Island species richness increases with habitat diversity.
Species richness is commonly thought to increase with habitat diversity. However, a recent theoretical model aiming to unify niche and island biogeography theories predicted a hump-shaped relationship between richness and habitat diversity. Given the contradiction between model results and previous knowledge, we examine whether the relationship between species richness and habitat diversity is consistently monotonically increasing and under which circumstances, if at all, such relationships could be hump shaped. We review the empirical evidence about the shape of such relationships and show that species richness on islands usually increases with habitat diversity and that it never decreases. We also critically examine the assumptions of the theoretical model and modify them to incorporate a less restrictive definition of niche width. The modified assumptions lead to simulations that better capture real patterns, using either simple parameters or observed distributions of niche breadth. Further work is needed to incorporate ecological interactions and metacommunity dynamics if the aim is to merge niche and island biogeography theories in a realistic modeling framework.


Using conjoint analysis to measure the acceptability of rectal microbicides among men who have sex with men in four South American cities.
Conjoint Analysis (CJA), a statistical market-based technique that assesses the value consumers place on product characteristics, may be used to predict acceptability of hypothetical products. Rectal Microbicides (RM)-substances that would prevent HIV infection during receptive anal intercourse-will require acceptability data from potential users in multiple settings to inform the development process by providing valuable information on desirable product characteristics and issues surrounding potential barriers to product use. This study applied CJA to explore the acceptability of eight different hypothetical RM among 128 MSM in Lima and Iquitos, Peru; Guayaquil, Ecuador; and Rio de Janeiro, Brazil. Overall RM acceptability was highest in Guayaquil and lowest in Rio. Product effectiveness had the greatest impact on acceptability in all four cities, but the impact of other product characteristics varied by city. This study demonstrates that MSM from the same region but from different cities place different values on RM characteristics that could impact uptake of an actual RM. Understanding specific consumer preferences is crucial during RM product development, clinical trials and eventual product dissemination.


Determinants of synaptic integration and heterogeneity in rebound firing explored with data-driven models of deep cerebellar nucleus cells.
Significant inroads have been made to understand cerebellar cortical processing but neural coding at the output stage of the cerebellum in the deep cerebellar nuclei (DCN) remains poorly understood. The DCN are unlikely to just present a relay nucleus because Purkinje cell inhibition has to be turned into an excitatory output signal, and DCN neurons exhibit complex intrinsic properties. In particular, DCN neurons exhibit a range of rebound spiking properties following hyperpolarizing current injection, raising the question how this could contribute to signal processing in behaving animals. Computer modeling presents an ideal tool to investigate how intrinsic voltage-gated conductances in DCN neurons could generate the heterogeneous firing behavior observed, and what input conditions could result in rebound responses. To enable such an investigation we built a compartmental DCN neuron model with a full dendritic morphology and appropriate active conductances. We generated a good match of our simulations with DCN current clamp data we recorded in acute slices, including the heterogeneity in the rebound responses. We then examined how inhibitory and excitatory synaptic input interacted with these intrinsic conductances to control DCN firing. We found that the output spiking of the model reflected the ongoing balance of excitatory and inhibitory input rates and that changing the level of inhibition performed an additive operation. Rebound firing following strong Purkinje cell input bursts was also possible, but only if the chloride reversal potential was more negative than -70 mV to allow de-inactivation of rebound currents. Fast rebound bursts due to T-type calcium current and slow rebounds due to persistent sodium current could be differentially regulated by synaptic input, and the pattern of these rebounds was further influenced by HCN current. Our findings suggest that active properties of DCN neurons could play a crucial role for signal processing in the cerebellum.


Clinical management of intractable constipation.
To review current management of intractable constipation. Original articles and reviews published in the English-language literature between 1965 and 1993 identified by MEDLINE search. Verbal feedback from attendees after presentation of the document as a clinical symposium at the 14th International Symposium on Gastrointestinal Motility in September 1993. Key words included constipation, epidemiology, colonic inertia, pseudo-obstruction, pelvic floor dysfunction, and results of therapeutic interventions, particularly the effects of biofeedback training and subtotal colectomy. In most patients, constipation is usually due to lack of dietary fiber and responds to simple measures to correct these factors, often without consulting a physician. In some, probably fewer than 10% of patients who consult their physicians, structural diseases of the colon and rectum, systemic disease, or medications that slow gut transit should be excluded, and regular exercise, dietary fiber, and an osmotic laxative prescribed. In a series of 277 highly selected patients from a tertiary referral center who had intractable constipation, only 29% had a definable abnormality; identification of abnormal transit facilitates selection of patients for further investigations identifying colonic inertia or pelvic floor dysfunction. An algorithmic approach can carefully select patients with intractable constipation for behavioral modification and biofeedback; the long-term outcome is excellent, with at least 75% success in several series. In a minority of patients with slow transit constipation unresponsive to medical treatment, subtotal colectomy with ileorectostomy is indicated and effective.


Advances in understanding chromosome silencing by the long non-coding RNA Xist.
In female mammals, one of the two X chromosomes becomes genetically silenced to compensate for dosage imbalance of X-linked genes between XX females and XY males. X chromosome inactivation (X-inactivation) is a classical model for epigenetic gene regulation in mammals and has been studied for half a century. In the last two decades, efforts have been focused on the X inactive-specific transcript (Xist) locus, discovered to be the master regulator of X-inactivation. The Xist gene produces a non-coding RNA that functions as the primary switch for X-inactivation, coating the X chromosome from which it is transcribed in cis. Significant progress has been made towards understanding how Xist is regulated at the onset of X-inactivation, but our understanding of the molecular basis of silencing mediated by Xist RNA has progressed more slowly. A picture has, however, begun to emerge, and new tools and resources hold out the promise of further advances to come. Here, we provide an overview of the current state of our knowledge, what is known about Xist RNA and how it may trigger chromosome silencing.


Minimal disease activity for rheumatoid arthritis: a preliminary definition.
Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: * The DAS28 definition places patients in MDA when DAS28 < or = 2.85; * The core set definition places patients in MDA when they meet 5 of 7 criteria: (1) Pain (0-10) < or = 2; (2) Swollen joint count (0-28) < or = 1; (3) Tender joint count (0-28) < or = 1; (4) Health Assessment Questionnaire (HAQ, 0-3) < or = 0.5; (5) Physician global assessment of disease activity (0-10) < or = 1.5; (6) Patient global assessment of disease activity (0-10) < or = 2; (7) ESR < or = 20. This set of 2 definitions gained approval of 73% of the attendees. These (and other) definitions will now be subject to further validation in other databases.


Assessing a New Method for Measuring Fetal Exposure to Mercury: Newborn Bloodspots.
Measuring mercury in newborn bloodspots to determine fetal exposures is a novel methodology with many advantages. Questions remain, however, about its reliability as an estimate of newborn exposure to mercury. We studied mercury concentrations in paired bloodspots and cord blood from a convenience sample of 48 Minnesota women and infants. The limit of detection for bloodspots was higher than for cord blood (0.7 and 0.3 μg/L in bloodspots and cord blood, respectively) with the result that mercury was detected in only 38% of newborn bloodspots compared to 62% of cord blood samples. The geometric mean mercury concentration in cord blood was 0.6 μg/L. Mercury concentrations were almost uniformly lower in bloodspots than in cord blood (mean ratio (±SD) = 0.85 ± 0.4), their mean value was significantly less than that for the cord blood (p = 0.02), and the two methods were highly correlated (r = 0.82). These preliminary findings indicate that newborn bloodspot mercury measurements have utility; however, until bloodspot analyses are more sensitive, they are likely to underestimate in utero exposure.


Structure and function of the interacting domains of Spire and Fmn-family formins.
Evidence for cooperation between actin nucleators is growing. The WH2-containing nucleator Spire and the formin Cappuccino interact directly, and both are essential for assembly of an actin mesh during Drosophila oogenesis. Their interaction requires the kinase noncatalytic C-lobe domain (KIND) domain of Spire and the C-terminal tail of the formin. Here we describe the crystal structure of the KIND domain of human Spir1 alone and in complex with the tail of Fmn2, a mammalian ortholog of Cappuccino. The KIND domain is structurally similar to the C-lobe of protein kinases. The Fmn2 tail is coordinated in an acidic cleft at the base of the domain that appears to have evolved via deletion of a helix from the canonical kinase fold. Our functional analysis of Cappuccino reveals an unexpected requirement for its tail in actin assembly. In addition, we find that the KIND/tail interaction blocks nucleation by Cappuccino and promotes its displacement from filament barbed ends providing insight into possible modes of cooperation between Spire and Cappuccino.


Exploration of functional health, mental well-being and cross-sex hormone use in a sample of Thai male-to-female transgendered persons (kathoeys).
Transgender people sometimes use cross-sex hormones without medical supervision. The use of cross-sex hormones, as well as the functional health and mental well-being, among male-to-female transgendered people ('kathoeys') in Chiang Mai, Thailand, was studied. Sixty kathoeys were interviewed regarding their use of cross-sex hormones and their family relationships. Individuals also completed the Life Orientation Test Revised (LOT-R) to assess dispositional optimism, the Social Functioning Questionnaire (SFQ) and the Short Form Health Survey 36 (SF-36). Three categories were established as follows: those who never cross-dress, those who sometimes cross-dress and those who always cross-dress in public. Of the 60 subjects, 44 had used hormones for prolonged periods (9.7±6.1 years). Their use was related to the permanence of cross-dressing but unrelated to functional health and mental well-being. Fifty percent of subjects had overdosed on commonly used oral contraceptives. Three people used injectable oestrogen in a higher-than-recommended dose. Self-acceptance was high or reasonably good (83%) compared to no acceptance (17%), and neither was related to the permanence of cross-dressing. Their acceptance by parents and siblings was also relatively high (85% and 89%, respectively). The permanence of cross-dressing had no effect on the scores of optimism, SF-36 scores and social functioning. Acceptance by oneself or one's parents did not seem to affect most aspects of functional health and mental well-being, but non-acceptance by siblings generated lower scores on the social functioning and general mental health subscales. Stressors tended to include physical rather than social factors. In conclusion, the unsupervised use of cross-sex hormones was common among kathoeys, and 50% of the sample had overdosed on them. Acceptance was relatively good, except by siblings. New strategies are needed for a more responsible use of cross-sex hormones.


