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    Schistosomiasis and Urinary Bladder Cancer in North Western Tanzania: A Retrospective Review of 185 Patients.

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    Worldwide, cancers of the urinary bladder are well known to be associated with environmental chemical carcinogens such as smoking and occupational exposure to polycyclic aromatic hydrocarbons. These cancers are typically transitional cell carcinoma (urothelial carcinoma). In areas where schistosomiasis is endemic there is a high incidence of squamous cell carcinoma of the urinary bladder. Schistosomiasis causes chronic granulomatous cystitis leading to squamous metaplasia of transitional epithelium, and subsequently development of squamous cell carcinoma. The western part of Tanzania on the shores of Lake Victoria is such an endemic area. This study was done to document the burden of urinary bladder cancer associated with schistosomiasis in this region. This was a descriptive retrospective study of histologically confirmed cases of urinary bladder cancer seen at the Department of Pathology Bugando Medical Centre (BMC) over a period of 10 years. Data were retrieved from the records of the Departments of Pathology, Medical Records and Surgery. Data were analyzed by the use of contingency tables. A total of 185 patients were diagnosed with cancer of the urinary bladder during the study period, where as 90 (48.6%) were males and 95 (51.4) were females. The mean age at diagnosis was 54.3 years. Squamous cell carcinoma was the most frequent histological type (55.1%), followed by conventional transitional cell carcinoma (40.5%). Eighty three of all cancer cases (44.9%) were found to have schistosomal eggs. Schistosomiasis was commonly associated with squamous cancers compared to non squamous cancers. Most of the cancers associated with schistosomiasis had invaded the muscularis propria of the urinary bladder at the time of diagnosis (p<0.001) and such cancers were frequent below 50 years of age with a significant statistical difference (p<0.001). Poorly differentiated tumors were more frequent in females than males with a significant statistical difference (p=0.006). The majority of urinary bladder cancers seen in the Lake Region were squamous cell carcinoma associated with schistosomiasis. These cancers showed an aggressive behavior and were commonly seen in the younger age groups. Effective control of schistosomiasis in this region should significantly reduce the burden of urinary bladder cancer

    Optimization of Cell Morphology Measurement via Single-Molecule Tracking PALM

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    In neurons, the shape of dendritic spines relates to synapse function, which is rapidly altered during experience-dependent neural plasticity. The small size of spines makes detailed measurement of their morphology in living cells best suited to super-resolution imaging techniques. The distribution of molecular positions mapped via live-cell Photoactivated Localization Microscopy (PALM) is a powerful approach, but molecular motion complicates this analysis and can degrade overall resolution of the morphological reconstruction. Nevertheless, the motion is of additional interest because tracking single molecules provides diffusion coefficients, bound fraction, and other key functional parameters. We used Monte Carlo simulations to examine features of single-molecule tracking of practical utility for the simultaneous determination of cell morphology. We find that the accuracy of determining both distance and angle of motion depend heavily on the precision with which molecules are localized. Strikingly, diffusion within a bounded region resulted in an inward bias of localizations away from the edges, inaccurately reflecting the region structure. This inward bias additionally resulted in a counterintuitive reduction of measured diffusion coefficient for fast-moving molecules; this effect was accentuated by the long camera exposures typically used in single-molecule tracking. Thus, accurate determination of cell morphology from rapidly moving molecules requires the use of short integration times within each image to minimize artifacts caused by motion during image acquisition. Sequential imaging of neuronal processes using excitation pulses of either 2 ms or 10 ms within imaging frames confirmed this: processes appeared erroneously thinner when imaged using the longer excitation pulse. Using this pulsed excitation approach, we show that PALM can be used to image spine and spine neck morphology in living neurons. These results clarify a number of issues involved in interpretation of single-molecule data in living cells and provide a method to minimize artifacts in single-molecule experiments

    Investigating Sub-Spine Actin Dynamics in Rat Hippocampal Neurons with Super-Resolution Optical Imaging

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    Morphological changes in dendritic spines represent an important mechanism for synaptic plasticity which is postulated to underlie the vital cognitive phenomena of learning and memory. These morphological changes are driven by the dynamic actin cytoskeleton that is present in dendritic spines. The study of actin dynamics in these spines traditionally has been hindered by the small size of the spine. In this study, we utilize a photo-activation localization microscopy (PALM)–based single-molecule tracking technique to analyze F-actin movements with ∼30-nm resolution in cultured hippocampal neurons. We were able to observe the kinematic (physical motion of actin filaments, i.e., retrograde flow) and kinetic (F-actin turn-over) dynamics of F-actin at the single-filament level in dendritic spines. We found that F-actin in dendritic spines exhibits highly heterogeneous kinematic dynamics at the individual filament level, with simultaneous actin flows in both retrograde and anterograde directions. At the ensemble level, movements of filaments integrate into a net retrograde flow of ∼138 nm/min. These results suggest a weakly polarized F-actin network that consists of mostly short filaments in dendritic spines

    Do Characteristics of Faces That Convey Trustworthiness and Dominance Underlie Perceptions of Criminality?

