102 research outputs found

    Attitude of students and parents towards the teaching of sex education in secondary schools in Cross Rivers State

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    This study was conducted to investigate the disposition of students and parents towards the inclusion of sex education in the school curriculum in Cross River State. Using a random sampling technique, 602 secondary school students and 180 parents from Calabar, were selected for the study. Data were collected with the aid of self -administered questionnaire and analysed using descriptive statistical techniques. The majority of the students (90.70%) and parents (93.89%) were in support of the inclusion of sex education in the school curriculum. They believed that the teaching of sex education would compliment efforts being made towards the control of HIV/AIDS. Baseb on the results of the study, some recommendations were generated

    Constraint-Based Modeling and Kinetic Analysis of the Smad Dependent TGF-β Signaling Pathway

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    Background Investigation of dynamics and regulation of the TGF-β signaling pathway is central to the understanding of complex cellular processes such as growth, apoptosis, and differentiation. In this study, we aim at using systems biology approach to provide dynamic analysis on this pathway. Methodology/Principal Findings We proposed a constraint-based modeling method to build a comprehensive mathematical model for the Smad dependent TGF-β signaling pathway by fitting the experimental data and incorporating the qualitative constraints from the experimental analysis. The performance of the model generated by constraint-based modeling method is significantly improved compared to the model obtained by only fitting the quantitative data. The model agrees well with the experimental analysis of TGF-β pathway, such as the time course of nuclear phosphorylated Smad, the subcellular location of Smad and signal response of Smad phosphorylation to different doses of TGF-β. Conclusions/Significance The simulation results indicate that the signal response to TGF-β is regulated by the balance between clathrin dependent endocytosis and non-clathrin mediated endocytosis. This model is useful to be built upon as new precise experimental data are emerging. The constraint-based modeling method can also be applied to quantitative modeling of other signaling pathways

    Mining social mixing patterns for infectious disease models based on a two-day population survey in Belgium

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    <p>Abstract</p> <p>Background</p> <p>Until recently, mathematical models of person to person infectious diseases transmission had to make assumptions on transmissions enabled by personal contacts by estimating the so-called WAIFW-matrix. In order to better inform such estimates, a population based contact survey has been carried out in Belgium over the period March-May 2006. In contrast to other European surveys conducted simultaneously, each respondent recorded contacts over two days. Special attention was given to holiday periods, and respondents with large numbers of professional contacts.</p> <p>Methods</p> <p>Participants kept a paper diary with information on their contacts over two different days. A contact was defined as a two-way conversation of at least three words in each others proximity. The contact information included the age of the contact, gender, location, duration, frequency, and whether or not touching was involved.</p> <p>For data analysis, we used association rules and classification trees. Weighted generalized estimating equations were used to analyze contact frequency while accounting for the correlation between contacts reported on the two different days.</p> <p>A contact surface, expressing the average number of contacts between persons of different ages was obtained by a bivariate smoothing approach and the relation to the so-called next-generation matrix was established.</p> <p>Results</p> <p>People mostly mixed with people of similar age, or with their offspring, their parents and their grandparents. By imputing professional contacts, the average number of daily contacts increased from 11.84 to 15.70. The number of reported contacts depended heavily on the household size, class size for children and number of professional contacts for adults. Adults living with children had on average 2 daily contacts more than adults living without children. In the holiday period, the daily contact frequency for children and adolescents decreased with about 19% while a similar observation is made for adults in the weekend. These findings can be used to estimate the impact of school closure.</p> <p>Conclusion</p> <p>We conducted a diary based contact survey in Belgium to gain insights in social interactions relevant to the spread of infectious diseases. The resulting contact patterns are useful to improve estimating crucial parameters for infectious disease transmission models.</p

    Influence of Contact Definitions in Assessment of the Relative Importance of Social Settings in Disease Transmission Risk