Characterization of ultrafiltration of undiluted and diluted stored urine.
Urine ultrafiltration (UF) was studied in terms of flux, permeability, resistance and fouling. Two types of samples were used: stored urine representing the feedstock obtained from urine diversion dry toilets; and diluted stored urine representing the feedstock obtained from urinals. Three different filtration experiment sets were adopted in this study. For the first case, pressure was set in an ascending order, i.e. from 10 to 60 kPa during filtration of stored urine. For the second case, pressure was set in a descending order, i.e. from 60 to 10 kPa for the same feed stream. The third case involved filtration of diluted urine with pressure in ascending order, i.e. from 10 to 60 kPa. The results indicated that diluted urine had higher flux than undiluted urine with maximum values of 43 and 26 L·m-2·h-1 respectively. Cake formation was the dominating fouling mechanism during urine filtration with a contribution of about 90% to the total hydraulic resistance. The contribution of chemically irreversible fouling was low (-2%), unless operating from high to low pressures. Indeed, irreversible fouling appeared to be greater during the experiments starting at higher pressure. Although undiluted urine had a higher fouling potential compared to diluted urine, the specific cake resistance was higher for diluted urine, probably due to a denser cake caused by lower particle sizes in that sample. The permeate obtained after urine filtration had much lower suspended solids content compared to the feedstock, with rejections up to 99%. The concentration of the ionic species remained unchanged, and 75% of the organic compounds and dissolved solids remained in the permeate. Urine UF could then be used as pre-treatment to remove suspended solids.


Impaired perfusion modifies the relationship between blood pressure and stroke risk in major cerebral artery disease.
Blood pressure (BP) lowering may increase stroke risk in patients with symptomatic major cerebral artery disease and impaired perfusion. To investigate the relationships among BP, impaired perfusion and stroke risk. We retrospectively analysed data from 130 non-disabled, medically treated patients with either symptomatic extracranial carotid occlusion or intracranial stenosis or occlusion of the carotid artery or middle cerebral arteries. All patients had baseline haemodynamic measurements with (15)O-gas positron emission tomography and were followed for 2 years or until stroke recurrence or death. There was a negative linear relationship between systolic BP (SBP) and risk of stroke in the territory of the diseased artery. The 2-year incidence of ischaemic stroke in the territory in patients with normal SBP (<130 mm Hg, 5/32 patients) was significantly higher than in patients with high SBP (2/98, p<0.005). Multivariate analysis revealed that normal SBP and impaired perfusion were independently associated with increased risk of stroke in the previously affected territory, while risk of stroke elsewhere was positively correlated with SBP. Overall, high total stroke risk was observed at lower BP in patients with impaired perfusion and at higher BPs in patients without (interaction, p<0.01). Overall, the relationship between SBP and total stroke recurrence was J-shaped. Impaired perfusion modified the relationship between blood pressure and stroke risk, although this study had limitations including the retrospective analysis, the potentially biased sample, the small number of critical events and the fact that BP was measured only as a snapshot in clinic.


Construction of a high efficiency retroviral vector for gene therapy of Hunter's syndrome.
As an alternative method to the conventional therapies for Hunter's syndrome, which is a lethal lysosomal storage disorder, we have developed gene delivery vehicles using a series of retroviral vectors. The objective of this study was to develop a safe and efficient retroviral vector and to optimize conditions for efficient transduction of human bone marrow CD34+ stem cells using our vector. We constructed three types of MLV-based retroviral vectors expressing iduronate-2-sulfatase (IDS) which is deficient in patients suffering from Hunter's syndrome: MIN-IDS and MIM-IDS, which express IDS along with bacterial neo and human MDR genes, respectively, and MT-IDS lacking any selectable marker. Respective producer lines were derived from the packaging line, PG13, and compared for viral titer and levels of gene expression. After comparing, the retroviral vector, MT-IDS, was used to transduce human bone marrow CD34+ stem cells on fibronectin under various MOIs. In comparison, MT-IDS not only produced the highest viral titer (close to 10(7) cfu/ml), but also showed the highest level of gene expression in various transduction assays and RNA analysis. When 1.5 x 10(5) human CD34+ bone marrow cells were transduced with MT-IDS under the most optimal MOIs, about 80% of total colony forming units were shown to contain the IDS cDNA. Minimum-sized retroviral vector that contains no selective marker as well as a viral coding sequences could drive a high level of gene expression, be produced efficiently from the producer line, and enter hematopoietic cells at a high frequency. Our data suggest the great potential for using MT-based vector(s) in a gene therapy trial for Hunter's syndrome utilizing human CD34+ stem cells as target cells.


IPET and FETR: experimental approach for studying molecular structure dynamics by cryo-electron tomography of a single-molecule structure.
The dynamic personalities and structural heterogeneity of proteins are essential for proper functioning. Structural determination of dynamic/heterogeneous proteins is limited by conventional approaches of X-ray and electron microscopy (EM) of single-particle reconstruction that require an average from thousands to millions different molecules. Cryo-electron tomography (cryoET) is an approach to determine three-dimensional (3D) reconstruction of a single and unique biological object such as bacteria and cells, by imaging the object from a series of tilting angles. However, cconventional reconstruction methods use large-size whole-micrographs that are limited by reconstruction resolution (lower than 20 Å), especially for small and low-symmetric molecule (<400 kDa). In this study, we demonstrated the adverse effects from image distortion and the measuring tilt-errors (including tilt-axis and tilt-angle errors) both play a major role in limiting the reconstruction resolution. Therefore, we developed a "focused electron tomography reconstruction" (FETR) algorithm to improve the resolution by decreasing the reconstructing image size so that it contains only a single-instance protein. FETR can tolerate certain levels of image-distortion and measuring tilt-errors, and can also precisely determine the translational parameters via an iterative refinement process that contains a series of automatically generated dynamic filters and masks. To describe this method, a set of simulated cryoET images was employed; to validate this approach, the real experimental images from negative-staining and cryoET were used. Since this approach can obtain the structure of a single-instance molecule/particle, we named it individual-particle electron tomography (IPET) as a new robust strategy/approach that does not require a pre-given initial model, class averaging of multiple molecules or an extended ordered lattice, but can tolerate small tilt-errors for high-resolution single "snapshot" molecule structure determination. Thus, FETR/IPET provides a completely new opportunity for a single-molecule structure determination, and could be used to study the dynamic character and equilibrium fluctuation of macromolecules.


Transactions within the family: Coparenting mediates associations between parents' relationship satisfaction and the parent-child relationship.
In the current study, we examined the potential for transactional relations among parents' marital satisfaction, coparental cooperation and conflict, and parent-child relationship satisfaction in a sample of 249 families with 2-3-year-old children. Using a novel multiwave design with frequent assessments to better capture transactional family processes, mothers and fathers were assessed across 5 waves with 2-month lags; mean age of the target children (53% girls) was 2.8 years (SD = 0.62) at baseline. Cross-lagged, multilevel structural equation modeling (SEM) analyses using an actor-partner interdependence modeling framework revealed coparental cooperation and conflict as likely mechanisms within the family system. Specifically, marital satisfaction from both parents was reciprocally linked to fathers' coparental cooperation over time, supporting transactional links between those two family subsystems. In addition, there were significant transactional links between both mothers' and fathers' coparental cooperation and father-reported parent-child relationship satisfaction across time, revealing within-parent and cross-parent mediation. Regarding coparental conflict, marital satisfaction from both parents was reciprocally linked to the same parents' reports of coparental conflict across time (i.e., actor effects). Furthermore, father-reported coparental conflict acted as a mediating or intervening mechanism between father-reported marital satisfaction and mother-reported parent-child relationship satisfaction (cross-parent mediation). Taken as a set, the findings supported coparental cooperation and conflict as significant links between marital functioning and the parent-child relationship. Findings build on a growing body of literature addressing the transactional associations embedded within the family system and highlight the importance of modeling the inherent interdependencies between mothers' and fathers' reports of family functioning. (PsycINFO Database Record


Blood pressure, antihypertensive treatment and stroke risk.
ASSOCIATION BETWEEN BLOOD PRESSURE AND STROKE: Data from prospective observational studies indicate that usual levels of blood pressure are directly and continuously related to the risk of stroke. The strength of this association has been substantially underestimated by many previous analyses that have not taken account of the regression dilution bias; correction for this increases the strength of the association between blood pressure levels and stroke risk by about 60%. From corrected analyses it is apparent that a prolonged difference in usual systolic/diastolic blood pressure levels of just 9/5 mmHg would eventually confer about a one-third difference in stroke risk, with similar proportional effects in hypertensives and normotensives. The results of randomized trials of antihypertensive drugs suggest that much or all of the long-term potential stroke avoidance associated with this level of prolonged blood pressure difference can be achieved within just a few years of beginning treatment. Overall, in 17 randomized trials of antihypertensive treatment, a net blood pressure reduction of 10-12 mmHg systolic and 5-6 mmHg diastolic conferred a reduction in stroke incidence of 38% (SD 4), with similar reductions in fatal and non-fatal strokes. Additionally, the sizes of the reductions were similar in trials in mild, moderate and more severe hypertension, in trials in older and younger patients and in trials in patients with a history of cerebrovascular disease and in patients without such a history. Because the proportional effects of treatment were similar in all these groups, the absolute effects of treatment on stroke varied in direct proportion to the background risk of stroke. Thus the greatest benefits were observed among those with a history of cerebrovascular disease, those above the age of 60 years and those with more severe hypertension.


