiotemporal parameters were observed for the participant. Further, after phase II, increased peak extension at the hip, knee, and ankle, decreased crouched gait, and improved minimum foot clearance during overground walking were observed. Most gait improvements were retained for 3 months after the cessation of the intervention. The small sample size of this study and wide variety of presentations within individuals with ACC limit the generalizability of our findings. TT may be a safe and effective treatment paradigm for children with ACC. Future research should investigate the effect of intervention dosage on gait improvements and generalization in individuals with ACC.


Color stability, gloss, and surface roughness of indirect composite resins.
This in vitro study evaluated the color stability, gloss, and surface roughness (Ra) of four indirect composites. Enamel and dentin shades of Radica, Sculpture Plus, Belleglass-NG, and Gradia Indirect were evaluated for color stability. Specimens were stored in a staining solution (coffee) and assessed every 3 days for a period of 21 days, after which color difference (∆E*) was calculated. Only enamel shades were used for measuring gloss and surface roughness at 0, 5000, 10,000, and 20,000 cycles of simulated toothbrushing. The results were statistically analyzed using repeated measures analysis of variance (ANOVA) and Tukey's test. Statistically significant changes in ∆E* during the 21-day period were observed in all indirect composites for enamel and dentin shades, and ∆E* was greater than the clinically acceptable value of 3.3. Belleglass-NG showed the least change in ∆E*, while Sculpture Plus had large changes in ∆E*. In all groups, gloss was 75% lower than baseline values after 10,000 cycles of toothbrushing. After 20,000 cycles, surface roughness was highest in Radica and lowest in Belleglass-NG. Belleglass-NG had higher color stability and gloss retention, and lower surface roughness, as compared with the other composite systems.


Vertebral osteomyelitis caused by non-tuberculous mycobacteria: Predisposing conditions and clinical characteristics of six cases and a review of 63 cases in the literature.
Background Several case series have reported on clinical and radiographic characteristics of patients with vertebral osteomyelitis (VO) caused by non-tuberculous mycobacteria (NTM). However, only a few patients were included, and systematic reviews are still lacking. The aim of this study was to update and summarise the pre-disposing conditions, clinical and radiographic characteristics of such cases due to NTM. Methods In this study, a systematic review was conducted of the English-language literature from 1961-2014 to investigate the pre-disposing conditions and characteristics of cases of VO due to NTM. Also, six additional cases diagnosed in the study hospitals were described; these cases are included in an analysis of a total of 69 cases of NTM VO. Results The most common species, regardless of the presence of HIV co-infection, was M. avium Complex followed by M. xenopi. Ten cases with HIV infection had a median CD4 lymphocyte count of 320/mm(3) (range = 41-465/mm(3)) at the time of diagnosis of NTM VO. The VO in the cases with HIV infections occurred at an earlier age and more often involved the thoracic spine than in the cases without HIV infection. Pre-disposing trauma or surgery was reported in 14.5% (10/69) of the cases. A variety of immunosuppressive diseases were observed in 49.3% of the patients, including the 10 with HIV infections and corticosteroids were used in 27.5% of the cases. Surgery was performed in 67.6% and improvement was reported in 80.6%. Conclusion NTM should be considered in immunocompromised patients with indolent VO without confirmation of tuberculosis.


Human aldolase B subunit-specific radioimmunoassay.
A radioimmunoassay was developed for the direct quantification of aldolase B in human serum and tissues. The method is a double antibody radioimmunoassay technique using radioiodinated aldolase B homopolymer as ligand, chicken antibodies to aldolase B and rabbit antibodies to chicken IgG. This radioimmunoassay was shown to be specific for the aldolase B subunit, with no cross-reactivity with either human aldolase A subunit or homopolymeric human aldolase C (C4). The lowest measurable amount by this method was 2 ng/ml. Aldolase B is predominantly found in normal liver tissue, with relatively high aldolase B levels also observed in kidney. Aldolase B levels in the serum obtained from 11 normal subjects ranged from 23 to 38 ng/ml, with a mean of 28.5 +/- 9.2 (S.D.) ng/ml. Almost all of patients with hepatitis had serum aldolase B levels greater than 30 ng/ml. In cancer patients, serum aldolase B was slightly elevated in patients with metastatic liver cancer and primary lever cell carcinoma, whereas no elevation of serum aldolase B was shown in patients without liver metastasis.


