The use of GIS for the integration of traditional and scientific knowledge in supporting artisanal fisheries management in southern Brazil.
The integration of local harvesters' knowledge of attitudes and practices toward the resources they harvest with scientific information is essential to natural resources management. However, the development and implementation of management policies have, in most cases, not been effective because of a failure to use all available sources of information and knowledge. In fisheries management, local knowledge is usually not collected in a systematic format and little published literature has discussed the use of local knowledge data collection and analysis methods. This paper describes the implementation of geographic information systems to systematize, analyze, and display traditional and scientific information to support fisheries management in the Patos Lagoon Estuary, southern Brazil. Artisanal fishing data were documented through a series of interviews conducted during and after fishing trips at harvest spots, and scientific data on environmental variables were obtained from different research institutions. A multi-layer GIS database integrating local fishers' and scientific knowledge information was developed with ArcGIS 8.3 ArcView tools to integrate and translate information into an accessible and interpretable format. The geo-spatial database interface allowed the selection of specific data characteristics by target species, harvest areas, fishers' communities, fishing gear, catch-per-unit of effort (CPUE), and monthly landings. The observed fishing spatial dynamics presented among the fishers' communities shows that, in most cases, artisanal fishermen tend to concentrate in shallow estuarine waters surrounding their villages.


What limits [V(·)]O(2max)? A symposium held at the BASES Conference, 6 September 2010.
Three modern views about the factors limiting oxygen uptake in healthy humans are set against the original (early 1920s) concept of A. V. Hill and colleagues. The majority view for most of the intervening time has been that cardiac output is the essential limiting function. Among recent research in support of this contention is that, in quadrupeds, pericardiectomy, which allows greater diastolic filling, elevates maximum oxygen uptake; however, the relevance to bipedal exercise can be questioned. In any case, algebraic analyses of model systems indicate that all identifiable stages on the oxygen transport pathway, from pulmonary diffusion to oxidative phosphorylation in skeletal muscle mitochondria, materially influence maximum uptake. Thus, if a high cardiac output is to be of benefit, all the other steps must function better too. Nevertheless, these two viewpoints concur that the limit to maximum oxygen uptake is somatic. In contrast, there are strong indications that at altitudes where oxygen availability is about half that at sea level, cerebral oxygenation is a limiting factor, and some recent experiments raise the possibility that it might be a substantial influence at sea level also. Clearly, consensus cannot yet be reached on the question posed in the title.


Synaptic specificity is generated by the synaptic guidepost protein SYG-2 and its receptor, SYG-1.
Synaptic connections in the nervous system are directed onto specific cellular and subcellular targets. Synaptic guidepost cells in the C. elegans vulval epithelium drive synapses from the HSNL motor neuron onto adjacent target neurons and muscles. Here, we show that the transmembrane immunoglobulin superfamily protein SYG-2 is a central component of the synaptic guidepost signal. SYG-2 is expressed transiently by primary vulval epithelial cells during synapse formation. SYG-2 binds SYG-1, the receptor on HSNL, and directs SYG-1 accumulation and synapse formation to adjacent regions of HSNL. syg-1 and syg-2 mutants have defects in synaptic specificity; the HSNL neuron forms fewer synapses onto its normal targets and forms ectopic synapses onto inappropriate targets. Misexpression of SYG-2 in secondary epithelial cells causes aberrant accumulation of SYG-1 and synaptic markers in HSNL adjacent to the SYG-2-expressing cells. Our results indicate that local interactions between immunoglobulin superfamily proteins can determine specificity during synapse formation.


Measuring the success of specific health problem consultations in cats and dogs: a systematic review.
Consultations are complex interactions, are central to achieving optimal outcomes for all stakeholders, yet what constitutes a successful consultation has not been defined. The aim of this systematic review was to describe the scope of the literature available on specific health problem consultations and appraise their identified success measures. Searches of CAB Abstracts and MEDLINE were performed in May 2016 using species and consultation terms. Systematic sorting of the results allowed identification of consultation 'success factors' cited in peer-reviewed veterinary literature which were appraised using an appropriate critical appraisal tool (AXIS). Searches returned 11 330 results with a total of 17 publications meeting the inclusion criteria, of which four measured consultation success. Journal of the American Veterinary Medical Association was the most common journal of publication (9 of 17) and the majority of included papers had been published since 2010 (12 of 17). Success factors measured were compliance, client satisfaction and veterinary surgeon satisfaction, and publications primarily used communication analysis tools to measure success. The review highlights the paucity of peer-reviewed literature examining small animal, health problem veterinary consultations. The available evidence is of variable quality and provides weak evidence as to which factors contribute to a successful consultation.


Immunomagnetic separation of tumor initiating cells by screening two surface markers.
Isolating tumor initiating cells (TICs) often requires screening of multiple surface markers, sometimes with opposite preferences. This creates a challenge for using bead-based immunomagnetic separation (IMS) that typically enriches cells based on one abundant marker. Here, we propose a new strategy that allows isolation of CD44+/CD24- TICs by IMS involving both magnetic beads coated by anti-CD44 antibody and nonmagnetic beads coated by anti-CD24 antibody (referred to as two-bead IMS). Cells enriched with our approach showed significant enhancement in TIC marker expression (examined by flow cytometry) and improved tumorsphere formation efficiency. Our method will extend the application of IMS to cell subsets characterized by multiple markers.


Utility of self-reported mental health measures for preventing unintentional injury: results from a cross-sectional study among French schoolchildren.
Identify children at-risk of having mental health problems is of value to prevent injury. But the limited agreement between informants might jeopardize prevention initiatives. The aims of the present study were 1) to test the concordance between parents and children reports, and 2) to investigate their relationships with parental reports of children' unintentional injuries. In a population-based sample of 1258 children aged 6 to 11, the associations between child psychopathology (using the Dominic Interactive and the Strengths and Difficulties Questionnaire) and unintentional injuries in the past 12 months were examined in univariate and multivariate models. As compared to children, parents tended to overestimate behavior problems and hyperactivity/inattention, and underestimate emotional symptoms. Unintentional injury in the last 12-month period was reported in 184 out of 1258 children (14.6%) and multivariate analyses showed that the risk of injury was twice as high in children self-reporting hyperactivity/inattention as compared to others. However this association was not retrieved with the parent-reported instrument. Our findings support evidence that child-reported measures of psychopathology might provide relevant information for screening and injury prevention purposes, even at a young age. It could be used routinely in combination with others validated tools.


Cholinesterase inhibitors for rarer dementias associated with neurological conditions.
Rarer dementias include Huntington's disease (HD), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), frontotemporal dementia (FTD), dementia in multiple sclerosis (MS) and progressive supranuclear palsy (PSP). Cholinesterase inhibitors, including donepezil, galantamine and rivastigmine, are considered to be the first-line medicines for Alzheimer's disease and some other dementias, such as dementia in Parkinson's disease. Cholinesterase inhibitors are hypothesised to work by inhibiting the enzyme acetylcholinesterase (AChE) which breaks down the neurotransmitter acetylcholine. Cholinesterase inhibitors may also lead to clinical improvement for rarer dementias associated with neurological conditions. To assess the efficacy and safety of cholinesterase inhibitors for cognitive impairment or dementia associated with neurological conditions. We searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, several trial registries and grey literature sources in August 2013. We included randomised, double-blind, controlled trials assessing the efficacy of treatment of rarer dementias associated with neurological conditions with currently marketed cholinesterase inhibitors. Two review authors independently assessed eligibility and quality of trials, and extracted data. We used the standard methodological procedures of the Cochrane Collaboration. We included eight RCTs involving 567 participants. Six studies used a simple parallel-group design; the other two consisted of an open-label treatment period followed by a randomised phase. All trials were well concealed for allocation and double-blind, however the sample sizes of most trials were small. All trials used placebo as control. We performed meta-analyses for some outcomes in patients with MS. For all other conditions, results are presented narratively.Two trials included patients with HD; one found that cholinesterase inhibitor use in the short-term had no statistically significant impact on the cognitive portion of the Alzheimer Disease Assessment Scale (ADAS-Cog; 1 study, WMD 1.00, 95% CI -1.66 to 3.66, P = 0.46; low quality evidence), Unified Huntington's Disease Rating Scale (UHDRS) Verbal Fluency Test (1 study, WMD -1.20, 95% CI -7.97 to 5.57, P = 0.73; low quality evidence), UHDRS Symbol Digit Modalities Test (SDMT; 1 study, WMD 2.70, 95% CI -0.95 to 6.35, P = 0.15; low quality evidence) and other psychometric tests. The other study found that cholinesterase inhibitor use in the medium-term improved the results of the verbal fluency test (1 study, WMD 6.43, 95% CI 0.66 to 12.20, P = 0.03; moderate quality evidence) and California Verbal Learning Test - Second Edition (CVLT-II) Recognition Task (1 study, WMD 2.42, 95% CI 0.17 to 4.67, P = 0.04; moderate quality evidence). There was no statistically significant difference between groups on the SDMT (1 study, WMD -0.31, 95% CI -7.77 to 7.15, P = 0.94; moderate quality evidence), CVLT-II trials 1-5 (1 study, WMD -2.09, 95% CI -11.65 to 7.47, P = 0.67; moderate quality evidence), short-delay recall (1 study, WMD 0.35, 95% CI -2.87 to 3.57, P = 0.83; moderate quality evidence), or long-delay recall (1 study, WMD -0.14, 95% CI -3.08 to 2.80, P = 0.93; moderate quality evidence), and other psychometric tests.Four trials included patients with MS; one found no differences between the cholinesterase inhibitors (short-term) and placebo groups on the Wechsler Memory Scales general memory score (1 study, WMD 0.90, 95% CI -0.52 to 2.32, P = 0.22; low quality evidence). The three other trials found that, in the medium-term - cholinesterase inhibitors improved the clinician's impression of cognitive change (2 studies, OR 1.96, 95% CI 1.06 to 3.62, P = 0.03; high quality evidence). However, the treatment effect on other aspects of cognitive change were unclear, measured by the Selective Reminding Test (3 studies, WMD 1.47, 95% CI -0.39 to 3.32, P = 0.12; high quality evidence), patient's self-reported impression of memory change (2 studies, OR 1.67, 95% CI 0.93 to 3.00, P = 0.08; high quality evidence) and cognitive change (1 study, OR 0.95, 95% CI 0.45 to 1.98, P = 0.89; high quality evidence), clinician's impression of memory change (1 study, OR 1.50, 95% CI 0.59 to 3.84, P = 0.39; moderate quality evidence), other psychometric tests, and activities of daily living - patient reported impact of multiple sclerosis activities (1 study, WMD -1.18, 95% CI -3.02 to 0.66, P = 0.21; low quality evidence).One study on patients with CADASIL found a beneficial effect of cholinesterase inhibitors on the Executive interview, and Trail Making Test parts A and B. The impact of cholinesterase inhibitors on the Vascular ADAS-Cog score (1 study, WMD 0.04, 95% CI -1.57 to 1.65, P = 0.96; high quality evidence), the Clinical Dementia Rating Scale Sum of Boxes (1 study, WMD -0.09, 95% CI -0.48 to 0.03, P = 0.65; high quality evidence) Disability Assessment for Dementia scale (1 study, WMD 0.58, 95% CI -2.72 to 3.88, P = 0.73; moderate quality evidence), and other measures was unclearOne study included patients with FTD. This trial consisted of an open-label treatment period followed by a randomised, double-blind, placebo-controlled phase. No data of primary outcomes were reported in this study.In the included studies, the most common side effect was gastrointestinal symptoms. For all conditions, compared to the treatment group, the placebo group experienced significantly less nausea (6 studies, 44/257 vs. 22/246, OR 2.10, 95% CI 1.22 to 3.62, P = 0.007; high quality evidence), diarrhoea (6 studies, 40/257 vs. 13/246, OR 3.26, 95% CI 1.72 to 6.19, P = 0.0003; moderate quality evidence) and vomiting (3 studies, 17/192 vs. 3/182, OR 5.76, 95% CI 1.67 to 19.87, P = 0.006; moderate quality evidence). The sample sizes of most included trials were small, and some of the results were extracted from only one study. There were no poolable data for HD, CADASIL and FTD patients and there were no results for patients with PSP. Current evidence shows that the efficacy on cognitive function and activities of daily living of cholinesterase inhibitors in people with HD, CADASIL, MS, PSP or FTD is unclear, although cholinesterase inhibitors are associated with more gastrointestinal side effects compared with placebo.


