Chronic constipation: a survey of the patient perspective.
Constipation is a common, often chronic, gastrointestinal motility disorder characterized by such symptoms as straining, hard stool, and infrequent defecation. Published literature is limited regarding symptom prevalence, healthcare-seeking behaviour, and patient satisfaction with traditional therapies for chronic constipation. To assess the prevalence of chronic constipation among a random sample of Americans, to identify the frequency, severity and bothersomeness of their symptoms, and to assess satisfaction levels with traditional treatments. All members (N = 37,004) of the Knowledge Networks Panel, representative of the US population, participated in a web-based survey. Eligibility was established using a six-question screener. Of the 24,090 panellists consenting to participate, 557 met eligibility requirements and took the 45-question survey. The most prevalent symptom was straining (79%). Hard stool and straining were the top two severe symptoms, and bloating, straining and hard stool were the top three bothersome symptoms. Symptoms affected quality of life of more than half (52%) the respondents. Among those who worked or went to school, 12% experienced reduced productivity and a mean of 2.4 days of absence in the month before the survey. Most respondents had used (96%) or were using (72%) constipation relief therapy; however, nearly half (47%) were not completely satisfied, mainly because of efficacy (82%) and safety (16%) concerns. Chronic constipation is common. Individual symptoms are often severe and bothersome, and many patients are dissatisfied with traditional treatment options, primarily because of lack of efficacy.


Home-based chemically-induced whitening (bleaching) of teeth in adults.
With the increased demand for whiter teeth, home-based bleaching products, either dentist-prescribed or over-the-counter products have been exponentially increasing in the past few decades. This is an update of a Cochrane Review first published in 2006. To evaluate the effects of home-based tooth whitening products with chemical bleaching action, dispensed by a dentist or over-the-counter. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 12 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 12 June 2018), MEDLINE Ovid (1946 to 12 June 2018), and Embase Ovid (1980 to 12 June 2018). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (12 June 2018) and the World Health Organization International Clinical Trials Registry Platform (12 June 2018) were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. We included in our review randomised controlled trials (RCTs) which involved adults who were 18 years and above, and compared dentist-dispensed or over-the-counter tooth whitening (bleaching) products with placebo or other comparable products.Quasi-randomised trials, combination of in-office and home-based treatments, and home-based products having physical removal of stains were excluded. Two review authors independently selected trials. Two pairs of review authors independently extracted data and assessed risk of bias. We estimated risk ratios (RRs) for dichotomous data, and mean differences (MDs) or standardised mean difference (SMD) for continuous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach. We included 71 trials in the review with 26 studies (1398 participants) comparing a bleaching agent to placebo and 51 studies (2382 participants) comparing a bleaching agent to another bleaching agent. Two studies were at low overall risk of bias; two at high overall risk of bias; and the remaining 67 at unclear overall risk of bias.The bleaching agents (carbamide peroxide (CP) gel in tray, hydrogen peroxide (HP) gel in tray, HP strips, CP paint-on gel, HP paint-on gel, sodium hexametaphosphate (SHMP) chewing gum, sodium tripolyphosphate (STPP) chewing gum, and HP mouthwash) at different concentrations with varying application times whitened teeth compared to placebo over a short time period (from 2 weeks to 6 months), however the certainty of the evidence is low to very low.In trials comparing one bleaching agent to another, concentrations, application method and application times, and duration of use varied widely. Most of the comparisons were reported in single trials with small sample sizes and event rates and certainty of the evidence was assessed as low to very low. Therefore the evidence currently available is insufficient to draw reliable conclusions regarding the superiority of home-based bleaching compositions or any particular method of application or concentration or application time or duration of use.Tooth sensitivity and oral irritation were the most common side effects which were more prevalent with higher concentrations of active agents though the effects were mild and transient. Tooth whitening did not have any effect on oral health-related quality of life. We found low to very low-certainty evidence over short time periods to support the effectiveness of home-based chemically-induced bleaching methods compared to placebo for all the outcomes tested.We were unable to draw any conclusions regarding the superiority of home-based bleaching compositions or any particular method of application or concentration or application time or duration of use, as the overall evidence generated was of very low certainty. Well-planned RCTs need to be conducted by standardising methods of application, concentrations, application times, and duration of treatment.


Therapy-induced Ph1 suppression in chronic myeloid leukemia: molecular and cytogenetic studies in patients treated with alpha-2b IFN, high-dose chemotherapy and autologous stem cell infusion.
In this study, cytogenetic and molecular analyses were employed to assess the response to therapy in 29 chronic myeloid leukemia patients undergoing high dose chemotherapy followed by autologous stem cell infusion. Of these, 11 had previously achieved hematologic remission and cytogenetic improvement after alpha-2b interferon (IFN) treatment, whereas 18 underwent autografting in an early phase of the disease. In each case bone marrow samples were examined pre-treatment and at +2, +6 and +12 months in order to verify the degree of Ph1 suppression. In addition, the position of the breakpoint within the BCR region was mapped with multiple restriction enzymes. In 17 cases (59%) a significant Ph1 reduction was observed at +60 days (0-57% residual Ph1+ cells). In three of these cases, a complete cytogenetic response was confirmed at the DNA level by Southern blotting, but specific amplification of the BCR/ABL junction by the polymerase chain reaction (PCR), performed in two cases, still showed residual disease. The remaining 12 patients (41%) revealed a substantial persistence of Ph1+ metaphases (90-100%). Nine of 17 responding patients (53%) showed an increase of Ph1+ cells at 6 months, and five of 20 evaluated had a further increase at 12 months. With the exception of the results seen by PCR, comparison of molecular and cytogenetic techniques did not show significant differences. The variable degrees of Ph1 suppression observed did not appear to be associated with the position of BCR breakpoints. The factors predicting cytogenetic response to IFN and stem cell autograft and long-term durability of cytoconversion should be elucidated in further studies and with longer follow-up.


Poly (ADP-ribose) polymerase 1 protein expression in normal and neoplastic prostatic tissue.
A genetic background has been implicated in the development of prostate cancer. Protein microarrays have enabled the identification of proteins, some of which associated with apoptosis, that may play a role in the development of such a tumor. Inhibition of apoptosis is a co-factor that contributes to the onset and progression of prostate cancer, though the molecular mechanisms are not entirely understood. Poly (ADP-ribose) polymerase 1 (PARP-1) gene is required for translocation of the apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. Hence, it is involved in programmed cell death. Different PARP-1 gene expression has been observed in various tumors such as glioblastoma, lung, ovarian, endometrial, and skin cancers. We evaluated the expression of PARP-1 protein in prostatic cancer and normal prostate tissues by immunohistochemistry in 40 men with prostate cancer and in 37 normal men. Positive nuclear PARP-1 staining was found in all samples (normal prostate and prostate cancer tissues). No cytoplasmic staining was observed in any sample. PARP-1-positive cells resulted significantly higher in patients with prostate carcinoma compared with controls (P<0.001). PARP-1 over-expression in prostate cancer tissue compared with normal prostate suggests a greater activity of PARP-1 in these tumors. These findings suggest that PARP-1 expression in prostate cancer is an attempt to trigger apoptosis in this type of tumor similarly to what reported in other cancers.


Characterisation of North American Brucella isolates from marine mammals.
Extension of known ecological niches of Brucella has included the description of two novel species from marine mammals. Brucella pinnipedialis is associated predominantly with seals, while two major Brucella ceti clades, most commonly associated with porpoises or dolphins respectively, have been identified. To date there has been limited characterisation of Brucella isolates obtained from marine mammals outside Northern European waters, including North American waters. To address this gap, and extend knowledge of the global population structure and host associations of these Brucella species, 61 isolates from marine mammals inhabiting North American waters were subject to molecular and phenotypic characterisation enabling comparison with existing European isolates. The majority of isolates represent genotypes previously described in Europe although novel genotypes were identified in both B. ceti clades. Harp seals were found to carry B. pinnipedialis genotypes previously confined to hooded seals among a diverse repertoire of sequence types (STs) associated with this species. For the first time Brucella isolates were characterised from beluga whales and found to represent a number of distinct B. pinnipedialis genotypes. In addition the known host range of ST27 was extended with the identification of this ST from California sea lion samples. Finally the performance of the frequently used diagnostic tool Bruce-ladder, in differentiating B. ceti and B. pinnipedialis, was critically assessed based on improved knowledge of the global population structure of Brucella associated with marine mammals.


Universal nevirapine upon presentation in labor to prevent mother-to-child HIV transmission in high prevalence settings.
To assess the uptake of and adherence to nevirapine to prevent mother-to-child HIV transmission among women of unknown HIV serostatus presenting in labor. We also assessed preliminary efficacy of the approach. Women of unknown HIV serostatus presenting in labor were offered single-dose nevirapine in a prospective cohort study. Two additional contemporaneous comparison populations were also studied. We measured uptake by counting the number of women that accepted enrollment when offered. We measured adherence with cord blood nevirapine assay. We measured preliminary efficacy with HIV DNA polymerase chain reaction of infant blood spots at 4-6 weeks of life. Of 1591 women approached in labor, 634 (40%) took up the intervention and received nevirapine, of whom 185 (29%) were HIV infected. Of 179 cord blood specimens from HIV-exposed infants that could be evaluated, 178 (99.4%) had nevirapine detected. This was higher than the 73 of 98 (74%) adherence rate observed in a comparison cohort in which women self-administered nevirapine before presenting to the labor ward (P < 0.001). Of 145 available infant specimens, 17 (11.7%) showed evidence of infection at 4-6 weeks, compared with 12 of 60 (20%) infants born immediately prior to study commencement whose HIV-infected mothers did not receive nevirapine (P < 0.05). Nevirapine without HIV testing upon presentation in labor was accepted by two-fifths of women. Because therapy is directly observed, adherence is nearly perfect. Labor ward dosing to enhance nevirapine coverage should be considered as an adjunct to antenatal nevirapine administration for prevention of mother-to-child transmission of HIV.


