Complex spatial language improves from 3 to 5 years: The role of prompting and overhearing in facilitating direction giving using between and middle.

The primary goal of this study was to specify age-related improvements in young children’s use of the complex spatial terms between and middle in response to prompting and overhearing supports. Three- to 5-year-old children described the location of a mouse hidden between two furniture items in a dollhouse. Three prompting conditions (Between Directive, Middle Directive, Nondirective) were compared with two overhearing conditions (Overhearing Between, Overhearing Middle). Children’s use of between and middle was much more frequent in response to directive prompting than in response to nondirective prompting or overhearing. Only 4-5-year-old children showed some evidence of using middle in response to nondirective prompting and overhearing, demonstrating developmental gains in sensitivity to subtle cues. The secondary goal was to assess young children’s production and comprehension of between and middle using tasks suitable for young children and parent report checklists. As expected, children’s spatial language showed strong developmental improvement and was related to direction-giving performance

Australian parents’ experiences with universal child and family health services

© 2018 Australian College of Nursing Ltd Background: Australian governments provide free services to promote maternal and child health, and to support parenting for families with children up to age five. Services are principally provided by dedicated child and family health nurses, but also by general practitioners, practice nurses, pharmacy nurses and midwives. Aim: This study aimed to examine the experiences of families with young children across Australia in accessing and receiving health care for well children, parenting support and advice from a range of providers. Methods: The study used quantitative and qualitative data from an online survey of 719 parents and carers with children aged up to five years. Findings: On quantitative scales, most respondents rated healthcare providers favourably for accessibility, credibility and their approach to families. However, qualitative responses revealed widely varying reactions to child and family health provision. Parents described both positive and negative experiences, highlighting elements of practice that are critical to consumer engagement. Discussion: Parents require health care and support that are accessible, consistent, affordable, encouraging, trustworthy, evidence-based and non-judgemental. Parents feel more confidence in the information and care provided by health professionals who are well-informed, resourceful and who respect their knowledge and beliefs. Conclusion: The findings demonstrate ways in which child and family health providers can engage and effectively support families with young children

Sindbis virus polyarthritis outbreak signalled by virus prevalence in the mosquito vectors

Polyarthritis and rash caused by Sindbis virus (SINV), was first recognised in northern Europe about 50 years ago and is known as Ockelbo disease in Sweden and Pogosta disease in Finland. This mosquito-borne virus occurs mainly in tropical and sub-tropical countries, and in northern Europe it is suggested to cause regularly reoccurring outbreaks. Here a seven-year cycle of SINV outbreaks has been referred to in scientific papers, although the hypothesis is based solely on reported human cases. In the search for a more objective outbreak signal, we evaluated mosquito abundance and SINV prevalence in vector mosquitoes from an endemic area in central Sweden. Vector mosquitoes collected in the River Dalälven floodplains during the years before, during, and after the hypothesised 2002 outbreak year were assayed for virus on cell culture. Obtained isolates were partially sequenced, and the nucleotide sequences analysed using Bayesian maximum clade credibility and median joining network analysis. Only one SINV strain was recovered in 2001, and 4 strains in 2003, while 15 strains were recovered in 2002 with significantly increased infection rates in both the enzootic and the bridge-vectors. In 2002, the Maximum Likelihood Estimated infection rates were 10.0/1000 in the enzootic vectors Culex torrentium/pipiens, and 0.62/1000 in the bridge-vector Aedes cinereus, compared to 4.9/1000 and 0.0/1000 in 2001 and 0.0/1000 and 0.32/1000 in 2003 Sequence analysis showed that all isolates belonged to the SINV genotype I (SINV-I). The genetic analysis revealed local maintenance of four SINV-I clades in the River Dalälven floodplains over the years. Our findings suggest that increased SINV-I prevalence in vector mosquitoes constitutes the most valuable outbreak marker for further scrutinising the hypothesized seven-year cycle of SINV-I outbreaks and the mechanisms behind

Novel TNF Receptor-1 Inhibitors Identified as Potential Therapeutic Candidates for Traumatic Brain Injury