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    BACKGROUND: This study tested whether the 2D face evaluation model proposed by Oosterhof and Todorov can parsimoniously account for why some faces are perceived as more criminal-looking than others. The 2D model proposes that trust and dominance are spontaneously evaluated from features of faces. These evaluations have adaptive significance from an evolutionary standpoint because they indicate whether someone should be approached or avoided. METHOD: Participants rated the emotional state, personality traits, and criminal appearance of faces shown in photographs. The photographs were of males and females taken under naturalistic conditions (i.e., police mugshots) and highly controlled conditions. In the controlled photographs, the emotion display of the actor was systematically varied (happy expression, emotionally neutral expression, or angry expression). RESULTS: Both male and female faces rated high in criminal appearance were perceived as less trustworthy and more dominant in police mugshots as well as in photographs taken under highly controlled conditions. Additionally, emotionally neutral faces were deemed as less trustworthy if they were perceived as angry, and more dominant if they were morphologically mature. Systematically varying emotion displays also affected criminality ratings, with angry faces perceived as the most criminal, followed by neutral faces and then happy faces. CONCLUSION: The 2D model parsimoniously accounts for criminality perceptions. This study extends past research by demonstrating that morphological features that signal high dominance and low trustworthiness can also signal high criminality. Spontaneous evaluations regarding criminal propensity may have adaptive value in that they may help us to avoid someone who is physically threatening. On the other hand, such evaluations could inappropriately influence decision making in criminal identification lineups. Hence, additional research is needed to discover whether and how people can avoid making evaluations regarding criminality from a person's facial appearance

    Routine clinical cardiovascular magnetic resonance in paediatric and adult congenital heart disease: patients, protocols, questions asked and contributions made

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    <p>Abstract</p> <p>Background</p> <p>Cardiovascular Magnetic Resonance (CMR) of patients with congenital heart disease (CHD) has become routine clinical practice. However, existing CMR protocols focus predominantly on patients with ischemic heart disease, and information is limited on the types of patient with CHD who benefit from CMR investigation, and in what ways. Therefore the aim of this study was to answer the questions: What type of patients were studied by CMR in a centre specializing in paediatric and adult CHD management? What questions were asked, which protocols were used and were the questions successfully answered? To answer these questions, we conducted a cohort study of all 362 patients that received routine clinical CMR during 2007 at the Department of Paediatric Cardiology and Congenital Heart Disease at the Deutsches Herzzentrum München.</p> <p>Results</p> <p>Underlying diagnosis was in 33% Fallot's tetralogy, 17% aortic coarctation, 8% Ebstein's disease, 6% Marfan's disease, 4% single ventricle with Fontan-like circulation, and 32% others. Median age was 26 years (7 days – 75 years). Ventricular volumes were assessed in 67% of the patients; flow in 74%; unknown anatomy only in 9%; specific individual morphology of known anatomy in 83%; myocardial fibrosis in 8%; stress-induced myocardial perfusion defects in 1%. Only in 3% of the cases the question could not be fully answered.</p> <p>Conclusion</p> <p>Contrary to common belief, routine CMR of patients with CHD was not requested to address global anatomical questions so much as to clarify specific questions of morphology and function of known anatomy. The CMR protocols used differed markedly from those widely used in patients with ischemic heart disease.</p

    Abnormal social reward processing in autism as indexed by pupillary responses to happy faces

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    Background: Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods: We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results: Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions: We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli

    Ideal and actual involvement of community pharmacists in health promotion and prevention: a cross-sectional study in Quebec, Canada

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    <p>Abstract</p> <p>Background</p> <p>An increased interest is observed in broadening community pharmacists' role in public health. To date, little information has been gathered in Canada on community pharmacists' perceptions of their role in health promotion and prevention; however, such data are essential to the development of public-health programs in community pharmacy. A cross-sectional study was therefore conducted to explore the perceptions of community pharmacists in urban and semi-urban areas regarding their ideal and actual levels of involvement in providing health-promotion and prevention services and the barriers to such involvement.</p> <p>Methods</p> <p>Using a five-step modified Dillman's tailored design method, a questionnaire with 28 multiple-choice or open-ended questions (11 pages plus a cover letter) was mailed to a random sample of 1,250 pharmacists out of 1,887 community pharmacists practicing in Montreal (Quebec, Canada) and surrounding areas. It included questions on pharmacists' ideal level of involvement in providing health-promotion and preventive services; which services were actually offered in their pharmacy, the employees involved, the frequency, and duration of the services; the barriers to the provision of these services in community pharmacy; their opinion regarding the most appropriate health professionals to provide them; and the characteristics of pharmacists, pharmacies and their clientele.</p> <p>Results</p> <p>In all, 571 out of 1,234 (46.3%) eligible community pharmacists completed and returned the questionnaire. Most believed they should be very involved in health promotion and prevention, particularly in smoking cessation (84.3%); screening for hypertension (81.8%), diabetes (76.0%) and dyslipidemia (56.9%); and sexual health (61.7% to 89.1%); however, fewer respondents reported actually being very involved in providing such services (5.7% [lifestyle, including smoking cessation], 44.5%, 34.8%, 6.5% and 19.3%, respectively). The main barriers to the provision of these services in current practice were lack of: time (86.1%), coordination with other health care professionals (61.1%), staff or resources (57.2%), financial compensation (50.8%), and clinical tools (45.5%).</p> <p>Conclusions</p> <p>Although community pharmacists think they should play a significant role in health promotion and prevention, they recognize a wide gap between their ideal and actual levels of involvement. The efficient integration of primary-care pharmacists and pharmacies into public health cannot be envisioned without addressing important organizational barriers.</p
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