lumpGEM: Systematic generation of subnetworks and elementally balanced lumped reactions for the biosynthesis of target metabolites.
In the post-genomic era, Genome-scale metabolic networks (GEMs) have emerged as invaluable tools to understand metabolic capabilities of organisms. Different parts of these metabolic networks are defined as subsystems/pathways, which are sets of functional roles to implement a specific biological process or structural complex, such as glycolysis and TCA cycle. Subsystem/pathway definition is also employed to delineate the biosynthetic routes that produce biomass building blocks. In databases, such as MetaCyc and SEED, these representations are composed of linear routes from precursors to target biomass building blocks. However, this approach cannot capture the nested, complex nature of GEMs. Here we implemented an algorithm, lumpGEM, which generates biosynthetic subnetworks composed of reactions that can synthesize a target metabolite from a set of defined core precursor metabolites. lumpGEM captures balanced subnetworks, which account for the fate of all metabolites along the synthesis routes, thus encapsulating reactions from various subsystems/pathways to balance these metabolites in the metabolic network. Moreover, lumpGEM collapses these subnetworks into elementally balanced lumped reactions that specify the cost of all precursor metabolites and cofactors. It also generates alternative subnetworks and lumped reactions for the same metabolite, accounting for the flexibility of organisms. lumpGEM is applicable to any GEM and any target metabolite defined in the network. Lumped reactions generated by lumpGEM can be also used to generate properly balanced reduced core metabolic models.


Integrating User-Centered Design and Behavioral Science to Design a Mobile Intervention for Obesity and Binge Eating: Mixed Methods Analysis.
Accounting for how end users engage with technologies is imperative for designing an efficacious mobile behavioral intervention. This mixed methods analysis examined the translational potential of user-centered design and basic behavioral science to inform the design of a new mobile intervention for obesity and binge eating. A total of 22 adults (7/22, 32% non-Hispanic White; 8/22, 36% male) with self-reported obesity and recurrent binge eating (≥12 episodes in 3 months) who were interested in losing weight and reducing binge eating completed a prototyping design activity over 1 week. Leveraging evidence from behavioral economics on choice architecture, participants chose treatment strategies from 20 options (aligned with treatment targets composing a theoretical model of the relation between binge eating and weight) to demonstrate which strategies and treatment targets are relevant to end users. The process by which participants selected and implemented strategies and their change in outcomes were analyzed. Although prompted to select one strategy, participants selected between 1 and 3 strategies, citing perceived achievability, helpfulness, or relevance as selection reasons. Over the week, all practiced a strategy at least once; 82% (18/22) struggled with implementation, and 23% (5/22) added a new strategy. Several themes emerged on successes and challenges with implementation, yielding design implications for supporting users in behavior change. In postexperiment reflections, 82% (18/22) indicated the strategy was helpful, and 86% (19/22) planned to continue use. One-week average within-subject changes in weight (-2.2 [SD -5.0] pounds) and binge eating (-1.6 [SD -1.8] episodes) indicated small clinical improvement. Applying user-centered design and basic behavioral science yielded design insights to incorporate personalization through user choice with guidance, which may enhance engagement with and potential efficacy of digital health interventions.


[Experimental imutiol stimulation of the primary immunological response to tetanus anatoxin].
The data on the influence of imuthiol on humoral and cell-mediated immunity developing after immunization against tetanus are presented. Experiments were made on 166 guinea pigs with the use of imuthiol in doses of 25 and 125 mg/kg and tetanus toxoid in doses of 1.5 and 6.0 BU/kg. The dynamic observation of the animals lasted 30 days. The data of the passive hemagglutination test and the neutralization test indicated that imuthiol had considerable influence on the formation of humoral immunity. The results of skin reactions with tetanin, in vitro cell reactions, as well as resistance tests, showed that imuthiol exerted influence on delayed hypersensitivity, the mechanisms of cell-mediated resistance and survival after challenge. The data on the influence of imuthiol could be registered even at early stages after immunization, the immunostimulating action of the preparation reaching its maximum with tetanus toxoid used in a dose of 6.0 BU/kg and imuthiol, in a dose of 125 mg/kg.


Bulbar urethroplasty: transecting vs. nontransecting techniques.
To transect or not to transect the bulbar urethra in nontraumatic urethral strictures still remains an issue that is open to debate. Herewith, we evaluate and compare the results of these two different options in the treatment of bulbar urethral strictures. In 404 patients, bulbar urethroplasty using transecting techniques (end-to-end anastomosis and augmented anastomotic repair) provided a success rate ranging from 90 to 98.6%. In 522 patients, bulbar urethroplasty using nontransecting techniques (nontransecting anastomotic urethroplasty and simple oral grafting techniques) provided approximately the same success rate, ranging from 81.8 to 100%. Future studies, including more homogenous series of patients and subjective evaluation of urinary and sexual complications after repair, are necessary to surely establish the gold standard of treatment for nontraumatic strictures located in the proximal bulbar urethra.


