CFEOM1, the classic familial form of congenital fibrosis of the extraocular muscles, is genetically heterogeneous but does not result from mutations in ARIX

BACKGROUND: To learn about the molecular etiology of strabismus, we are studying the genetic basis of 'congenital fibrosis of the extraocular muscles' (CFEOM). These syndromes are characterized by congenital restrictive ophthalmoplegia affecting muscles in the oculomotor and trochlear nerve distribution. Individuals with the classic form of CFEOM are born with bilateral ptosis and infraducted globes. When all affected members of a family have classic CFEOM, we classify the family as a CFEOM1 pedigree. We have previously determined that a CFEOM1 gene maps to the FEOM1 locus on chromosome 12cen. We now identify additional pedigrees with CFEOM1 to determine if the disorder is genetically heterogeneous and, if so, if any affected members of CFEOM1 pedigrees or sporadic cases of classic CFEOM harbor mutations in ARIX, the CFEOM2 disease gene. RESULTS: Eleven new CFEOM1 pedigrees were identified. All demonstrated autosomal dominant inheritance, and nine were consistent with linkage to FEOM1. Two small CFEOM1 families were not linked to FEOM1, and both were consistent with linkage to FEOM3. We screened two CFEOM1 families consistent with linkage to FEOM2 and 5 sporadic individuals with classic CFEOM and did not detect ARIX mutations. CONCLUSIONS: The phenotype of two small CFEOM1 families does not map to FEOM1, establishing genetic heterogeneity for this disorder. These two families may harbor mutations in the FEOM3 gene, as their phenotype is consistent with linkage to this locus. Thus far, we have not identified ARIX mutations in any affected members of CFEOM1 pedigrees or in any sporadic cases of classic CFEOM

In vivo clearance of surfactant lipids during acute pulmonary inflammation.

BACKGROUND: A decrease in pulmonary surfactant has been suggested to contribute to the lung dysfunction associated with pulmonary inflammation. A number of studies have implicated surfactant clearance as a possible mechanism for altered pool sizes. The objective of the current study was to specifically investigate the mechanisms of surfactant clearance in a rodent model of acute pulmonary inflammation. METHODS: Inflammation was induced by intrapulmonary instillation of lipopolysaccharide (LPS: 100 μg/kg). Lipid clearance was assessed at 18 and 72 hours post-LPS instillation by intratracheal administration of radiolabel surfactant-like liposomes 2 hours prior to isolation and analysis of inflammatory cells and type II cells. RESULTS: At both 18 and 72 hours after LPS instillation there was significantly less radioactivity recovered in the lavage fluid compared to respective control groups (p < 0.05). At both time points, the number of cells recovered by lavage and their associated radioactivity was greater compared to control groups (p < 0.01). There was no difference in recovery of radioactivity by isolated type II cells or other cells obtained from enzymatic digestion of lung tissue. CONCLUSION: These results show that increased clearance of surfactant lipids in our model of acute pulmonary inflammation is primarily due to the inflammatory cells recruited to the airspace and not increased uptake by alveolar type II cells

An approach to heroin use disorder intervention within the South African context: A content analysis study

<p>Abstract</p> <p>Background</p> <p>The field of heroin use disorder intervention has been in transition in South Africa since the outbreak of the heroin epidemic. Yet despite growing evidence of an association between heroin users' use of supplementary intervention services and intervention outcomes, heroin use disorder intervention programmes in South Africa generally fail to meet international research-based intervention standards.</p> <p>Methods</p> <p>Semi-structured interviews with ten heroin use disorder specialists were conducted and the interviews were subjected to content analysis.</p> <p>Results and Discussion</p> <p>In terms of theory and practice, findings of the study suggest that the field of heroin use disorder intervention in South Africa remains fragmented and transitional. Specifically, limited strategic public health care polices that address the syndromes' complexities have been implemented within the South Africa context.</p> <p>Conclusions</p> <p>Although many interventions and procedures have begun to be integrated routinely into heroin use disorder clinical practice within the South African context, comorbidity factors, such as psychiatric illness and HIV/AIDS, need to be more cogently addressed. Pragmatic and evidence-based public health care policies designed to reduce the harmful consequences associated with heroin use still needs to be implemented in the South African context.</p

Functional Connectivity in Tactile Object Discrimination—A Principal Component Analysis of an Event Related fMRI-Study