Ligand-induced and nonfusogenic dissolution of a viral membrane.
Hitherto, all enveloped viruses were thought to shed their lipid membrane during entry into cells by membrane fusion. The extracellular form of Vaccinia virus has two lipid envelopes surrounding the virus core, and consequently a single fusion event will not deliver a naked core into the cell. Here we report a previously underscribed mechanism in which the outer viral membrane is disrupted by a ligand-induced nonfusogenic reaction, followed by the fusion of the inner viral membrane with the plasma membrane and penetration of the virus core into the cytoplasm. The dissolution of the outer envelope depends on interactions with cellular polyanionic molecules and requires the virus glycoproteins A34 and B5. This discovery represents a remarkable example of how viruses manipulate biological membranes, solves the topological problem of how a double-enveloped virus enters cells, reveals a new effect of polyanions on viruses, and provides a therapeutic approach for treatment of poxvirus infections, such as smallpox.


Quantitative proteomic profiling of matched normal and tumor breast tissues.
Proteomic analysis of breast cancer tissue has proven difficult due to its inherent histological complexity. This pilot study presents preliminary evidence for the ability to differentiate adenoma and invasive carcinoma by measuring changes in proteomic profile of matched normal and disease tissues. A dual lysis buffer method was used to maximize protein extraction from each biopsy, proteins digested with trypsin, and the resulting peptides iTRAQ labeled. After combining, the peptide mixtures they were separated using preparative IEF followed by RP nanoHPLC. Following MALDI MS/MS and database searching, identified proteins were combined into a nonredundant list of 481 proteins with associated normal/tumor iTRAQ ratios for each patient. Proteins were categorized by location as blood, extracellular, and cellular, and the iTRAQ ratios were normalized to enable comparison between patients. Of those proteins significantly changed (upper or lower quartile) between matched normal and disease tissues, those from two invasive carcinoma patients had >50% in common with each other but <22% in common with an adenoma patient. In invasive carcinoma patients, several cellular and extracellular proteins that were significantly increased (Periostin, Small breast epithelial mucin) or decreased (Kinectin) have previously been associated with breast cancer, thereby supporting this approach for a larger disease-stage characterization effort.


Audio-visual active speaker tracking in cluttered indoors environments.
We propose a system for detecting the active speaker in cluttered and reverberant environments where more than one person speaks and moves. Rather than using only audio information, the system utilizes audiovisual information from multiple acoustic and video sensors that feed separate audio and video tracking modules. The audio module operates using a particle filter (PF) and an information-theoretic framework to provide accurate acoustic source location under reverberant conditions. The video subsystem combines in 3-D a number of 2-D trackers based on a variation of Stauffer's adaptive background algorithm with spatiotemporal adaptation of the learning parameters and a Kalman tracker in a feedback configuration. Extensive experiments show that gains are to be expected when fusion of the separate modalities is performed to detect the active speaker.


[Methicillin-resistant Staphylococcus aureus. Detection of carriers among hospitalized children and healthy children from the community].
A descriptive punctual study was conducted to search for nasal carriers of Staphylococcus aureus strains resistant to methycilin (SARM) among sound children attended in nurseries and hospitalized children exposed to one or more risk factors predisposing to the colonization by this type of strains from October, 2000, to February, 2001, in Marianao municipality. For the primary isolation of the SARM strains, it was used the oxacillin-manitol-salt-agar (OMSA) and the sensitivity to antimicrobial drugs was determined in all strains identified as S. aureus by using the Kirby-Bauer method. In order to identify the resistance to oxacillin in the strains recovered from OMSA, the oxacillin salt-agar screening-plate method and the determination of inhibitory minimum concentration (IMC) in agar and broth were applied. The presence of the mecA gene was nvestigated by polymerase chain reaction in those strains with an IMC > or = 4 mg/mL of oxacillin. Of the sound children. 0.35 % and of the hospitalized, 2 %, were nasal carriers of SARM strains. The strains isolated in both study groups showed high indexes of resistance to penicillin, tetracycline and erythromycin by the Kirby-Bauer method. The mecA gene was identified in a SARM strain isolated from a hospitalized nasal carrier and it was defined that its behaviour agreed with the one described for a strain homoresistant to oxacillin.


The relationship of cancer incidence to terrestrial radiation and population density in Connecticut, 1935-1974.
The relationship of cancer incidence to terrestrial radiation and population density was investigated. Cancer incidence was obtained using 40 years of age-standardized data from the Connecticut Tumor Registry, and environmental radiation was estimated using data from an airborne gamma radiation survey of the entire state. These variables were examined ecologically, using the 169 towns of the state as the analytic units in a weighted regression analysis. The study design involves a large population base in a state having relatively high terrestrial radiation exposure levels overall and reasonable variation in exposure between towns. For all cancer combined, only one of the eight sex-specific analyses by decade yielded a significant radiation regression coefficient, and this was negative. In the sex- and site-specific analyses, almost all the coefficients for radiation were not significantly different from zero. In contrast, significant positive relationships of cancer incidence with population density were found for all cancer, for cancer of the lung for both sexes, for stomach, colonic, and prostatic cancer for males, and for lymphomas, thyroid, breast, and ovarian cancer for females. Both the radiation and population density relationships were adjusted for socioeconomic status. Socioeconomic status was significantly negatively associated with stomach and lung cancer in males and with cervical cancer in females; it was also positively associated with lymphomas and breast cancer in females. A power calculation revealed that, despite the relatively large size of this study, there was only a small probability of detecting a radiation effect of the strength anticipated from previous estimates.


Optimization of moving bed biofilm reactors for the treatment of municipal wastewater.
The properties of biocarriers significantly influence the performance of a moving bed-biofilm reactor (MBBR). This study aimed to assess the impact of media type, filling ratio, and hydraulic retention time (HRT) on biofilm formation and MBBR performance in both batch and continuous setups using real municipal wastewater. Two different media, high-density polyethylene (HDPE) and polypropylene (PPE), with varying surface area and properties were used. Biofilm growth and MBBR performance were monitored and optimized using response surface methodology. The effect of different media was investigated for three filling ratios of 20%, 40% and 60% and HRT of 4, 6 and 8 h. Results depicted a better biofilm growth on HDPE media in comparison to PPE carriers due to difference in media structure and surface properties. At all the conditions tested, HDPE media showed comparatively better performance for the removal of organic matter and nutrients than PPE media. The maximum organic matter removal efficiency was found as 77% and 75% at an HRT of 6 h and filling ratio of 40% for HDPE and PPE media, respectively. The ammonia removal was also found better for HDPE media due to its geometry and structure favoring the anoxic conditions with maximum removal of 89% achieved at 6-h HRT and 40% filling ratio. Overall, the system with HDPE media indicated more stability in terms of reactor performance than PPE carriers with variations in the operating conditions.


Stem Families, Joint Families, and the European Pattern: What Kind of a Reconsideration Do We Need?
[[family systemsliving arrangementsdemographic variationstem familyjoint familyelderly ]] This article makes a new contribution to the discussion of historical European family forms. Its starting points are two recent contributions by Steven Ruggles in which the author discussed the historical appearances of stem and joint families across the globe. Drawing on most recent developments in census microdata infrastructure from historical Eastern, Central, and Southeastern Europe, the authors pinpoint limitations pertaining to the usage of IPUMS (Integrated Public Use Microdata Series) and NAPP (North Atlantic Population Project) collections for the investigation of European family systems. Using newly acquired materials and refined conceptual tools, they enhance the knowledge about the spatiotemporal distribution of stem- and joint-family arrangements in a broader European context. As the frequency of joint families in the regions under study cannot be fully accounted for by referring to measures of economic conditions and demographic structures alone, the authors speculate about some additional factors which may explain the observed differences in joint-family coresidence across historic Eastern Europe.


Natural propolis extract NIVCRISOL in the treatment of acute and chronic rhinopharyngitis in children.
In the work there are shown the results of a "case control" study carried out in a children collectivity (preschool children and school-children), regarding the action of an aqueous propolis extract, NIVCRISOL, in acute and chronic inflammatory diseases of the upper airways. The preparation, which had a rich content of flavonoids, was administered to a group of preschool children and school-children treated during the whole cold season 1994-1995. The monitoring of the subgroups investigated was performed by clinical observation of the health state and recording of the incidence of symptoms characteristic to acute or chronic rhinopharyngeal diseases, as well as by a periodical laboratory examination for the detection and characterization of viral, microbial and fungal germs carriage. The analysis of the data obtained pointed out the favourable effects of this local treatment, expressed by lowering of the number of cases with acute or chronic symptoms, and decrease and sometimes suppression of the viral-microbial flora carriage of the upper airways. These positive results, the good tolerance of the preparation, the advantages of the therapy with natural products and more economic criteria entitle us to propose the administration of this preparation as an adjuvant medication in the local treatment of some clinical forms of acute or chronic rhinopharyngeal diseases.


Age and sex distribution of subclinical aortic atherosclerosis: a magnetic resonance imaging examination of the Framingham Heart Study.
Autopsy data demonstrate a correlation between subclinical aortic atherosclerosis and cardiovascular disease. Therefore, noninvasive cardiovascular magnetic resonance (CMR) of subclinical atherosclerosis may provide a novel measure of cardiovascular risk, but it has not been applied to an asymptomatic population-based cohort to establish age- and sex-specific normative data. Participants in the Framingham Heart Study offspring cohort who were free of clinically apparent coronary disease were randomly sampled from strata of sex, quartiles of age, and quintiles of Framingham Coronary Risk Score. Subjects (n=318, aged 60+/-9 years, range 36 to 78 years, 51% women) underwent ECG-gated T2-weighted black-blood thoracoabdominal aortic CMR scanning. CMR evidence of aortic atherosclerosis was noted in 38% of the women and 41% of the men. Plaque prevalence and all measures of plaque burden increased with age group and were greater in the abdomen than in the thorax for both sexes and across all age groups. In addition, the Framingham Coronary Risk Score was significantly correlated with all plaque prevalence and burden measures for women but only for men after age adjustment. These noninvasive CMR data extend the prior autopsy-based prevalence estimates of subclinical atherosclerosis and may help to lay the foundation for future studies of risk stratification and treatment of affected individuals.