The Grog Mob: lessons from an evaluation of a multi-disciplinary alcohol intervention for Aboriginal clients.
To evaluate a 12-month trial of an evidence-based non-residential treatment program for Indigenous clients with alcohol problems, offering three streams of care: pharmacotherapy, psychological and social support. Process evaluation of program implementation; outcome evaluation of client outcomes. despite constraints of time and remoteness, the trial demonstrated the feasibility of implementing such a program. The medical stream generated fewer pharmacotherapy prescriptions than expected. The most active stream was the psychological therapy stream. between March 2008 and April 2009, 129 clients were referred to the program, of whom 49 consented to have de-identified data used for the evaluation. Of these, 19 clients received one or more streams of care, 15 of whom (78.9%) subsequently stopped or reduced drinking. However, among the remaining 30 consenting clients who had not received an intervention, 70.0% also reported stopping or reducing drinking. The evidence of program effectiveness is therefore equivocal and evaluation over a longer period is required. The trial demonstrated the viability of, and demand for, evidence-based non-residential treatment for Indigenous clients with alcohol problems. Reasons behind an apparent reluctance among GPs to prescribe pharmacotherapy for Indigenous clients, and steps to overcome this, need further attention.


Freeform LED lens for uniform illumination.
Light flux from LED must be redistributed to meet the needs of lighting in most cases, a new method is proposed for its secondary optic design. Based on refractive equation and energy conservation, a set of first-order partial differential equations which represent the characters of LED source and desired illumination were presented. The freeform lens was constructed by solving these equations numerically. The numerical results showed that we can get a freeform lens for the illumination of uniformity near to 90%, with considerable high computation speed. This method can shorten the designing time of the freeform lens with high accepted tolerance.


Genetic variation in hyaluronan metabolism loci is associated with plasma plasminogen activator inhibitor-1 concentration.
Elevated plasma plasminogen activator inhibitor-1 (PAI-1) concentration is associated with cardiovascular disease risk. PAI-1 is the primary inhibitor of fibrinolysis within both the circulation and the arterial wall, playing roles in both atherosclerosis and thrombosis. To define the heritable component, subjects within the population-based SHARE (Study of Health Assessment and Risk in Ethnic groups) and SHARE-AP (Study of Health Assessment and Risk Evaluation in Aboriginal Peoples) studies, composed of Canadians of South Asian (n = 298), Chinese (n = 284), European (n = 227), and Aboriginal (n = 284) descent, were genotyped using the gene-centric Illumina HumanCVD BeadChip. After imputation, more than 150,000 single nucleotide polymorphisms (SNPs) in more than 2000 loci were tested for association with plasma PAI-1 concentration. Marginal association was observed with the PAI-1 locus itself (SERPINE1; P < .05). However, 5 loci (HABP2, HSPA1A, HYAL1, MBTPS1, TARP) were associated with PAI-1 concentration at a P < 1 × 10(-5) threshold. The protein products of 2 of these loci, hyaluronan binding protein 2 (HABP2) and hyaluronoglucosaminidase 1 (HYAL1), play key roles in hyaluronan metabolism, providing genetic evidence to link these pathways.


[Papillary carcinoma developing in thyroglossal duct cyst. Apropos of 2 cases].
The authors report two cases of papillary carcinoma of a thyreoglossal duct cyst. In both cases, the thyroïd gland was normal. Clinical manifestations are not specific and the diagnosis is usually made by histopathologic examination which reveals in the majority of cases a papillary carcinoma. When loco-regional or metastatic extension are absent surgical excision of the cyst is sufficient.