BACKGROUND: Tactile object discrimination is an essential human skill that relies on functional connectivity between the neural substrates of motor, somatosensory and supramodal areas. From a theoretical point of view, such distributed networks elude categorical analysis because subtraction methods are univariate. Thus, the aim of this study was to identify the neural networks involved in somatosensory object discrimination using a voxel-based principal component analysis (PCA) of event-related functional magnetic resonance images. METHODOLOGY/PRINCIPAL FINDINGS: Seven healthy, right-handed subjects aged between 22 and 44 years were required to discriminate with their dominant hand the length differences between otherwise identical parallelepipeds in a two-alternative forced-choice paradigm. Of the 34 principal components retained for analysis according to the 'bootstrapped' Kaiser-Guttman criterion, t-tests applied to the subject-condition expression coefficients showed significant mean differences between the object presentation and inter-stimulus phases in PC 1, 3, 26 and 32. Specifically, PC 1 reflected object exploration or manipulation, PC 3 somatosensory and short-term memory processes. PC 26 evinced the perception that certain parallelepipeds could not be distinguished, while PC 32 emerged in those choices when they could be. Among the cerebral regions evident in the PCs are the left posterior parietal lobe and premotor cortex in PC 1, the left superior parietal lobule (SPL) and the right cuneus in PC 3, the medial frontal and orbitofrontal cortex bilaterally in PC 26, and the right intraparietal sulcus, anterior SPL and dorsolateral prefrontal cortex in PC 32. CONCLUSIONS/SIGNIFICANCE: The analysis provides evidence for the concerted action of large-scale cortico-subcortical networks mediating tactile object discrimination. Parallel to activity in nodes processing object-related impulses we found activity in key cerebral regions responsible for subjective assessment and validation

Comparison of the caries-protective effect of fluoride varnish with treatment as usual in nursery school attendees receiving preventive oral health support through the Childsmile oral health improvement programme - the Protecting Teeth@3 Study:a randomised controlled trial

Background: The Scottish Government set out its policy on addressing the poor oral health of Scottish children in 2005. This led to the establishment of Childsmile, a national programme designed to improve the oral health of children in Scotland. One element of the programme promotes daily tooth brushing in all nurseries in Scotland (Childsmile Core). A second targeted component (Childsmile Nursery) offers twice-yearly application of fluoride varnish to children attending nurseries in deprived areas. Studies suggest that fluoride varnish application can reduce caries in both adult and child populations. This trial aims to explore the effectiveness and cost-effectiveness of additional preventive value fluoride varnish application compared to Childsmile Core. Methods/Design: The Protecting Teeth@3 Study is an ongoing 2 year parallel group randomised treatment as usual controlled trial. Three-year-old children attending the ante pre-school year are randomised (1:1) to the intervention arm (fluoride varnish &#38; treatment as usual) or the control arm (treatment as usual). Children in the intervention arm will have Duraphat® fluoride varnish painted on the primary tooth surfaces and will continue to receive treatment as usual: the core Childsmile Nursery intervention. Children in the treatment as usual arm will receive the same series of contacts, without the application of varnish and will also continue with the Childsmile Core intervention. Interventions are undertaken by Childsmile trained extended duty dental nurses at six-monthly intervals. Participants receive a baseline dental inspection in nursery and an endpoint inspection in Primary 1 at the age of 5 years old. We will use primary and secondary outcome measures to compare the effectiveness of Duraphat® fluoride varnish plus treatment as usual with treatment as usual only in preventing any further dental decay. We will also undertake a full economic evaluation of the trial

The effect of temperature, gradient and load carriage on oxygen consumption, posture and gait characteristics

Purpose The purpose of this experiment was to evaluate the effect of load carriage in a range of temperatures to establish the interaction between cold exposure, the magnitude of change from unloaded to loaded walking and gradient. Methods Eleven participants (19-27 years) provided written informed consent before performing six randomly ordered walking trials in six temperatures (20°C, 10°C, 5°C, 0°C, -5°C and -10°C). Trials involved two unloaded walking bouts before and after loaded walking (18.2 kg) at 4 km.hr⁻¹, on 0% and 10% gradients in 4 minute bouts. Results The change in absolute oxygen consumption (V̇O₂) from the first unloaded bout to loaded walking was similar across all six temperatures. When repeating the second unloaded bout, V̇O₂ at both -5°C and-10°C was greater compared to the first. At -10°C, V̇O₂ was increased from 1.60 ± 0.30 L.min⁻¹ to 1.89 ± 0.51 L.min⁻¹. Regardless of temperature, gradient had a greater effect on V̇O₂ and heart rate (HR) than backpack load. HR was unaffected by temperature. Stride length (SL) decreased with decreasing temperature but trunk forward lean was greater during cold exposure. Conclusion Decreased ambient temperature did not influence the magnitude of change in V̇O₂ from unloaded to loaded walking. However, in cold temperatures, V̇O₂ was significantly higher than in warm conditions. The increased V̇O₂ in colder temperatures at the same exercise intensity is predicted to ultimately lead to earlier onset of fatigue and cessation of exercise. These results highlight the need to consider both appropriate clothing and fitness during cold exposure