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    BACKGROUND: Realistic models of disease transmission incorporating complex population heterogeneities require input from quantitative population mixing studies. We use contact diaries to assess the relative importance of social settings in respiratory pathogen spread using three measures of person contact hours (PCH) as proxies for transmission risk with an aim to inform bipartite network models of respiratory pathogen transmission. METHODS AND FINDINGS: Our survey examines the contact behaviour for a convenience sample of 65 adults, with each encounter classified as occurring in a work, retail, home, social, travel or "other" setting. The diary design allows for extraction of PCH-interaction (cumulative time in face-face conversational or touch interaction with contacts)--analogous to the contact measure used in several existing surveys--as well as PCH-setting (product of time spent in setting and number of people present) and PCH-reach (product of time spent in setting and number of people in close proximity). Heterogeneities in day-dependent distribution of risk across settings are analysed using partitioning and cluster analyses and compared between days and contact measures. Although home is typically the highest-risk setting when PCH measures isolate two-way interactions, its relative importance compared to social and work settings may reduce when adopting a more inclusive contact measure that considers the number and duration of potential exposure events. CONCLUSIONS: Heterogeneities in location-dependent contact behaviour as measured by contact diary studies depend on the adopted contact definition. We find that contact measures isolating face-face conversational or touch interactions suggest that contact in the home dominates, whereas more inclusive contact measures indicate that home and work settings may be of higher importance. In the absence of definitive knowledge of the contact required to facilitate transmission of various respiratory pathogens, it is important for surveys to consider alternative contact measures

    Varicella susceptibility and transmission dynamics in Slovenia

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    <p>Abstract</p> <p>Background</p> <p>A cross-sectional, age-stratified study was conducted to determine varicella-zoster seroprevalence and force of infection in Slovenia.</p> <p>Methods</p> <p>3689 serum samples were tested for VZV IgG antibodies with an enzyme immunoassay. Semiparametric and parametric modelling were used to estimate the force of infection.</p> <p>Results</p> <p>Overall, 85.6% of serum samples were seropositive. Age-specific prevalence rose rapidly in preschool children and over 90% of 8 years old tested positive for VZV. However, 2.8% of serum samples among women of childbearing age were seronegative. Semiparametric modelling yielded force of infection estimates of 0.182 (95% CI 0.158-0.206), 0.367 (95% CI 0.285-0.448) and 0.008 (95% CI 0.0-0.032) for age groups 0.5- < 6, 6-11 and ≥12 years, respectively, and 0.175 (95% CI 0.147-0.202), 0.391 (95% CI 0.303-0.480) and 0.025 (95% CI 0.003-0.046) for age groups 0.5- < 5, 5-9 and ≥10 years, respectively.</p> <p>Conclusions</p> <p>Regardless of the age grouping used, the highest transmission occurred in children in their first years of school.</p

    Social Contact Patterns in Vietnam and Implications for the Control of Infectious Diseases

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    BACKGROUND: The spread of infectious diseases from person to person is determined by the frequency and nature of contacts between infected and susceptible members of the population. Although there is a long history of using mathematical models to understand these transmission dynamics, there are still remarkably little empirical data on contact behaviors with which to parameterize these models. Even starker is the almost complete absence of data from developing countries. We sought to address this knowledge gap by conducting a household based social contact diary in rural Vietnam. METHODS AND FINDINGS: A diary based survey of social contact patterns was conducted in a household-structured community cohort in North Vietnam in 2007. We used generalized estimating equations to model the number of contacts while taking into account the household sampling design, and used weighting to balance the household size and age distribution towards the Vietnamese population. We recorded 6675 contacts from 865 participants in 264 different households and found that mixing patterns were assortative by age but were more homogenous than observed in a recent European study. We also observed that physical contacts were more concentrated in the home setting in Vietnam than in Europe but the overall level of physical contact was lower. A model of individual versus household vaccination strategies revealed no difference between strategies in the impact on R(0). CONCLUSIONS AND SIGNIFICANCE: This work is the first to estimate contact patterns relevant to the spread of infections transmitted from person to person by non-sexual routes in a developing country setting. The results show interesting similarities and differences from European data and demonstrate the importance of context specific data

    Close Encounters in a Pediatric Ward: Measuring Face-to-Face Proximity and Mixing Patterns with Wearable Sensors