18F-florbetapir PET in patients with frontotemporal dementia and Alzheimer disease.
Pathologic deposition of amyloid β (Aβ) protein is a key component in the pathogenesis of Alzheimer disease (AD) but not a feature of frontotemporal dementia (FTD). PET ligands for Aβ protein are increasingly used in diagnosis and research of dementia syndromes. Here, we report a PET study using (18)F-florbetapir in healthy controls and patients with AD and FTD. Ten healthy controls (mean age ± SD, 62.5 ± 5.2 y), 10 AD patients (mean age ± SD, 62.6 ± 4.5), and 8 FTD patients (mean age ± SD, 62.5 ± 9.6) were recruited to the study. All patients underwent detailed clinical and neuropsychologic assessment and T1-weighted MR imaging and were genotyped for apolipoprotein E status. All participants underwent dynamic (18)F-florbetapir PET on a high-resolution research tomograph, and FTD patients also underwent (18)F-FDG PET scans. Standardized uptake value ratios (SUVRs) were extracted for predefined gray and white matter regions of interest using cerebellar gray matter as a reference region. Static PET images were evaluated by trained raters masked to clinical status and regional analysis. Total cortical gray matter (18)F-florbetapir uptake values were significantly higher in AD patients (median SUVR, 1.73) than FTD patients (SUVR, 1.13, P = 0.002) and controls (SUVR, 1.26, P = 0.04). (18)F-Florbetapir uptake was also higher in AD patients than FTD patients and controls in the frontal, parietal, occipital, and cingulate cortices and in the central subcortical regions. Only 1 FTD patient (homozygous for apolipoprotein E ε4) displayed high cortical (18)F-florbetapir retention, whereas (18)F-FDG PET demonstrated mesiofrontal hypometabolism consistent with the clinical diagnosis of FTD. Most visual raters classified 1 control (10%) and 8 AD (80%) and 2 FTD (25%) patients as amyloid-positive, whereas ratings were tied in another 2 FTD patients and 1 healthy control. Cortical (18)F-florbetapir uptake is low in most FTD patients, providing good discrimination from AD. However, visual rating of FTD scans was challenging, with a higher rate of discordance between interpreters than in AD and control subjects.


Promoting Health Equality and Nondiscrimination for Transgender and Gender-Diverse Youth.
Adolescent and young adult health-care providers often care for transgender and gender-diverse (TGD) youth-youth whose gender identity is incongruent with the gender assigned to them at birth. This patient population faces health challenges distinct from their cisgender peers (i.e., youth whose gender identity aligns with their assigned gender at birth), which include the health impacts from gender dysphoria and from societal stigma and discrimination. SAHM encourages adolescent and young adult health-care providers to receive training in providing culturally effective, evidence-based care for TGD youth; calls for more research on gender-affirming health care; and advocates for policies that protect the rights of TGD youth and minimize barriers to attaining healthcare. Consistent with other medical organizations, the Society for Adolescent Health and Medicine promotes the call for gender affirmation as a mainstay of treatment and is opposed to the notion that diversity in gender is pathological.


Collagen platelet receptor polymorphisms integrin alpha2beta1 C807T and GPVI Q317L and risk of ischemic stroke.
Several polymorphisms of integrin alpha2beta1 and glycoprotein (GP) VI that may modify platelet-collagen interactions or subsequent signaling have been described. We conducted a case-control study involving 180 stroke patients and 172 controls to determine whether the alpha2 C807T and GPVI Q317L polymorphisms were associated with an increased risk of ischemic stroke. We found no statistically significant differences in the distribution of alpha2 C807T and GPVI Q317L in patients and controls overall or after stratification by etiological subtype. The GPVI 317QQ genotype was found to be over-represented in a subgroup of patients >/=60 years compared to corresponding controls. However, this association did not remain significant after adjustment for other cardiovascular risk factors. Our results do not support a role for the integrin alpha2 C807T and GPVI Q317L polymorphisms in the development of first-ever ischemic stroke. However, larger studies are required to confirm this.


Linking Global Youth Tobacco Survey (GYTS) data to the WHO Framework Convention on Tobacco Control (FCTC): the case for Lebanon.
The purpose of this paper is to use data collected in the 2001 and 2005 Lebanon Global Youth Tobacco Survey (GYTS) to monitor articles in the WHO Framework Convention on Tobacco Control (WHO FCTC). This information is necessary to enhance the capacity of the Ministry of Health and relevant organizations to design, implement, and evaluate tobacco control and prevention programs in Lebanon, especially among adolescents. The GYTS is a school-based survey which uses a two-stage sample design to produce representative, independent, cross-sectional estimates. The GYTS was conducted in 2001 and 2005 in Lebanon to produce representative national estimates. Data in this report are limited to students aged 13-15 years. In total, 5035 students from 50 schools participated in 2001; and 3341 students from 50 schools participated in 2005. The data in this report show that, in 2005, 8.6% of the students currently smoked cigarettes, but 33.9% currently smoked narguileh. Half of current smokers wanted to stop smoking and 6 in 10 have tried to stop during the past year but have failed. In 2005, exposure to SHS at home (78.4%) and in public places (74.4%) was very high; while 85.2% thought smoking should be banned in public places. Nearly 9 in 10 students who usually buy their cigarettes in stores were not refused purchase because of their age. Overall, only half of the students in Lebanon reported that during the past school year they had been taught about the dangers of smoking. Data in this report can be used as baseline measures for future evaluation of the tobacco control programs implemented by the Ministry of Health with particular attention to youth. The key for the Lebanese parliament is to develop, endorse, implement and enforce these new tobacco control laws and use the data from GYTS to monitor progress toward achieving the goals of the WHO FCTC. One key component of tobacco control needs to be the monitoring of Narguileh use among youth, a new emergency.