Structure and function of the genomically encoded fosfomycin resistance enzyme, FosB, from Staphylococcus aureus.
The Gram-positive pathogen Staphylococcus aureus is a leading cause of global morbidity and mortality. Like many multi-drug-resistant organisms, S. aureus contains antibiotic-modifying enzymes that facilitate resistance to a multitude of antimicrobial compounds. FosB is a Mn(2+)-dependent fosfomycin-inactivating enzyme found in S. aureus that catalyzes nucleophilic addition of either l-cysteine (l-Cys) or bacillithiol (BSH) to the antibiotic, resulting in a modified compound with no bactericidal properties. The three-dimensional X-ray crystal structure of FosB from S. aureus (FosB(Sa)) has been determined to a resolution of 1.15 Å. Cocrystallization of FosB(Sa) with either l-Cys or BSH results in a disulfide bond between the exogenous thiol and the active site Cys9 of the enzyme. An analysis of the structures suggests that a highly conserved loop region of the FosB enzymes must change conformation to bind fosfomycin. While two crystals of FosB(Sa) contain Zn(2+) in the active site, kinetic analyses of FosB(Sa) indicated that the enzyme is inhibited by Zn(2+) for l-Cys transferase activity and only marginally active for BSH transferase activity. Fosfomycin-treated disk diffusion assays involving S. aureus Newman and the USA300 JE2 methicillin-resistant S. aureus demonstrate a marked increase in the sensitivity of the organism to the antibiotic in either the BSH or FosB null strains, indicating that both are required for survival of the organism in the presence of the antibiotic. This work identifies FosB as a primary fosfomycin-modifying pathway of S. aureus and establishes the enzyme as a potential therapeutic target for increased efficacy of fosfomycin against the pathogen.


CD146-HIF-1α hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease of cardiopulmonary units. No cure is currently available due to an incomplete understanding of vascular remodeling. Here we identify CD146-hypoxia-inducible transcription factor 1 alpha (HIF-1α) cross-regulation as a key determinant in vascular remodeling and PAH pathogenesis. CD146 is markedly upregulated in pulmonary artery smooth muscle cells (PASMCs/SMCs) and in proportion to disease severity. CD146 expression and HIF-1α transcriptional program reinforce each other to physiologically enable PASMCs to adopt a more synthetic phenotype. Disruption of CD146-HIF-1α cross-talk by genetic ablation of Cd146 in SMCs mitigates pulmonary vascular remodeling in chronic hypoxic mice. Strikingly, targeting of this axis with anti-CD146 antibodies alleviates established pulmonary hypertension (PH) and enhances cardiac function in two rodent models. This study provides mechanistic insights into hypoxic reprogramming that permits vascular remodeling, and thus provides proof of concept for anti-remodeling therapy for PAH through direct modulation of CD146-HIF-1α cross-regulation.


The relationship between executive function, risky behaviour and HIV in young women from the HPTN 068 study in rural South Africa.
Executive function (EF) may predict sexual risk-taking and HIV risk in young women in rural South Africa. We tested associations between EF and seven risky behavioural outcomes: binge drinking, illicit substance use, unprotected vaginal sex, concurrent sexual relationships, transactional sex, herpes simplex virus type 2 (HSV-2) infection, and HIV infection. We compared EF in young women with HIV to matched controls. 1080 young women underwent cognitive assessments. Better verbal short-term memory was associated with a lower risk of HSV-2 (OR 0.77; 95% CI 0.69, 0.86; p < 0.001). Uncorrected trends (p < 0.05) were better verbal working memory being associated with a lower risk of concurrency, better planning with a lower risk of illicit drug use, and better affective inhibition with a lower risk of transactional sex. 78 participants with sexually acquired HIV were matched with 153 HIV-negative controls and had poorer verbal working memory than controls (Hedge's g = -0.38; 95% CI -0.66, -0.10; p = 0.0076), but this was non-significant after adjustment. EF's contribution to young women's risky behaviour in this context does not hold when stringent statistical corrections are applied, with only verbal short term memory reaching statistical significance as predictor. Replication in other samples is recommended.


Identification of persons at high risk for kidney disease via targeted screening: the NKF Kidney Early Evaluation Program.
More than 340,000 individuals were receiving renal replacement therapy in the United States at the end of 1999; this number is projected to double by the year 2010. Almost half had a primary diagnosis of diabetes mellitus particularly type 2, and more than one quarter a primary diagnosis of hypertension. Studies have demonstrated effective maneuvers to prevent or delay the rate of progression of kidney disease, and decrease morbidity and mortality. The objective of early diagnosis is early detection of asymptomatic disease at a time when intervention has a reasonable potential to have a positive impact on outcome. In 1997, the National Kidney Foundation launched KEEP trade mark (Kidney Early Evaluation Program), a free community-based screening that targets first order relatives of persons with hypertension, diabetes or kidney disease, and those with a personal history of diabetes or hypertension. Of the 889 individuals screened in the pilot study, 71.4% had at least one abnormality. The program includes an educational component and referral to a physician for follow-up of abnormal values. Targeted screenings are an effective means of identifying persons at risk for kidney disease, and can identify individuals at risk early enough in the course of their disease to allow for effective intervention.


Qualitative and quantitative ethnobotanical study of the Pangkhua community in Bilaichari Upazilla, Rangamati District, Bangladesh.
The present study documents the ethnomedicinal knowledge among the traditional healers of the Pangkhua indigenous community of Bangladesh. The documented data from this area was quantitatively analyzed for the first time. We aimed to record ethnomedicinal information from both the traditional healers and also the elderly men and women of the community, in order to compile and document all available information concerning plant use and preserve it for the coming generations. We aimed to compare how already known species are used compared to elsewhere and particularly to highlight new ethnomedicinal plant species alongside their therapeutic use(s). All ethnomedicinal information was collected following established techniques. Open-ended and semi-structured techniques were primarily utilized. Data was analyzed using different quantitative indices. The level of homogeneity between information provided by different informants was calculated using the Informant Consensus Factor. All recorded plant species are presented in tabular format, alongside corresponding ethnomedicinal usage information. This investigation revealed the traditional use of 117 plant species, distributed among 104 genera and belonging to 54 families. There was strong agreement among the informants regarding ethnomedicinal uses of plants, with Factor of Informant Consensus (FIC) values ranging from 0.50 to 0.66, with the highest number of species (49) being used for the treatment of digestive system disorders (FIC 0.66). In contrast, the least agreement (FIC = 0.50) between informants regarding therapeutic uses was observed for plants used to treat urinary disorders. The present study was compared with 43 prior ethnomedicinal studies, conducted both nationally and in neighboring countries, and the results revealed that the Jaccard index (JI) ranged from 1.65 to 33.00. The highest degree of similarity (33.00) was found with another study conducted in Bangladesh, while the lowest degree of similarity (1.65) was found with a study conducted in Pakistan. This study recorded 12 new ethnomedicinal plant species, of which 6 have never been studied pharmacologically to date. This study showed that the Pangkhua community still depends substantially on ethnomedicinal plants for the treatment of various ailments and diseases and that several of these plants are used in novel ways or represented their first instances of use for medicinal applications.


Noise reduction in oncology FDG PET images by iterative reconstruction: a quantitative assessment.
Tumor detection depends on the contrast between tumor activity and background activity and on the image noise in these 2 regions. The lower the image noise, the easier the tumor detection. Tumor activity contrast is determined by physiology. Noise, however, is affected by many factors, including the choice of reconstruction algorithm. Previous simulation and phantom measurements indicated that the ordered-subset expectation maximization (OSEM) algorithm may produce less noisy images than does the usual filtered backprojection (FBP) method, at equivalent resolution. To see if this prediction would hold in actual clinical situations, we quantified noise in clinical images reconstructed with both OSEM and FBP. Three patients (2 with colon cancer, 1 with breast cancer) were imaged with FDG PET using a "gated replicate" technique that permitted accurate measurement of noise at each pixel. Each static image was acquired as a gated image sequence, using a pulse generator with a 1-s period, yielding 40 replicate images over the 10- to 15-min imaging time. The images were or were not precorrected for attenuation and were reconstructed with both FBP and OSEM at comparable resolution. From these data, images of pixel mean, SD, and signal-to-noise ratio (S/N) could be produced, reflecting only noise caused by the statistical fluctuations in the emission process. Noise did not vary greatly over each FBP image, even when image intensity varied greatly from one region to the next, causing S/N to be worse in low-activity regions than in high-activity regions. In contrast, OSEM had high noise in hot regions and low noise in cold regions. OSEM had a much better S/N than did FBP in cold regions of the image, such as the lungs (in the attenuation-corrected images), where improvements in S/N averaged 160%. Improvements with OSEM were less dramatic in hotter areas such as the liver (averaging 25% improvement in the attenuation-corrected images). In very hot tumors, FBP actually produced higher S/Ns than did OSEM. We conclude that OSEM reconstruction can significantly reduce image noise, especially in relatively low-count regions. OSEM reconstruction failed to improve S/N in very hot tumors, in which S/N may already be adequate for tumor detection.