Procalcitonin Predicts Response to Beta-Lactam Treatment in Hospitalized Children with Community-Acquired Pneumonia

BACKGROUND: Antibiotic treatment of community-acquired pneumonia (CAP) in children remains mostly empirical because clinical and paraclinical findings poorly discriminate the principal causes of CAP. Fast response to beta-lactam treatment can be considered a proxy of pneumococcal aetiology. We aimed to identify the best biological predictor of response to beta-lactam therapy in children hospitalized for CAP. METHODS: A retrospective, single-centre cohort study included all consecutive patients 1 month to 16 years old hospitalized in a teaching hospital in Paris, France, because of CAP empirically treated with a beta-lactam alone from 2003 to 2010. Uni- and multivariate analyses were used to study the ability of routine biological parameters available in the Emergency Department to predict a favourable response to beta-lactam (defined as apyrexia within 48 hours of treatment onset). RESULTS: Among the 125 included patients, 85% (106) showed a favourable response to beta-lactam. In multivariate logistic regression, we found procalcitonin (PCT) the only independent predictor of apyrexia (p = 0.008). The adjusted odds ratio for the decadic logarithm of PCT was 4.3 (95% CI 1.5-12.7). At ≥ 3 ng/mL, PCT had 55.7% sensitivity (45.7-65.3), 78.9% specificity (54.4-93.9), 93.7% positive predictive value (84.5-98.2), 24.2% negative predictive value (14.2-36.7), 2.64 positive likelihood ratio (1.09-6.42) and 0.56 negative likelihood ratio (0.41-0.77). In the 4 children with a PCT level ≥ 3 ng/mL and who showed no response to beta-lactam treatment, secondary pleural effusion had developed in 3, and viral co-infection was documented in 1. CONCLUSIONS: PCT is the best independent biologic predictor of favourable response to beta-lactam therapy in children hospitalized for CAP. Thus, a high PCT level is highly suggestive of pneumococcal aetiology. However, a 3-ng/mL cut-off does not seem compatible with daily medical practice, and additional research is needed to further define the role of PCT in managing CAP in children

Evaluating environmental tobacco smoke exposure in a Group of turkish primary school students and developing intervention methods for prevention

<p>Abstract</p> <p>Background</p> <p>In countries like Turkey where smoking is highly prevalent, children's exposure to tobacco smoke is an important public health problem. The goals of this study were to determine the self-reported environmental tobacco smoke exposure status of primary school students in grades 3 to 5, to verify self-reported exposure levels with data provided from a biomarker of exposure, and to develop methods for preventing school children from passive smoking.</p> <p>Methods</p> <p>The study was conducted on 347 primary school students by using a standard questionnaire and urinary cotinine tests. Children with verified ETS exposure were randomly assigned to 2 intervention groups. Two phone interviews were conducted with the parents of the first group regarding their children's passive smoking status and its possible consequences. On the other hand, a brief note concerning urinary cotinine test result was sent to parents of the second group. Nine months after the initial urinary cotinine tests, measurements were repeated in both groups.</p> <p>Results</p> <p>According to questionnaire data, 59.9% of the study group (208 of 347) were exposed to ETS. Urinary cotinine measurements of children were highly consistent with the self-reported exposure levels (P < 0.001). Two different intervention methods were applied to parents of the exposed children. Control tests suggested a remarkable reduction in the proportion of those children demonstrating a recent exposure to ETS in both groups. Proportions of children with urinary cotinine concentrations 10 ng/ml or lower were 79.5% in Group I and 74.2% in Group II (P > 0.05).</p> <p>Conclusion</p> <p>Self-reported ETS exposure was found to be pretty accurate in the 9–11 age group when checked with urinary cotinine tests. Only informing parents that their childrens' ETS exposure were confirmed by a laboratory test seems to be very promising in preventing children from ETS.</p

Variance and Autocorrelation of the Spontaneous Slow Brain Activity

Slow (<0.1 Hz) oscillatory activity in the human brain, as measured by functional magnetic imaging, has been used to identify neural networks and their dysfunction in specific brain diseases. Its intrinsic properties may also be useful to investigate brain functions. We investigated the two functional maps: variance and first order autocorrelation coefficient (r1). These two maps had distinct spatial distributions and the values were significantly different among the subdivisions of the precuneus and posterior cingulate cortex that were identified in functional connectivity (FC) studies. The results reinforce the functional segregation of these subdivisions and indicate that the intrinsic properties of the slow brain activity have physiological relevance. Further, we propose a sample size (degree of freedom) correction when assessing the statistical significance of FC strength with r1 values, which enables a better understanding of the network changes related to various brain diseases