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    International audienceBackground Nosocomial infections place a substantial burden on health care systems and represent one of the major issues in current public health, requiring notable efforts for its prevention. Understanding the dynamics of infection transmission in a hospital setting is essential for tailoring interventions and predicting the spread among individuals. Mathematical models need to be informed with accurate data on contacts among individuals. Methods and Findings We used wearable active Radio-Frequency Identification Devices (RFID) to detect face-to-face contacts among individuals with a spatial resolution of about 1.5 meters, and a time resolution of 20 seconds. The study was conducted in a general pediatrics hospital ward, during a one-week period, and included 119 participants, with 51 health care workers, 37 patients, and 31 caregivers. Nearly 16,000 contacts were recorded during the study period, with a median of approximately 20 contacts per participants per day. Overall, 25% of the contacts involved a ward assistant, 23% a nurse, 22% a patient, 22% a caregiver, and 8% a physician. The majority of contacts were of brief duration, but long and frequent contacts especially between patients and caregivers were also found. In the setting under study, caregivers do not represent a significant potential for infection spread to a large number of individuals, as their interactions mainly involve the corresponding patient. Nurses would deserve priority in prevention strategies due to their central role in the potential propagation paths of infections. Conclusions Our study shows the feasibility of accurate and reproducible measures of the pattern of contacts in a hospital setting. The obtained results are particularly useful for the study of the spread of respiratory infections, for monitoring critical patterns, and for setting up tailored prevention strategies. Proximity-sensing technology should be considered as a valuable tool for measuring such patterns and evaluating nosocomial prevention strategies in specific settings

    Graded Smad2/3 Activation Is Converted Directly into Levels of Target Gene Expression in Embryonic Stem Cells

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    The Transforming Growth Factor (TGF) β signalling family includes morphogens, such as Nodal and Activin, with important functions in vertebrate development. The concentration of the morphogen is critical for fate decisions in the responding cells. Smad2 and Smad3 are effectors of the Nodal/Activin branch of TGFβ signalling: they are activated by receptors, enter the nucleus and directly transcribe target genes. However, there have been no studies correlating levels of Smad2/3 activation with expression patterns of endogenous target genes in a developmental context over time. We used mouse Embryonic Stem (ES) cells to create a system whereby levels of activated Smad2/3 can be manipulated by an inducible constitutively active receptor (Alk4*) and an inhibitor (SB-431542) that blocks specifically Smad2/3 activation. The transcriptional responses were analysed by microarrays at different time points during activation and repression. We identified several genes that follow faithfully and reproducibly the Smad2/3 activation profile. Twenty-seven of these were novel and expressed in the early embryo downstream of Smad2/3 signalling. As they responded to Smad2/3 activation in the absence of protein synthesis, they were considered direct. These immediate responsive genes included negative intracellular feedback factors, like SnoN and I-Smad7, which inhibit the transcriptional activity of Smad2/3. However, their activation did not lead to subsequent repression of target genes over time, suggesting that this type of feedback is inefficient in ES cells or it is counteracted by mechanisms such as ubiquitin-mediated degradation by Arkadia. Here we present an ES cell system along with a database containing the expression profile of thousands of genes downstream of Smad2/3 activation patterns, in the presence or absence of protein synthesis. Furthermore, we identify primary target genes that follow proportionately and with high sensitivity changes in Smad2/3 levels over 15–30 hours. The above system and resource provide tools to study morphogen function in development

    Clinical and laboratory features associated with macrophage activation syndrome in Still’s disease: data from the international AIDA Network Still’s Disease Registry

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    To characterize clinical and laboratory signs of patients with Still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. Patients with Still's disease classified according to internationally accepted criteria were enrolled in the AutoInflammatory Disease Alliance (AIDA) Still's Disease Registry. Clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p &lt; 0.001), platelet abnormalities (p &lt; 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p &lt; 0.001). At multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. Clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data. © 2023, The Author(s)

    c-Met activation leads to the establishment of a TGFβ-receptor regulatory network in bladder cancer progression

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    Treatment of muscle-invasive bladder cancer remains a major clinical challenge. Aberrant HGF/c-MET upregulation and activation is frequently observed in bladder cancer correlating with cancer progression and invasion. However, the mechanisms underlying HGF/c-MET-mediated invasion in bladder cancer remains unknown. As part of a negative feedback loop SMAD7 binds to SMURF2 targeting the TGFβ receptor for degradation. Under these conditions, SMAD7 acts as a SMURF2 agonist by disrupting the intramolecular interactions within SMURF2. We demonstrate that HGF stimulates TGFβ signalling through c-SRC-mediated phosphorylation of SMURF2 resulting in loss of SMAD7 binding and enhanced SMURF2 C2-HECT interaction, inhibiting SMURF2 and enhancing TGFβ receptor stabilisation. This upregulation of the TGFβ pathway by HGF leads to TGFβ-mediated EMT and invasion. In vivo we show that TGFβ receptor inhibition prevents bladder cancer invasion. Furthermore, we make a rationale for the use of combinatorial TGFβ and MEK inhibitors for treatment of high-grade non-muscle-invasive bladder cancers
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