Prenatal vitamin C deficiency results in differential levels of oxidative stress during late gestation in foetal guinea pig brains

AbstractAntioxidant defences are comparatively low during foetal development making the brain particularly susceptible to oxidative stress during antioxidant deficiencies. The brain is one of the organs containing the highest concentration of vitamin C (VitC) and VitC deficiency during foetal development may place the brain at risk of redox status imbalance. In the present study, we investigated the developmental pattern and effect of VitC deficiency on antioxidants, vitamin E and superoxide dismutase (SOD), assessed oxidative damage by measuring malondialdehyde (MDA), hydroxynonenal (HNE) and nitrotyrosine (NT) and analysed gene and protein expression of apoptosis marker caspase-3 in the guinea pig foetal brain at two gestational (GD) time points, GD 45/pre-term and GD 56/near term following either a VitC sufficient (CTRL) or deficient (DEF) maternal dietary regime. We show that except for SOD, antioxidants and oxidative damage markers are differentially expressed between the two GDs, with high VitC (p<0.0001), NT modified proteins (p<0.0001) and active caspase-3 levels (p<0.05) at pre-term and high vitamin E levels (p<0.0001), HNE (p<0.0001) and MDA (p<0.0001) at near term. VitC deficiency significantly increased SOD activity (p<0.0001) compared to CTRLs at both GDs indicating a compensatory response, however, low levels of VitC significantly elevated MDA levels (p<0.05) in DEF at near term. Our results show a differential regulation of the investigated markers during late gestation and suggest that immature brains are susceptible to oxidative stress due to prenatal vitC deficiency in spite of an induction of protective adaptation mechanisms

Determinants of fruit and vegetable intake among 11-year-old schoolchildren in a country of traditionally low fruit and vegetable consumption

BACKGROUND: Fruit and vegetable consumption is traditionally low in Iceland. The results of the Pro Children cross-Europe survey showed that the consumption was lowest among children in Iceland. The aim of this study was to identify determinants of fruit and vegetable intake among 11-year-old schoolchildren in Iceland. METHODS: A cross-sectional survey was performed in Iceland in the autumn of 2003 as a part of the Pro Children cross-Europe survey. The survey was designed to provide information on actual consumption levels of vegetables and fruits by 11-year-old school children and to assess potential determinants of consumption patterns. A total of 1235 Icelandic children (89%) from 32 randomly chosen schools participated. Hierarchical regression analyses were performed to determine the explained variance of the children's fruit and vegetable intake. In these analyses socio-demographic background variables were entered as a first block, perceived physical-environmental variables as a second block, perceived socio-environmental variables as a third block and personal variables as a fourth block. RESULTS: 64% of the children ate fruit less than once a day, and 61% ate vegetables less than once a day. Respectively, 31% and 39% of the variance in children's fruit and vegetable intake was explained by the determinants studied. About 7% and 13% of the variance in fruit and vegetable intake was explained by the perceived physical-environmental determinants, mainly by availability at home. About 18% and 16% of the variance in fruit and vegetable intake was explained by the personal determinants. For both fruit and vegetable intake, the significant personal determinants were preferences, liking, knowledge of recommendations and self-efficacy. CONCLUSION: Interventions to increase fruit and vegetable intake among children should aim at both environmental factors such as greater availability of fruit and vegetables, and personal factors as self-efficacy and knowledge levels concerning nutrition

Primary health care staff's perceptions of childhood tuberculosis: a qualitative study from Tanzania

<p>Abstract</p> <p>Background</p> <p>Diagnosing tuberculosis in children remains a great challenge in developing countries. Health staff working in the front line of the health service delivery system has a major responsibility for timely identification and referral of suspected cases of childhood tuberculosis. This study explored primary health care staff's perception, challenges and needs pertaining to the identification of children with tuberculosis in Muheza district in Tanzania.</p> <p>Methods</p> <p>We conducted a qualitative study that included 13 semi-structured interviews and 3 focus group discussions with a total of 29 health staff purposively sampled from primary health care facilities. Analysis was performed in accordance with the principles of a phenomenological analysis.</p> <p>Results</p> <p>Primary health care staff perceived childhood tuberculosis to be uncommon in the society and tuberculosis was rarely considered as a likely differential diagnosis. Long duration and severe signs of disease together with known exposure to tuberculosis were decisive for the staff to suspect tuberculosis in children and refer them to hospital. None of the staff felt equipped to identify cases of childhood tuberculosis and they experienced lack of knowledge, applicable tools and guidelines as the main challenges. They expressed the need for more training, supervision and referral feedback to improving case identification.</p> <p>Conclusions</p> <p>Inadequate awareness of the burden of childhood tuberculosis, limited knowledge of the wide spectrum of clinical presentation and lack of clinical decision support strategies is detrimental to the health staff's central responsibility of suspecting and referring children with tuberculosis especially in the early disease stages. Activities to improve case identification should focus on skills required by primary health care staff to fulfil their responsibility and reflect primary health care level capacities and challenges.</p