Effect of steroid and serum starvation on a human breast cancer adenocarcinoma cell line.
Breast cancer is one of the most frequent cancers in women. Although there are many treatment protocols for this disease, there are still many patients who do not respond satisfactorily to the current treatment protocols. A better understanding of the nature of the tumor cells might provide a guide for better therapeutic procedures. In this study, the effect of metabolic stress was assessed on the human adenocarcinoma MCF-7 cell line. The cells were seeded in culture plates and after reaching log phase of their growth, cells were exposed to phenol red free-media supplemented with 10%, 0.5%, 0.25% and 0% charcoal-treated serum for 1 to 6 consecutive days. At 24-hour intervals, the cells' ability to proliferate (trypan blue assay), cells mitochondrial content (MTT assay) and intracellular protein content (SRB assay) was assessed. In each day of the study, the cells were released in complete media containing 10% serum for 24 hours and the effect of release was observed on cells. This study showed reduced basal growth rate and proliferation in response to harsh environmental conditions. Protein content of the cells also decreased. Mitochondrial content/activity of the cells however did not decrease, but instead a relative increase was observed at some time points. Releasing the cells caused increased cell proliferation in media with up to 0.5% serum, with an increase in intracellular protein content, although no significant mitochondrial function increase was observed. The results of this study confirm the adaptation of MCF-7 cells to environmental harsh conditions.


[Hydration to prevent contrast-induced nephropathy].
In 2007, a national guideline was issued in the Netherlands to prevent contrast-induced nephropathy. This guideline recommended preventive hydration with 0.9% NaCl in patients with reduced estimated glomerular filtration rate (eGFR 30-69 ml/min/1.73 m2) prior to administration of contrast. The recent AMACING study compared hydration versus no hydration, and found that hydration did not prevent contrast-induced nephropathy but did lead to complications and higher costs. The latest 2017 guideline recommends hydration only for patients with eGFR < 30 ml/min/1.73 m2. Although this is an improvement, an even more recent study, PRESERVE, showed no differences in the incidence of contrast-induced nephropathy between sodium chloride, sodium bicarbonate, acetylcysteine, or placebo - even in patients with lower eGFRs (15-60 ml/min/1.73 m2) undergoing elective angiography. This raises the question whether preventive measures are only effective in patients with the highest risk, i.e. hospitalized patients with multiple risk factors undergoing emergency procedures.


Prediction of the Seizure Suppression Effect by Electrical Stimulation via a Computational Modeling Approach.
In this paper, we identified factors that can affect seizure suppression via electrical stimulation by an integrative study based on experimental and computational approach. Preferentially, we analyzed the characteristics of seizure-like events (SLEs) using our previous in vitro experimental data. The results were analyzed in two groups classified according to the size of the effective region, in which the SLE was able to be completely suppressed by local stimulation. However, no significant differences were found between these two groups in terms of signal features or propagation characteristics (i.e., propagation delays, frequency spectrum, and phase synchrony). Thus, we further investigated important factors using a computational model that was capable of evaluating specific influences on effective region size. In the proposed model, signal transmission between neurons was based on two different mechanisms: synaptic transmission and the electrical field effect. We were able to induce SLEs having similar characteristics with differentially weighted adjustments for the two transmission methods in various noise environments. Although the SLEs had similar characteristics, their suppression effects differed. First of all, the suppression effect occurred only locally where directly received the stimulation effect in the high noise environment, but it occurred in the entire network in the low noise environment. Interestingly, in the same noise environment, the suppression effect was different depending on SLE propagation mechanism; only a local suppression effect was observed when the influence of the electrical field transmission was very weak, whereas a global effect was observed with a stronger electrical field effect. These results indicate that neuronal activities synchronized by a strong electrical field effect respond more sensitively to partial changes in the entire network. In addition, the proposed model was able to predict that stimulation of a seizure focus region is more effective for suppression. In conclusion, we confirmed the possibility of a computational model as a simulation tool to analyze the efficacy of deep brain stimulation (DBS) and investigated the key factors that determine the size of an effective region in seizure suppression via electrical stimulation.


Crystallization and preliminary crystallographic analysis of BbCRASP-1, a complement regulator-acquiring surface protein of Borrelia burgdorferi.
Borrelia burgdorferi is the causative agent of Lyme disease. Serum-resistant strains of the pathogen are able to reduce the host's immune response to infection by recruiting fluid-phase complement regulators from the serum. B. burgdorferi complement regulator-acquiring surface protein-1 (BbCRASP-1) binds factor H and factor-H-like protein-1 to the bacterial surface, where they actively down-regulate complement response. Crystals of native and selenomethionine-substituted BbCRASP-1 have been obtained and a native data set to 2.7 A as well as selenomethionine MAD data to 3.2 A resolution have been collected. The selenium substructure has been solved and initial phases have been refined to 3.0 A by density-modification methods. Model building and refinement are under way.


From stride period to stride frequency.
The stride-cycle frequency of gait data is often estimated by taking the inverse of the average stride-cycle time (stride period) over several stride-cycles. We derive the density function of the stride-cycle frequency frequency (stride frequency) and describe some of its properties. We also show the conditions under which the inverse of the mean stride period is a 'good' estimate of the mean stride frequency. Copyright 1998 Elsevier Science B.V.


A point mutation in cycA partially contributes to the D-cycloserine resistance trait of Mycobacterium bovis BCG vaccine strains.
In mycobacteria, CycA a D-serine, L- and D-alanine, and glycine transporter also functions in the uptake of D-cycloserine, an important second-line anti-tubercular drug. A single nucleotide polymorphism identified in the cycA gene of BCG was hypothesized to contribute to the increased resistance of Mycobacterium bovis bacillus Calmette-Guérin (BCG) to D-cycloserine compared to wild-type Mycobacterium tuberculosis or Mycobacterium bovis. Working along these lines, a merodiploid strain of BCG expressing Mycobacterium tuberculosis CycA was generated and found to exhibit increased susceptibility to D-cycloserine albeit not to the same extent as wild-type Mycobacterium tuberculosis or Mycobacterium bovis. In addition, recombinant Mycobacterium smegmatis strains expressing either Mycobacterium tuberculosis or Mycobacterium bovis CycA but not BCG CycA were rendered more susceptible to D-cycloserine. These findings support the notion that CycA-mediated uptake in BCG is impaired as a result of a single nucleotide polymorphism; however, the partial contribution of this impairment to D-cycloserine resistance suggests the involvement of additional genetic lesions in this phenotype.


Quantitative study of vibrational symmetry of injured vocal folds via digital kymography in excised canine larynges.
Digital kymography and vocal fold curve fitting are blended with detailed symmetry analysis of kymograms to provide a comprehensive characterization of the vibratory properties of injured vocal folds. Vocal fold vibration of 12 excised canine larynges was recorded under uninjured, unilaterally injured, and bilaterally injured conditions. Kymograms were created at 25%, 50%, and 75% of the vocal fold length, and vibratory parameters were compared quantitatively among conditions and were studied with respect to right-left and anterior-posterior symmetries. Anterior-posterior amplitude asymmetry was found in the bilateral condition. The unilateral condition showed significant right-left amplitude asymmetry, and it showed the lowest right-left phase symmetry among the conditions. In condition comparisons, vertical phase difference did not show significant differences among conditions, whereas amplitudes were significantly different among conditions at all line scan positions and most vocal fold lips. Significant differences in frequency were found among the conditions at all 4 vocal fold lips, with the bilateral condition exhibiting the greatest frequency. Digital kymography and curve fitting provide detailed information about the vibratory behavior of injured vocal folds. Awareness of vibratory properties associated with vocal fold injury may aid in diagnosis, and the quantitative abilities of digital kymography may allow for objective treatment selection.


Healthy Behaviors: Prevalence of Uptake Among Cancer Survivors.
Although most cancer survivors adhere to recommendations to refrain from tobacco and minimize alcohol use, survivors of certain cancers are not meeting these recommendations. In addition, most cancer survivors do not achieve optimal recommendations for diet and physical activity, further decreasing survivor health and quality of life. Sun protective and sleep behaviors also tend to be suboptimal among survivors. Uptake of age-appropriate vaccinations is variable among survivors. The purpose of this article is to review the prevalence of healthy behavior uptake among cancer survivors and provide nurses with an overview of effective interventions, strategies, and resources to help patients improve these behaviors. An expert panel was convened to conduct an integrative review and synthesis on the state of the science of healthy behavior uptake among cancer survivors. Not meeting recommendations for healthy lifestyle behaviors increases the risk of second cancers and mortality and decreases overall health and quality of life. Healthy lifestyle behaviors can contribute to improved function, quality of life, and overall survival for cancer survivors. Nurses can help survivors to understand and improve their behaviors.


Contrast-Dependence of Temporal Frequency Tuning in Mouse V1.
The perception of speed is influenced by visual contrast. In primary visual cortex (V1), an early stage in the visual perception pathway, the neural tuning to speed is directly related to the neural tuning to temporal frequency of stimulus changes. The influence of contrast on speed perception can be caused by the joint dependency of neural responses in V1 on temporal frequency and contrast. Here, we investigated how tuning to contrast and temporal frequency in V1 of anesthetized mice are related. We found that temporal frequency tuning is contrast-dependent. V1 was more responsive at lower temporal frequencies than the dLGN, consistent with previous work at high contrast. The temporal frequency tuning moves toward higher temporal frequencies with increasing contrast. The low half-maximum temporal frequency does not change with contrast. The Heeger divisive normalization equation provides a good fit to many response characteristics in V1, but does not fit the dependency of temporal frequency and contrast with set of parameters for all temporal frequencies. Different mechanisms for normalization in the visual cortex may predict different relationships between temporal frequency and contrast non-linearity. Our data could help to make a model selection.