A web exercise in evidence-based medicine using cognitive theory.
Our aim was to improve clinical reasoning skills by applying an established theory of memory, cognition, and decision making (fuzzy-trace theory) to instruction in evidence-based medicine. Decision-making tasks concerning chest pain evaluation in women were developed for medical students and internal medicine residents. The fuzzy-trace theory guided the selection of online sources (e.g., target articles) and decision-making tasks. Twelve students and 22 internal medicine residents attended didactic conferences emphasizing search, evaluation, and clinical application of relevant evidence. A 17-item Likert scale questionnaire assessed participants' evaluation of the instruction. Ratings for each of the 17 items differed significantly from chance in favor of this alternative approach to instruction. We concluded that fuzzy-trace theory may be a useful guide for developing learning exercises in evidence-based medicine.


Determinants of proximal bicarbonate, chloride, and water reabsorption during carbonic anhydrase inhibition.
To examine the magnitude and load dependency of proximal reabsorption during carbonic anhydrase inhibition with acetazolamide, Munich-Wistar rats were studied in hydropenia and following an increase in single nephron glomerular filtration rate (SNGFR) by either plasma or colloid-free Ringer expansion. During acetazolamide administration, when plasma loading increased SNGFR 50% compared with hydropenia, total CO2, chloride, and water proximal reabsorption rose proportionally, so that fractional proximal reabsorption rates remained constant (0.20-0.27). When SNGFR was comparably increased with Ringer expansion, total CO2, chloride, and water reabsorption were decreased relative to their respective rates during plasma expansion and, in fact, were not changed compared with hydropenic values. At all flow rates during carbonic anhydrase inhibition, end-proximal total CO2 and chloride concentrations were only slightly higher than in the glomerular ultrafiltrate, so that reabsorption was isohydric. In further studies, proximal reabsorption remained isohydric when the glomerular ultrafiltrate bicarbonate concentration was reduced in metabolic acidosis. In conclusion, absolute proximal reabsorption of bicarbonate, chloride, and water during carbonic anhydrase inhibition 1) proceeds isohydrically, with minimal anion concentration gradients generated, over a wide range of filtered loads, and 2) can be flow dependent (with plasma loading) as well as modulated by peritubular protein concentration, even though passive chloride transport is minimized.


Conception of man and the preservation of his health in circumpolar regions.
The preservation of human health in polar and circumpolar regions depends mainly on the strategy for future development of these regions. The consequences of human intervention into northern ecology are irreversible, as in the case of the greenhouse effect, the industrial and atomic pollution of polar nature, the tundra devastation, the destruction of northern flora and fauna etc. The ongoing creation of large industrial population centres in the North by means of newcomers is to be stopped. Polar regions are to be used for biospheric reservation and tourist sanitary zones, to preserve specific flora and fauna, to provide the rhythms and customs necessary to survive in extreme climatic and geophysical conditions of high latitudes. The program for securing man's survival in circumpolar regions should comprise several stages of practical measures to provide necessary resources and to combine international efforts. The preservation of man's health must be based on the understanding of the interrelation between health and biospheric processes and the assessment of the role of human intervention into polar ecology. A program facilitating the preservation of human health and survival in the North and in the Antarctic should be initiated.


Immunopharmacological actions of the new antiallergic drug butyl 3'-(1H-tetrazol-5-yl)oxanilate. 2nd communication: inhibitory effects on histamine release from rat mast cells and lung fragments.
The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on its ability to inhibit histamine release from both peritoneal mast cells and lung fragments of rats were investigated. WP-833 inhibited in a dose-dependent fashion immunoglobulin E (IgE)-mediated histamine release from mast cells. Such potent inhibition was observed in glucose-free as well as complete Tyrode's solution but neither in Ca2+-free nor D2O-supplemented Tyrode's solution. In addition, WP-833 significantly increased intracellular cyclic adenosine monophosphate (AMP) levels in purified mast cells. On the other hand, WP-833 inhibited compound 48/80-but not calcium ionophore A23187-induced histamine release from normal mast cells. Also both IgE- and IgG-mediated histamine release from lung fragments were inhibited by WP-833. WP-833 showed non-competitive inhibition of cyclic AMP-dependent phosphodiesterase derived from lung preparations.


Chapter 12. Therapists' narratives of therapeutic relationships in the treatment of drug-dependent patients.
The article explores and analyzes therapists' narratives, using selected stories, and their strategies for achieving a positive therapeutic relationship and a therapeutic alliance with their patients as a critical dimension to enable effective treatment with patients manifesting dependency problems. Although the therapists are applying different treatment and dependency theories and methods they all emphasize the importance of the therapeutic alliance in order to be successful in the treatment process.


Effect of exposure to short-wavelength light on susceptibility to motion sickness.
This randomized cross-over study tested the hypothesis that exposure to short-wavelength light induces symptoms of motion sickness (MS). The study participants were 28 healthy adults (14 women; mean age±SD, 25.96±3.11 years). Two stimuli oscillating within a range of 0.4-0.6 Hz were used to induce MS: a blue wave stimulus with short-wavelength light (460 nm) and a green wave stimulus with middle-wavelength light (555 nm). All participants were exposed to both stimuli throughout two separate periods. After a baseline period, participants were exposed to each stimulus three times for 4 min. The Simulator Sickness Questionnaire, a self-report checklist composed of three subscales (Oculomotor, Disorientation, and Nausea), heart rate variability, and electrogastrography were used to measure the degree of symptoms related to MS. A linear mixed-effects model was used for statistical analysis. The results showed significant main effects for Period (P<0.01), Color (P<0.01), and Time Point (P<0.01) scores on the Simulator Sickness Questionnaire Nausea subscale. A post-hoc test indicated that scores on the Nausea subscale were significantly higher after the third exposure to blue light than after the first and second exposures. The linear mixed-effects model showed significant main effects for Color (P<0.01) with respect to the normogastria/tachygastria ratio. These findings suggest that short-wavelength light induces symptoms of MS, especially gastrointestinal symptoms.


Spontaneous pneumothorax.
The incidence of spontaneous pneumothorax is 24/100,000 a year in men and 9.9/100,000 a year in women in England and Wales. The major contributing factor is smoking, which increases the likelihood by 22 times in men, and by 8 times in women. While death from spontaneous pneumothorax is rare, rates of recurrence are high, with one study of men in the USA finding a total recurrence rate of 35%. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people presenting with spontaneous pneumothorax? What are the effects of interventions to prevent recurrence in people with previous spontaneous pneumothorax? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 17 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: chest-tube drainage (alone or plus suction), chest tubes (small, standard sizes, one-way valves), needle aspiration, and pleurodesis.


Kasabach-Merritt Syndrome: a case study of successful treatment with vincristine and propranolol.
Kasabach-Merritt syndrome is a rare condition, characterised by the presence of an enlarging vascular tumour associated with thrombocytopenia, microangiopathic haemolytic anaemia and consumptive coagulopathy. The syndrome manifests in infancy, with high morbidity and mortality rates. No standard guidelines have been established for the treatment of Kasabach-Merritt syndrome to date. To existing literature we add this report of a four-month-old female child with Kasabach-Merritt syndrome who was successfully treated with propranolol and vincristine. This drug combination helped reverse the severe thrombocytopenia as well as decrease in size of her haemangioma. Management of Kasabach-Merritt syndrome continues to be a challenge, with varying response to first line drugs. Early diagnosis and initiation of treatment in a closely monitored setting is essential to ensure good outcomes. Since this is a relatively rare condition and large studies are not feasible, documenting treatment experience for single cases or small series becomes even more important.


Impact of age, gender and race on patient and graft survival following renal transplantation--developing country experience.
Optimising renal allograft survival is crucially important in developing countries because of limited resources to treat irreversible renal failure. However, although many factors can be manipulated to improve outcome, certain demographic factors are immutable in individual patients. The present study evaluated the impact of age, gender and race on the outcome of renal transplantation. Relevant data were reviewed for 542 patients receiving primary renal allografts over a 23-year period. The survival of patients and grafts were calculated using the Kaplan-Meier method. Both univariate and multivariate analyses were used to determine the association between the demographic factors and patient and graft survival. Actuarial survival of both patients and grafts decreased with increasing age. The most striking differences were demonstrated when patients older than 40 years were compared with younger patients. However, when patient survival was censored for death with functioning grafts--a very important cause of graft loss--then actuarial graft survival improved with increasing age. There was no gender difference in graft survival, but female recipients of renal allografts had a higher mortality than their male counterparts. There were no racial differences in either patient or graft survival. Age is an important determinant of outcome after renal transplantation, but race is not. Gender does not influence graft survival, but females do have a higher overall mortality rate following renal transplantation at our centre.