Evolution and Expression of the Immune System of a Facultatively Anadromous Salmonid.
Vertebrates have evolved a complex immune system required for the identification of and coordinated response to harmful pathogens. Migratory species spend periods of their life-cycle in more than one environment, and their immune system consequently faces a greater diversity of pathogens residing in different environments. In facultatively anadromous salmonids, individuals may spend parts of their life-cycle in freshwater and marine environments. For species such as the brown trout Salmo trutta, sexes differ in their life-histories with females more likely to migrate to sea while males are more likely to stay and complete their life-cycle in their natal river. Salmonids have also undergone a lineage-specific whole genome duplication event, which may provide novel immune innovations but our current understanding of the differences in salmonid immune expression between the sexes is limited. We characterized the brown trout immune gene repertoire, identifying a number of canonical immune genes in non-salmonid teleosts to be duplicated in S. trutta, with genes involved in innate and adaptive immunity. Through genome-wide transcriptional profiling ("RNA-seq") of male and female livers to investigate sex differences in gene expression amplitude and alternative splicing, we identified immune genes as being generally male-biased in expression. Our study provides important insights into the evolutionary consequences of whole genome duplication events on the salmonid immune gene repertoire and how the sexes differ in constitutive immune expression.


Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor.
Plasmodium falciparum adenylosuccinate lyase (PfADSL) is an important enzyme in purine metabolism. Although several benzimidazole derivatives have been commercially developed into drugs, the template design as inhibitor against PfADSL has not been fully explored. This study aims to model the 3-dimensional (3D) structure of PfADSL, design and predict in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) of 8 substituted benzo[d]imidazol-1-yl)methyl)benzimidamide compounds as well as predict the potential interaction modes and binding affinities of the designed ligands with the modelled PfADSL. PfADSL 3D structure was modelled using SWISS-MODEL, whereas the compounds were designed using ChemDraw Professional. ADMET predictions were done using OSIRIS Property Explorer and Swiss ADME, whereas molecular docking was done with AutoDock Tools. All designed compounds exhibited good in silico ADMET properties, hence can be considered safe for drug development. Binding energies ranged from -6.85 to -8.75 kcal/mol. Thus, they could be further synthesised and developed into active commercial antimalarial drugs.


Comparative value of Dapsone "spot test" and Dapsone "tile test" in leprosy control programme.
The sensitivity of Dapsone "spot test" with modified Ehrlich's reagent (Balakrishnan, 1968) and Dapsone "tile test" using Barton-Marshall reagents (Irudayraj, 1981)--both being qualitative tests for screening of dapsone in urine are compared with Dapsone/creatinine ratio--a quantitative test (Ellard, 1974). 316 urine samples were processed by paramedical worker in the fields for Dapsone "Tile test" and Dapsone "Spot test". The same samples were brought to the laboratory and subjected to these two tests besides Dapsone/creatinine estimation. These three tests correlated well at the level of 91%. The results obtained by paramedical workers and experienced worker at the laboratory are also showed 97% concordance. An earlier investigations revealed that monitoring through frequent and surprise check-up of urines for drug content (4-5 samples/year/patient) and subsequent motivation and persuation of leprosy patient, the irregularity rate of drug consumption by patient could be brought down from 36% to 17% in one year. The kit for performing DDS "spot test" and DDS "tile test" being light and easy to carry in the field and the tests being simple to perform with reliable results. This procedure is recommended to be applied in the field on a mass scale. The routine frequent and surprise checking of urine for drug content will give early idea about irregularity status of drug consumption by patients as compared to the judgement relying on clinical assessment and reduction of bacteriological index of infectious patients.


Designer stabilizer for preparation of pristine graphene/polysiloxane films and networks.
A conductive polymer film containing pristine graphene was prepared by designing a polysiloxane-based stabilizer for graphene. The stabilizer was prepared by grafting 1-ethynylpyrene to the backbone of a poly(dimethylsiloxane)-co-(methylhydrosiloxane) (PDMS-PHMS) random copolymer by Pt-catalyzed hydrosilylation with a SiH-ethynyl ratio of 1.0 : 1.3. The resulting copolymer was able to stabilize pristine graphene in chloroform solution viaπ-π interactions between the pyrene groups and graphene sheets. TEM and SEM images show a homogeneous distribution of the graphene in cast films deposited from chloroform. The conductivity of a graphene/PDMS film prepared from copolymer with a 1.7 vol.% graphene loading was measured as 220 S m(-1) after the removal of unbound polymer by a simple separation technique. With a SiH-ethynyl ratio of 1.7 : 1.0, the copolymer self-crosslinked at 110 °C in the presence of adventitious moisture, providing a straightforward route to incorporate graphene into silicone elastomers. The crosslinking process (with and without added graphene) was characterized by FT-IR spectroscopy and by swelling and extraction of the obtained networks. Again, unbound polymer removal increases the conductivity of the composite.