Occurrence, aetiology and challenges in the management of congestive heart failure in sub-Saharan Africa: experience of the Cardiac Centre in Shisong, Cameroon.
The aim of the study was to investigate the occurrence, the aetiology and the management of congestive heart failure in the cardiac centre of the St. Elizabeth catholic general hospital Shisong in Cameroon. Between November 2002 and November 2008, a population of 8121 patients was consulted in the referral cardiac centre of St. Elizabeth Catholic General Hospital. Of these patients, 462 were diagnosed with congestive heart failure according to the modified Framingham criteria for the diagnosis of heart failure. Complementary investigations used to confirm and establish the aetiology of the disease were the chest X-ray, electrocardiography, bi-dimensional Doppler echocardiography. The results showed that the occurrence of congestive heart failure in our centre was 5.7%. Congestive heart failure was diagnosed in 198 females and 264 males, aged between 8 and 86 years old (42.5±18 years old). Post rheumatic valvulopathies (14.6%) and congenital heart diseases (1.9%) were the first aetiologic factor of congestive heart failure in the young, meanwhile cardiomyopathies (8.3%) in elderly followed by hypertensive cardiomyopathy (4.4%). Congestive heart failure was also seen in adults with congenital heart diseases in 0.01%. In this zone of Cameroon, we discovered that HIV cardiomyopathy (1.6%) and Cor pulmonale (8%) were represented, aetiological factors not mentioned in previous studies conducted in urban areas of Cameroon. The mean duration of hospital stay for the compensation treatment was thirteen days, ranging between 7 and 21 days), the mortality being 9.2%. All the medications recommended for the treatment of congestive heart failure are available in our centre but many patients are not compliant to the therapy or cannot afford them. Financial limitation is causing the exacerbation of the disease and premature death. Our data show a high incidence of congestive heart failure mainly due to post rheumatic valvulopathies in young patients in our centre. National program to fight against rheumatic fever and complications are of great urgency in our country. The compensation treatment of congestive heart failure is challenging in our milieu, characterized by poor compliance and financial limitations.


Observing Interactions between Children and Adolescents and their Parents: The Effects of Anxiety Disorder and Age.
Parental behaviors, most notably overcontrol, lack of warmth and expressed anxiety, have been implicated in models of the development and maintenance of anxiety disorders in children and young people. Theories of normative development have proposed that different parental responses are required to support emotional development in childhood and adolescence, yet age has not typically been taken into account in studies of parenting and anxiety disorders. In order to identify whether associations between anxiety disorder status and parenting differ in children and adolescents, we compared observed behaviors of parents of children (7-10 years) and adolescents (13-16 years) with and without anxiety disorders (n = 120), while they undertook a series of mildly anxiety-provoking tasks. Parents of adolescents showed significantly lower levels of expressed anxiety, intrusiveness and warm engagement than parents of children. Furthermore, offspring age moderated the association between anxiety disorder status and parenting behaviors. Specifically, parents of adolescents with anxiety disorders showed higher intrusiveness and lower warm engagement than parents of non-anxious adolescents. A similar relationship between these parenting behaviors and anxiety disorder status was not observed among parents of children. The findings suggest that theoretical accounts of the role of parental behaviors in anxiety disorders in children and adolescents should distinguish between these different developmental periods. Further experimental research to establish causality, however, would be required before committing additional resources to targeting parenting factors within treatment.


Geographical and seasonal barriers to mammography services and breast cancer stage at diagnosis.
Routine mammography screening and early detection are important prognostic indicators for breast cancer. Geographical and seasonal barriers to mammography services and relationship to breast cancer stage at diagnosis were examined. Travel time to mammography center, seasonal distribution of mammogram use, mammography frequency, and stage of cancer were retrospectively examined in 1428 female patients diagnosed with primary breast cancer at a tertiary care clinic system in Wisconsin, USA, from 2002 to 2008. Women with no missed mammograms before diagnosis lived a median of 15 minutes from the nearest facility, while those who missed five of their past five annual mammograms lived nearly twice as far, with a median travel time of 27 minutes (p<0.0001). There was a direct relationship between travel time to nearest mammogram facility and stage of breast cancer at diagnosis, with travel time increasing from 17 to 24 minutes for stage 0 and stage 4 breast cancers, respectively (p=0.0586). Women were less likely to undergo mammography screening during the winter months (p<0.0001), especially women with greater than 30 mi (48.3 km) to travel to the nearest mammogram facility (p=0.0448). In the studied service area, travel time to nearest mammogram center appears inversely related to regular mammography screening and breast cancer stage at diagnosis. Mammograms are less common in the winter, especially in women with further to travel. This is the first study to demonstrate that inclement winter weather may impact on screening behaviors in rural areas and demonstrates the importance of considering climate as part of geographical access to preventative care.


Conscientious objection and reproductive health service delivery in sub-Saharan Africa.
Lack of access to quality reproductive health services is the main contributor to the high maternal mortality and morbidity in sub-Saharan Africa (SSA). This is partly due to a shortage of qualified and experienced health care providers. However conscientious objection amongst the available few is a hitherto undocumented potential factor influencing access to health care in SSA. Provision of certain reproductive health services goes counter to some individual's religious and moral beliefs and practices. Health providers sometimes refuse to participate in or provide such services to clients/patients on moral and/or religious grounds. While the rights to do so are protected by the principles of freedom of religion, among other documents, their refusal exposes clients/patients to the risk of reproductive health morbidity as well as mortality. Such providers are required to refer the clients/patients to other equally qualified and experienced providers who do not hold similar conscientious objection. Access to high quality and evidence-based reproductive health services by all in need is critical to attaining MDG5. In addressing factors contributing to delay in attaining MDG5 in SSA it is instructive to consider the role of conscientious objection in influencing access to quality reproductive health care services and strategies to address it.


Data sharing by scientists: practices and perceptions.
Scientific research in the 21st century is more data intensive and collaborative than in the past. It is important to study the data practices of researchers--data accessibility, discovery, re-use, preservation and, particularly, data sharing. Data sharing is a valuable part of the scientific method allowing for verification of results and extending research from prior results. A total of 1329 scientists participated in this survey exploring current data sharing practices and perceptions of the barriers and enablers of data sharing. Scientists do not make their data electronically available to others for various reasons, including insufficient time and lack of funding. Most respondents are satisfied with their current processes for the initial and short-term parts of the data or research lifecycle (collecting their research data; searching for, describing or cataloging, analyzing, and short-term storage of their data) but are not satisfied with long-term data preservation. Many organizations do not provide support to their researchers for data management both in the short- and long-term. If certain conditions are met (such as formal citation and sharing reprints) respondents agree they are willing to share their data. There are also significant differences and approaches in data management practices based on primary funding agency, subject discipline, age, work focus, and world region. Barriers to effective data sharing and preservation are deeply rooted in the practices and culture of the research process as well as the researchers themselves. New mandates for data management plans from NSF and other federal agencies and world-wide attention to the need to share and preserve data could lead to changes. Large scale programs, such as the NSF-sponsored DataNET (including projects like DataONE) will both bring attention and resources to the issue and make it easier for scientists to apply sound data management principles.


