Physicians, Primary Caregivers and Topical Repellent: All Under-Utilised Resources in Stopping Dengue Virus Transmission in Affected Households

BACKGROUND: Primary health care facilities frequently manage dengue cases on an ambulatory basis for the duration of the patient’s illness. There is a great opportunity for specific messaging, aimed to reduce dengue virus (DENV) transmission in and around the home, to be directly targeted toward this high-risk ambulatory patient group, as part of an integrated approach to dengue management. The extent however, to which physicians understand, and can themselves effectively communicate strategies to stop focal DENV transmission around an ambulatory dengue case is unknown; the matter of patient comprehension and recollection then ensues. In addition, the effectiveness of N,N-diethyl-3-methylbenzamide (DEET)-based insect repellent in protecting dengue patients from Aedes aegypti mosquitoes’ bites has not been investigated. METHODOLOGY: A knowledge, attitude and practice (KAP) survey, focusing on the mechanisms of DENV transmission and prevention, was performed using semi-structured questionnaires. This survey was targeted towards the patients and family members providing supportive care, and physicians routinely involved in dengue patient management in Southern Vietnam. An additional clinical observational study was conducted to measure the efficacy of a widely-used 13% DEET-based insect repellent to repel Ae. aegypti mosquitoes from the forearms of dengue cases and matched healthy controls. PRINCIPAL FINDINGS: Among both the physician (n = 50) and patient (n = 49) groups there were several respondents lacking a coherent understanding of DENV transmission, leading to some inappropriate attitudes and inadequate acute preventive practices in the household. The application of insect repellent to protect patients and their relatives from mosquito bites was frequently recommended by majority of physicians (78%) participating in the survey. Nevertheless, our tested topical application of 13% DEET conferred only ~1hr median protection time from Ae. aegypti landing. This is notably shorter than that advertised on the manufacturer’s label. No differences in landing time between febrile dengue cases or matched healthy controls (n = 19 experiments) were observed. CONCLUSIONS/SIGNIFICANCE: Our study identifies missed opportunities for primary care physicians to improve public health through communication of strategies that could prevent focal dengue transmission in and around a case household. We advocate better access to more efficient communication methods for physicians and auxilliary health workers, supporting to educate those at high risk of DENV transmission. Our empirical testing of a widely-available 13% DEET-based repellent was limited in its protective efficacy against Ae. aegypti mosquito bites, and therefore DENV transmission, suggesting more frequent application is necessary to be beneficial

Arduous implementation: Does the Normalisation Process Model explain why it's so difficult to embed decision support technologies for patients in routine clinical practice

Background: decision support technologies (DSTs, also known as decision aids) help patients and professionals take part in collaborative decision-making processes. Trials have shown favorable impacts on patient knowledge, satisfaction, decisional conflict and confidence. However, they have not become routinely embedded in health care settings. Few studies have approached this issue using a theoretical framework. We explained problems of implementing DSTs using the Normalization Process Model, a conceptual model that focuses attention on how complex interventions become routinely embedded in practice.Methods: the Normalization Process Model was used as the basis of conceptual analysis of the outcomes of previous primary research and reviews. Using a virtual working environment we applied the model and its main concepts to examine: the 'workability' of DSTs in professional-patient interactions; how DSTs affect knowledge relations between their users; how DSTs impact on users' skills and performance; and the impact of DSTs on the allocation of organizational resources.Results: conceptual analysis using the Normalization Process Model provided insight on implementation problems for DSTs in routine settings. Current research focuses mainly on the interactional workability of these technologies, but factors related to divisions of labor and health care, and the organizational contexts in which DSTs are used, are poorly described and understood.Conclusion: the model successfully provided a framework for helping to identify factors that promote and inhibit the implementation of DSTs in healthcare and gave us insights into factors influencing the introduction of new technologies into contexts where negotiations are characterized by asymmetries of power and knowledge. Future research and development on the deployment of DSTs needs to take a more holistic approach and give emphasis to the structural conditions and social norms in which these technologies are enacte

Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis

Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors

Physicians, Primary Caregivers and Topical Repellent: All Under-Utilised Resources in Stopping Dengue Virus Transmission in Affected Households