The Promise of Interoperability.
Despite technological advancements in health care documentation and the proliferation of electronic health records, health information and health data remain disparate. Patients and health care teams benefit from access to comprehensive patient records to make informed health care decisions. Significant governmental policy and investments have been made to promote interoperability of systems that connect health information with the ultimate intent of developing a longitudinal patient record. In this article, we discuss how health data, interoperability, and related systems are influenced by federal policy. The intent is to expand occupational therapy practitioners' understanding of the promise of interoperability and the role the occupational therapy profession can play in advancing the infrastructure needed to optimize health care delivery.


Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis treated with methotrexate, and the effect of low dose folic acid supplement.
To investigate the effect of methotrexate (MTX) treatment of rheumatoid arthritis (RA) on folate metabolism, and to determine the effect of low dose folic acid on toxicity, efficacy, and folate status. A 52-week prospective study of 81 patients with RA treated with MTX and self-administered low dose folic acid; 38 patients were included prior to MTX therapy, 33 patients continued established MTX therapy, and 10 patients were excluded. Drug efficacy and side effects were monitored with biochemical and clinical indicators. MTX treatment resulted in decreased concentrations of red blood cell (RBC) folate and a rise in plasma homocysteine. Intracellular concentrations of MTX were inversely correlated to RBC folate levels after treatment for a longer period (mean 41 months). Supplement with low dose folic acid prevented or diminished the influence of MTX on folate status and had a protective effect on MTX induced liver toxicity without changing the efficacy of MTX. MTX interferes with folate and homocysteine metabolism, and the intracellular concentration of MTX may play a role. Our results indicate low dose folic acid supplementation has a beneficial effect on MTX toxicity.


Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices.
A detailed understanding of GABAB receptor assembly is an important issue in view of its role as attractive target for treatment of epilepsy, anxiety, depression, cognitive defects, and nociceptive disorders. Heteromerization of GABAB-R1 and GABAB-R2 subunits is a prerequisite for the formation of a functional GABAB receptor. Each individual subunit contains one stretch of approximately 30 amino acid residues within its intracellular C-terminal domain that mediates heteromer formation. To investigate the mechanism of the GABAB-R1/GABAB-R2 interaction and to assess the subunit stoichiometry of the complex, recombinant polypeptide chain fragments containing the heteromerization site were produced by heterologous gene expression in Escherichia coli. When mixed in equimolar amounts, these peptides preferentially formed parallel coiled-coil heterodimers under physiological buffer conditions. This demonstrates that the short C-terminal regions are sufficient to determine the specificity of interaction between GABAB receptor subunits. In contrast, isolated GABAB-R1 peptides folded into relatively unstable homodimers, whereas GABAB-R2 peptides were largely unstructured. Together with the data reported in the literature, the results presented here indicate that the functional GABAB receptor is a heterodimer assembled by parallel coiled-coil alpha-helices.


Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium and lead in the equine liver and kidneys.
The concentrations of specific elements in the equine liver and kidneys are of practical relevance since horses are not only food-producing animals, but also partially serve as an indicator for the environmental pollution, as the basic feed includes plants like grass, grain and fruits. In this study, the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se) and lead (Pb) were measured in the liver, renal cortex and renal medulla of 21 horses (8 male; 13 female; aged between 5 months-28 years), using inductively coupled plasma mass spectrometry. Comparable Cu and Zn concentrations were detected in the liver and renal cortex, while approximately 50% lower concentrations were measured in the renal medulla. The lowest Sr, Cd and Se, but the highest Mn, Sb and Pb concentrations were measured in the liver. The Ba concentrations were comparable in the renal cortex and medulla, but lower in the liver of the horses. Gender-related differences were observed for Cd, Mn and Cr, with higher Cd concentrations in the liver, but lower Mn concentrations in the renal cortex and lower Cr concentrations in the renal medulla of female horses. Age-related differences were detected for most measured elements, however, the animal number per age-group was only low. In conclusion, the present study provides important reference data for the storage of Sr, Ba, Cd, Cu, Zn, Mn, Cr, Sb, Se and Pb in the liver and kidneys of horses, which are of practical relevance for an evaluation of the exposure of horses to these elements, either via feed or the environment.