A systematic review of clinical outcomes, clinical process, healthcare utilization and costs associated with telerehabilitation.
To identify clinical outcomes, clinical process, healthcare utilization and costs associated with telerehabilitation for individuals with physical disabilities. Relevant databases were searched for articles on telerehabilitation published until February 2007. Reference lists were examined and key journals were hand searched. Studies that included telerehabilitation for individuals with physical impairments and used experimental or observational study designs were included in the analysis, regardless of the specific clientele or location of services. Data was extracted using a form to record methodological aspects and results relating to clinical, process, healthcare utilization and cost outcomes. Study quality of randomized clinical trials was assessed using the PEDro rating scale. Some 28 articles were analysed. These dealt with rehabilitation of individuals in the community, neurological rehabilitation, cardiac rehabilitation, follow-up of individuals with spinal cord injuries, rehabilitation for speech-language impairments, and rehabilitation for varied clienteles. Clinical outcomes were generally improved following a telerehabilitation intervention and were at least similar to or better than an alternative intervention. Clinical process outcomes, such as attendance and compliance, were high with telerehabilitation although few comparisons are made to alternative interventions. Consultation time tended to be longer with telerehabilitation. Satisfaction with telerehabilitation was consistently high, although it was higher for patients than therapists. Few studies examined healthcare utilization measures and those that did reported mixed findings with respect to adverse events, use of emergency rooms and doctor visits. Only five of the studies examined costs. There is some preliminary evidence of potential cost savings for the healthcare facility. While evidence is mounting concerning the efficacy and effectiveness of telerehabilitation, high-quality evidence regarding impact on resource allocation and costs is still needed to support clinical and policy decision-making.


fliU and fliV: two flagellar genes essential for biosynthesis of Salmonella and Escherichia coli flagella.
The possible functions of two recently described flagellar genes, fliU and fliV, have been examined. Introduction of gene fliC, encoding the bacterial flagellin protein, into a number of flagellin-deficient Salmonella and Escherichia coli strains failed to complement the mutations in these strains, and the FliC flagellin was accumulated in the bacterial cytoplasm. Complementation with fliU and fliV, which map downstream of fliC, restored motility to some of the mutants which became flagellated. After inactivation of either fliU or fliV, such complementation no longer occurred and the flagellin protein accumulated in the cytoplasm, which suggested that both genes are required for the secretion of flagellin and expression of motility. Expression of these genes from high copy number plasmids resulted in the synthesis of exceptionally long flagella and in detection of the FliV protein on polyacrylamide gels.


Neurofibromatosis Type 1-Associated Optic Pathway Glioma in Children: A Follow-Up of 10 Years or More.
This study reports on neurofibromatosis type 1 (NF1)-associated optic pathway gliomas (OPGs) and a follow-up period of at least 10 years in a cohort of children. OPGs are a common manifestation of NF1 and can cause significant visual morbidity. Long-term follow-up in children with NF1-associated OPGs has not been reported previously. Retrospective observational case series. This study included children with a documented follow-up of at least 10 years. Three final outcomes were evaluated: visual acuity (VA) per eye (i.e., in the more severely affected eye), VA per patient (i.e., VA when both eyes were open), and the presence of optic nerve head pallor. A total of 45 children were included, followed for a mean of 14 years (range, 10-21 years). At the end of follow-up, abnormal VA (considered moderate to severe impairment) in the more severely affected eye was present in 36% of the patients and in both eyes in 11%. Optic nerve head pallor of 1 or both nerves was present in 62%. In multivariate analysis, only initial VA and optic nerve head appearance at presentation were found to predict the final outcomes. All patients, except for 1, were asymptomatic at presentation and had normal VA and nerves that appeared normal, preserved their good vision in both eyes. Only 1 patient, who had normal VA and normal appearing nerves at presentation, had moderate to severe VA loss at long term follow-up. In this study, children with NF1-associated OPG whose examination signs and symptoms were normal had a normal initial examination and excellent long-term visual and anatomical outcomes. VA and the appearance of the optic nerve head at presentation predict long-term outcome.


[An opisthorchiasis epidemic in Ukraine].
Based on the parasitologic evaluation of 3926 individuals in different climatic and geographic areas of Ukraine it has been ascertained that levels of affection of people with opisthorchiasis depend upon natural as well as social conditions, age of the examinees (but not sex of those infected), remoteness from riverbeds. It has been shown that high levels of contamination of soil with eggs of helminths and cysts of intestinal protozoans in those foci of opisthorchiasis having very high incidence rates of this invasion make for formation in the population of multicomponent intestinal parasite cenoses.


Impact of iodine supplementation and mtDNA mutations on papillary thyroid cancer in saudi women following a vegetarian diet.
This study examined the influence of iodine supplementation and mitochondrial DNA (mtDNA) mutations in Saudi vegetarian women with papillary thyroid cancer (PTC). Blood and tissue samples from PTC-diagnosed women were analyzed for thyroid function, mtDNA mutations, and immunohistological features. Statistical analysis using Sigmastat was employed to compare thyroid hormone levels and mtDNA mutations between groups. Serum total levels of tri-iodothyronine and thyroid-stimulating hormone were significantly different in patients following a vegetarian diet (P<0.05). Patients with PTC showed an increased frequency of mtDNA mutations in the D-loop region, with significantly higher mutation rates observed in patients following a vegetarian diet compared to other PTC patient groups (P<0.001) and controls (P<0.01). Notably, the mutations were predominantly somatic in Group 3 and germline in Groups 1 and 2. The findings suggest a possible link between iodine deficiency and accelerated PTC tumorigenesis. Furthermore, mtDNA mutations may serve as potential biomarkers for the diagnosis and prognosis of PTC.


Poor self-rated health associated with an increased risk of subsequent development of lung cancer.
Self-rated health has shown to be a strong predictor of mortality and some major chronic diseases. The purpose of this study was to investigate whether poor self-rated health also was related to an increased risk of subsequent development of cancer. Information on self-rated health, life-style factors, and other health-related risk factors was ascertained in a cohort of 25,532 persons participating in the Hordaland Health Study in 1997-1999. Information on development of cancer during 10 years of follow-up was obtained from the Norwegian Cancer Registry. The relationship between self-rated health and development of cancer was examined using Cox regression analysis adjusting for smoking and other life-style factors. Respondents reporting a poor health showed a non-significant increased risk of overall cancer. Sub-analysis of the four most common types of cancer showed a statistically significant association between self-rated health and lung cancer. The adjusted hazard ratio was 3.88 (95% CI; 0.99, 15.8) for those rating their health as poor compared to very good (p for trend = 0.038). For the other types of cancer, we found a non-significant elevated risk associated with poor self-rated health. Respondents who perceive their health as poor had an increased risk of developing lung cancer also after adjusting for smoking. This suggests that self-rated health reflects a broad range of factors important for development of this cancer type. Nevertheless, due to the explorative analysis of the specific cancer types, these findings need to be repeated before elaborate interpretations can be made.


Cervical lymph node metastases of squamous cell carcinoma from an unknown primary site: a favourable prognosis subset of patients with CUP.
Squamous cervical cancer of unknown primary site (SQCCUP) presents in patients as neck lymph nodes involved by squamous carcinoma in the absence of identifiable primary in the head, neck or lung. This CUP subset affects male patients previously exposed to alcohol and tobacco, though a proportion of cases may be related to chronic infection of the oropharynx by human papilloma virus. A standardised diagnostic work-up consisting of panendoscopy of the upper aerodigestive tract, CT of the chest/abdomen and histology supplemented by immunohistochemistry is warranted for the diagnosis. The scant available evidence on the molecular biology of the disease is reviewed. The cornerstones of management are excisional biopsy or surgical extirpation of the disease followed by bilateral neck external beam radiotherapy and chemotherapy. The necessity for complete surgical resection of involved neck nodes, irradiation of all head/neck mucosal sites and administration of concurrent chemotherapy is currently being debated. Aggressive multimodal therapy results in longterm disease control in 50-60% of patients, though data are mainly based on retrospective cohorts. Factors predicting for superior patient outcome are radical management with surgery or radiotherapy, low stage and volume of disease, absence of extracapsular spread and good performance status. Recently introduced molecular profiling platforms may provide biological classification to a primary tissue of origin as well as insights into the pathophysiology of this clinical entity.


Light extraction enhancement from nano-imprinted photonic crystal GaN-based blue light-emitting diodes.
The nano-imprint lithography method was employed to incorporate wide-area (375 x 330 mum(2)) photonic-crystal (PC) patterns onto the top surface of GaN-based LEDs. When the 280-nm-thick p-GaN was partly etched to ~140 nm, the maximal extraction-efficiency was observed without deteriorating electrical properties. After epoxy encapsulation, the light output of the PC LED was enhanced by 25% in comparison to the standard LED without pattern, at a standard current of 20 mA. By three-dimensional finite-difference time-domain method, we found that the extraction efficiency of the LED tends to be saturated as the etch-depth in the GaN epitaxial-layer becomes larger than the wavelength of the guided modes.


Neuronal loss from cervical dorsal root ganglia in adriamycin induced peripheral neuropathy--a quantitative study.
The neurotoxic effects of some of the more recent chemotherapeutic drugs are not well studied. Adriamycin is such a drug, used in the treatment of some cancers in both children and adults. An examination of its effects on the peripheral nervous system was therefore undertaken particularly in view of its use in children. Sprague-Dawley rats, 1 week of age, were injected with a subcutaneous injection of adriamycin (10 mg/kg/wt.). Cervical dorsal root ganglia were removed and prepared for quantitative study at the light microscopic level. Quantitative analysis of neuronal counts of the ganglia showed a statistically significant loss (P less than 0.001) of sensory neurons in the treated rats. The remaining neurons displayed many abnormal morphological features suggestive of a degenerative process. From this study, functional loss cannot be correlated to neuronal type but the significant loss of neurons and numbers of affected cells observed would have a serious effect on sensory function.