Clinical picture of primary HIV infection presenting as a glandular-fever-like illness.
The clinical symptoms and signs were assessed in 20 consecutive patients developing infection with the human immunodeficiency virus (HIV). All were male homosexuals and all presented with a glandular-fever-like illness. Changes in laboratory values were compared with findings in 40 HIV negative male homosexual controls. In the 10 patients for whom date of exposure to the virus could be established the incubation period was 11-28 days (median 14). One or two days after the sudden onset of fever patients developed sore throat, lymphadenopathy, rash, lethargy, coated tongue, tonsillar hypertrophy, dry cough, headache, myalgia, conjunctivitis, vomiting, night sweats, nausea, diarrhoea, and palatal enanthema. Twelve patients had painful, shallow ulcers in the mouth or on the genitals or anus or as manifested by oesophageal symptoms; these ulcers may have been the site of entry of the virus. During the first week after the onset of symptoms mild leucopenia, thrombocytopenia, and increased numbers of banded neutrophils were detected (p less than 0.0005). The mean duration of acute illness was 12.7 days (range 5-44). All patients remained healthy during a mean follow up period of 2.5 years. Heightened awareness of the typical clinical picture in patients developing primary HIV infection will alert the physician at an early stage and so aid prompt diagnosis and help contain the epidemic spread of AIDS.


Improved anti-inflammatory effects in rabbit eye model using biodegradable poly beta-amino ester nanoparticles of triamcinolone acetonide.
Results of previous studies on the benefits of ocular drug delivery using polymeric mucoadhesive nanoparticles suggested longer presence and better penetration of nanoparticles, and, thus, increased effect and bioavailability of drugs entrapped in nanoparticles. In this study, a novel polymer, poly β-amino ester, was used for the preparation of triamcinolone acetonide-loaded nanoparticles using a modified emulsification/solvent diffusion method. Mucoadhesiveness studies, in vitro drug release, x-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy were used for physicochemical characterization of nanoparticles. Thirty-six hours after inducing uveitis by intravitreal injection of a lipopolysaccharide, sampling from the aqueous humor was done and inflammatory factors, such as cell, protein, nitric oxide, and prostaglandin E2, were compared. Nanoparticles with a mean size of 178 nm and drug loading of 5.3% were prepared and used for in vivo studies in rabbits with uveitis. Higher anti-inflammatory effect was observed for polymeric nanoparticles of triamcinolone acetonide compared with microparticles of prednisolone acetate and triamcinolone acetonide, and an equal effect compared with subconjunctival injection of triamcinolone acetonide in terms of inhibiting inflammation and inflammatory mediators. It can be concluded that polymeric nanoparticles of triamcinolone acetonide will provide as good an anti-inflammatory effect as the subconjunctival injection method and are better compared with other drug delivery systems.


Elevation of interleukin-10 levels in malignant pleural effusion.
Human immunity has been found to have two major components, cellular and humoral immunity. T-helper type 1 (Th1) pathway favors cellular immunity and Th2 pathway favors humoral immunity. Early determination toward Th1 and Th2 cells in the immune response is dependent on the balance between interleukin-12 (IL-12), which favors Th1 responses, and IL-4, which favors Th2 responses. IL-2 and interferon-gamma (IFN-gamma) are produced in the Th1 pathway, and IL-4 and IL-10 are produced in the Th2 pathway. Lack of cellular immunity, IL-2, and IFN-gamma had been reported in malignant pleural effusions. However, to our knowledge, there are no previous reports on other cytokine components involving Th1 or Th2 pathway. The present study was designed to answer these questions. Cytokine levels in peripheral blood and pleural fluid of 21 patients with malignant pleural effusion, including IL-4, IL-10, and IL-12, were analyzed with enzyme-linked immunosorbent assays. Lymphocyte subpopulations of peripheral blood and pleural effusion were also studied by using flow cytometry. The results showed a significant increase in IL-10 level as compared with blood samples. IL-4 and IL-12 were below minimal detectable concentrations both in the blood and the effusion. The ratio of pleural helper T cells was significantly higher than in the blood (p = 0.0002). The ratio of pleural natural killer (NK) cells was significantly lower than in the blood (p = 0.0001). The ratio of pleural suppressor T cells was lower than blood with borderline significance (p = 0.0522). No significant change in B-lymphocyte ratio between blood and pleural effusion was found (p = 0.2471). There was no correlation between difference in IL-10 level and lymphocyte subpopulation of pleural effusion and blood samples. Helper T-cell subpopulations were increased while NK and suppressor T-cell subpopulations were decreased in malignant pleural effusions. The decrease in NK cell subpopulations with elevated IL-10 and minimal IL-12 concentration in neoplastic pleural effusion would suggest the usage of IL-12 or antibody of IL-10 to improve local cellular immunity. Further study is needed.


Colombo Twin and Singleton Study (CoTASS): a description of a population based twin study of mental disorders in Sri Lanka.
The Sri Lankan twin registry is one of the first to be established in a developing country, and its design has ensured sampling from a wide range of environmental conditions. It thus has great potential to examine environmental and genetic influences on diverse phenotypes, including psychiatric disorders, in the context of a diversity of environmental exposures, which may not have been fully explored in previous twin studies in developed countries. This paper presents the rationale for the study, describes its context, and the methods for twin ascertainment and data collection. A population-based twin register was established in the Colombo district of Sri Lanka using infrastructure designed to periodically update the electoral register. We invited a subsample from this register to participate in the project on common mental disorders, using random ascertainment. A separate non-twin sample was randomly selected from the geographical areas where twins were found. Home interviewers collected diagnostic information on common mental disorders, as well as environmental exposures including life events, socio-economic conditions, and the impact of the civil war and the Tsunami of 2004. We identified 19,302 individuals in the creation of the population based twin register. We randomly selected a subsample, of whom 4,387 were eligible to participate and 4,024 agreed to be interviewed (including data on 1,954 complete pairs of twins and 5 sets of triplets). Those who refused consent had a similar mean age and sex ratio to those who were interviewed. We invited 2,485 singletons to participate and 2,019 were interviewed. Initial exploration of the data suggests the samples are very representative of the Colombo district of Sri Lanka, so we have created a unique resource for understanding the influences on mental disorders in developing countries, and to compare to the influences found in developed countries.


Patterns and implications of MR contrast enhancement in perinatal asphyxia: a preliminary report.
To determine the presence and location of MR contrast enhancement in infants with perinatal asphyxia and to evaluate the utility of enhancement in assessing extent of brain damage. Precontrast and postcontrast MR examinations within the first 10 days of life were evaluated in 10 infants with suspected hypoxic-ischemic birth injury. Findings were correlated with clinical birth history and short-term neurologic follow-up. All four infants with MR signal abnormalities and contrast enhancement in the basal ganglia and brain stem had early seizures and profound neurologic deficits at early follow-up. Two infants had abnormal scans but no contrast enhancement; one with MR signal abnormality within the basal ganglia is neurologically healthy at 10-month follow-up, whereas the other, in status epilepticus at the time of imaging at age 2 days, died. Two infants with minimal parasagittal subcortical white matter enhancement had no early seizure activity and only mild developmental delay at early follow-up. Two infants with normal precontrast and postcontrast MR had no early seizures and remain healthy at early follow-up, despite initial clinical parameters similar to more severely injured infants. Although the number of patients is small, our results indicate that the presence of contrast enhancement in asphyxiated neonates may indicate more severe brain damage and, hence, a poorer prognosis.


Measurement of Single-Molecule Forces in Cholesterol and Cyclodextrin Host-Guest Complexes.
Biological host molecules such as β-cyclodextrins (β-CDs) have been used to remove cholesterol guests from membranes and artery plaques. In this work, we calibrated the host-guest intermolecular mechanical forces (IMMFs) between cholesterol and cyclodextrin complexes by combining single-molecule force spectroscopy in optical tweezers and computational molecular simulations for the first time. Compared to native β-CD, methylated beta cyclodextrins complexed with cholesterols demonstrated higher mechanical stabilities due to the loss of more high-energy water molecules inside the methylated β-CD cavities. This result is consistent with the finding that methylated β-CD is more potent at solubilizing cholesterols than β-CD, suggesting that the IMMF can serve as a novel indicator to evaluate the solubility of small molecules such as cholesterols. Importantly, we found that the force spectroscopy measured in such biological host-guest complexes is direction-dependent: pulling from the alkyl end of the cholesterol molecule resulted in a larger IMMF than that from the hydroxyl end of the cholesterol molecule. Molecular dynamics coupled with umbrella sampling simulations further revealed that cholesterol molecules tend to enter or leave from the wide opening of cyclodextrins. Such an orientation rationalizes that cyclodextrins are rather efficient at extracting cholesterols from the phospholipid bilayer in which hydroxyl groups of cholesterols are readily exposed to the hydrophobic cavities of cyclodextrins. We anticipate that the IMMF measured by both experimental and computational force spectroscopy measurements help elucidate solubility mechanisms not only for cholesterols in different environments but also to host-guest systems in general, which have been widely exploited for their solubilization properties in drug delivery, for example.


Increased prevalence of Helicobacter pylori antibodies among nurses.
Numerous studies have suggested that Helicobacter pylori infection in asymptomatic subjects is transmitted from person to person. Its prevalence is higher in the institutionalized setting. If that is the case, persons involved in patient care should have a higher prevalence of the infection. We estimated the prevalence of H pylori antibodies among groups of asymptomatic medical and nursing staff and compared them with volunteer blood donors of similar age and sex. One hundred fifty-eight nurses and aides, 59 residents, 46 senior medical students, and 22 senior nursing students were enrolled in this study. Serum samples were tested for IgG antibodies against H pylori by enzyme-linked immunosorbent assay. Sixty-two (39%) of 158 nurses were found to be positive for antibodies to H pylori compared with 114 (26%) of 441 specimens from the blood donor group. Within the youngest age group (20 to 34 years), 13 (25%) of 51 nurses were positive for H pylori antibodies compared with 19 (13%) of 143 age-matched serum samples from the blood donor group. Within the middle age group (35 to 49 years), 32 (39%) of 83 nurses were positive for H pylori antibodies vs 43 (26%) of 167 age-matched blood donors. In the oldest age group (> 50 years), 17 (71%) of 24 nurses were positive for H pylori antibodies compared with 52 (40%) of 131 age-matched blood donors. Twenty-three (27%) of 86 nurses with 1 to 15 years of occupational exposure were positive for H pylori antibodies compared with 40 (56%) of 72 nurses with more than 15 years of occupational exposure. Nurses have an increased prevalence of H pylori antibodies that is significantly higher than the comparable prevalence of volunteer blood donors and is evident in the youngest age group. In addition, the increased prevalence is related to a longer duration of patient exposure in the nursing group.