Background: Traumatic brain injury (TBI) begins with the application of mechanical force to the head or brain, which initiates systemic and cellular processes that are hallmarks of the disease. The pathological cascade of secondary injury processes, including inflammation, can exacerbate brain injury-induced morbidities and thus represents a plausible target for pharmaceutical therapies. We have pioneered research on post-traumatic sleep, identifying that injury-induced sleep lasting for 6 h in brain-injured mice coincides with increased cortical levels of inflammatory cytokines, including tumor necrosis factor (TNF). Here, we apply post-traumatic sleep as a physiological bio-indicator of inflammation. We hypothesized the efficacy of novel TNF receptor (TNF-R) inhibitors could be screened using post-traumatic sleep and that these novel compounds would improve functional recovery following diffuse TBI in the mouse. Methods: Three inhibitors of TNF-R activation were synthesized based on the structure of previously reported TNF CIAM inhibitor F002, which lodges into a defined TNFR1 cavity at the TNF-binding interface, and screened for in vitro efficacy of TNF pathway inhibition (IκB phosphorylation). Compounds were screened for in vivo efficacy in modulating post-traumatic sleep. Compounds were then tested for efficacy in improving functional recovery and verification of cellular mechanism. Results: Brain-injured mice treated with Compound 7 (C7) or SGT11 slept significantly less than those treated with vehicle, suggesting a therapeutic potential to target neuroinflammation. SGT11 restored cognitive, sensorimotor, and neurological function. C7 and SGT11 significantly decreased cortical inflammatory cytokines 3 h post-TBI. Conclusions: Using sleep as a bio-indicator of TNF-R-dependent neuroinflammation, we identified C7 and SGT11 as potential therapeutic candidates for TBI

Identifying the motivations of African American volunteers working to prevent HIV/AIDS

Community-based organizations that are engaged in HIV/AIDS prevention and support services often rely on volunteers. This article describes the development of a 22-item inventory that measures the motivations of volunteers who deliver HIV prevention education in the African American community. In a statewide survey of volunteers (N = 102), the two strongest motivations for volunteer activity were concern for the African American community and a desire to understand the causes and consequences of the epidemic. These motives predicted the frequency that volunteers held discussions about HIV/AIDS with members of their community. Discussion focuses on the relevance of the results for the recruitment, training, and retention of volunteers

The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias.

BACKGROUND: The Ras-association family (RASSF) of tumour suppressor genes (TSGs) contains 10 members that encode proteins containing Ras-association (RA) domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1-10 in a series of childhood acute lymphocytic leukaemias (ALL) and normal blood and bone marrow samples. RESULTS: COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51) B-ALL and 41% (12/29) T-ALL, whilst RASSF10 was methylated in 16% (8/51) B-ALL and 88% (23/26) T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC). CONCLUSION: This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Lynch Syndrome Associated with Two MLH1 Promoter Variants and Allelic Imbalance of MLH1 Expression

© 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc. Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A > G and c.-7C > T) within the MLH1 5â²untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expr ession and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A > G and c.-7C > T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5â²UTR in the pathogenesis of Lynch syndrome.Link_to_subscribed_fulltex

Serum Amyloid P Therapeutically Attenuates Murine Bleomycin-Induced Pulmonary Fibrosis via Its Effects on Macrophages

Macrophages promote tissue remodeling but few mechanisms exist to modulate their activity during tissue fibrosis. Serum amyloid P (SAP), a member of the pentraxin family of proteins, signals through Fcγ receptors which are known to affect macrophage activation. We determined that IPF/UIP patients have increased protein levels of several alternatively activated pro-fibrotic (M2) macrophage-associated proteins in the lung and monocytes from these patients show skewing towards an M2 macrophage phenotype. SAP therapeutically inhibits established bleomycin-induced pulmonary fibrosis, when administered systemically or locally to the lungs. The reduction in aberrant collagen deposition was associated with a reduction in M2 macrophages in the lung and increased IP10/CXCL10. These data highlight the role of macrophages in fibrotic lung disease, and demonstrate a therapeutic action of SAP on macrophages which may extend to many fibrotic indications caused by over-exuberant pro-fibrotic macrophage responses