Predictors of outcome in patients with (sub)acute low back pain differ across treatment groups.
Prospective study with 6 weeks of follow-up. To examine the predictors of outcome for patients with (sub)acute low back pain (LBP) receiving usual care (UC) or a minimal intervention strategy (MIS) aimed at psychosocial factors. A randomized controlled trial in general practice showed no differences in average effect between UC and MIS. Socio-demographic variables, characteristics of LBP, and psychosocial factors were included as potential predictors of outcome. The outcome clinically important improvement was defined as a reduction of at least 30% on functional disability plus patient perceived recovery. Logistic regression analyses were used to study the associations between predictors and outcome at 6 weeks follow-up. In the UC group (n = 163), the multivariable model included a shorter duration of the LBP episode, few previous episodes, less pain catastrophizing, and good perceived general health. The area under the curve (AUC) of the model was 0.77 (95% confidence interval, 0.70-0.85). In the MIS group (n = 142), the multivariable model included less somatizing symptoms, more solicitous responses by an important other, lower perceived risk for chronic LBP, more fear avoidance beliefs, higher level of education, and shorter duration of the LBP episode. This AUC was 0.78 (95% confidence interval, 0.71-0.86). As we found two different profiles, our approach may contribute to the important question: what intervention works for whom?


Longitudinal reproducibility of default-mode network connectivity in healthy elderly participants: A multicentric resting-state fMRI study.
To date, limited data are available regarding the inter-site consistency of test-retest reproducibility of functional connectivity measurements, in particular with regard to integrity of the Default Mode Network (DMN) in elderly participants. We implemented a harmonized resting-state fMRI protocol on 13 clinical scanners at 3.0T using vendor-provided sequences. Each site scanned a group of 5 healthy elderly participants twice, at least a week apart. We evaluated inter-site differences and test-retest reproducibility of both temporal signal-to-noise ratio (tSNR) and functional connectivity measurements derived from: i) seed-based analysis (SBA) with seed in the posterior cingulate cortex (PCC), ii) group independent component analysis (ICA) separately for each site (site ICA), and iii) consortium ICA, with group ICA across the whole consortium. Despite protocol harmonization, significant and quantitatively important inter-site differences remained in the tSNR of resting-state fMRI data; these were plausibly driven by hardware and pulse sequence differences across scanners which could not be harmonized. Nevertheless, the tSNR test-retest reproducibility in the consortium was high (ICC=0.81). The DMN was consistently extracted across all sites and analysis methods. While significant inter-site differences in connectivity scores were found, there were no differences in the associated test-retest error. Overall, ICA measurements were more reliable than PCC-SBA, with site ICA showing higher reproducibility than consortium ICA. Across the DMN nodes, the PCC yielded the most reliable measurements (≈4% test-retest error, ICC=0.85), the medial frontal cortex the least reliable (≈12%, ICC=0.82) and the lateral parietal cortices were in between (site ICA). Altogether these findings support usage of harmonized multisite studies of resting-state functional connectivity to characterize longitudinal effects in studies that assess disease progression and treatment response.


Whey Peptides Stimulate Differentiation and Lipid Metabolism in Adipocytes and Ameliorate Lipotoxicity-Induced Insulin Resistance in Muscle Cells.
Deregulation of lipid metabolism and insulin function in muscle and adipose tissue are hallmarks of systemic insulin resistance, which can progress to type 2 diabetes. While previous studies suggested that milk proteins influence systemic glucose homeostasis and insulin function, it remains unclear whether bioactive peptides generated from whey alter lipid metabolism and its accumulation in muscle and adipose tissue. Therefore, we incubated murine 3T3-L1 preadipocytes and C2C12 myotubes with a whey peptide mixture produced through pepsin-pancreatin digestion, mimicking peptides generated in the gut from whey protein hydrolysis, and examined its effect on indicators of lipid metabolism and insulin sensitivity. Whey peptides, particularly those derived from bovine serum albumin (BSA), promoted 3T3-L1 adipocyte differentiation and triacylglycerol (TG) accumulation in accordance with peroxisome proliferator-activated receptor γ (PPARγ) upregulation. Whey/BSA peptides also increased lipolysis and mitochondrial fat oxidation in adipocytes, which was associated with the upregulation of peroxisome proliferator-activated receptor δ (PPARδ). In C2C12 myotubes, whey but not BSA peptides ameliorated palmitate-induced insulin resistance, which was associated with reduced inflammation and diacylglycerol accumulation, and increased sequestration of fatty acids in the TG pool. Taken together, our study suggests that whey peptides generated via pepsin-pancreatin digestion profoundly alter lipid metabolism and accumulation in adipocytes and skeletal myotubes.


Clinical Management of Anemia in Patients with Myelodysplastic Syndromes: An Update on Emerging Therapeutic Options.
For the majority of patients with lower-risk myelodysplastic syndrome (LR-MDS), one of the primary clinical goals is to alleviate the symptoms associated with the resultant cytopenias and to minimize the transfusion burden. While supportive red blood cell (RBC) transfusions and erythropoiesis-stimulating agents (ESAs) may lead to clinical improvement, frequent transfusions are often complicated by iron overload and decreased quality of life; furthermore, most patients either do not respond to ESAs or will eventually develop resistance. As such, there is a great need for further therapeutic options in the management of anemia related to MDS. Several additional therapeutics are now available in select patients with LR-MDS and symptomatic anemia including luspatercept, lenalidomide, and immunosuppressive therapy. Furthermore, several novel agents are currently in development to address this area of clinical need such as imetelstat and roxadustat. In this article, we review the currently available therapeutic options for symptomatic anemia in LR-MDS as well as review the therapeutic agents in development.


Preventable infant mortality and quality of health care: maternal perception of the child's illness and treatment.
This study used a qualitative methodology to analyze the discourse of mothers from Greater Metropolitan Belo Horizonte, Minas Gerais, Brazil, whose infant children had died from what were considered avoidable causes (diarrhea, malnutrition, and pneumonia), seeking to elucidate the factors associated with utilization of health care services. Identification of the illness by the mother was related to perception of specific alterations in the child's state of health. Analysis of the alterations helped identify the principal characteristics ascribed to each alteration and their relationship to the search for treatment. The authors also studied the mother's assessment of treatment received at health care facilities; 43.0% of the cases involved problems related to the structure of health care services or the attending health care professionals. In 46.0% of the cases, mothers associated the child's death with flaws in the health care service. The study group showed a variety of interpretations of illness, often distinct from the corresponding biomedical concepts. The fact that attending health care personnel overlooked or underrated the mother's perception of the illness and the lack of communications between health care personnel and the child's family had an influence on the child's evolution and subsequent death.


Protection against clinical malaria by heterologous immunoglobulin G antibodies against malaria-infected erythrocyte variant surface antigens requires interaction with asymptomatic infections.
Erythrocytes infected with mature stages of Plasmodium falciparum express variant surface antigens (VSAs) of parasite origin, including P. falciparum erythrocyte membrane protein 1. Anti-VSA antibodies protect against clinical malaria caused by parasites bearing VSAs to which they are specific (homologous), but their role in protecting against heterologous infection is unclear. Here, we report that, among 256 Kenyan children involved in a 1-year active case surveillance study, asymptomatic parasitemia was associated with an enlarged repertoire of anti-VSA immunoglobulin G (IgG) antibodies specific to apparently heterologous parasite isolates, as measured by flow cytometry. Together, asymptomatic infection and anti-VSA IgG were associated with reduced odds of experiencing an episode of clinical malaria during follow-up, whereas, independently, they were associated with increased susceptibility. These results support previous findings and underline the importance of considering the parasitological status of study participants when examining the role that immune responses to VSAs and other malaria antigens play.


Equality judgments cannot distinguish between attention effects on appearance and criterion: a reply to Schneider (2011).
Whether attention modulates the appearance of stimulus features is debated. Whereas many previous studies using a comparative judgment have found evidence for such an effect, two recent studies using an equality judgment have not. Critically, these studies have relied on the assumption that the equality paradigm yields bias-free PSE estimates and is as sensitive as the comparative judgment, without testing these assumptions. Anton-Erxleben, Abrams, and Carrasco (2010) compared comparative judgments and equality judgments with and without the manipulation of attention. They demonstrated that the equality paradigm is less sensitive than the comparative judgment and also bias-prone. Furthermore, they reported an effect of attention on the PSE using both paradigms. Schneider (2011) questions the validity of the latter finding, stating that the data in the equality experiment are corrupted because of skew in the response distributions. Notably, this argument supports the original conclusion by Anton-Erxleben et al.: that the equality paradigm is bias-prone. Additionally, the necessary analyses to show that the attention effect observed in Anton-Erxleben et al. was due to skew in the data were not conducted. Here, we provide these analyses and show that although the equality judgment is bias-prone, the effects we observe are consistent with an increase of apparent contrast by attention.


Targeting of prion-infected lymphoid cells to the central nervous system accelerates prion infection.
Prions, composed of a misfolded protein designated PrP(Sc), are infectious agents causing fatal neurodegenerative diseases. We have shown previously that, following induction of experimental autoimmune encephalomyelitis, prion-infected mice succumb to disease significantly earlier than controls, concomitant with the deposition of PrP(Sc) aggregates in inflamed white matter areas. In the present work, we asked whether prion disease acceleration by experimental autoimmune encephalomyelitis results from infiltration of viable prion-infected immune cells into the central nervous system. C57Bl/6 J mice underwent intraperitoneal inoculation with scrapie brain homogenates and were later induced with experimental autoimmune encephalomyelitis by inoculation of MOG(35-55) in complete Freund's adjuvant supplemented with pertussis toxin. Spleen and lymph node cells from the co-induced animals were reactivated and subsequently injected into naïve mice as viable cells or as cell homogenates. Control groups were infected with viable and homogenized scrapie immune cells only with complete Freund's adjuvant. Prion disease incubation times as well as levels and sites of PrP(Sc) deposition were next evaluated. We first show that acceleration of prion disease by experimental autoimmune encephalomyelitis requires the presence of high levels of spleen PrP(Sc). Next, we present evidence that mice infected with activated prion-experimental autoimmune encephalomyelitis viable cells succumb to prion disease considerably faster than do mice infected with equivalent cell extracts or other controls, concomitant with the deposition of PrP(Sc) aggregates in white matter areas in brains and spinal cords. Our results indicate that inflammatory targeting of viable prion-infected immune cells to the central nervous system accelerates prion disease propagation. We also show that in the absence of such targeting it is the load of PrP(Sc) in the inoculum that determines the infectivity titers for subsequent transmissions. Both of these conclusions have important clinical implications as related to the risk of prion disease contamination of blood products.