Toward a harmonized approach to animal welfare law in Canada.
Animal protection law in Canada varies across the country. Federal animal protection law exists in the Criminal Code, in regulations for the transport of animals, and in regulations for humane handling and slaughter at abattoirs that are inspected by the Canadian Food Inspection Agency. Provincial animal protection laws often include provisions that i) describe a duty of care toward animals; ii) prohibit causing or permitting animal "distress;" iii) specify exemptions from prosecution; and iv) reference various national and other standards. Inconsistencies lead to duplication of effort, create difficulty in working across jurisdictions, and may erode public trust. A more consistent approach might be achieved by i) referencing a common suite of standards in provincial statutes; ii) citing the federal transport and humane slaughter regulations in provincial regulations; iii) establishing agreements so provincial authorities may enforce federal regulations; iv) wider and more uniform adoption of enforcement tools that require people to take immediate action to protect animal welfare; v) developing new standards; and vi) national consultation to define frequently used terms.


Lower Female Genital Tract Tumors With Adenoid Cystic Differentiation: P16 Expression and High-risk HPV Detection.
Lower female genital tract tumors with adenoid cystic differentiation are rare, and data on their relationship with high-risk human papillomavirus (HPV) are limited. Here we report the clinicopathologic features from a case series. Tumors with adenoid cystic differentiation, either pure or as part of a carcinoma with mixed differentiation, arising in the lower female genital tract were evaluated by means of immunohistochemical analysis for p16 expression and in situ hybridization using 1 or more probes for high-risk HPV (a high-risk probe covering multiple types, a wide-spectrum probe, and separate type-specific probes for HPV16 and HPV18) and when possible by polymerase chain reaction for high-risk HPV. Six cervical carcinomas with adenoid cystic differentiation admixed with various combinations of at least 1 other pattern of differentiation, including adenoid basal tumor (epithelioma and/or carcinoma), squamous cell carcinoma (basaloid or keratinizing), and small cell carcinoma were identified in patients ranging in age from 50 to 86 years (mean, 73 y; median, 76 y). All of these tumors were characterized by diffuse p16 expression. High-risk HPV was detected in 5 of 6 tested cases: 4 cases by in situ hybridization (all positive for HPV-wide-spectrum and HPV16) and 1 by polymerase chain reaction (HPV45). Seven pure adenoid cystic carcinomas (6 vulvar and 1 cervical) were identified in patients ranging in age from 27 to 74 years (mean, 48 y; median, 48 y). All of these tumors were characterized by variable p16 expression ranging from very limited to more extensive but never diffuse. No high-risk HPV was detected in any of these pure tumors. Lower female genital tract carcinomas with adenoid cystic differentiation appear to comprise 2 pathogenetically distinct groups. Cervical carcinomas with mixed differentiation, including adenoid cystic, adenoid basal, squamous, and small cell components, are etiologically related to high-risk HPV and can be identified by diffuse p16 expression. Pure vulvar and cervical adenoid cystic carcinomas appear to be unrelated to high-risk HPV and are distinguished from the mixed carcinomas by nondiffuse p16 expression.


Pyogenic brain abscess.
Brain abscesses have been one of the most challenging lesions, both for surgeons and internists. From the beginning of the computed tomography (CT) era, the diagnosis and treatment of these entities have become easier and less invasive. The outcomes have become better with the improvement of diagnostic techniques, neurosurgery, and broad-spectrum antibiotics. Atypical bacterial abscesses are more often due to chemotherapy usage in oncology, long life expectancy in patients with human immunodeficiency virus (HIV) infection, and immunosuppression in conjunction with organ transplantation. Surgical treatment options showed no significant difference with respect to mortality levels, but lower morbidity rates were achieved with stereotactically guided aspiration. Decompression with stereotactically guided aspiration, antibiotic therapy based on results of pus culture, and repeated aspirations if indicated from results of periodic CT follow-up scans seem to be the most appropriate treatment modality for brain abscesses. Immunosuppression and comorbidities, initial neurological status, and intraventricular rupture were significant factors influencing the outcomes of patients. The pitfalls and evolution in the diagnosis and treatment of brain abscesses are discussed in this study.


Insight into the Pathophysiologic Mechanisms behind Cognitive Dysfunction in Trigonocephaly.
The relationship between trigonocephaly and cognitive problems might be explained by: secondary mechanical factors related to growth restriction of the skull, and primary structural defects caused by a shared mechanism related to brain developmental disorder(s) and skull malformation. However, because the exact pathophysiology remains unknown, we examined the pathophysiologic mechanisms behind cognitive dysfunction in patients with trigonocephaly, with an aim of providing a model for cognitive dysfunction based on routinely available variables. Included were 72 patients with trigonocephaly who were operated on. Postoperatively, intelligence was assessed prospectively. The two independent variables, secondary mechanical and primary brain developmental mechanisms, were evaluated retrospectively. Computed tomographic imaging was used to assess skull volume and severity of the frontal stenosis (secondary mechanical factors), width of the central part of the lateral ventricles, and other structural brain anomalies (primary brain developmental factors). Extracranial congenital anomalies were also taken into account. No association was found between secondary mechanical factors and postoperative IQ score. Width of the central part of the lateral ventricles, and an interaction effect between this width and additional extracranial anomalies, showed a significant negative association with postoperative IQ. Primary brain developmental disorders seem to play an important role in the development of cognitive problems in trigonocephaly. Assessment of width of the central part of the lateral ventricle scores and additional extracranial congenital anomalies for the early prediction of cognitive problems in patients with trigonocephaly could be clinically valuable and can be performed using routinely available tools.


Albumin influences sulfobromophthalein transport by hepatocytes of each acinar zone.
To determine whether profiles of decreasing concentration were generated among hepatocytes of the liver acinus during the transport of sulfobromophthalein sodium (BSP), rat livers were perfused with various concentrations of this dye (10 microM to 1 mM) in the presence and absence of albumin. After steady-state conditions for the biliary secretion of BSP had been attained, pieces of liver were rapidly frozen. Following the alkalinization of cryostat-cut sections, the relative concentration of BSP in hepatocytes of each zone and the effect of albumin on this localization were quantitated by microspectrophotometry. The results showed that BSP, perfused in the absence of albumin, was efficiently extracted by the liver (95% on a single pass), generating distinct profiles of decreasing cellular concentration from zone 1 to zone 3 at every concentration of BSP. However, the addition of albumin to the perfusate greatly reduced the extraction of BSP from the sinusoidal compartment and resulted in the abolition of the differences in BSP content between hepatocytes of zone 1 and zone 3. These results represent a direct demonstration that, as predicted by mathematical modeling, binding of BSP to albumin indeed results in a more homogeneous distribution of BSP within the liver acinus. A simple and direct microspectrophotometric method is therefore available to follow the changes in the relative concentration of BSP among the hepatocytes of the various acinar zones.


Phase constraint for the waves diffracted by lossless symmetrical gratings at Littrow mount.
The energy conservation of grating diffraction is analyzed in a particular condition of incidence in which two incident waves reach a symmetrical grating from the two sides of the grating normal at the first-order Littrow mounting. In such a situation the incident waves generate an interference pattern with the same period as the grating. Thus in each direction of diffraction, interference occurs between two consecutive diffractive orders of the symmetrical incident waves. By applying only energy conservation and the geometrical symmetry of the grating profile to this problem it is possible to establish a general constraint for the phases and amplitudes of the diffracted orders of the same incident wave. Experimental and theoretical results are presented confirming the obtained relations.


Left atrial volume combined with atrial pump function identifies hypertensive patients with a history of paroxysmal atrial fibrillation.
Identifying patients at high risk for the occurrence of atrial fibrillation is one means by which subsequent thromboembolic complications may be prevented. Left atrial enlargement is associated with progression of atrial remodeling, which is a substrate for atrial fibrillation, but impaired atrial pump function is also another aspect of the remodeling. Our objective was to differentiate patients with a history of paroxysmal atrial fibrillation using echocardiography. We studied 280 hypertensive patients (age: 66+/-7 years; left ventricular ejection fraction: 65+/-8%), including 140 consecutive patients with paroxysmal atrial fibrillation and 140 age- and sex-matched control subjects. Left atrial volume was measured using the modified Simpson method at both left ventricular end systole and preatrial contraction and was indexed to body surface area. Peak late-diastolic mitral annular velocity was measured during atrial contraction using pulsed tissue Doppler imaging as an atrial pump function. Left atrial volume index measured at left ventricular end systole had a 74% diagnostic accuracy and a 71% positive predictive value for identifying patients with paroxysmal atrial fibrillation; these values for the ratio of left atrial volume index at left ventricular end systole to the peak late-diastolic mitral annular velocity were 82% and 81%, respectively, and those for the ratio of left atrial volume index at preatrial contraction to the peak late-diastolic mitral annular velocity were 86% and 90%, respectively. In conclusion, left atrial size combined with atrial pump function enabled a more accurate diagnosis of a history of paroxysmal atrial fibrillation than conventional parameters.


The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.
Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health.


The influence of culture on breast-feeding decisions by African American and white women.
The purpose of this study was to examine how culture influenced breast-feeding decisions in African American and white women, using the Theory of Culture Care Diversity and Universality as a framework. One hundred eighty-six participants responded to the following: The word culture means beliefs and traditions passed down by your family and friends. How has culture affected how you plan to feed your baby? Qualitative content analysis was used to analyze the data. Four categories of responses were identified: influences of family, known benefits of breast-feeding, influences of friends, and personal choice. The findings suggest that race alone may not be as influential in infant feeding decisions as other factors. Although some women acknowledged the effect of their cultural background and experiences, most women reported that their culture did not affect their infant feeding decision. In this population, breast-feeding decisions were based on the influences of family, friends, self, and the perceived knowledge of breast-feeding benefits. Although breast-feeding statistics are commonly reported by race, cultural influences on infant feeding decisions may transcend race and include the influence of family and friends, learned information from impersonal sources, and information that is shared and observed from other people.


Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders.
Exposure to prenatal infection has been suggested to cause deficiencies in fetal neurodevelopment. In this study we included all children born in Denmark from 1980, through 2005. Diagnoses of autism spectrum disorders (ASDs) and maternal infection were obtained through nationwide registers. Data was analyzed using Cox proportional hazards regression. No association was found between any maternal infection and diagnosis of ASDs in the child when looking at the total period of pregnancy: adjusted hazard ratio = 1.14 (CI: 0.96-1.34). However, admission to hospital due to maternal viral infection in the first trimester and maternal bacterial infection in the second trimester were found to be associated with diagnosis of ASDs in the offspring, adjusted hazard ratio = 2.98 (CI: 1.29-7.15) and adjusted hazard ratio = 1.42 (CI: 1.08-1.87), respectively. Our results support prior hypotheses concerning early prenatal viral infection increasing the risk of ASDs.


How the parallel channels of the retina contribute to depth processing.
Reconstructing the third dimension in the visual scene from the two dimensional images that impinge on the retinal surface is one of the major tasks of the visual system. We have devised a visual display that makes it possible to study stereoscopic depth cues and motion parallax cues separately or in concert using rhesus macaques. By varying the spatial frequency of the display and its luminance and chrominance, it is possible to selectively activate channels that originate in the primate retina. Our results show that (i) the parasol system plays a central role in processing motion parallax cues; (ii) the midget system plays a central role in stereoscopic depth perception at high spatial frequencies, and (iii) red/green colour selective neurons can effectively process both cues but blue/yellow neurons cannot do so.


Different types of dietary advice for women with gestational diabetes mellitus.
Gestational diabetes mellitus (GDM) affects a significant number of women each year and is associated with a wide range of adverse outcomes for women and their babies. Dietary counselling is the main strategy in managing GDM, but it remains unclear which dietary therapy is best. To assess the effects of different types of dietary advice for women with GDM on pregnancy outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 May 2012) and the WOMBAT Perinatal Trials Registry (17 April 2012). Randomised controlled trials (RCTs) and cluster-RCTs assessing the effects of different types of dietary advice for women with GDM on pregnancy outcomes.We intended to compare two or more forms of the same type of dietary advice against each other, i.e. standard dietary advice compared with individualised dietary advice, individual dietary education sessions compared with group dietary education sessions. We intended to compare different intensities of dietary intervention with each other, i.e. single dietary counselling session compared with multiple dietary counselling sessions. Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included studies. Data were checked for accuracy. We included nine trials; 429 women (436 babies) provided outcome data. All nine included trials had small sample sizes with variation in levels of risk of bias. A total of 11 different types of dietary advice were assessed under six different comparisons, including:low-moderate glycaemic index (GI) food versus high-moderate GI food, low-GI diet versus high-fibre moderate-GI diet, energy-restricted diet versus no energy restriction diet, low-carbohydrate diet (≤ 45% daily total energy intake from carbohydrate) versus high-carbohydrate diet (≥ 50% daily total energy intake from carbohydrate), high-monounsaturated fat diet (at least 20% total energy from monounsaturated fat) versus high-carbohydrate diet (at least 50% total energy from carbohydrate), standard-fibre diet (American Diabetes Association (ADA) diet) (20 grams fibre/day) versus fibre-enriched diet (80 grams fibre/day).In the low-moderate GI food versus moderate-high GI food comparison, no significant differences were seen for macrosomia or large-for-gestational age (LGA), (two trials, 89 babies) (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.10 to 2.08), (RR 0.95, 95% CI 0.27 to 3.36), respectively; or caesarean section (RR 0.66, 95% CI 0.29 to 1.47, one trial, 63 women).In the low-GI diet versus high-fibre moderate-GI diet comparison, no significant differences were seen for macrosomia or LGA (one trial, 92 babies) (RR 0.32, 95% CI 0.03 to 2.96), (RR 2.87, 95% CI 0.61 to 13.50), respectively; or caesarean section (RR 1.80, 95% CI 0.66 to 4.94, one trial, 88 women).In the energy-restricted versus unrestricted diet comparison, no significant differences were seen for macrosomia (RR 1.56, 95% CI 0.61 to 3.94, one trial, 122 babies); LGA (RR 1.17, 95% CI 0.65 to 2.12, one trial, 123 babies); or caesarean section (RR 1.18, 95% CI 0.74 to 1.89, one trial, 121 women).In the low- versus high-carbohydrate diet comparison, none of the 30 babies in a single trial were macrosomic; and no significant differences in caesarean section rates were seen (RR 1.40, 95% CI 0.57 to 3.43, one trial, 30 women).In the high-monounsaturated fat versus high-carbohydrate diet comparison, neither macrosomia or LGA (one trial 27 babies) (RR 0.65, 95% CI 0.91 to 2.18), (RR 0.54 95% CI 0.21 to 1.37), respectively showed significant differences. Women having a high-monounsaturated fat diet had a significantly higher body mass index (BMI) at birth (mean difference (MD) 3.90 kg/m², 95% CI 2.41 to 5.39, one trial, 27 women) and at six to nine months postpartum (MD 4.10 kg/m², 95% CI 2.34 to 5.86, one trial, 27 women) when compared with those having a high-carbohydrate diet. However, these findings were based on a single, small RCT with baseline imbalance in maternal BMI.Perinatal mortality was reported in only trial which recorded no fetal deaths in either the energy- restricted or unrestricted diet group.A single trial comparing ADA diet (20 grams gram fibre/day) with fibre-enriched fibre enriched diet (80 grams gram fibre/day) did not report any of our prespecified primary outcomes.Very limited data were reported on the prespecified outcomes for each of the six comparisons. Only one trial reported on early postnatal outcomes. No trial reported long-term health outcomes for women and their babies. No data were reported on health service cost or women's quality of life. Data for most comparisons were only available from single studies and they are too small for reliable conclusions about which types of dietary advice are the most suitable for women with GDM. Based on the current available evidence, we did not find any significant benefits of the diets investigated.Further larger trials with sufficient power to assess the effects of different diets for women with GDM on maternal and infant health outcomes are needed. Outcomes such as longer-term health outcomes for women and their babies, women's quality of life and health service cost should be included.


Heart rate variability in adolescents: relations to physical activity, fitness, and adiposity.
We determined the degree to which variation in cardiac autonomic modulation was explained by race, sex, moderate-vigorous physical activity (MVPA), cardiovascular fitness (CVF), percent body fat (%BF), waist girth, subcutaneous abdominal adipose tissue (SAAT), and visceral adipose tissue (VAT). Subjects were 304 adolescents; SAAT and VAT values were available for 168 youths. Cardiac parasympathetic modulation (PM) was the root mean square of successive differences (RMSSD). Sympathetic-parasympathetic balance was the ratio of low- to high-frequency power (LFnu:HFnu). MVPA was measured with accelerometry, CVF with a treadmill, %BF with dual-energy x-ray absorptiometry (DXA), and SAAT and VAT with magnetic resonance imaging (MRI). Root mean square of successive differences was higher, and LFnu:HFnu was lower, in blacks than in whites. The final regression model revealed positive relations with CVF and MVPA, and a %BF by race by sex interaction, such that higher %BF was associated with lower RMSSD in black females and higher RMSSD in white females. Higher RMSSD was associated with lower VAT; for SAAT, the relationship was negative for blacks and positive for whites. For LFnu:Hfnu, a negative relationship was seen with MVPA and higher waist girth was associated with a higher ratio in blacks, but not in whites. Both higher VAT and SAAT were related to higher LFnu:HFnu. Black youths had a more favorable HRV profile than white youths. After controlling for age, race, and sex, more favorable HRV profiles were associated with more MVPA, better CVF, and less visceral and subcutaneous adiposity. The deleterious impact of higher adiposity was greater in blacks, especially females, than in whites. Enhancement of cardiac autonomic modulation may be a pathway through which physical activity, fitness, and leanness contribute to cardiovascular health early in life.


Engineering silica particles as oral drug delivery vehicles.
Porous silica particles are emerging as complementary systems to polyester microspheres for the encapsulation and controlled delivery of small-organic drugs. Their recent application in pharmaceutics is strengthened by well-established characterization and synthetic routes from the chemical engineering sciences. Silica is an interesting scaffold material for the encapsulation of organic molecules. It can be formed into hierarchical structures over a wide range of length scales and interconnectivities. Encapsulation can therefore be tailored not only to the drug but the desired release properties. In addition to surfactant-templating of hierarchical silica structures, polypeptides from marine organisms may offer biological routes to novel silica materials. Silica sol-gels have also been evaluated as delivery vehicles, particularly with regard to generating hybrid systems with mesoporous silica or composite xerogels. This review will first focus on the detailed characterisation of pore size and structure of mesoporous silica with regards water penetration and drug diffusion. We then describe the pharmaceutical applications of silica materials with regard to improving oral bioavailability, multiparticulate systems for gastroretention or sustained release, composite xerogels and in vivo biocompatibility.


Cognitive dysfunction in elderly females with depressive symptoms.
A depressive state is a common symptom in the elderly and often accompanies cognitive impairment. The coexistence of depressive symptoms and cognitive impairment is a serious problem, as it increases adverse outcomes for health, functional status, and mortality. It would thus be of great value to clarify the cognitive dysfunction associated with depressive symptoms. We aimed to identify the cognitive dysfunction, in particular, impairment of the response inhibition component of executive function, associated with depressive symptoms in elderly females using the Simple Color Reaction Test and Modified Stroop Color-Word Test. The study group consisted of 35 elderly women. They performed cognitive function task trials for 9 min. Univariate logistic regression analyses were performed to identify factors associated with the prevalence of the depressive state. Longer reaction time and lower correction rate of response inhibition trials were related to the prevalence of the depressive symptoms. Impaired function of response inhibition may be a specific feature of the depressive state. Our findings may help clarify the neural mechanisms underlying the depressive state of elderly females.