The value-action gap in waste recycling: the case of undergraduates in Hong Kong.
The discrepancy between verbal and actual commitment in waste recycling and environmental behavior is thought to have attenuated the effectiveness of many environmental policy and measures. Studies purport to show the existence of such a value-action gap in environmental issues has been largely based on matching the verbal commitment to environmental value through self-reported environmental behavioral data. Therefore, there is a lack of direct evidence to prove that such a discrepancy exists. This study demonstrates a methodology (contrasting on-site observation with self-reported results) to measure the gap between verbal commitment and actual recycling behavior and provides an explanation on the recycling behavior of students at Hong Kong Baptist University in the hope that the lessons learnt can be generalized to a wider context. Our findings indicate that a gap between verbal recycling commitment and corresponding action does exist in waste recycling on this university campus. By using multiple linear regression analysis, we found that the self-reported recycling behavior of undergraduates cannot be meaningfully explained by most variables previously suggested in the general value-action model.


The Holliday junction resolvase RecU is required for chromosome segregation and DNA damage repair in Staphylococcus aureus.
The Staphylococcus aureus RecU protein is homologous to a Bacillus subtilis Holliday junction resolvase. Interestingly, RecU is encoded in the same operon as PBP2, a penicillin-binding protein required for cell wall synthesis and essential for the full expression of resistance in Methicillin Resistant S. aureus strains. In this work we have studied the role of RecU in the clinical pathogen S. aureus. Depletion of RecU in S. aureus results in the appearance of cells with compact nucleoids, septa formed over the DNA and anucleate cells. RecU-depleted cells also show increased septal recruitment of the DNA translocase SpoIIIE, presumably to resolve chromosome segregation defects. Additionally cells are more sensitive to DNA damaging agents such as mitomycin C or UV radiation. Expression of RecU from the ectopic chromosomal spa locus showed that co-expression of RecU and PBP2 was not necessary to ensure correct cell division, a process that requires tight coordination between chromosome segregation and septal cell wall synthesis. RecU is required for correct chromosome segregation and DNA damage repair in S. aureus. Co-expression of recU and pbp2 from the same operon is not required for normal cell division.


[Role of the cholinergic system in the dorsal and ventral striatum of the brain in regulation of a learned movement in rats].
Administration of carbachol into the rat brain ventral striatum increased the number of movements with prolonged extension and decreased the number of short not reinforced movements, whereas the same administration into the dorsal striatum deteriorated slow movements. Scopolamine administration, irrespective of the site, increased the number of fast not reinforced movements. The findings suggest that cholinergic system of the rat ventral striatum is involved in the maintenance of the rat forepaw muscle tone.


Effects of Glenoid and Humeral Bone Defects on Recurrent Anterior Instability of the Shoulder.
For proper treatment of recurrent anterior instability of the shoulder with a bone defect, the defect size should be assessed preoperatively with three-dimensional computed tomography or magnetic resonance imaging. In general, the risk of postoperative recurrence of instability is estimated on the basis of preoperative imaging of bipolar bone defects: more than 20%-25% glenoid bone loss and off-track Hill-Sachs lesions have been considered risk factors for recurrence. In patients with a glenoid bone defect more than 20%-25%, a bone graft procedure, such as the Latarjet procedure, is preferred regardless of the glenoid track concept, because compared with arthroscopic stabilization procedure, it provides greater postoperative stability. For patients with a borderline glenoid bone defect (around 20%), surgeons should discuss surgical options with the patients, considering their demand and physical activity level. In addition, the surgeon should take care to prevent postoperative instability and long-term complications. Arthroscopic soft-tissue reconstruction including labral repair and capsular plication combined with the additional remplissage procedure is an anatomical procedure and could be considered as one of the primary treatment methods for patients with glenoid bone defects around 20%. Therefore, treatment strategies for recurrent anterior shoulder instability combined with bone defects should be determined more flexibly on the basis of the patient's individual condition.


Sex prevalence of focal dystonias.
The sex prevalence of idiopathic focal dystonia is reported from a data base review of all patients seen at the National Hospital of Neurology, Queen Square and King's College, London up to 1993. There was a higher prevalence of females to males in all categories of focal dystonia involving the craniocervical region. The female to male ratio for cranial dystonia was 1.92:1 (P < 0.01) and 1.6:1 (P < 0.001) for spasmodic torticollis. On the other hand, twice as many men than women had writer's cramp (M:F = 2.0:1, P < 0.01). At present, there is no clear explanation to account for this differences in the sex prevalence of different types of focal dystonia.