BACKGROUND: Primary health care facilities frequently manage dengue cases on an ambulatory basis for the duration of the patient’s illness. There is a great opportunity for specific messaging, aimed to reduce dengue virus (DENV) transmission in and around the home, to be directly targeted toward this high-risk ambulatory patient group, as part of an integrated approach to dengue management. The extent however, to which physicians understand, and can themselves effectively communicate strategies to stop focal DENV transmission around an ambulatory dengue case is unknown; the matter of patient comprehension and recollection then ensues. In addition, the effectiveness of N,N-diethyl-3-methylbenzamide (DEET)-based insect repellent in protecting dengue patients from Aedes aegypti mosquitoes’ bites has not been investigated. METHODOLOGY: A knowledge, attitude and practice (KAP) survey, focusing on the mechanisms of DENV transmission and prevention, was performed using semi-structured questionnaires. This survey was targeted towards the patients and family members providing supportive care, and physicians routinely involved in dengue patient management in Southern Vietnam. An additional clinical observational study was conducted to measure the efficacy of a widely-used 13% DEET-based insect repellent to repel Ae. aegypti mosquitoes from the forearms of dengue cases and matched healthy controls. PRINCIPAL FINDINGS: Among both the physician (n = 50) and patient (n = 49) groups there were several respondents lacking a coherent understanding of DENV transmission, leading to some inappropriate attitudes and inadequate acute preventive practices in the household. The application of insect repellent to protect patients and their relatives from mosquito bites was frequently recommended by majority of physicians (78%) participating in the survey. Nevertheless, our tested topical application of 13% DEET conferred only ~1hr median protection time from Ae. aegypti landing. This is notably shorter than that advertised on the manufacturer’s label. No differences in landing time between febrile dengue cases or matched healthy controls (n = 19 experiments) were observed. CONCLUSIONS/SIGNIFICANCE: Our study identifies missed opportunities for primary care physicians to improve public health through communication of strategies that could prevent focal dengue transmission in and around a case household. We advocate better access to more efficient communication methods for physicians and auxilliary health workers, supporting to educate those at high risk of DENV transmission. Our empirical testing of a widely-available 13% DEET-based repellent was limited in its protective efficacy against Ae. aegypti mosquito bites, and therefore DENV transmission, suggesting more frequent application is necessary to be beneficial

"I'm not being rude, I'd want somebody normal" Adolescents' perception of their peers with Tourette's syndrome; an exploratory study

Background: Tourette’s syndrome (TS) is a highly stigmatised condition, and typically developing adolescents’ motives and reason for excluding individuals with TS have not been examined. Aims: The aim of the study was to understand how TS is conceptualised by adolescents and explore how individuals with TS are perceived by their typically developing peers. Method: Free text writing and focus groups were used to elicit the views of twenty-two year ten students from a secondary school in South East England. Grounded theory was used to develop an analytical framework. Result: Participants’ understanding about the condition was construed from misconceptions, unfamiliarity and unanswered questions. Adolescents who conceived TS as a disorder beyond the individual’s control perceived their peers as being deprived of agency and strength and as straying from the boundaries of normalcy. People with TS were viewed as individuals deserving pity, and in need of support. Although participants maintained they had feelings of social politeness towards those with TS, they would avoid initiating meaningful social relationships with them due to fear of “social contamination”. Intergroup anxiety would also inhibit a close degree of social contact. Participants that viewed those with TS as responsible for their condition expressed a plenary desire for social distance. However, these behavioural intentions were not limited to adolescents that elicited inferences of responsibility to people with TS, indicating that attributional models of stigmatisation may be of secondary importance in the case of TS. Implications for interventions to improve school belonging among youths with TS are discussed

Genotoxic capacity of Cd/Se semiconductor quantum dots with differing surface chemistries.