Weak-noise limit of a piecewise-smooth stochastic differential equation.
We investigate the validity and accuracy of weak-noise (saddle-point or instanton) approximations for piecewise-smooth stochastic differential equations (SDEs), taking as an illustrative example a piecewise-constant SDE, which serves as a simple model of Brownian motion with solid friction. For this model, we show that the weak-noise approximation of the path integral correctly reproduces the known propagator of the SDE at lowest order in the noise power, as well as the main features of the exact propagator with higher-order corrections, provided the singularity of the path integral associated with the nonsmooth SDE is treated with some heuristics. We also show that, as in the case of smooth SDEs, the deterministic paths of the noiseless system correctly describe the behavior of the nonsmooth SDE in the low-noise limit. Finally, we consider a smooth regularization of the piecewise-constant SDE and study to what extent this regularization can rectify some of the problems encountered when dealing with discontinuous drifts and singularities in SDEs.


The effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts.
Previous studies have shown that the number of myoblastically differentiated fibroblasts known as myofibroblasts (MFs) is significantly increased in stiff joint capsules, indicating their crucial role in the pathogenesis of post-traumatic joint stiffness. Although the mode of MFs' function has been well defined for different diseases associated with tissue fibrosis, the underlying mechanisms of their regulation in the pathogenesis of post-traumatic joint capsule contracture are largely unknown. In this study, we examined the impact of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) on cellular functions of human joint capsule MFs. MFs were challenged with different concentrations of TNF-alpha with or without both its specifically inactivating antibody infliximab (IFX) and cyclooxygenase-2 (COX2) inhibitor diclofenac. Cell proliferation, gene expression of both alpha-smooth muscle actin (alpha-SMA) and collagen type I, the synthesis of prostaglandin derivates E2, F1A, and F2A, as well as the ability to contract the extracellular matrix were assayed in monolayers and in a three-dimensional collagen gel contraction model. The alpha-SMA and COX2 protein expressions were evaluated by immunofluorescence staining and Western blot analysis. The results indicate that TNF-alpha promotes cell viability and proliferation of MFs, but significantly inhibits the contraction of the extracellular matrix in a dose-dependent manner. This effect was associated with downregulation of alpha-SMA and collagen type I by TNF-alpha application. Furthermore, we found a significant time-dependent upregulation of prostaglandin E2 synthesis upon TNF-alpha treatment. The effect of TNF-alpha on COX2-positive MFs could be specifically prevented by IFX and partially reduced by the COX2 inhibitor diclofenac. Our results provide evidence that TNF-alpha specifically modulates the function of MFs through regulation of prostaglandin E2 synthesis and therefore may play a crucial role in the pathogenesis of joint capsule contractures.


Paediatric meningitis in the western Cape. A 3-year hospital-based prospective survey.
Between July 1981 and June 1984 1223 cases of meningitis were seen in the Department of Paediatrics, Tygerberg Hospital. The commonest form in each population group was aseptic meningitis. Positive viral cultures were obtained from the CSF in 108 cases. The median age of white children with aseptic meningitis, 64 months, was significantly greater than that of coloured children, 45 months (P greater than 0.0001), and black children, 26 months (P greater than 0.014). The commonest cause of confirmed bacterial meningitis was Neisseria meningitidis (140 cases; 11.5%), which continues to affect mainly young coloured children (median age 16.9 months). Resistance to sulphonamides was found among 21% of 114 N. meningitidis isolates. Among white children Haemophilus influenzae was responsible for 9 of the 18 cases of confirmed bacterial meningitis. Tuberculosis was responsible for 62 cases of meningitis (5%) and was a commoner cause of meningitis than either H. influenzae (47 cases) or Streptococcus pneumoniae (34 cases). Thirty-four confirmed cases of bacterial meningitis were seen in children less than 1 month old. Klebsiella species were responsible for 8 cases (24%), Escherichia coli for 6 cases (12%), group B beta-haemolytic Streptococcus for 5 cases (15%) while 4 cases each were due to N. meningitidis and Strept. pneumoniae.


Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons.
Topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] is a structurally novel antiepileptic drug that has broad efficacy in epilepsy, but the mechanisms underlying its therapeutic activity are not fully understood. We have found that topiramate selectively inhibits GluK1 (GluR5) kainate receptor-mediated excitatory postsynaptic responses in rat basolateral amygdala (BLA) principal neurons and protects against seizures induced by the GluK1 kainate receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA). Here, we demonstrate that topiramate also modulates inhibitory function in the BLA. Using whole-cell recordings in rat amygdala slices, we found that 0.3 to 10 microM topiramate 1) inhibited ATPA-evoked postsynaptic currents recorded from BLA interneurons; 2) suppressed ATPA-induced enhancement of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from BLA pyramidal cells; and 3) blocked ATPA-induced suppression of evoked IPSCs, which is mediated by presynaptic GluK1 kainate receptors present on BLA interneurons. Topiramate (10 microM) had no effect on the AMPA [(R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid]-induced enhancement of spontaneous activity of BLA neurons. Thus, although topiramate inhibits GluK1 kainate receptor-mediated enhancement of interneuron firing, it promotes evoked GABA release, leading to a net inhibition of circuit excitability. In addition, we found that topiramate (0.3-10 microM) increased the amplitude of evoked, spontaneous, and miniature IPSCs in BLA pyramidal neurons, indicating an enhancement of postsynaptic GABA(A) receptor responses. Taken together with our previous findings, we conclude that topiramate protects against hyperexcitability in the BLA by suppressing the GluK1 kainate receptor-mediated excitation of principal neurons by glutamatergic afferents, blocking the suppression of GABA release from interneurons mediated by presynaptic GluK1 kainate receptors and directly enhancing GABA(A) receptor-mediated inhibitory currents.


A role for mitogen-activated protein kinase in mediating activation of the glycoprotein hormone alpha-subunit promoter by gonadotropin-releasing hormone.
Gonadotropin-releasing hormone (GnRH) interacts with a G protein-coupled receptor and increases the transcription of the glycoprotein hormone alpha-subunit gene. We have explored the possibility that mitogen-activated protein kinase (MAPK) plays a role in mediating GnRH effects on transcription. Activation of the MAPK cascade by an expression vector for a constitutively active form of the Raf-1 kinase led to stimulation of the alpha-subunit promoter in a concentration-dependent manner. GnRH treatment was found to increase the phosphorylation of tyrosine residues of MAPK and to increase MAPK activity, as determined by an immune complex kinase assay. A reporter gene assay using the MAPK-responsive, carboxy-terminal domain of the Elk1 transcription factor was also consistent with GnRH-induced activation of MAPK. Interference with the MAPK pathway by expression vectors for kinase-defective MAPKs or vectors encoding MAPK phosphatases reduced the transcription-stimulating effects of GnRH. The DNA sequences which are required for responses to GnRH include an Ets factor-binding site. An expression vector for a dominant negative form of Ets-2 was able to reduce GnRH effects on expression of the alpha-subunit gene. These findings provide evidence that GnRH treatment leads to activation of the MAPK cascade in gonadotropes and that activation of MAPK contributes to stimulation of the alpha-subunit promoter. It is likely that an Ets factor serves as a downstream transcriptional effector of MAPK in this system.


2D label-free imaging of resonant grating biochips in ultraviolet.
2D images of label-free biochips exploiting resonant waveguide grating (RWG) are presented. They indicate sensitivities on the order of 1 pg/mm2 for proteins in air, and hence 10 pg/mm2 in water can be safely expected. A 320x256 pixels Aluminum-Gallium-Nitride-based sensor array is used, with an intrinsic narrow spectral window centered at 280 nm. The additional role of characteristic biological layer absorption at this wavelength is calculated, and regimes revealing its impact are discussed. Experimentally, the resonance of a chip coated with protein is revealed and the sensitivity evaluated through angular spectroscopy and imaging. In addition to a sensitivity similar to surface plasmon resonance (SPR), the RWGs resonance can be flexibly tailored to gain spatial, biochemical, or spectral sensitivity.


Myelodysplastic Syndrome with concomitant t(5;21)(q15;q22) and del(5)(q13q33): case report and review of literature.
Chromosomal abnormalities lead to the development of hematologic malignancies such as Myelodysplastic Syndrome (MDS). Known chromosomal changes causing MDS include deletion of the long arm of chromosome 5, runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1), and very rarely fusion genes involving RUNX1 at t(5;21)(q15;q22). We present a case of a 71-year-old female with MDS, refractory anemia with excess blasts, type 1, with a combination of two cytogenetic abnormalities, specifically a concomitant translocation between chromosomes 5q15 and 21q22 and deletion of chromosome 5q13q33. Fluorescence in-situ hybridization (FISH) using a probe for RUNX1 (AML1), localized to 21q22, showed three FISH signals for RUNX1, consistent with rearrangement of RUNX1. Therapy was started with Lenalidomide leading to normal blood counts. Most significantly, repeat cytogenetics revealed normal karyotype and resolution of deletion on the long arm of chromosome 5 and a t(5;21). FISH negative for deletion 5q. The results altogether meet criteria for a complete cytogenetic remission (CR). We report a new case of t(5;21)(q15;q22) involving the RUNX1 gene and del(5)(q13q33) in a MDS patient, a combination of chromosomal abnormalities heretofore not reported in the literature. RUNX1 rearrangement is usually associated with an adverse prognosis in AML and MDS. Deletions of 5q are typically associated with poor prognosis in AML, however it is usually associated with a favorable prognosis in MDS. Our patient responded very well to Lenalidomide therapy with achievement of CR. Lenalidomide is approved for treatment of anemia in low and intermediate risk MDS with del (5q), however based on a search of literature it seems that RUNX1 mutations are also more prominent in patients who have responded to Lenalidomide therapy. MDS is a genomically unstable disease. Hence, it is conceivable that our patient started with a 5q minus syndrome and then acquired the second hit RUNX1 translocation leading to an accelerated phase of myeloid neoplasm or refractory anemia with excess blasts, type 1. Hence, the temporal relationship between acquisition of del 5q and RUNX1 rearrangement may have influenced the clinical outcome and possibly response to therapy.