Exploring life-space in the nursing home. An observational longitudinal study

Background Traditional performance-based measurements of mobility fail to recognize the interaction between the individual and their environment. Life-space (LS) forms a central element in the broader context of mobility and has received growing attention in gerontology. Still, knowledge on LS in the nursing home (NH) remains sparse. The aim of this study was to identify LS trajectories in people with dementia from time of NH admission, and explore characteristics associated with LS over time. Methods In total, 583 people with dementia were included at NH admission and assessed biannually for 3 years. LS was assessed using the Nursing Home Life-Space Diameter. Association with individual (age, sex, general medical health, number of medications, pain, physical performance, dementia severity, and neuropsychiatric symptoms) and environmental (staff-to-resident ratio, unit size, and quality of the physical environment) characterises was assessed. We used a growth mixture model to identify LS trajectories and linear mixed model was used to explore characteristics associated with LS over time. Results We identified four groups of residents with distinct LS trajectories, labelled Group 1 (n = 19, 3.5%), Group 2 (n = 390, 72.1%), Group 3 (n = 56, 10.4%), Group 4 (n = 76, 14.0%). Being younger, having good compared to poor general medical health, less severe dementia, more agitation, less apathy, better physical performance and living in a smaller unit were associated with a wider LS throughout the study period. Conclusion From NH admission most NH residents’ LS trajectory remained stable (Group 2), and their daily lives unfolded within their unit. Better physical performance and less apathy emerged as potentially modifiable characteristics associated with wider LS over time. Future studies are encouraged to determine whether LS trajectories in NH residents are modifiable, and we suggest that future research further explore the impact of environmental characteristics.publishedVersio

A Novel SCN5A Mutation in a Patient with Coexistence of Brugada Syndrome Traits and Ischaemic Heart Disease

Brugada syndrome (BrS) is a primary electrical heart disease, which can lead to sudden cardiac death. In older patients with BrS, the disease may coexist with ischaemic heart disease (IHD) and recent studies support a synergistic proarrhythmic effect of the two disease entities. We report a case that illustrates this. The index patient was a middle-aged patient with BrS traits, IHD, and aborted sudden cardiac death. Mutation analysis discovered a novel mutation P468L in the NaV1.5 sodium channel. Surprisingly, voltage-clamp experiments on the wild-type and mutant NaV1.5 channels expressed in HEK cells revealed no functional effect of the mutation. In a patient like ours, the distinction between IHD and BrS as the cause of an aborted sudden cardiac death is hard to establish and mounting evidence shows that coexistence of the two may have a synergistic proarrhythmic effect

Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer

AbstractBackground and purposeHPV is found in head and neck cancer from all sites with a higher prevalence in oropharynx cancer (OPC) compared to non-OPC. HPV/p16-status has a significant impact on radiotherapy (RT) outcome in advanced OPC, but less is known about the influence in non-OPC. We analyzed HPV-associated p16-expression in a cohort of patients with stage III–IV pharynx and larynx cancer treated with primary, curatively intended (chemo-)RT, aiming to test the hypothesis that the impact of HPV/p16 also extends to tumors of non-oropharyngeal origin.Material and methods1294 patients enrolled in previously conducted DAHANCA-trials between 1992 and 2012 were identified. Tumors were evaluated by p16-immunohistochemistry and classified as positive in case of staining in >70% of tumors cells.ResultsThirty-eight percent (490/1294) of the tumors were p16-positive with a significantly higher frequency in OPC (425/815) than in non-OPC (65/479), p<.0001. In OPC p16-positivity significantly improved loco-regional control (LRC) (adjusted HR [95% CI]: 0.43 [0.32–0.57]), event-free survival (EFS) (HR 0.44 [0.35–0.56]), and overall survival (OS) (HR: 0.38 [0.29–0.49]), respectively, compared with p16-negativity. In non-OPC no prognostic impact of p16-status was found for either endpoint: LRC (HR: 1.13 [0.75–1.70]), EFS (HR: 1.06 [0.76–1.47]), and OS (HR: 0.82 [0.59–1.16]).ConclusionsThe independent influence of HPV-associated p16-expression in advanced OPC treated with primary RT was confirmed. However, RT-outcome in the group of non-OPC did not differ by tumor p16-status, indicating that the prognostic impact may be restricted to OPC only