The RAB39B p.G192R mutation causes X-linked dominant Parkinson's disease.
To identify the causal gene in a multi-incident U.S. kindred with Parkinson's disease (PD). We characterized a family with a classical PD phenotype in which 7 individuals (5 males and 2 females) were affected with a mean age at onset of 46.1 years (range, 29-57 years). We performed whole exome sequencing on 4 affected and 1 unaffected family members. Sanger-sequencing was then used to verify and genotype all candidate variants in the remainder of the pedigree. Cultured cells transfected with wild-type or mutant constructs were used to characterize proteins of interest. We identified a missense mutation (c.574G > A; p.G192R) in the RAB39B gene that closely segregated with disease and exhibited X-linked dominant inheritance with reduced penetrance in females. The mutation occurred in a highly conserved amino acid residue and was not observed among 87,725 X chromosomes in the Exome Aggregation Consortium dataset. Sequencing of the RAB39B coding region in 587 familial PD cases yielded two additional mutations (c.428C > G [p.A143G] and c.624_626delGAG [p.R209del]) that were predicted to be deleterious in silico but occurred in families that were not sufficiently informative to assess segregation with disease. Experiments in PC12 and SK-N-BE(2)C cells demonstrated that p.G192R resulted in mislocalization of the mutant protein, possibly by altering the structure of the hypervariable C-terminal domain which mediates intracellular targeting. Our findings implicate RAB39B, an essential regulator of vesicular-trafficking, in clinically typical PD. Further characterization of normal and aberrant RAB39B function might elucidate important mechanisms underlying neurodegeneration in PD and related disorders.


Is robotic technology facilitating the minimally invasive approach to partial nephrectomy?
• To establish its current status, this study reviews the literature, and reports developments in robotic-assisted partial nephrectomy (RPN), highlighting results from various studies that investigate the oncological and functional efficacy of RPN. Partial nephrectomy has become the standard therapy for the management of small renal masses. In an effort to overcome the perioperative morbidity associated with an open approach, and the extended warm ischaemia times associated with a laparoscopic approach, robotic platforms have been introduced. • A search of Medline, EMBASE and Cochrane library databases was completed in July 2010 and used to identify pertinent original articles, editorials, comments and reviews, using the search term 'partial nephrectomy'. Links to related references were surveyed, and all articles finally included were based on relevance and importance of content, as determined by the authors. • The robotic platform may offer the solution to bridge the gap between open and laparoscopic approaches, achieving warm ischaemia times that consistently average 20 minutes, and providing similar oncological and functional results via a shorter learning curve. It offers cosmesis and convalescence equivalent to that from laparoscopic partial nephrectomy, but with potentially fewer postoperative complications. • In terms of oncological and functional outcomes, the early experiences of RPN in selected series of patients appear at least equivalent to open and laparoscopic partial nephrectomy series. Randomized comparisons between the approaches are lacking, as are longer-term follow-up data for the robotic technique and formal cost analysis; these will be necessary before RPN can replace open partial nephrectomy as the new standard for the management of small renal masses. Trends continue to emerge that highlight the advantage of using the robotic platform to achieve a minimally invasive approach for partial nephrectomy, and with time and increasing expertise, this may become further apparent.


Spectral response of an upconversion detector and spectrometer.
We investigate the spectral response of an upconversion detector theoretically and experimentally, and discuss implications for its use as an infrared spectrometer. Upconversion detection is based on high-conversion-efficiency, sum-frequency generation (SFG). The spectral selectivity of an upconversion spectrometer is determined by the SFG spectral response function. This function changes with varying pump power. Working at maximum internal conversion efficiency is desirable for high sensitivity of the system, but the spectral response function is different at this pump power compared to the response function at low power. We calculate the theoretical spectral response of the upconversion detector as a function of pump power and obtain excellent agreement with upconversion spectra measured in a periodically poled LiNbO₃ waveguide.


Evaluation of Rural vs Urban Trauma Patients Served by 9-1-1 Emergency Medical Services.
Despite a large rural US population, there are potential differences between rural and urban regions in the processes and outcomes following trauma. To describe and evaluate rural vs urban processes of care, injury severity, and mortality among injured patients served by 9-1-1 emergency medical services (EMS). This was a preplanned secondary analysis of a prospective cohort enrolled from January 1 through December 31, 2011, and followed up through hospitalization. The study included 44 EMS agencies transporting to 28 hospitals in 2 rural and 5 urban counties in Oregon and Washington. A population-based, consecutive sample of 67 047 injured children and adults served by EMS (1971 rural and 65 076 urban) was enrolled. Among the 53 487 patients transported by EMS, a stratified probability sample of 17 633 patients (1438 rural and 16 195 urban) was created to track hospital outcomes (78.9% with in-hospital follow-up). Data analysis was performed from June 12, 2015, to May 20, 2016. Rural was defined at the county level by 60 minutes or more driving proximity to the nearest level I or II trauma center and/or rural designation in the Centers for Medicare & Medicaid Services ambulance fee schedule by zip code. Mortality (out-of-hospital and in-hospital), need for early critical resources, and transfer rates. Of the 53 487 injured patients transported by EMS (17 633 patients in the probability sample), 27 535 were women (51.5%); mean (SD) age was 51.6 (26.1) years. Rural vs urban sensitivity of field triage for identifying patients requiring early critical resources was 65.2% vs 80.5%, and only 29.4% of rural patients needing critical resources were initially transported to major trauma centers vs 88.7% of urban patients. After accounting for transfers, 39.8% of rural patients requiring critical resources were cared for in major trauma centers vs 88.7% of urban patients. Overall mortality did not differ between rural and urban regions (1.44% vs 0.89%; P = .09); however, 89.6% of rural deaths occurred within 24 hours compared with 64% of urban deaths. Rural regions had higher transfer rates (3.2% vs 2.7%) and longer transfer distances (median, 97.4 km; interquartile range [IQR], 51.7-394.5 km; range, 47.8-398.6 km vs 22.5 km; IQR, 11.6-24.6 km; range, 3.5-97.4 km). Most high-risk trauma patients injured in rural areas were cared for outside of major trauma centers and most rural trauma deaths occurred early, although overall mortality did not differ between regions. There are opportunities for improved timeliness and access to major trauma care among patients injured in rural regions.


Nanoparticle plasmon resonances in the near-static limit.
Localized surface plasmon resonances of metal nanoparticles of arbitrary shape are analyzed in the near-static limit with retardation included to the second order. Starting from the electrostatic approximation, the second-order correction to the resonant dielectric constant is expressed by means of a triple surface integral. For arbitrary nanoparticles with cylindrical symmetry we show how the triple surface integral can be significantly simplified, resulting in a computationally efficient scheme for evaluation of nanoparticle plasmon eigenresonances in the near-static limit. The approach allows for calculation of both dipolar and higher-order resonances.


Power Production and Biochemical Markers of Metabolic Stress and Muscle Damage Following a Single Bout of Short-Sprint and Heavy Strength Exercise in Well-Trained Cyclists.
Purpose: Although strength and sprint training are widely used methods in competitive cycling, no previous studies have compared the acute responses and recovery rates following such sessions among highly trained cyclists. The primary aim of the current study was to compare power production and biochemical markers of metabolic stress and muscle damage following a session of heavy strength (HS) and short-sprint training (SS). Methods: Eleven well-trained male cyclists (18 ± 2 years with maximal oxygen uptake of 67.2 ± 5.0 mL·kg-1·min-1) completed one HS session and one SS session in a randomized order, separated by 48 h. Power production and biochemical variables were measured at baseline and at different time points during the first 45 h post exercise. Results: Lactate and human growth hormone were higher 5 min, 30 min and 1 h post the SS compared to the HS session (all p ≤ 0.019). Myoglobin was higher following the HS than the SS session 5 min, 30 min and 1 h post exercise (all p ≤ 0.005), while creatine kinase (CK) was higher following the HS session 21 and 45 h post exercise (p ≤ 0.038). Counter movement jump and power production during 4 sec sprint returned to baseline levels at 23 and 47 h with no difference between the HS and SS session, whereas the delayed muscle soreness score was higher 45 h following the HS compared to the SS session (p = 0.010). Conclusion: Our findings indicate that SS training provides greater metabolic stress than HS training, whereas HS training leads to more muscle damage compared to that caused by SS training. The ability to produce power remained back to baseline already 23 h after both training sessions, indicating maintained performance levels although higher CK level and muscle soreness were present 45 h post the HS training session.