PUBLIC AND PATIENT INVOLVEMENT IN HEALTH TECHNOLOGY ASSESSMENT: A FRAMEWORK FOR ACTION.
As health technology assessment (HTA) organizations in Canada and around the world seek to involve the public and patients in their activities, frameworks to guide decisions about whom to involve, through which mechanisms, and at what stages of the HTA process have been lacking. The aim of this study was to describe the development and outputs of a comprehensive framework for involving the public and patients in a government agency's HTA process. The framework was informed by a synthesis of international practice and published literature, a dialogue with local, national and international stakeholders, and the deliberations of a government agency's public engagement subcommittee in Ontario, Canada. The practice and literature synthesis failed to identify a single, optimal approach to involving the public and patients in HTA. Choice of methods should be considered in the context of each HTA stage, goals for incorporating societal and/or patient perspectives into the process, and relevant societal and/or patient values at stake. The resulting framework is structured around four actionable elements: (i) guiding principles and goals for public and patient involvement (PPI) in HTA, (ii) the establishment of a common language to support PPI efforts, (iii) a flexible array of PPI approaches, and (iv) on-going evaluation of PPI to inform adjustments over time. A public and patient involvement framework has been developed for implementation in a government agency's HTA process. Core elements of this framework may apply to other organizations responsible for HTA and health system quality improvement.


Na⁺ ions as spatial intracellular messengers for co-ordinating Ca²⁺ signals during pH heterogeneity in cardiomyocytes.
Contraction of the heart is regulated by electrically evoked Ca(2+) transients (CaTs). H(+) ions, the end products of metabolism, modulate CaTs through direct interactions with Ca(2+)-handling proteins and via Na(+)-mediated coupling between acid-extruding proteins (e.g. Na(+)/H(+) exchange, NHE1) and Na(+)/Ca(2+) exchange. Restricted H(+) diffusivity in cytoplasm predisposes pH-sensitive Ca(2+) signalling to becoming non-uniform, but the involvement of readily diffusible intracellular Na(+) ions may provide a means for combatting this. CaTs were imaged in fluo3-loaded rat ventricular myocytes paced at 2 Hz. Cytoplasmic [Na(+)] ([Na(+)]i) was imaged using SBFI. Intracellular acidification by acetate exposure raised diastolic and systolic [Ca(2+)] (also observed with acid-loading by ammonium prepulse or CO₂ exposure). The systolic [Ca(2+)] response correlated with a rise in [Na(+)]i and sarcoplasmic reticulum Ca(2+) load, and was blocked by the NHE1 inhibitor cariporide (CO₂/HCO₃(-)-free media). Exposure of one half of a myocyte to acetate using dual microperfusion (CO₂/HCO₃(-)-free media) raised diastolic [Ca(2+)] locally in the acidified region. Systolic [Ca(2+)] and CaT amplitude increased more uniformly along the length of the cell, but only when NHE1 was functional. Cytoplasmic Na(+) diffusivity (DNa) was measured in quiescent cells, with strophanthidin present to inhibit the Na(+)/K(+) pump. With regional acetate exposure to activate a local NHE-driven Na(+)-influx, DNa was found to be sufficiently fast (680 µm(2)/s) for transmitting the pH-systolic Ca(2+) interaction over long distances. Na(+) ions are rapidly diffusible messengers that expand the spatial scale of cytoplasmic pH-CaT interactions, helping to co-ordinate global Ca(2+) signalling during conditions of intracellular pH non-uniformity.


[Free oxygen radiacals and kidney diseases--part I].
ADVERSE EFFECTS OF OXYGEN: Adverse effect of oxygen on anaerobes implies oxidation of the basic cell constituents NAD(P)H, thiols, iron-sulphur proteins, pteridines and others) and inactivation of the essential components of the active site of enzymes. Oxygen can also adversely affect the aerobes, especially if long-term influence is taken into consideration, while exposition to high-pressure oxygen causes considerable damages. Direct influence of oxygen on aerobes due to slow and limited enzyme inactivation (for example glutamate decarboxylase) and small number of affected "targets" is not responsible for total adverse effects of oxygen. Even in 1954 it was supposed that oxygen free radicals are the most responsible for the adverse effects of oxygen. ATMOSPHERIC (TRIPLET) OXYGEN: Electron configuration of triplet oxygen explains its reactivity since it is a biradical. The reactions of oxygen with non-radicals are possible with participation of transition metals (except zinc), while its reactivity is much more expressed in case of reactions with other radical species. ACTIVE OXYGEN: More reactive forms of oxygen, known as singlet oxygen, can be generated by an input of energy to triplet oxygen. Singlet-oxygen is obtained mainly by photoexcitation in the presence of initiators (methylene blue, chlorophyll etc.) and as a product of reactions of ozone with certain biomolecules. REDUCED FORMS OF OXYGEN: If a single electron is added to the triplet oxygen, it must enter one of the antibonding molecular orbitals and produce the superoxide radical--(O2.-). Addition of one more electron produces peroxide ion--O2(2-), which forms hydro peroxide in presence of H+, the most common two-electron reduction product of oxygen in biological systems. The four-reduction product of oxygen in biological systems is water. SUPEROXIDE RADICAL: The in vivo production of superoxide radical is possible in many different ways mentioned in this paper. This radical species is unstable in water solutions because of dismutation reaction leading to non-enzymic generation of hydroperoxide. The most reactive radical species--hydroxyl radical is produced from hydro peroxide by Fenton or Haber-Weiss reactions in the presence of catalytic transition metals (iron or copper). HYDROXYL RADICAL: Hydroxyl radicals are the most reactive radical species. The way of their generation has been shown in detail in this paper with special emphasis given to Fenton and Haber-Weiss reactions, that is, transition metals (iron and copper) as catalizators for these reactions. The reactivity of hydroxyl radical can be recognized by monitoring the second-order rate constants for reactions of the hydroxyl radical with some organic compounds in aqueous solution presented in this paper. Although the number of compounds that can be affected and damaged by hydroxyl radicals is great, until now, attention has been paid mostly to investigation of attacks of these radical species on lipids, proteins and DNA. LIPID PEROXIDATION: Radicals react with lipids and cause oxidative destruction of unsaturated, that is, polyunsaturated fatty acids, known as lipid peroxidation. Both lipids in biological systems and lipids as food constituents are submitted to this process. Lipid peroxidation is a chain reaction and its mechanism has been shown in detail in this paper. Lipid peroxidation in cells leads to direct damage of cell membranes with indirect damages of other cell constituents, caused by reactivity of secondary products of this reaction, aldehydes. This complex reaction is responsible for damages of many tissues and progress of some diseases (atherosclerosis). OXIDATIVE STRESS: Protection of an organism from oxygen free radicals implies activity of enzymatic (catalase, SOD, glutathione peroxidase, glutathione reductase etc.) and nonenzymatic (vitamin E. vitamin C. glutathione, uric acid etc.) systems of protection. Disturbance of the balance between production of oxygen free radicals (or some other radical species) and activity of antioxidative system of protection causes the so called oxidative stress. An organism can tolerate a mild oxidative stress but a higher disturbance between the production of free radicals and the activity of the antioxidative protection results in lipid protein and DNA as well as numerous diseases.


Herbicide loading to shallow ground water beneath Nebraska's Management Systems Evaluation Area.
Better management practices can counter deterioration of ground water quality. From 1991 through 1996 the influence of improved irrigation practices on ground water pesticide contamination was assessed at the Nebraska Management Systems Evaluation Area. Three 13.4-ha corn (Zea mays L.) fields were studied: a conventional furrow-irrigated field, a surge-irrigated field and a center pivot-irrigated field, and a center pivot-irrigated alfalfa (Medicago sativa L.) field. The corn fields received one identical banded application of Bicep (atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4,-diamine] + metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamidel) annually; the alfalfa field was untreated. Ground water samples were collected three times annually from 16 depths of 31 multilevel samplers. Six years of sample data indicated that a greater than 50% reduction in irrigation water on the corn management fields lowered average atrazine concentrations in the upper 1.5 m of the aquifer downgradient of the corn fields from approximately 5.5 to <0.5 microg L(-1). Increases in deethylatrazine (DEA; 2-chloro-4-amino-6-isopropylamino-s-triazine) to atrazine molar ratios indicated that reducing water applications enhanced microbial degradation of atrazine in soil zones. The occurrence of peak herbicide loading in ground water was unpredictable but usually was associated with heavy precipitation within days of herbicide application. Focused recharge of storm runoff that ponded in the surge-irrigated field drainage ditch, in the upgradient road ditch, and at the downgradient end of the conventionally irrigated field was a major mechanism for vertical transport. Sprinkler irrigation technology limited areas for focused recharge and promoted significantly more soil microbial degradation of atrazine than furrow irrigation techniques and, thereby, improved ground water quality.


Standardization of the Prosody in Use Battery (PUB): a speech prosody perception test in Danish.
Assessment of prosody perception may be useful in a number of clinical scenarios, including the rehabilitation of cochlear implant recipients. It is with this group in mind that we have derived and standardized a battery of tests that assess speech prosody perception in the Danish language. The prosodic contrasts included in the battery are vowel length, compounds and phrases, emotions, questions and statements, prominence and pronoun reference, all of which are commonly encountered in everyday communication. Lists of candidate stimuli were compiled and recorded by a representative speaker of Danish. All candidate stimuli were presented to normal hearing subjects (n = 12) in both unprocessed and 8-channel noise vocoded conditions. Subjects performed closed-set identification and the results were used to derive the final stimulus set. We report the results of the six subtests, in which we observed a bias to compounds in the compound/phrase subtest, and to statements in question/statement subtest. The pronoun reference subtest assessed the ability of a listener to infer a referent from the stress status of a pronoun, and we found high accuracy rates on this task indicating that it is suitable for inclusion in the battery. We discuss the possible uses of the Prosody in Use Battery in cochlear implant mapping and device verification. We also consider the role of the results from the test battery in guiding clinicians to material suitable for aural rehabilitation.


Quantification of rotational thallium-201 myocardial tomography.
A comprehensive method is described for quantification of the relative 3-dimensional distribution of Tl-201 in the myocardium, following stress and subsequent washout. The method uses maximal-count circumferential profiles of well-defined long- and short-axis tomograms to determine the 3-dimensional distribution of Tl-201; it then maps this distribution onto a 2-dimensional polar representation. Abnormal thallium distribution or washout is identified by automatic computer comparison of each patient's profile with the corresponding lower limits of normal profiles. Abnormality is expressed as a percentage of the entire myocardium by use of polar maps for extent and severity. The binary extent map expresses the degree of abnormality. Preliminary criteria for abnormality were derived from the tomographic results of 25 normals and 28 patients with documented coronary artery disease. The results were normal in 23 of the 25 normals and were abnormal in 25 of the 28 CAD patients. In addition, the computer output correctly localized the presence or absence of disease in 46 of 56 coronary circulations.