Quantum dots (QD) have unique electronic and optical properties promoting biotechnological advances. However, our understanding of the toxicological structure-activity relationships remains limited. This study aimed to determine the biological impact of varying nanomaterial surface chemistry by assessing the interaction of QD with either a negative (carboxyl), neutral (hexadecylamine; HDA) or positive (amine) polymer coating with human lymphoblastoid TK6 cells. Following QD physico-chemical characterisation, cellular uptake was quantified by optical and electron microscopy. Cytotoxicity was evaluated and genotoxicity was characterised using the micronucleus assay (gross chromosomal damage) and the HPRT forward mutation assay (point mutagenicity). Cellular damage mechanisms were also explored, focusing on oxidative stress and mitochondrial damage. Cell uptake, cytotoxicity and genotoxicity were found to be dependent on QD surface chemistry. Carboxyl-QD demonstrated the smallest agglomerate size and greatest cellular uptake, which correlated with a dose dependent increase in cytotoxicity and genotoxicity. Amine-QD induced minimal cellular damage, while HDA-QD promoted substantial induction of cell death and genotoxicity. However, HDA-QD were not internalised by the cells and the damage they caused was most likely due to free cadmium release caused by QD dissolution. Oxidative stress and induced mitochondrial reactive oxygen species were only partially associated with cytotoxicity and genotoxicity induced by the QD, hence were not the only mechanisms of importance. Colloidal stability, nanoparticle (NP) surface chemistry, cellular uptake levels and the intrinsic characteristics of the NPs are therefore critical parameters impacting genotoxicity induced by QD

Simulating the midlatitude atmospheric circulation: what might we gain from high-resolution modeling of air-sea interactions?

Purpose of Review. To provide a snapshot of the current research on the oceanic forcing of the atmospheric circulation in midlatitudes and a concise update on previous review papers. Recent findings. Atmospheric models used for seasonal and longer timescales predictions are starting to resolve motions so far only studied in conjunction with weather forecasts. These phenomena have horizontal scales of ~ 10–100 km which coincide with energetic scales in the ocean circulation. Evidence has been presented that, as a result of this matching of scale, oceanic forcing of the atmosphere was enhanced in models with 10–100 km grid size, especially at upper tropospheric levels. The robustness of these results and their underlying mechanisms are however unclear. Summary. Despite indications that higher resolution atmospheric models respond more strongly to sea surface temperature anomalies, their responses are still generally weaker than those estimated empirically from observations. Coarse atmospheric models (grid size greater than 100 km) will miss important signals arising from future changes in ocean circulation unless new parameterizations are developed

Spontaneous Reorientation Is Guided by Perceived Surface Distance, Not by Image Matching Or Comparison

Humans and animals recover their sense of position and orientation using properties of the surface layout, but the processes underlying this ability are disputed. Although behavioral and neurophysiological experiments on animals long have suggested that reorientation depends on representations of surface distance, recent experiments on young children join experimental studies and computational models of animal navigation to suggest that reorientation depends either on processing of any continuous perceptual variables or on matching of 2D, depthless images of the landscape. We tested the surface distance hypothesis against these alternatives through studies of children, using environments whose 3D shape and 2D image properties were arranged to enhance or cancel impressions of depth. In the absence of training, children reoriented by subtle differences in perceived surface distance under conditions that challenge current models of 2D-image matching or comparison processes. We provide evidence that children’s spontaneous navigation depends on representations of 3D layout geometry.National Institutes of Health (U.S.) (Grant HD 23103

Cell type-dependent changes in CdSe/ZnS quantum dot uptake and toxic endpoints.

Toxicity of nanoparticles (NPs) is often correlated with the physicochemical characteristics of the materials. However, some discrepancies are noted in in-vitro studies on quantum dots (QDs) with similar physicochemical properties. This is partly related to variations in cell type. In this study, we show that epithelial (BEAS-2B), fibroblast (HFF-1), and lymphoblastoid (TK6) cells show different biological responses following exposure to QDs. These cells represented the 3 main portals of NP exposure: bronchial, skin, and circulatory. The uptake and toxicity of negatively and positively charged CdSe:ZnS QDs of the same core size but with different surface chemistries (carboxyl or amine polymer coatings) were investigated in full and reduced serum containing media following 1 and 3 cell cycles. Following thorough physicochemical characterization, cellular uptake, cytotoxicity, and gross chromosomal damage were measured. Cellular damage mechanisms in the form of reactive oxygen species and the expression of inflammatory cytokines IL-8 and TNF-α were assessed. QDs uptake and toxicity significantly varied in the different cell lines. BEAS-2B cells demonstrated the highest level of QDs uptake yet displayed a strong resilience with minimal genotoxicity following exposure to these NPs. In contrast, HFF-1 and TK6 cells were more susceptible to toxicity and genotoxicity, respectively, as a result of exposure to QDs. Thus, this study demonstrates that in addition to nanomaterial physicochemical characterization, a clear understanding of cell type-dependent variation in uptake coupled to the inherently different capacities of the cell types to cope with exposure to these exogenous materials are all required to predict genotoxicity