The wave speed of intergradation zone in two-species lattice Müllerian mimicry model.
A spatially explicit model is studied to analyse the movement of coupled clines in two-species Müllerian mimicry system as exemplified by the comimicking helicoiine butterflies in Central-South America Heliconius erato and Heliconius melpomene. In this system, a pair of comimicking wing patterns of two species (mimicry ring) is found in a geographical region but another pair of wing patterns is found in a different geographical region. The distribution of mimicry rings thus forms a spatial mosaic in a large geographical scale, and the mechanism responsible for their stable maintenance has been a long-standing question in evolutionary biology. We here examine the speed of the movement of boundaries that divide the regions inhabited by different mimetic morphs in each comimicking species, by assuming coupled two-state stochastic cellular automatons where the flipping rate of the site occupied by a mimetic morph depends on the local density of the same morph and of the comimicking morph in the other species. The speed of cline movement shows a complex dependence on the coupling parameter between mimetic species--greater coupling of comimicking morphs between species slows down the cline movement only when the reduction in predation rate exhibits diminishing return to the increase of local mimetic morph density. The analytical predictions are confirmed by the results of Monte Carlo simulations. The speed of advance is quite different from that predicted from the conventional reaction-diffusion model, indicating that demographic stochasticity plays a critical role in determining the speed of cline movement. We also examine if the spatial heterogeneity in migration rate can stably maintain clines.


Evidence that dirty electricity is causing the worldwide epidemics of obesity and diabetes.
The epidemics of obesity and diabetes most apparent in recent years had their origins with Thomas Edison's development of distributed electricity in New York City in 1882. His original direct current (DC) generators suffered serious commutator brush arcing which is a major source of high-frequency voltage transients (dirty electricity). From the onset of the electrical grid, electrified populations have been exposed to dirty electricity. Diesel generator sets are a major source of dirty electricity today and are used almost universally to electrify small islands and places unreachable by the conventional electric grid. This accounts for the fact that diabetes prevalence, fasting plasma glucose and obesity are highest on small islands and other places electrified by generator sets and lowest in places with low levels of electrification like sub-Saharan Africa and east and Southeast Asia.


Src Inhibition with saracatinib reverses fulvestrant resistance in ER-positive ovarian cancer models in vitro and in vivo.
More effective, less toxic treatments for recurrent ovarian cancer are needed. Although more than 60% of ovarian cancers express the estrogen receptor (ER), ER-targeted drugs have been disappointing due to drug resistance. In other estrogen-sensitive cancers, estrogen activates Src to phosphorylate p27 promoting its degradation and increasing cell-cycle progression. Because Src is activated in most ovarian cancers, we investigated whether combined Src and ER blockade by saracatinib and fulvestrant would circumvent antiestrogen resistance. ER and Src were assayed in 338 primary ovarian cancers. Dual ER and Src blockade effects on cell cycle, ER target gene expression, and survival were assayed in ERα+ ovarian cancer lines, a primary human ovarian cancer culture in vitro, and on xenograft growth. Most primary ovarian cancers express ER. Src activity was greater in ovarian cancer lines than normal epithelial lines. Estrogen activated Src, ER-Src binding, and ER translocation from cytoplasm to nucleus. Estrogen-mediated mitogenesis was via ERα, not ERβ. While each alone had little effect, combined saracatinib and fulvestrant increased p27 and inhibited cyclin E-Cdk2 and cell-cycle progression. Saracatinib also impaired induction of ER-target genes c-Myc and FOSL1; this was greatest with dual therapy. Combined therapy induced autophagy and more effectively inhibited ovarian cancer xenograft growth than monotherapy. Saracatinib augments effects of fulvestrant by opposing estrogen-mediated Src activation and target gene expression, increasing cell-cycle arrest, and impairing survival, all of which would oppose antiestrogen resistance in these ER+ ovarian cancer models. These data support further preclinical and clinical evaluation of combined fulvestrant and saracatinib in ovarian cancer.


Nurses' view of the family in psychiatric care.
The aim of this study is to examine nurses' view of the family in psychiatric care. The families of people who are mentally ill carry a heavy burden. Research has shown that they experience sorrow, shame and guilt. They are often involved in informal caring and there is evidence of families playing an important role in the recovery of the patient. In spite of this, a great deal could still be made to create more family-oriented care. This development depends to a large extent on nurses' view of involving families in the care and the perceived value of family-oriented work. Four focus groups, with four to six carers in each group, were conducted. The recorded focus groups lasted 75-90 minutes and the data were transcribed and interpreted using content analysis. The results present four themes: compassion for and understanding of close relatives, the carer as the recipient of negative feelings, difficulties and dilemmas in the meeting with close relatives and preconceptions of mental illnesses in the family and in society. The results were interpreted as meaning that the carers found themselves in something that can be described as a double-bind situation. From analysis and interpretation, the conclusion is drawn that improved communication between nurses, patients and families could be a way to resolve the double-bind situation. To promote family health and also improve things for the patient, it can be argued, from the results of this study, that nurses should carefully consider whether and how to involve family members in care.


Pregnancy following liver transplantation: review of outcomes and recommendations for management.
Liver transplantation is considered to be the treatment of choice for end-stage liver disease and its success has led to an increase in the number of female liver transplant recipients who are of childbearing age. Several key issues that are noted when counselling patients who are considering pregnancy following liver transplantation include the optimal timing of pregnancy, optimal contraception methods and the management of immunosuppression during pregnancy. The present review summarizes the most recent literature so that the clinician may address these issues with their patient and enable them to make informed decisions about pregnancy planning. The authors review recent studies examining maternal and fetal outcomes, and the rates of complications including risk of graft rejection. Subsequently, the authors provide recommendations for counselling prospective mothers and the management of the pregnant liver transplant recipient.


Different sex ratios of children born to Indian and Pakistani immigrants in Norway.
A low female-to-male ratio has been observed in different Asian countries, but this phenomenon has not been well studied among immigrants living in Western societies. In this study, we investigated whether a low female-to-male ratio exists among Indian and Pakistani immigrants living in Norway. In particular, we investigated whether the determination of sex via ultrasound examination, a common obstetric procedure that has been used in Norway since the early 1980 s, has influenced the female-to-male ratio among children born to parents of Indian or Pakistani origin. We performed a retrospective cohort study of live births in mothers of Indian (n = 1597) and Pakistani (n = 5617) origin. Data were obtained from "Statistics Norway" and the female-to-male (F/M) sex ratio was evaluated among 21,325 children born, in increasing birth order, during three stratified periods (i.e., 1969-1986, 1987-1996, and 1997-2005). A significant low female-to-male sex ratio was observed among children in the third and fourth birth order (sex ratio 65; 95% CI 51-80) from mothers of Indian origin who gave birth after 1987. Sex ratios did not deviate from the expected natural variation in the Indian cohort from 1969 to 1986, and remained stable in the Pakistani cohort during the entire study period. However, the female-to-male sex ratio seemed less skewed in recent years (i.e., 1997-2005). Significant differences were observed in the sex ratio of children born to mothers of Indian origin compared with children born to mothers of Pakistani origin. A skewed number of female births among higher birth orders (i.e., third or later) may partly reflect an increase in sex-selective abortion among mothers of Indian origin, although the numbers are too small to draw firm conclusions. Further research is needed to explain the observed differences in the female-to-male ratio among members of these ethnic groups who reside in Norway.


Inhibiting Ras prenylation increases the radiosensitivity of human tumor cell lines with activating mutations of ras oncogenes.
The influence of activated ras oncogenes on the sensitivity of human tumor cells to killing by radiation has been an unresolved question in radiobiology. We have examined this question by measuring the radiation sensitivity of human tumor cell lines with oncogenic mutations in their H- or K-ras genes after treatment with prenyltransferase inhibitors that prevent the posttranslational modification of ras required for its activity. Using two measures of clonogenic survival, we have demonstrated radiosensitization in cell lines with oncogenic H-ras mutations or with oncogenic K-ras mutations when ras processing was inhibited by prenyltransferase inhibitor treatment. In contrast, the inhibition of ras processing in cell lines expressing wild-type ras had no effect on radiation-induced cell death. The prenyltransferase inhibitors themselves inhibited clonogenic survival in some cases, but this inhibition did not correlate with ras mutational status. Although treatment with prenyltransferase inhibitors and radiation resulted in a greater reduction of clonogenicity than either treatment alone in cells with wild-type ras, treatment with both agents had a synergistic effect on cell killing in tumor cells with ras mutations. Our results demonstrate that the inhibition of oncogenic ras activity in human tumor cells can reduce the radiation survival of these cells, suggesting that oncogenic ras can contribute to radiation resistance in human tumors. These results further demonstrate the potential of using prenyltransferase inhibitors in combination with radiotherapy in the treatment of human malignancies.


Multi-generational effects of four selected environmental oestrogens on Daphnia magna.
The objective of this study was to determine whether vertebrate-type oestrogens have ecotoxicological effects on a crustacean species. The effects of 17beta-oestradiol (E2), diethylstilbestrol (DES), bisphenol A (BPA) and 4-nonylphenol (4-NP) on the freshwater invertebrate Daphnia magna were assessed over first and second generations. The acute EC(50) 48 h, based on immobilisation, for E2, DES, BPA and 4-NP were 2.87 mg/l, 1.55 mg/l, 7.75 mg/l and 0.13 mg/l, respectively. The impact of the test chemicals on moulting frequency was also assessed. The EC(50) 48 h, based on the inhibition of moult number for E2, DES and 4-NP were 2.04 mg/l, 1.87 mg/l and 0.14 mg/l, respectively. BPA was not observed to impact the moulting frequency of D. magna at concentrations tested. In a series of separate studies, the effects of the four selected test compounds on the survival, moulting frequency and reproduction of first and second generational D. magna were assessed over a period of 21 d. Exposure of D. magna to 4-NP decreased the number of offspring produced in both first and second generation testing. DES proved to have no significant (p0.05) inhibition of fecundity in first generation but when second generation daphnids were exposed to DES, a significant (p0.05) reduction in the number of offspring was recorded. When D. magna were exposed to E2 or BPA, no statistically significant (p0.05) inhibition in the number of moults or offspring produced was observed.