Air-stable self-powered photodetector based on TaSe2/WS2/TaSe2 asymmetric heterojunction with surface self-passivation.
Two-dimensional (2D) transition metal dichalcogenides are highly suitable for constructing junction photodetectors because of their suspended bond-free surface and adjustable bandgap. Additional stable layers are often used to ensure the stability of photodetectors. Unfortunately, they often increase the complexity of preparation and cause performance degradation of devices. Considering the self-passivation behavior of TaSe2, we designed and fabricated a novel self-powered TaSe2/WS2/TaSe2 asymmetric heterojunction photodetector. The heterojunction photodetector shows excellent photoelectric performance and photovoltaic characteristics, achieving a high responsivity of 292 mA/W, an excellent specific detectivity of 2.43 × 1011 Jones, a considerable external quantum efficiency of 57 %, a large optical switching ratio of 2.6 × 105, a fast rise/decay time of 43/54 μs, a high open-circuit voltage of 0.23 V, and a short-circuit current of 2.28 nA under 633 nm laser irradiation at zero bias. Moreover, the device also shows a favorable optical response to 488 and 532 nm lasers. Notably, it exhibits excellent environmental long-term stability with the performance only decreasing ∼ 5.6 % after exposed to air for 3 months. This study provides a strategy for the development of air-stable self-powered photodetectors based on 2D materials.


Clinical implications of sex in acute temporomandibular disorders.
Previous research on temporomandibular disorders, or TMDs, has been somewhat limited, with studies having low numbers of subjects, restricting the focus to women or looking at patients already diagnosed with chronic TMD. Because early intervention is beneficial, it is important to understand the symptoms that men and women have in the acute stage of TMD. A total of 233 patients (161 women, 72 men) with acute TMD symptoms were assessed with a battery of biopsychosocial measures. Patients were diagnosed as having TMD on the basis of research diagnostic criteria, or RDC, or RDC, for TMD. After six months, patients were reassessed to determine whether they continued to have pain, thus classifying them as having chronic TMD. The authors found that 153 patients (47 men, 106 women) had developed a chronic condition, while 80 patients (25 men, 55 women) no longer reported pain (nonchronic). Female and male patients who developed chronic TMD differed significantly from patients who had acute symptoms that subsided. Women who developed chronic TMD exhibited significantly more psychosocial distress and impairment than women who did not develop chronic TMD, in terms of Diagnostic and Statistical Manual, Fourth Edition, or DSM-IV, diagnoses; Beck Depression Inventory, or BDI, scores; Minnesota Multiphasic Personality Inventory scores; Multidimensional Pain Inventory, or MPI, scores; and physical and psychological measures assessed with the RDC for TMD. Men who developed chronic TMD differed significantly from men who did not develop chronic TMD, in that they exhibited more impairment in terms of DSM-IV diagnoses and BDI and RDC measures. These findings provide evidence that significant differences exist between men and women in regard to acute TMD symptoms. The biopsychosocial differences between men and women suggest that some treatments may be more beneficial for women than for men.


Sdf1/Cxcr4 signaling controls the dorsal migration of endodermal cells during zebrafish gastrulation.
During vertebrate gastrulation, both mesodermal and endodermal cells internalize through the blastopore beneath the ectoderm. In zebrafish, the internalized mesodermal cells move towards the dorsal side of the gastrula and, at the same time, they extend anteriorly by convergence and extension (C&E) movements. Endodermal cells showing characteristic filopodia then migrate into the inner layer within the hypoblast next to the yolk syncytial layer (YSL). However, little is known about how the movement of endodermal cells is regulated during gastrulation. Here we show that sdf1a- and sdf1b-expressing mesodermal cells control the movements of the cxcr4a-expressing endodermal cells. The directional migration of endodermal cells during gastrulation is inhibited by knockdown of either cxcr4a or sdf1a/sdf1b (sdf1). We also show that misexpressed Sdf1 acts as a chemoattractant for cxcr4a-expressing endodermal cells. We further found, using the endoderm-specific transgenic line Tg(sox17:EGFP), that Sdf1/Cxcr4 signaling regulates both the formation and orientation of filopodial processes in endodermal cells. Moreover, the accumulation of phosphoinositide 3,4,5-trisphosphate (PIP(3)), which is known to occur at the leading edge of migrating cells, is not observed at the filopodia of endodermal cells. Based on our results, we propose that sdf1-expressing mesodermal cells, which overlie the endodermal layer, guide the cxcr4a-expressing endodermal cells to the dorsal side of the embryo during gastrulation, possibly through a PIP(3)-independent pathway.


Predisposing factors for individuals' Lyme disease prevention practices: Connecticut, Maine, and Montana.
This study examined factors that predispose individuals to protect against Lyme disease. Knowledge, attitude, and practice questions concerning Lyme disease prevention were included in the Behavioral Risk Factor Surveillance surveys in Connecticut, Maine, and Montana. A total of 4246 persons were interviewed. Perceived risk of acquiring Lyme disease, knowing anyone with Lyme disease, knowledge about Lyme disease, and believing Lyme disease to be a common problem were significantly associated with prevention practices. Predisposing factors differ substantially between states and appear related to disease incidence. Personal risk, knowing someone with Lyme disease, and cognizance about Lyme disease and acting on this information are consistent with social learning theories.


Effect of preinterventional ultrasound examination on frequency of procedure-related vascular complications in percutaneous coronary interventions with transfemoral approach.
Vascular complications are the most frequent adverse events associated with percutaneous coronary interventions (PCIs) leading to an increase in morbidity and mortality. Puncture of the common femoral artery in its middle segment is proved to decrease the risk of procedure-related vascular complications. Real-time ultrasound-guided puncture of the vessel is effective to decrease access site-related vascular complications but complex to perform. We evaluated whether an ultrasonic preinterventional examination of the femoral puncture site and skin marking of anatomic structures and specific vascular characteristics results in a decrease of access site-related vascular complications in PCIs with transfemoral access. Over a period of 12 months we prospectively examined all puncture sites before elective PCIs with transfemoral access (n = 848) using ultrasound. Presence, extent, and location of plaques and stenoses and exact location of bifurcation of the femoral artery were marked by a sonographer on the skin to guide the interventionists in vascular puncture. Postinterventional access site ultrasound was performed to determine possible access site-related complications. Frequency of vascular access site complications was compared to a control cohort (n = 1,027) that did not undergo ultrasound examination before intervention. With ultrasonic vascular access site management the rate of access site-related vascular complications was decreased from 4.2% to 1.9% (odds ratio 0.44, 0.23 to 0.80, p = 0.005). In conclusion, preinterventional ultrasonic access site examination and skin marking decreases the risk of vascular complications in elective PCI with femoral access.


MHC class I genes in a New World primate, the cotton-top tamarin (Saguinus oedipus), have evolved by an active process of loci turnover.
Lymphocytes of a New World primate, the cotton-top tamarin (Saguinus oedipus), express classical G-related major histocompatibility complex (MHC) class I molecules with unusually limited polymorphism and variability. Three G-related loci, an F locus, an E locus, and two pseudogenes (So-N1 and So-N3) have been identified by cDNA library screening and extensive PCR analysis of both cDNA and genomic DNA from the cotton-top tamarin. Furthermore, each genus of the subfamily Callitrichinae (tamarins and marmosets) appears to express its own unique set of MHC class I genes, likely due to a rapid turnover of loci. The rapid emergence of unique MHC class I genes in the Callitrichinae genera, resulting from an active process of duplication and inactivation of loci, may account for the limited diversity of the MHC class I genes in the cotton-top tamarin. To determine the nature of the entire complement of MHC class I genes in the cotton-top tamarin, we synthesized a genomic DNA library and screened it with MHC class I-specific probes. We isolated nine new MHC class I pseudogenes from this library. These newly isolated tamarin G-related MHC class I pseudogenes are not closely related to any of their functional counterparts in the tamarin, suggesting that they do not share a recent common ancestral gene with the tamarin's currently expressed MHC class I loci. In addition, these tamarin sequences display a high rate of nonsynonymous substitutions in their putative peptide binding region. This indicates that the genes from which they have derived were likely subject to positive selection and, therefore, were once functional. Our data support the notion that an extremely high rate of loci turnover is largely responsible for the limited diversity of the MHC class I genes in the cotton-top tamarin.


Lower extremity regional anesthesia: essentials of our current understanding.
The advent of ultrasound guidance has led to a renewed interest in regional anesthesia of the lower limb. In keeping with the American Society of Regional Anesthesia and Pain Medicine's ongoing commitment to provide intensive evidence-based education, this article presents a complete update of the 2005 comprehensive review on lower extremity peripheral nerve blocks. The current review article strives to (1) summarize the pertinent anatomy of the lumbar and sacral plexuses, (2) discuss the optimal approaches and techniques for lower limb regional anesthesia, (3) present evidence to guide the selection of pharmacological agents and adjuvants, (4) describe potential complications associated with lower extremity nerve blocks, and (5) identify informational gaps pertaining to outcomes, which warrant further investigation.


Jointly registering images in domain and range by piecewise linear comparametric analysis.
This paper describes an approach whereby comparametric analysis is used in jointly registering image pairs in their domain and range, i.e., in their spatial coordinates and pixel values, respectively. This is accomplished by approximating a camera's nonlinear comparametric function with a constrained piecewise linear one. The optimal fitting of this approximation to comparagram data is then used in a re-parameterized version of the camera's comparametric function to estimate the exposure difference between images. Doing this allows the inherently nonlinear problem of joint domain and range registration to be performed using a computationally attractive least squares formalism. The paper first presents the range registration process and then describes the strategy for performing the joint registration. The models used allow for the pair-wise registration of images taken from a camera that can automatically adjust its exposure as well as tilt, pan, rotate and zoom about its optical center. Results concerning the joint registration as well as range-only registration are provided to demonstrate the method's effectiveness.


