Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

Development and Validation of the Behavioral Tendencies Questionnaire

At a fundamental level, taxonomy of behavior and behavioral tendencies can be described in terms of approach, avoid, or equivocate (i.e., neither approach nor avoid). While there are numerous theories of personality, temperament, and character, few seem to take advantage of parsimonious taxonomy. The present study sought to implement this taxonomy by creating a questionnaire based on a categorization of behavioral temperaments/tendencies first identified in Buddhist accounts over fifteen hundred years ago. Items were developed using historical and contemporary texts of the behavioral temperaments, described as “Greedy/Faithful”, “Aversive/Discerning”, and “Deluded/Speculative”. To both maintain this categorical typology and benefit from the advantageous properties of forced-choice response format (e.g., reduction of response biases), binary pairwise preferences for items were modeled using Latent Class Analysis (LCA). One sample (n1 = 394) was used to estimate the item parameters, and the second sample (n2 = 504) was used to classify the participants using the established parameters and cross-validate the classification against multiple other measures. The cross-validated measure exhibited good nomothetic span (construct-consistent relationships with related measures) that seemed to corroborate the ideas present in the original Buddhist source documents. The final 13-block questionnaire created from the best performing items (the Behavioral Tendencies Questionnaire or BTQ) is a psychometrically valid questionnaire that is historically consistent, based in behavioral tendencies, and promises practical and clinical utility particularly in settings that teach and study meditation practices such as Mindfulness Based Stress Reduction (MBSR)

Clinical study of the factors affecting radioulnar deviation of the wrist joint

<p>Abstract</p> <p>Background</p> <p>The radioulnar carpal joint is critical for hand and wrist function. Radioulnar deviation indicates distal radioulnar joint flexibility and reflects the structure and function of the carpal bones, ulna, radius and ligaments. The present study examined whether radioulnar deviation is affected by gender, manual labor, playing a musical instrument, playing sport, handedness, previous fracture or prior inflammation. The study used clinical findings based on anatomical landmarks</p> <p>Methods</p> <p>The ulnar, radial and total deviations for both left and right hands were measured in 300 subjects (157 men and 143 women) of mean age 21.7 years. Measurements were made with the forearm in a fixed pronated position using a novel specially designed goniometer. The gender of each subject was recorded, and information on playing of sport, playing a musical instrument, manual labor, handedness, and history of fracture or inflammation was sought. Data were analyzed using a multifactor ANOVA test.</p> <p>Results</p> <p>No statistically significant difference (p-value > 0.05) was found between those comparing groups except the total deviation of athletes' left hand versus the total deviation of non athletes' left hand (p-value 0.041 < 0.05) and the radial deviation of manual workers' left hand and non manual workers' left hand (p-value 0.002 < 0.05).</p> <p>Conclusions</p> <p>This study was based on clinical findings using anatomical landmarks. We found that manual workers and athletes showed greater left hand flexibility. This suggests that activities that place chronic stress on the radiocarpal joint can independently affect radioulnar deviation.</p

Who sleeps under bednets in Ghana? A doer/non-doer analysis of malaria prevention behaviours

BACKGROUND: Malaria prevention programmes should be based in part on knowledge of why some individuals use bednets while others do not. This paper identifies factors and characteristics of women that affect bednet use among their children less than five years of age in Ghana. METHODS: Data come from the baseline component of an evaluation of Freedom from Hunger's malaria curriculum. A quasi-experimental design was used to select clients (n = 516) of Credit with Education (an integrated package of microfinance and health education) and non-clients (n = 535). Chi-squares, Fisher's Exact tests and logistic regression were used to compare the characteristics of mothers whose children use bednets (doers) with those whose children do not (non-doers) and to identify factors associated with bednet use among children less than five years of age. RESULTS: The following factors were most closely associated with bednet use: region of residence; greater food security; and caregivers' beliefs about symptoms, causation and groups most vulnerable to malaria. Most respondents knew mosquitoes caused malaria; however, 20.6% of doers and 12.3% of non-doers (p = .0228) thought overworking oneself caused malaria. Ninety percent of doers and 77.0% of non-doers felt that sleeping under a net was protective against malaria (p = .0040). In addition, 16.5% of doers and 7.5% of non-doers (p = .0025) identified adult males as most vulnerable to malaria. CONCLUSION: Greater knowledge about malaria does not always translate into improved bednet use. Though culturally-based ideas about malaria may vary between communities, integrating them into traditional health education messages may enhance the effectiveness of public health efforts

Mesoscopic organization reveals the constraints governing C. elegans nervous system