Bacteriocins of gram-positive bacteria.
In recent years, a group of antibacterial proteins produced by gram-positive bacteria have attracted great interest in their potential use as food preservatives and as antibacterial agents to combat certain infections due to gram-positive pathogenic bacteria. They are ribosomally synthesized peptides of 30 to less than 60 amino acids, with a narrow to wide antibacterial spectrum against gram-positive bacteria; the antibacterial property is heat stable, and a producer strain displays a degree of specific self-protection against its own antibacterial peptide. In many respects, these proteins are quite different from the colicins and other bacteriocins produced by gram-negative bacteria, yet customarily they also are grouped as bacteriocins. Although a large number of these bacteriocins (or bacteriocin-like inhibitory substances) have been reported, only a few have been studied in detail for their mode of action, amino acid sequence, genetic characteristics, and biosynthesis mechanisms. Nevertheless, in general, they appear to be translated as inactive prepeptides containing an N-terminal leader sequence and a C-terminal propeptide component. During posttranslational modifications, the leader peptide is removed. In addition, depending on the particular type, some amino acids in the propeptide components may undergo either dehydration and thioether ring formation to produce lanthionine and beta-methyl lanthionine (as in lantibiotics) or thio ester ring formation to form cystine (as in thiolbiotics). Some of these steps, as well as the translocation of the molecules through the cytoplasmic membrane and producer self-protection against the homologous bacteriocin, are mediated through specific proteins (enzymes). Limited genetic studies have shown that the structural gene for such a bacteriocin and the genes encoding proteins associated with immunity, translocation, and processing are present in a cluster in either a plasmid, the chromosome, or a transposon. Following posttranslational modification and depending on the pH, the molecules may either be released into the environment or remain bound to the cell wall. The antibacterial action against a sensitive cell of a gram-positive strain is produced principally by destabilization of membrane functions. Under certain conditions, gram-negative bacterial cells can also be sensitive to some of these molecules. By application of site-specific mutagenesis, bacteriocin variants which may differ in their antimicrobial spectrum and physicochemical characteristics can be produced. Research activity in this field has grown remarkably but sometimes with an undisciplined regard for conformity in the definition, naming, and categorization of these molecules and their genetic effectors. Some suggestions for improved standardization of nomenclature are offered.


Poxvirus-induced angiogenesis after a thermal burn.
Orf (contagious ecthyma) is a zoonotic infection caused by a dermatotropic parapoxvirus that commonly infects sheep, goats, and oxen. Parapoxviruses are transmitted to humans through contact with an infected animal or fomites. Orf virus infections can induce ulceration, and papulonodular, pustular, or ecthymic lesions of the skin after contact with an infected animal or contaminated fomite. Rarely, orf virus provokes extensive vasculo-endothelial proliferation as a skin manifestation. Here, we present the case of an 8-year old female with poxvirus-induced vascular angiogenesis that developed 10 days after a thermal burn. An 8-year-old female presented at our outpatient clinic with red swellings and a yellow-brown crust on them. After a thermal burn with hot water, she went to a clinic and the burn was dressed with nitrofurazone and covered for 2 days. When the dressing was removed after 2 days, nodules were seen in the burnt areas. When the clinical findings were considered with the histopathological features, a reactive vascular proliferation due to a viral agent was suspected. Following PCR, parapoxvirus ovis was detected. Viral infections such as pox virus can trigger pyogenic granulomas or pyogenic granuloma-like vascular angiogenesis. Infectious agents must be considered when dealing with pyogenic granuloma-like lesions.


Reading comprehension in autism spectrum disorders: the role of oral language and social functioning.
Reading comprehension is an area of difficulty for many individuals with autism spectrum disorders (ASD). According to the Simple View of Reading, word recognition and oral language are both important determinants of reading comprehension ability. We provide a novel test of this model in 100 adolescents with ASD of varying intellectual ability. Further, we explore whether reading comprehension is additionally influenced by individual differences in social behaviour and social cognition in ASD. Adolescents with ASD aged 14-16 years completed assessments indexing word recognition, oral language, reading comprehension, social behaviour and social cognition. Regression analyses show that both word recognition and oral language explain unique variance in reading comprehension. Further, measures of social behaviour and social cognition predict reading comprehension after controlling for the variance explained by word recognition and oral language. This indicates that word recognition, oral language and social impairments may constrain reading comprehension in ASD.


Psychogeriatric inpatient unit design: a literature review.
In many parts of the world the provision of psychogeriatric inpatient units (PGUs) remains limited. More units will be required over coming decades given rapid population aging. Medline (1950-2010), psycINFO (1806-2009), EMBASE (1980-2009) and CINAHL (1982-2009) were searched for papers about PGU design. Selected non-peer reviewed literature such as government reports and unpublished academic dissertations were also reviewed. Data were also obtained from the literature related to general adult psychiatry inpatient units where there was limited information from studies of units designed for older people. Over 200 papers were reviewed and 130 were included. There are few good quality studies to guide the design of acute PGUs and much of the existing literature is based on opinion and anecdote or, at best, based on observational studies. Randomized controlled studies comparing different designs and assessing outcomes are virtually non-existent. Several studies have identified violence and trauma resulting from hospitalization as significant problems with current acute PGU care. Despite its limitations the available literature provides useful guidance on how PGU design can optimize patient and staff safety and improve clinical outcomes. There are significant problems with current acute PGUs, and patient mix on existing units is an important issue. Future research should examine patient and staff perceptions of different PGU ward environments, the relationship between ward design and clinical outcomes, the effects of segregating patients with challenging behaviors in dementia and the benefits or otherwise of gender segregation.


T cell immunity in neonates.
Typically, neonates exhibit decreased or aberrant cellular immune responses when compared to adults, resulting in increased susceptibility to infection. However, it is clear that newborns are able to generate adult-like protective T cell responses under certain conditions. The focus of our research is to understand the deficiencies within the neonatal immune system that lead to improper cellular responses and how priming conditions can be altered to elicit the appropriate T cell response necessary to protect against development of pathogen-induced disease. With these goals in mind, we are exploring the attributes of neonatal T cells and their development, as well as the conditions during priming that influence the resulting response to immune challenge during the neonatal period.


An evaluation of post-campaign knowledge and practices of exclusive breastfeeding in Uganda.
Despite the benefits of exclusive breastfeeding for the health of mothers and children, its practice has markedly declined throughout the developing world. Mass media-communication programmes could play an important role in reversing this trend. This study evaluated the extent to which exposure to behaviour change communication (BCC) messages in the media determined recent improvements in exclusive breastfeeding knowledge and practices in areas targeted by the Delivery of Improved Services for Health (DISH) Project of Uganda. Data were drawn from the 1999 DISH Evaluation Survey. The survey collected information from representative samples of women and men of reproductive age. Multiple logistic regressions were used for assessing the independent influences of BCC exposure on breastfeeding knowledge and practices, controlling for several confounding factors. The results indicated that the exposure to BCC messages was strongly associated with women's knowledge of six months as the ideal duration for exclusive breastfeeding. Positive influences on knowledge of men were also found. Media effects on women's current practice of exclusively breastfeeding their infants up to six months were less conclusive, possibly because of the short interval between the launch of the BCC campaign and survey implementation. While there was some evidence of bias of self-reported exposure, results of exploratory analysis of the indirect effects of communication campaigns suggest that impacts may be compounded as overall awareness is increased at the community level eventually leading to improved knowledge among individuals.


Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation.
Mesothelioma is a rare cancer of the mesothelial cell layer of the pleura, peritoneum, pericardium and tunica vaginalis. It is typically caused by asbestos, notoriously resistant to chemotherapy and generally considered incurable with a poor life expectancy. Transglutaminase 2 (TG2), a GTP binding regulatory protein, is an important cancer stem cell survival and therapy resistance factor. We show that TG2 is highly expressed in human mesothelioma tumors and in mesothelioma cancer stem cells (MCS cells). TG2 knockdown or TG2 inhibitor treatment reduces MCS cell spheroid formation, matrigel invasion, migration and tumor formation. Time to tumor first appearance is doubled in TG2 knockout cells as compared to wild-type. In addition, TG2 loss is associated with reduced expression of stemness, and epithelial mesenchymal transition markers, and enhanced apoptosis. These studies indicate that TG2 is an important MCS cell survival protein and suggest that TG2 may serve as a mesothelioma cancer stem cell therapy target.


Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity.
Inherited severe hypoplasminogenaemia is a multisystemic disorder leading to deficient extravascular fibrinolysis. As a clinical consequence wound healing capacity of mucous membranes is markedly impaired leading to ligneous conjunctivitis and several other manifestations. Here we report the molecular genetic and clinical findings on 23 new cases with severe hypoplasminogenaemia. Homozygous or compound-heterozygous mutations in the plasminogen (PLG) gene were found in 16 of 23 patients (70%), three of which were novel mutations reported here for the first time (C166Y, Y264S, IVS10-7T/G). Compared to 79 previously published cases, clinical manifestations of the current group of patients showed higher percentages of ligneous periodontitis, congenital hydrocephalus, and involvement of the female genital tract. In contrast, involvement of the gastrointestinal or urogenital tract was not observed in any of the cases. Patients originated to a large extent (61%) from Turkey and the Middle East, and showed a comparably frequent occurrence of consanguinity of affected families and a greater female to male ratio than was derived from previous reports in the literature. Individual treatment of ligneous conjunctivitis included topical plasminogen or heparin eye drops, topical or systemic fresh frozen plasma, and surgical removal of ligneous pseudomembranes, mostly with modest or transient efficacy. In conclusion, the present study underscores the broad range of clinical manifestations in PLG-deficient patients with a trend to regional differences. Transmission of genetic and clinical data to the recently established Plasminogen Deficiency Registry should help to determine the prevalence of the disease and to develop more efficient treatment strategies.