Comparison between retrograde and transeptal approach in radiofrequency catheter ablation of left accessory pathways.
To study a series of patients submitted to radiofrequency catheter ablation (RFA) of left accessory pathways (AP) using the transeptal approach (TSA) as compared to the conventional retrograde arterial approach (RAA). Sixty consecutive patients (44 male; mean age of 35.60±11.63 years) with 60 left APs (39 overt and 21 concealed) underwent catheter ablation using the TS method (30 patients) and the RAA method (30 patients) in an alternate fashion. The analysis was performed according to the intention-to-treat principle. The transeptal puncture was successfully performed in 29 patients (96%). This access allowed primary success in the ablation in all the patients without any complication. When we compared this approach with the RAA there was no difference as regards the primary success (p=0.103), fluoroscopy time (p=0.565) and total time (p=0.1917). Three patients in the RAA group presented a vascular complication. The TSA allowed shorter ablation times (p=0.006) and smaller number of radiofrequency applications (p=0.042) as compared to the conventional RAA. The patients who had unsuccessful ablation in the first session in each approach underwent with the opposite technique (cross-over), with a final ablation success rate of 100%.The TS and RA approaches showed similar efficacy and safety for the ablation of left accessory pathways. The TSA allowed shorter ablation times and smaller number of radiofrequency applications. When the techniques were used in a complementary fashion, they increased the final efficacy of the ablation.


Quantitative assessment of dynamic control of fingertip forces after pollicization.
Dexterity after finger pollicization (reconstruction to thumb) is critical to functional outcomes. While most tests of hand function evaluate a combination of strength, coordination, and motor control, the Strength-Dexterity (S-D) paradigm focuses on the dynamic control of fingertip forces. We evaluated 10 pollicized and 5 non-pollicized hands from 8 participants ages 4-17 years (2 female, 6 male; 10.6 ± 4.5 years). Participants partially compressed and held an instrumented spring prone to buckling between the thumb and first finger to quantify dynamic control over the direction and magnitude of fingertip forces. They also completed traditional functional tests including grip, lateral pinch, and tripod pinch strength, Box and Blocks, and 9-hole peg test. Six of 10 pollicized hands and all non-pollicized hands had S-D scores comparable to typically developing children. However, dynamical analysis showed that pollicized hands exhibit greater variability in compression force, indicating poorer corrective action. Almost all pollicized hands scored below the normal range for the traditional functional tests. The S-D test Z-scores correlated moderately with Z-scores from the other functional tests (r = 0.54-0.61; p = 0.02-0.04) but more weakly than amongst the other functional measures (r = 0.58-0.83; p = 0.0002-0.02), suggesting that the S-D test captures a different domain of function. A higher incidence of radial absence in the hands with poor S-D scores (3/4 vs. 0/6 in hands with normal S-D scores, p = 0.03) was the only clinical characteristic associated with S-D outcome. Overall, these results suggest that while most pollicized hands can control fingertip forces, the nature of that control is altered.


Predictors and course of daily living skills development in toddlers with autism spectrum disorders.
Self-sufficiency is central to child and family well-being. This report focuses on predictors of adaptive daily living skills (DLS) development in young children with ASD and whether DLS gains predict decreases in parenting stress. Participants were 162 toddlers with ASD and their parents, assessed at 3 annual timepoints. Hierarchical Linear Models showed that age, DQ, and autism symptom severity uniquely predicted initial DLS and DLS growth. Child problem behaviors predicted initial DLS only. DLS was associated with change in parenting stress above and beyond DQ, autism symptom severity, and problem behaviors. Children with lower IQ and more severe symptoms showed slower DLS gains. Given its relation to parenting stress, DLS are an important intervention target in young children with ASD.


Direct measurement of single and ensemble average particle-surface potential energy profiles.
This work involves the development of a novel technique that integrates total internal reflection and video microscopy methods to simultaneously measure single particle and ensemble average particle-surface interactions. For the 2 mum silica colloids and glass coverslip used in this study, particle size polydispersity is found to be a dominant factor in determining the distribution of single particle profiles about ensemble average profiles. In conjunction with this observation, chemical and physical nonuniformity are not evident in any of our measurements even with sensitivity to interactions on the order of kT. One advantage of using ensemble averaging in conjunction with time averaging is the ability to dramatically decrease the time required to measure average particle-wall interactions which scales inversely with interfacial particle concentration. A number of experimental issues are addressed in the development of this technique including (1) combining single particle distribution functions, (2) statistical sampling of distribution functions using both time and ensemble averaging, and (3) correcting overlapping scattering signals between adjacent particles. The capabilities of the ensemble averaging technique are also demonstrated to provide unique measurements of particle-surface interactions in metastable systems by selecting only height excursions of levitated particles when calculating potentials. Ultimately, this new technique provides several important advantages over single particle measurements, which provides a foundation for measuring interactions in increasingly complex interfacial systems.


Aberrant Effective Connectivity During Eye Gaze Processing Is Linked to Social Functioning and Symptoms in Schizophrenia.
Patients with schizophrenia show abnormal gaze processing, which is associated with social dysfunction. These abnormalities are related to aberrant connectivity among brain regions that are associated with visual processing, social cognition, and cognitive control. In this study, we investigated 1) how effective connectivity during gaze processing is disrupted in schizophrenia and 2) how this may contribute to social dysfunction and clinical symptoms. Thirty-nine patients with schizophrenia/schizoaffective disorder (SZ) and 33 healthy control participants completed an eye gaze processing task during functional magnetic resonance imaging. Participants viewed faces with different gaze angles and performed explicit and implicit gaze processing. Four brain regions-the secondary visual cortex, posterior superior temporal sulcus, inferior parietal lobule, and posterior medial frontal cortex-were identified as nodes for dynamic causal modeling analysis. Both the SZ and healthy control groups showed similar model structures for general gaze processing. Explicit gaze discrimination led to changes in effective connectivity, including stronger excitatory, bottom-up connections from the secondary visual cortex to the posterior superior temporal sulcus and inferior parietal lobule and inhibitory, top-down connections from the posterior medial frontal cortex to the secondary visual cortex. Group differences in top-down modulation from the posterior medial frontal cortex to the posterior superior temporal sulcus and inferior parietal lobule were noted, such that these inhibitory connections were attenuated in the healthy control group but further strengthened in the SZ group. Connectivity was associated with social dysfunction and symptom severity. The SZ group showed notably stronger top-down inhibition during explicit gaze discrimination, which was associated with more social dysfunction but less severe symptoms among patients. These findings help pinpoint neural mechanisms of aberrant gaze processing and may serve as future targets for interventions that combine neuromodulation with social cognitive training.


Quality and rapidity of anticoagulation in patients with acute pulmonary embolism undergoing mechanical thrombectomy.
The primary objective of our study was to determine the proportion of intermediate-risk PE patients undergoing mechanical thrombectomy (MT) who achieved therapeutic anticoagulation (AC) at the time of the procedure. The salient findings of our study showed that only a minority of patients (14.3%) were in the therapeutic range by ACT at the time of MT (primary outcome). Furthermore, in this higher-risk PE cohort selected for MT, 18.2% of patients were subtherapeutic after initially reaching therapeutic AC, 43% experienced supratherapeutic AC at some point before MT, and less than half (43%) attained therapeutic AC at 6 hours, highlighting the necessity for optimizing anticoagulation practices in acute PE.


[The effects of medazepam on memory trace reproduction during learning and amnesia in aggressive and submissive C57Bl/6J mice].
Experiments were conducted on C57B1 mice to study the role of the social status on the reproduction of a conditioned reaction of passive avoidance and the effect of medazepam on the processes of reproduction. Aggressive and submissive animals were selected according to the test for agonistic confrontations. No effect of the animals' social status on the formation of a conditioned habit was revealed, but a significant increase in the level of defecation was recorded in the aggressive mice. Medazepam administration before the test reduced the reproduction of the conditioned reaction only in the control mice. An amnestic effect blocked reproduction in control and submissive mice but did not change it in the aggressors. Medazepam restored the amnestic memory trace only in submissive individuals. In aggressive mice it reduced the emotional response but did not change reproduction. The data obtained suggest that variations of the social status determine both the behavioral responsiveness to training and the changes in reproduction in response to medazepam.


Between- and within-host species selection on cytoplasmic incompatibility-inducing Wolbachia in haplodiploids.
The most common effect of the endosymbiont Wolbachia is cytoplasmic incompatibility (CI), a form of postzygotic reproductive isolation that occurs in crosses where the male is infected by at least one Wolbachia strain that the female lacks. We revisited two puzzling features of Wolbachia biology: how Wolbachia can invade a new species and spread among populations, and how the association, once established in a host species, can evolve, with emphasis on the possible process of infection loss. These questions are particularly relevant in haplodiploid species, where males develop from unfertilized eggs, and females from fertilized eggs. When CI occurs in such species, fertilized eggs either die (female mortality type: FM), or develop into males (male development type: MD), raising one more question: how transition among CI types is possible. We reached the following conclusions: (1) the FM type is a better invader and should be retained preferentially after a new host is captured; (2) given the assumptions of the models, FM and MD types are selected on neither the bacterial side nor the host side; (3) selective pressures acting on both partners are more or less congruent in the FM type, but divergent in the MD type; (4) host and symbiont evolution can drive infection to extinction for all CI types, but the MD type is more susceptible to the phenomenon; and (5) under realistic conditions, transition from MD to FM type is possible. Finally, all these results suggest that the FM type should be more frequent than the MD type, which is consistent with the results obtained so far in haplodiploids.