Kinetics of acetyl CoA: arylamine N-acetyltransferase from rapid and slow acetylator human liver.
Michaelis-Menten kinetic constants for sulfamethazine (SMZ) and p-aminobenzoic acid (PABA) metabolism were determined in 2 very rapid, 8 intermediate, and 10 slow acetylator human livers. The mean apparent KM values for the monomorphic substrate PABA were 70 +/- 20, 180 +/- 50, and 310 +/- 30 microM for the slow, intermediate, and very rapid enzymes, respectively, whereas the polymorphic substrate SMZ exhibited little interphenotypic KM variation. Compared to the slow enzymes, the rapid acetylators exhibited mean apparent Vmax values 15- and 20-fold greater for PABA and SMZ, respectively. Furthermore, under in vitro conditions where enzyme saturation was achieved, PABA showed polymorphic acetylation characteristics, in contrast to events in vivo, where monomorphic acetylation patterns were observed. As the acetyl coenzyme A concentration in the reaction mixture was increased, the KM and Vmax for PABA increased, in accordance with "ping-pong" kinetic principles. As occurs with polymorphic substrates, a binary ping-pong mechanism appears to govern N-acetylation of monomorphic substrates in human liver, as evidenced by initial velocity patterns and limiting values for the KM and Vmax for PABA.


Weight loss interventions for chronic asthma.
Asthma and obesity are both public health problems with increasing prevalence globally. Several epidemiological studies have shown an association between asthma and obesity, however there is no good quality evidence on the effect of weight loss on asthma control. To assess the effect of various interventions for weight loss on measures of asthma control and weight loss amongst overweight or obese patients with chronic asthma. We searched the Cochrane Airways Group's Specialized Register of Trials (CAGR) (derived from systematic searches of bibliographic databases, including the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, AMED and PsycINFO, and handsearching of respiratory journals and meeting abstracts). We also searched ongoing trials web sites and dissertation databases up to March 2012. We contacted experts in the field and searched reference lists for additional studies. We included randomized controlled trials (RCTs) of weight loss interventions for overweight or obese participants with asthma compared to either no intervention for weight loss or an alternative weight loss intervention. Two authors independently assessed study eligibility and risk of bias, and extracted data using a data extraction form. We did not undertake any meta-analysis as there were no suitable data to combine. We included four completed studies conducted amongst adults (n = 197). Two were published as abstracts, and two as full articles. Interventions included supervised physical activity, low calorie diet and anti-obesity drugs (singly or in combination), and were compared to usual care (two studies), low calorie diet (one study), while one study had three intervention arms (physical activity versus low calorie diet versus a combination of the two). Two studies were conducted in high-income countries, while two were conducted in upper, middle-income countries.All studies had an unclear risk of selection and a high risk of detection bias. One of the studies found a statistically significant reduction in symptoms scores in treatment compared to control groups: the difference between groups in total St. George's Respiratory Questionnaire (SGRQ) score was -10 units (95% CI -18 to-1; P = 0.02). One study showed reduction in doses of rescue medication in treatment compared with control groups in the short term. Weight loss was associated with some improvement in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in one study, which was statistically significant, but clinically unimportant; there was no improvement in peak expiratory flow rate (PEFR). No data were reported on health care utilization and adverse effects. One study reported statistically significant weight loss in the treatment group compared to controls with no intervention, which was still significant at one year follow-up. Implications for practice This review found one randomized trial that showed that weight loss may be beneficial for improving asthma control in overweight and obese patients, in conjunction with weight loss in intervention groups in the short term. Applying the GRADE system to the results of this review however, shows that the quality of evidence is low, because although all four studies are RCTs there were serious methodological limitations in the studies (unclear risk of selection bias and high risk of detection bias) and imprecision (small sample size). There is inadequate evidence to comment on the effect of weight loss interventions on quality of life and health care utilization. In addition, there was inadequate reporting of data on adverse effects to permit proper balancing of harms and benefits of the interventions. On account of this low quality of evidence, the benefit of weight loss as an intervention for asthma control remains uncertain, and as such, clinicians should be prepared to help patients to make a decision that is consistent with their own values.Implications for research The finding that most of the included studies were of low methodological quality highlights the need for further well designed RCTs, with emphasis on adequate methods of allocation sequence generation as well as allocation concealment and longer follow-up periods. These studies need to report more fully on relevant outcomes (both statistically significant and otherwise) such as: asthma symptoms/control, use of rescue medication, change in lung function parameters (actual mean/median values), hospital utilization, quality of life, and adverse effects. There is also a need for longer intervention as well as follow-up durations to evaluate the effect of sustained measures to achieve weight loss, and to determine if these effects are still significantly present after a considerable period of time.There is also a need for these well designed studies in children and adolescents, as well as in low-income countries such as Africa, where the prepackaged, low energy diets, as well as structured physical activity-based interventions utilized in these included studies, may not be feasible or applicable.