One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations, such as optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis, we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key functional role as a processor of information.Comment: Published version, Minor modifications, 16 pages, 9 figure

An investigation into the performance of the Adjuvant! Online prognostic programme in early breast cancer for a cohort of patients in the United Kingdom

BACKGROUND: Adjuvant! Online is an internet-based computer programme providing 10-year prognosis predictions for early breast cancer patients. It was developed in the United States, has been successfully validated in Canada, and is used in the United Kingdom and elsewhere. This study investigates the performance of Adjuvant! in a cohort of patients from the United Kingdom. METHODS: Data on the prognostic factors and management of 1065 women with early breast cancer diagnosed consecutively at the Churchill Hospital in Oxford between 1986 and 1996 were entered into Adjuvant! to generate predictions of overall survival (OS), breast cancer-specific survival (BCSS), and event-free survival (EFS) at 10 years. Such predictions were compared with the observed 10-year outcomes of these patients. RESULTS: For the whole cohort, Adjuvant! significantly overestimated OS (by 5.54%, P&lt;0.001), BCSS (by 4.53%, P&lt;0.001), and EFS (by 3.51%, P=0.001). For OS and BCSS, overestimation persisted across most demographic, pathologic, and treatment subgroups investigated. Differences between Adjuvant! predicted and observed EFS appeared smaller, and were significant for far fewer subgroups, only 5 out of the 28. The likely explanation for such discordance is that US breast cancer mortality rates (upon which Adjuvant! is based) appear to be systematically lower than breast cancer mortality rates in the United Kingdom. Differences in survival after recurrence would seem to be one contributory factor, with data suggesting that prognosis after relapse appears poorer in the United Kingdom. This may reflect the fact that new and more effective cancer drugs are often only approved for use in the United Kingdom many years after their adoption in the United States. CONCLUSION: The use of Adjuvant! by clinicians within the UK National Health Service is increasing, under the assumption that the programme is transferrable to the United Kingdom. At least for women treated for breast cancer at the Churchill Hospital in Oxford, however, Adjuvant!'s predictions were on the whole overoptimistic. If the findings reported here could be shown to be generalisable to other areas of the United Kingdom, then thought should perhaps be given to the development of a UK-specific version of the programme

Case report: Malignant teratoma of the uterine corpus

<p>Abstract</p> <p>Background</p> <p>Teratomas are the commonest germ cell tumours and are most frequently found in the testes and ovary. Extragonadal teratomas are rare and mainly occur in midline structures. Uterine teratomas are extremely rare with only a few previous case reports, usually involving mature teratomas of the uterine cervix.</p> <p>Case Presentation</p> <p>We report an 82-year-old lady presenting with post-menopausal bleeding. Initial investigations revealed a benign teratoma of the uterus which was removed. Her symptoms persisted and a recurrent, now malignant, teratoma of the uterine corpus was resected at hysterectomy. Six months after surgery she relapsed with para-aortic lymphadenopathy and was treated with a taxane, etoposide and cisplatin-containing chemotherapy regimen followed by retroperitoneal lymph node dissection.</p> <p>Conclusion</p> <p>In this report we discuss the aetiology, diagnosis and management of uterine teratomas, and review previous case studies.</p

Effects of larval growth condition and water availability on desiccation resistance and its physiological basis in adult Anopheles gambiae sensu stricto

<p>Abstract</p> <p>Background</p> <p>Natural populations of the malaria mosquito <it>Anopheles gambiae </it>s.s. are exposed to large seasonal and daily fluctuations in relative humidity and temperature, which makes coping with drought a crucial aspect of their ecology.</p> <p>Methods</p> <p>To better understand natural variation in desiccation resistance in this species, the effects of variation in larval food availability and access to water as an adult on subsequent phenotypic quality and desiccation resistance of adult females of the Mopti chromosomal form were tested experimentally.</p> <p>Results</p> <p>It was found that, under normal conditions, larval food availability and adult access to water had only small direct effects on female wet mass, dry mass, and water, glycogen and body lipid contents corrected for body size. In contrast, when females subsequently faced a strong desiccation challenge, larval food availability and adult access to water had strong carry-over effects on most measured physiological and metabolic parameters, and affected female survival. Glycogen and water content were the most used physiological reserves in relative terms, but their usage significantly depended on female phenotypic quality. Adult access to water significantly influenced the use of water and body lipid reserves, which subsequently affected desiccation resistance.</p> <p>Conclusions</p> <p>These results demonstrate the importance of growth conditions and water availability on adult physiological status and subsequent resistance to desiccation.</p