Fraction of total plasma vitamin B12 bound to transcobalamin correlates with cognitive function in elderly Latinos with depressive symptoms.
The fraction of total plasma vitamin B(12) bound to transcobalamin (holoTC/B12 ratio) may reflect tissue levels of the vitamin, but its clinical relevance is unclear. We assessed associations between cognitive function and total B12, holoTC, and holoTC/B12 ratio in a cohort of elderly Latinos (n = 1089, age 60-101 years). We assessed cognitive function using the Modified Mini-Mental State Examination (3MSE) and a delayed recall test; we diagnosed clinical cognitive impairment by neuropsychological and clinical exam with expert adjudication; and we assessed depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D). We measured total B12 and holoTC using radioassays. HoloTC/B12 ratio was directly associated with 3MSE score (P = 0.026) but not delayed recall score. Interactions between holoTC/B12 and CES-D score were observed for 3MSE (P = 0.026) and delayed recall scores (P = 0.013) such that associations between the ratio and cognitive function scores were confined to individuals with CES-D >/=16. For individuals with CES-D > or = 16, the odds ratio for clinical cognitive impairment for the lowest holoTC/B12 tertile was 3.6 (95% CI 1.2-11.2) compared with the highest tertile (P = 0.03). We observed no associations between cognitive function and total B12 or holoTC alone, except between holoTC and 3MSE score (P = 0.021), and no interactions between holoTC or total B12 and CES-D score on cognitive function. HoloTC/B12 ratio is associated with cognitive function in elderly Latinos with depressive symptoms and may better reflect the adequacy of B12 for nervous system function than either holoTC or total B12 alone.


Fat implant is superior to muscle implant in vestibular schwannoma surgery for the prevention of cerebrospinal fluid fistulae.
Meticulous sealing of opened air cells in the petrous bone is necessary for the prevention of cerebrospinal fluid (CSF) fistulae after vestibular schwannoma surgery. We performed a retrospective analysis to determine whether muscle or fat tissue is superior for this purpose. Between January 2001 and December 2006, 420 patients underwent retrosigmoidal microsurgical removal by a standardized procedure. The opened air cells at the inner auditory canal and the mastoid bone were sealed with muscle in 283 patients and with fat tissue in 137 patients. Analysis was performed regarding the incidence of postoperative CSF fistulae and correlation with the patient's sex and tumor grade. The rate of postoperative CSF leak after application of fat tissue was lower (2.2%) than after use of muscle (5.7%). Women had less postoperative CSF leakage (3.4%) than men (5.6%). There was an inverse correlation with tumor grade. Patients with smaller tumors seemed to have a higher rate of CSF leakage than those with large tumors without hydrocephalus. Only large tumors with severe dislocation of the brainstem causing hydrocephalus showed a higher incidence of CSF leaks. Fat implantation is superior to muscle implantation for the prevention of CSF leakage after vestibular schwannoma surgery and should, therefore, be used for the sealing of opened air cells in cranial base surgery.


Split liver transplantation.
Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.


The phase stability network of all inorganic materials.
One of the holy grails of materials science, unlocking structure-property relationships, has largely been pursued via bottom-up investigations of how the arrangement of atoms and interatomic bonding in a material determine its macroscopic behavior. Here, we consider a complementary approach, a top-down study of the organizational structure of networks of materials, based on the interaction between materials themselves. We unravel the complete "phase stability network of all inorganic materials" as a densely connected complex network of 21,000 thermodynamically stable compounds (nodes) interlinked by 41 million tie line (edges) defining their two-phase equilibria, as computed by high-throughput density functional theory. Analyzing the topology of this network of materials has the potential to uncover previously unidentified characteristics inaccessible from traditional atoms-to-materials paradigms. Using the connectivity of nodes in the phase stability network, we derive a rational, data-driven metric for material reactivity, the "nobility index," and quantitatively identify the noblest materials in nature.


Patterned surfaces in the drying of films composed of water, polymer, and alcohol.
A study of the complex drying dynamics of polymeric mixtures with optical microscopy and gravimetric measurement is presented. Droplet formation is observed, followed by a collapse that leads to the residual craters in the dried film. The process is followed in situ under well-defined temperature and hygrometric conditions to determine the origin and nature of these droplets and craters. The drying process is usually completed within 1 h. The observations are explained using a simple diffusion model based on experimental results collected from mass and optical measurements as well as Raman confocal microspectrometry. Although the specific polymeric mixtures used here are of interest to the cosmetic industry, the general conclusions reached can apply to other polymeric aqueous solutions with applications to commercial and artistic painting.


Cellular Durotaxis Revisited: Initial-Position-Dependent Determination of the Threshold Stiffness Gradient to Induce Durotaxis.
Directional cell movement from a softer to a stiffer region on a culture substrate with a stiffness gradient, so-called durotaxis, has attracted considerable interest in the field of mechanobiology. Although the strength of a stiffness gradient has been known to influence durotaxis, the precise manipulation of durotactic cells has not been established due to the limited knowledge available on how the threshold stiffness gradient (TG) for durotaxis is determined. In the present study, to clarify the principles for the manipulation of durotaxis, we focused on the absolute stiffness of the soft region and evaluated its effect on the determination of TG required to induce durotaxis. Microelastically patterned gels that differed with respect to both the absolute stiffness of the soft region and the strength of the stiffness gradient were photolithographically prepared using photo-cross-linkable gelatins, and the TG for mesenchymal stem cells (MSCs) was examined systematically for each stiffness value of the soft region. As a result, the TG values for soft regions with stiffnesses of 2.5, 5, and 10 kPa were 0.14, 1.0, and 1.4 kPa/μm, respectively, i.e., TG markedly increased with an increase in the absolute stiffness of the soft region. An analysis of the area and long-axis length for focal adhesions revealed that the adhesivity of MSCs was more stable on a stiffer soft region. These results suggested that the initial location of cells starting durotaxis plays an essential role in determining the TG values and furthermore that the relationship between the position-dependent TG and intrinsic stiffness gradient (IG) of the culture substrate should be carefully reconsidered for inducing durotaxis; IG must be higher than TG (IG ≥ TG). This principle provides a fundamental guide for designing biomaterials to manipulate cellular durotaxis.


Drop-shape analysis of receptor-ligand binding at the oil/water interface.
Drop-shape analysis was used to study the binding of streptavidin to biotin at the interface between water and a pendant chloroform droplet. Polyethylene oxide molecules were synthesized with a hydrophobic tail at one end of the molecule and a hydroxyl or biotin group at the other end. The interfacial tension of the water/chloroform interface was measured before and after addition of these amphiphiles to the chloroform phase and before and after addition of streptavidin to the aqueous phase. The hydroxyl-terminated amphiphiles eliminate nonspecific adsorption of the streptavidin to the interface, while streptavidin binds irreversibly to the biotin-terminated molecules. Molecular interactions within this bound layer were studied by measuring changes in the interfacial pressure as the layer is contracted and expanded by changing the volume of the chloroform droplet. A picture of the interfacial structure was obtained from quantitative comparisons between the experimental results and a molecular theory of protein binding to tethered ligands. These comparisons suggest that protein binding is controlled by the extension of the PEO tethers away from the interface.


Predictors of Improved Walking after a Supervised Walking Exercise Program in Men and Women with Peripheral Artery Disease.
We compared the changes in ambulatory outcomes between men and women with symptomatic peripheral arterial disease (PAD) following completion of a supervised, on-site, treadmill exercise program, and we determined whether exercise training variables and baseline clinical characteristics were predictive of changes in ambulatory outcomes in men and women. Twenty-three men and 25 women completed the supervised exercise program, consisting of intermittent walking to mild-to-moderate claudication pain for three months. Men and women significantly increased claudication onset time (COT) (p < 0.001 and p < 0.01, resp.) and peak walking time (PWT) (p < 0.001 for each group). However, change in PWT was less in women (54%) than in men (77%) (p < 0.05). Neither group significantly changed 6-minute walk distance (6MWD). In women, baseline COT was the only predictor for the change in COT (p = 0.007) and the change in PWT (p = 0.094). In men, baseline COT (p < 0.01) and obesity (p < 0.10) were predictors for the change in COT, and obesity was the only predictor for the change in PWT (p = 0.002). Following a supervised, on-site, treadmill exercise program, women had less improvement in PWT than men, and neither men nor women improved submaximal, overground 6MWD. Furthermore, obese men and patients with lower baseline COT were least responsive to supervised exercise. This trial is registered with ClinicalTrial.gov, unique identifier: NCT00618670.


Three-dimensional cavity nanoantenna coupled plasmonic nanodots for ultrahigh and uniform surface-enhanced Raman scattering over large area.
We propose and demonstrate a new SERS substrate architecture that couples a dense three-dimensional (3-D) cavity nanoantenna array, through nano-gaps, with dense plasmonic nanodots; and a new nanofabrication that combines nanoimprint, guided self-assembly and self-alignment and has fabricated the architecture precisely, simply, inexpensively and over large area (4-inch wafer). We experimentally achieved not only high area-average SERS enhancement (1.2×10⁹) but also excellent uniformity (22.4% variation) at the same time over the entire large-area sample by measuring 90 points with a regular mapping distance. The best uniformity achieved is 15% variation over 1.6 mm by 1.6 mm area at slightly lower enhancement factor and is independent of the excitation laser probe size, which had an area varying from ~1 to 10,000 μm2.


Comparison of fractal dimension estimation algorithms for epileptic seizure onset detection.
Fractal dimension (FD) is a natural measure of the irregularity of a curve. In this study the performances of three waveform FD estimation algorithms (i.e. Katz's, Higuchi's and the k-nearest neighbour (k-NN) algorithm) were compared in terms of their ability to detect the onset of epileptic seizures in scalp electroencephalogram (EEG). The selection of parameters involved in FD estimation, evaluation of the accuracy of the different algorithms and assessment of their robustness in the presence of noise were performed based on synthetic signals of known FD. When applied to scalp EEG data, Katz's and Higuchi's algorithms were found to be incapable of producing consistent changes of a single type (either a drop or an increase) during seizures. On the other hand, the k-NN algorithm produced a drop, starting close to the seizure onset, in most seizures of all patients. The k-NN algorithm outperformed both Katz's and Higuchi's algorithms in terms of robustness in the presence of noise and seizure onset detection ability. The seizure detection methodology, based on the k-NN algorithm, yielded in the training data set a sensitivity of 100% with 10.10 s mean detection delay and a false positive rate of 0.27 h(-1), while the corresponding values in the testing data set were 100%, 8.82 s and 0.42 h(-1), respectively. The above detection results compare favourably to those of other seizure onset detection methodologies applied to scalp EEG in the literature. The methodology described, based on the k-NN algorithm, appears to be promising for the detection of the onset of epileptic seizures based on scalp EEG.