Pulmonary nocardiosis due to Nocardia farcinica in a renal transplant recipient.
Nocardia farcinica is an infrequent cause of nocardiosis among the renal transplant recipients and it has not been reported so far from India. We report a case of pulmonary nocardiosis due to N. farcinica in a 32-year-old woman with hypothyroidism and post-renal transplant status, currently on immunosuppressive therapy (prednisolone, azathioprine and tacrolimus). The N. farcinica isolate was susceptible to trimethoprim-sulfamethoxazole (TMP-SMZ), linezolid, imipenem, gentamicin but resistant to ceftriaxone, ciprofloxacin, tobramycin, erythromycin, amoxycillin-clavulanic acid and tetracycline. Treatment with TMP-SMZ and linezolid resulted in marked clinico-radiological improvement but after two weeks both of the drugs had to be stopped due to severe pancytopenia as adverse effect of their use. Currently, the patient is on imipenem and remains stable after four weeks of treatment. In N. farcinica infections, multi antibiotic resistance and toxicity of some specific drugs enhances the risk of therapeutic failure in renal transplant recipients.


Simulated physician learning program improves glucose control in adults with diabetes.
Inexpensive and standardized methods to deliver medical education to primary care physicians (PCPs) are desirable. Our objective was to assess the impact of an individualized simulated learning intervention on diabetes care provided by PCPs. Eleven clinics with 41 consenting PCPs in a Minnesota medical group were randomized to receive or not receive the learning intervention. Each intervention PCP was assigned 12 simulated type 2 diabetes cases that took about 15 min each to complete. Cases were designed to remedy specific physician deficits found in their electronic medical record observed practice patterns. General linear mixed models that accommodated the cluster randomized study design were used to assess patient-level change from preintervention to 12-month postintervention of A1C, blood pressure, and LDL cholesterol. The relationship between the study arm and the total of intervention and patient health care costs was also analyzed. Intervention clinic patients with baseline A1C >or=7% significantly improved glycemic control at the last postintervention A1C measurement, intervention effect of -0.19% mean A1C (P = 0.034) and +6.7% in A1C <7% goal achievement (P = 0.0099). Costs trended lower, with the cost per patient -$71 (SE = 142, P = 0.63) relative to nonintervention clinic patients. The intervention did not significantly improve blood pressure or LDL control. Models adjusting for age, sex, and comorbidity showed similar results. PCPs reported high satisfaction. A brief individualized case-based simulated learning intervention for PCPs led to modest but significant glucose control improvement in adults with type 2 diabetes without increasing costs.


The timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.
Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immunity and play a crucial role in the first phase of host defense against infections and tumors. Listeria monocytogenes (Lm) is an intracellular pathogen that colonizes the cytosol of eukaryotic cells. Recent findings have shown Lm specifically in splenic CD8a(+) DCs shortly after intravenous infection. We examined gene expression profiles of mouse DCs exposed to Lm to elucidate the molecular mechanisms underlying DCs interaction with Lm. Using a functional genomics approach, we found that Lm infection induced a cluster of late response genes including type I IFNs and interferon responsive genes (IRGs) in DCs. Type I INFs were produced at the maximal level only at 24 h post infection indicating that the regulation of IFNs in the context of Lm infection is delayed compared to the rapid response observed with viral pathogens. We showed that during Lm infection, IFNγ production and cytotoxic activity were severely impaired in NK cells compared to E. coli infection. These defects were restored by providing an exogenous source of IFNβ during the initial phase of bacterial challenge. Moreover, when treated with IFNβ during early infection, NK cells were able to reduce bacterial titer in the spleen and significantly improve survival of infected mice. These findings show that the timing of IFNβ production is fundamental to the efficient control of the bacterium during the early innate phase of Lm infection.


Combined effect of volumetric breast density and body mass index on breast cancer risk.
Breast density and body mass index (BMI) are used for breast cancer risk stratification. We evaluate whether the positive association between volumetric breast density and breast cancer risk is strengthened with increasing BMI. The San Francisco Mammography Registry and Mayo Clinic Rochester identified 781 premenopausal and 1850 postmenopausal women with breast cancer diagnosed between 2007 and 2015 that had a screening digital mammogram at least 6 months prior to diagnosis. Up to three controls (N = 3535) were matched per case on age, race, date, mammography machine, and state. Volumetric percent density (VPD) and dense volume (DV) were measured with Volpara™. Breast cancer risk was assessed with logistic regression stratified by menopause status. Multiplicative interaction tests assessed whether the association of density measures was differential by BMI categories. The increased risk of breast cancer associated with VPD was strengthened with higher BMI for both premenopausal (pinteraction = 0.01) and postmenopausal (pinteraction = 0.0003) women. For BMI < 25, 25-30, and ≥ 30 kg/m2, ORs for breast cancer for a 1 SD increase in VPD were 1.24, 1.65, and 1.97 for premenopausal, and 1.20, 1.55, and 2.25 for postmenopausal women, respectively. ORs for breast cancer for a 1 SD increase in DV were 1.39, 1.33, and 1.51 for premenopausal (pinteraction = 0.58), and 1.31, 1.34, and 1.65 (pinteraction = 0.03) for postmenopausal women for BMI < 25, 25-30 and ≥ 30 kg/m2, respectively. The effect of volumetric percent density on breast cancer risk is strongest in overweight and obese women. These associations have clinical relevance for informing prevention strategies.


Assessment of data quality in an international multi-centre randomised trial of coronary artery surgery.
ART is a multi-centre randomised trial of cardiac surgery which provided a unique opportunity to evaluate the data from a large number of centres from a variety of countries. We attempted to assess data quality, including recruitment rates, timeliness and completeness of the data obtained from the centres in different socio-economic strata. The analysis was based on the 2-page CRF completed at the 6 week follow-up. CRF pages were categorised into "clean" (no edit query) and "dirty" (any incomplete, inconsistent or illegible data). The timelines were assessed on the basis of the time interval from the visit and receipt of complete CRF. Data quality was defined as the number of data queries (in percent) and time delay (in days) between visit and receipt of correct data. Analyses were stratified according to the World Bank definitions into: "Developing" countries (Poland, Brazil and India) and "Developed" (Italy, UK, Austria and Australia). There were 18 centres in the "Developed" and 10 centres in the "Developing" countries. The rate of enrolment did not differ significantly by economic level ("Developing":4.1 persons/month, "Developed":3.7 persons/month). The time interval for the receipt of data was longer for "Developing" countries (median:37 days) compared to "Developed" ones (median:11 days) (p < 0.001). The median number of data queries was 23% in "Developed" countries compared to 19% in "Developing" ones (p = ns). In this study we showed that data quality was comparable between centres from "Developed" and "Developing" countries. Data was received in a less timely fashion from Developing countries and appropriate systems should be instigated to minimize any delays. Close attention should be paid to the training of centres and to the central management of data quality. ISRCTN46552265.


Knowledge and attitude of the population toward cancer prostate Riyadh, Saudi Arabia.
The aim of the following study is to assess the knowledge and attitude of men, in our region, regarding cancer prostate and its screening practices. The field work was conducted in Riyadh City, during the period February through July 2011. It was a population - based cross-sectional study comprising 400 men over 40 years. In addition to socio-demographic data, history of the present and past medical illness, history of prostatic diseases and examination, family history of cancer prostate; participants were inquired about their knowledge and attitude toward prostate cancer (PC) and screening behavior using through two different Likert scales. Only 10% of the respondents had practiced a regular PC examination checkup. Their knowledge about PC was poor and their attitude toward examination and screening was fair, where the mean of total correct knowledge score was 10.25 ± 2.5 (51.25%), while the mean of total attitude score was 18.3 ± 4.08 (65.3%). The respondents identified the physicians as the main sources of this information (62.4%), though they were not the main motives for a regular checkup. Knowledge represented the only significant predictor for participants' attitude. Beliefs and attitudes have a great impact, at every stage of the cancer continuum, this attitudes depends mainly on level of knowledge and quantity of information provided to patients and their families. Such attitudes should rely on a solid background of proper information and motivation from physicians to enhance and empower attitudes toward PC screening behavior.


Characteristics of Escherichia coli strains belonging to enteropathogenic E. coli serogroups isolated in Italy from children with diarrhea.
Fifty-five Escherichia coli strains belonging to enteropathogenic E. coli (EPEC) serogroups were examined for phenotypic and genetic factors associated with virulence. The strains were isolated in Italy from children with diarrhea and identified as EPEC by clinical laboratories using commercially available antisera. O:H serotyping showed that 35 strains (27 of O26, O111, and O128 serogroups) belonged to 11 serotypes considered to be classical EPEC O:H serotypes. The other 20 isolates were classified as 15 nonclassical EPEC O:H serotypes. All the potential EPEC virulence factors associated with bacterial adhesion (localized adherence, fluorescentactin staining test positivity, presence of the attaching and effacing [eaeA] gene), the production of verotoxin, and the positivity with the enterohemorrhagic E. coli probe were significantly more frequent among isolates belonging to classical than nonclassical serotypes. Strains displaying an aggregative adhesion and hybridizing with the enteroaggregative DNA probe were found in serogroups O86, O111, and O126. Verotoxin-producing isolates belonged to serogroups O26, O111, and O128. Only one of the isolates hybridized with the EPEC adherence factor (EAF) probe, but 33 strains gave positive results with the eae probe, confirming that the former is more suitable in epidemiological studies in European countries. These results indicate that up to 75% of strains identified as EPEC by commercial antisera may possess potential virulence properties and/or belong to classical EPEC O:H serotypes and suggest that O grouping is still a useful diagnostic tool for presumptive identification of diarrheagenic E. coli in clinical laboratories.