Gastrostomy use in children: a 3-year single centre experience.
Monocentric retrospective paediatric study describing indications for gastrostomy and major complications, compared to literature data as part of a quality check. Records of all gastrostomy patients consulting at the UZ Ghent paediatric gastro-enterology department between January 2007-December 2009 were reviewed in December 2010 regarding indication, age and weight at tube insertion, insertion method, major complications and current gastrostomy tube type. 178 patients were included of which 165 (93%) were placed using the endoscopic pull technique, the others were placed surgically (n = 13). Neurodevelopmental disability with oral motor dysfunction was the major indication (113, 63%). Other indications were failure to thrive due to concomitant disease (65, 37%). Median age at tube insertion was 3yr (interquartile range (IQR) 0.6-9) with median tube time of 3.9 yr (IQR 1.9-7.2). Immediate complications were 1 peritonitis and 1 post-insertion fever episode. Late complications (10, 5.6%) were 1 gastrocolic fistula, 1 dislocation and 8 buried bumpers after 4 yr (range 35-10.4) of tube insertion. The incidence of buried bumper increased significantly with increasing PEG tube time (P < 0.01). Gastro-oesophageal reflux disease (GORD) led to Nissen fundoplication in 45 (25.3%) patients. The proportion of patients receiving a fundoplication remained about 20% over time but the time lapse between the 2 procedures decreased significantly. The development of buried bumper is associated to prolonged PEG tube use. In case of important GORD laparoscopic Nissen procedure and PEG placement can be performed simultaneously without increasing complication rate.


Polycystic ovary syndrome and ovulation induction.
Polycystic ovary syndrome (PCOS) is likely the most common cause of anovulatory infertility. Although many options are available for ovulation induction in these patients, there is currently no evidence-based algorithm to guide the initial and subsequent choices of ovulation induction methods. In obese women with PCOS, mild to moderate weight loss results in improvement of ovulatory dysfunction, and should be advocated at the onset of the evaluation. Clomiphene citrate is currently the 1st line medical therapy for ovulation induction. Glucocorticoids do not result in consistent ovulation and have significant side effects. Exogenous pulsatile GnRH treatment has low ovulation and pregnancy rates with a high risk of miscarriage. The most commonly used medical agents for ovulation induction in clomiphene-resistant women with PCOS are parenteral gonadotropins. Various gonadotropin preparations and different protocols are available; however the risk of multiple pregnancy and ovarian hyperstimulation is high with gonadotropin therapy. The frequent association between PCOS and insulin resistance has prompted recent studies on the effect of insulin-sensitizing agents on spontaneous and as an adjuvant to conventional ovulation induction therapies. Overall, the improvement in ovulation with insulin sensitizing drugs is modest, and unresolved issues such as variability in ovarian response remain to be addressed in future studies. Nevertheless, these agents may be beneficial in a subset of PCOS patients. Surgical ovulation induction methods such as ovarian diathermy have been reported to be moderately effective. However, due to the inherent associated risks and unknown effect on long-term reproductive potential, this modality should be reserved for patients who are clomiphene-resistant and unable or unwilling to proceed to gonadotropin therapy.


Chemical facilitation of thermal conduction in physiological systems.
Experimental evidence supports the concept that solutes capable of reversible chemical reaction can passively facilitate thermnal conduction within their solutions. Myoglobin and bicarbonate are suggested as energy carriers in muscle, having the combined capacity for conveying all waste metabolic heat produced under normal physiological conditions. The concept is extended to convective heat transfer in vivo; this implicates hemoglobin.


Clinical informatics training in medical school education curricula: a scoping review.
This scoping review evaluates the existing literature on clinical informatics (CI) training in medical schools. It aims to determine the essential components of a CI curriculum in medical schools, identify methods to evaluate the effectiveness of a CI-focused education, and understand its delivery modes. This review was informed by the methodological guidance of the Joanna Briggs Institute. Three electronic databases including PubMed, Scopus, and Web of Science were searched for articles discussing CI between January 2010 and December 2021. Fifty-nine out of 3055 articles were included in our final analysis. Components of CI education include its utilization in clinical practice, ethical implications, key CI-related concepts, and digital health. Evaluation of educational effectiveness entails external evaluation by organizations external to the teaching institute, and internal evaluation from within the teaching institute. Finally, modes of delivery include various pedagogical strategies and teaching CI using a multidisciplinary approach. Given the broad discussion on the required competencies, we propose 4 recommendations in CI delivery. These include situating CI curriculum within specific contexts, developing evidence-based guidelines for a robust CI education, developing validated assessment techniques to evaluate curriculum effectiveness, and equipping educators with relevant CI training. The literature reveals that CI training in the core curricula will complement if not enhance clinical skills, reiterating the need to equip students with relevant CI competencies. Furthermore, future research needs to comprehensively address current gaps in CI training in different contexts, evaluation methodologies, and delivery modes to facilitate structured training.


Presynaptic alpha 7- and beta 2-containing nicotinic acetylcholine receptors modulate excitatory amino acid release from rat prefrontal cortex nerve terminals via distinct cellular mechanisms.
Nicotine can enhance working memory and attention. Activation of both alpha7 and beta2(*) nicotinic acetylcholine receptors (nAChRs) in the prefrontal cortex (PFC) has been implicated in these processes. The ability of presynaptic nAChRs to modulate neurotransmitter release, notably glutamate release, is postulated to contribute to nicotine's effects. We have examined the cellular mechanisms underlying alpha7 and beta2(*) nAChR-mediated [(3)H]d-aspartate release from the PFC in vitro. Using the alpha7 and beta2(*) nAChR-selective agonists (R)-N-(1-azabicyclo[2.2.2]-oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide) (compound A) and 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380), respectively, in conjunction with inhibitors of voltage-operated Ca(2+) channels (VOCCs) and intracellular Ca(2+) stores, we show that [(3)H]d-aspartate release evoked by activation of beta2(*) nAChRs occurs via VOCCs. In contrast, alpha7 nAChR-evoked release was unaffected by VOCC blockers but was abolished by modulators of Ca(2+) stores, including ryanodine. The alpha7 nAChR ligand alpha-bungarotoxin and ryanodine receptors were colocalized to a subpopulation of PFC synaptosomes. Compound A-evoked [(3)H]d-aspartate release was also blocked by mitogen-activated protein kinase kinase 1 inhibitors, implicating extracellular signal-regulated kinase (ERK)1/2 in alpha7 nAChR-evoked exocytosis. Western blotting confirmed that compound A, but not 5-iodo-A-85380, application increased ERK2 phosphorylation in PFC synaptosomes, and this was dependent on ryanodine-sensitive stores. Compound A also promoted synapsin-1 phosphorylation at ERK1/2-dependent sites, in a ryanodine-sensitive manner. Thus, beta2(*) and alpha7 nAChR subtypes in the PFC mediate [(3)H]d-aspartate release via distinct mechanisms as a result of their differential coupling to VOCCs and Ca(2+)-induced Ca(2+) release (CICR), respectively. The ability of alpha7 nAChRs to promote the phosphorylation of presynaptic ERK2 and synapsin-1, downstream of CICR, provides a potential mechanism for presynaptic facilitation in the PFC.


Conjugated bile acids in serum and secretions in response to cholecystokinin/secretin stimulation in children with cystic fibrosis.
More than 80% of patients with cystic fibrosis have poor pancreatic function, and have large daily faecal bile acid losses. This has been postulated to lower luminal bile acid concentrations and adversely affect fat absorption. We studied, for the first time, quantitative individual conjugated duodenal bile acid secretion rates into the duodenum during cholecystokinin/secretin infusion in 55 cystic fibrosis patients and six controls, using a quantitative non-absorbable marker technique. We were able to show adequate duodenal total bile acid concentrations and normal secretion rates in these children. The bile acid secretion pattern in cystic fibrosis patients showed a marked increase in bile acid concentration during cholecystokinin/secretin infusion, to levels which were above the critical micellar concentration indicating that the gall bladder is a functional organ in this disease. The subsequent fall in secretion rate was similar to controls. We have documented a significantly raised glycine/taurine bile acid conjugation ration in duodenal juice from cystic fibrosis patients and suggest that the combined effects of lowered ileal pH and increased glycine conjugated proportion of bile acids may cause precipitation of bile acids leading to decreased fat absorption and large faecal bile acid losses. To further investigate bile acid secretion in children with cystic fibrosis, we modified the high performance thin layer chromatography/densitometry method to enable measurement of individual glycine and taurine conjugates in serum. In comparing cystic fibrosis patients and controls, we were able to determine a group of 18 (36%) with bile acid evidence of liver damage who also showed reduced bile acid secretion into the duodenum. We were unable to study changes in serum bile acids during cholecystokinin/secretin infusion because of the high level of bile acid contamination in Boots Secretin. Some patients showed raised fasting serum bile acid concentrations more than two years before changes in conventional liver function tests or clinically evident liver disease. We have shown fasting serum bile acids to be a sensitive measure of liver dysfunction in cystic fibrosis and postulate that raised proportions of glycine conjugated bile acids may be responsible for the high incidence of liver disease in cystic fibrosis.