Preconceptional factors associated with very low birthweight delivery in East and West Berlin: a case control study

BACKGROUND: Very low birthweight, i.e. a birthweight < 1500 g, is among the strongest determinants of infant mortality and childhood morbidity. To develop primary prevention approaches to VLBW birth and its sequelae, information is needed on the causes of preterm birth, their personal and social antecedents, and on conditions associated with very low birthweight. Despite the growing body of evidence linking sociodemographic variables with preterm delivery, little is known as to how this may be extrapolated to the risk of very low birthweight. METHODS: In 1992, two years after the German unification, we started to recruit two cohorts of very low birthweight infants and controls in East and West Berlin for a long-term neurodevelopmental study. The present analysis was undertaken to compare potential preconceptional risk factors for very low birthweight delivery in a case-control design including 166 mothers (82 East vs. 84 West Berlin) with very low birthweight delivery and 341 control mothers (166 East vs. 175 West). RESULTS: Multivariate logistic regression analysis was used to assess the effects of various dichotomous parental covariates and their interaction with living in East or West Berlin. After backward variable selection, short maternal school education, maternal unemployment, single-room apartment, smoking, previous preterm delivery, and fetal loss emerged as significant main effect variables, together with living in West Berlin as positive effect modificator for single-mother status. CONCLUSION: Very low birthweight has been differentially associated with obstetrical history and indicators of maternal socioeconomic status in East and West Berlin. The ranking of these risk factors is under the influence of the political framework

An Educational and Physical Program to Reduce Headache, Neck/Shoulder Pain in a Working Community: A Cluster-Randomized Controlled Trial

Background: Noninvasive physical management is often prescribed for headache and neck pain. Systematic reviews, however, indicate that the evidence of its efficacy is limited. Our aim was to evaluate the effectiveness of a workplace educational and physical program in reducing headache and neck/shoulder pain. Methodology/Principal Findings: Cluster-randomized controlled trial. All municipal workers of the City of Turin, Italy, were invited to participate. Those who agreed were randomly assigned, according to their departments, to the intervention group (IG) or to the control group and were given diaries for the daily recording of pain episodes for 1 month (baseline). Subsequently, only the IG (119 departments, 923 workers) began the physical and educational program, whereas the control group (117 departments, 990 workers) did not receive any intervention. All participants were again given diaries for the daily recording of pain episodes after 6 months of intervention. The primary outcome was the change in the frequency of headache (expressed as the proportion of subjects with a 6550% reduction of frequency; responder rate); among the secondary outcomes there were the absolute reduction of the number of days per month with headache and neck/shoulder pain. Differences between the two groups were evaluated using mixed-effect regression models. The IG showed a higher responder rate [risk ratio, 95% confidence interval (CI)] for headache (1.58; 1.28 to 1.92) and for neck/shoulder pain (1.53; 1.27 to 1.82), and a larger reduction of the days per month (95% CI) with headache (-1.72; -2.40 to -1.04) and with neck/shoulder pain (-2.51; -3.56 to -1.47). Conclusions: The program effectively reduced headache and neck/shoulder pain in a large working community and appears to be easily transferable to primary-care settings. Further trials are needed to investigate the program effectiveness in a clinical setting, for highly selected patients suffering from specific headache types. Trial Registration: ClinicalTrials.gov NCT00551980. \ua9 2012 Mongini et al

Structure–properties relationships in fibre drawing of bioactive phosphate glasses

New bioactive phosphate glasses suitable for continuous fibre production are investigated in this work. The structure of both bulk and fibres from Na2O–CaO–MgO–P2O5 glasses has been studied by means of Raman and 31P and 23Na nuclear magnetic resonance spectroscopies, and the structural results have been correlated with the mechanical properties of the fibres and the dissolution rate of the bulk glasses. It has been observed that the mechanical properties of the phosphate glass fibres are influenced by the glass network connectivity, while the dissolution rates are governed by the Qi speciation of the PO4 units. As seen in previous studies, molar volume seems to play an important role in the fragility behaviour of phosphate glasses. Here, a lower molar volume resulting from the increase in the oxygen packing density hinders the cooperative flow of the PO4 units throughout the glass network and, therefore, causes a reduction in the kinetic fragility

Concordance and Discordance Between Brain Perfusion and Atrophy in Frontotemporal Dementia

The aim of this study was to determine if a dissociation between reduced cerebral perfusion and gray matter (GM) atrophy exists in frontotemporal dementia (FTD). The study included 28 patients with FTD and 29 cognitive normal (CN) subjects. All subjects had MRI at 1.5 T, including T1-weighted structural and arterial spin labeling (ASL) perfusion imaging. Non-parametric concordance/discordance tests revealed that GM atrophy without hypoperfusion occurs in the premotor cortex in FTD whereas concordant GM atrophy and hypoperfusion changes are found in the right prefrontal cortex and bilateral medial frontal lobe. The results suggest that damage of brain function in FTD, assessed by ASL perfusion, can vary regionally despite widespread atrophy. Detection of discordance between brain perfusion and structure in FTD might aid diagnosis and staging of the disease

Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications

In the past decade, positron emission tomography (PET) with carbon-11-labeled Pittsburgh Compound B (PIB) has revolutionized the neuroimaging of aging and dementia by enabling in vivo detection of amyloid plaques, a core pathologic feature of Alzheimer's disease (AD). Studies suggest that PIB-PET is sensitive for AD pathology, can distinguish AD from non-AD dementia (for example, frontotemporal lobar degeneration), and can help determine whether mild cognitive impairment is due to AD. Although the short half-life of the carbon-11 radiolabel has thus far limited the use of PIB to research, a second generation of tracers labeled with fluorine-18 has made it possible for amyloid PET to enter the clinical era. In the present review, we summarize the literature on amyloid imaging in a range of neurodegenerative conditions. We focus on potential clinical applications of amyloid PET and its role in the differential diagnosis of dementia. We suggest that amyloid imaging will be particularly useful in the evaluation of mildly affected, clinically atypical or early age-at-onset patients, and illustrate this with case vignettes from our practice. We emphasize that amyloid imaging should supplement (not replace) a detailed clinical evaluation. We caution against screening asymptomatic individuals, and discuss the limited positive predictive value in older populations. Finally, we review limitations and unresolved questions related to this exciting new technique

A Differential Role for Macropinocytosis in Mediating Entry of the Two Forms of Vaccinia Virus into Dendritic Cells

Vaccinia virus (VACV) is being developed as a recombinant viral vaccine vector for several key pathogens. Dendritic cells (DCs) are specialised antigen presenting cells that are crucial for the initiation of primary immune responses; however, the mechanisms of uptake of VACV by these cells are unclear. Therefore we examined the binding and entry of both the intracellular mature virus (MV) and extracellular enveloped virus (EV) forms of VACV into vesicular compartments of monocyte-derived DCs. Using a panel of inhibitors, flow cytometry and confocal microscopy we have shown that neither MV nor EV binds to the highly expressed C-type lectin receptors on DCs that are responsible for capturing many other viruses. We also found that both forms of VACV enter DCs via a clathrin-, caveolin-, flotillin- and dynamin-independent pathway that is dependent on actin, intracellular calcium and host-cell cholesterol. Both MV and EV entry were inhibited by the macropinocytosis inhibitors rottlerin and dimethyl amiloride and depended on phosphotidylinositol-3-kinase (PI(3)K), and both colocalised with dextran but not transferrin. VACV was not delivered to the classical endolysosomal pathway, failing to colocalise with EEA1 or Lamp2. Finally, expression of early viral genes was not affected by bafilomycin A, indicating that the virus does not depend on low pH to deliver cores to the cytoplasm. From these collective results we conclude that VACV enters DCs via macropinocytosis. However, MV was consistently less sensitive to inhibition and is likely to utilise at least one other entry pathway. Definition and future manipulation of these pathways may assist in enhancing the activity of recombinant vaccinia vectors through effects on antigen presentation

Retrograde traffic in the biosynthetic-secretory route

In the biosynthetic-secretory route from the rough endoplasmic reticulum, across the pre-Golgi intermediate compartments, the Golgi apparatus stacks, trans Golgi network, and post-Golgi organelles, anterograde transport is accompanied and counterbalanced by retrograde traffic of both membranes and contents. In the physiologic dynamics of cells, retrograde flow is necessary for retrieval of molecules that escaped from their compartments of function, for keeping the compartments’ balances, and maintenance of the functional integrities of organelles and compartments along the secretory route, for repeated use of molecules, and molecule repair. Internalized molecules may be transported in retrograde direction along certain sections of the secretory route, and compartments and machineries of the secretory pathway may be misused by toxins. An important example is the toxin of Shigella dysenteriae, which has been shown to travel from the cell surface across endosomes, and the Golgi apparatus en route to the endoplasmic reticulum, and the cytosol, where it exerts its deleterious effects. Most importantly in medical research, knowledge about the retrograde cellular pathways is increasingly being utilized for the development of strategies for targeted delivery of drugs to the interior of cells. Multiple details about the molecular transport machineries involved in retrograde traffic are known; a high number of the molecular constituents have been characterized, and the complicated fine structural architectures of the compartments involved become more and more visible. However, multiple contradictions exist, and already established traffic models again are in question by contradictory results obtained with diverse cell systems, and/or different techniques. Additional problems arise by the fact that the conditions used in the experimental protocols frequently do not reflect the physiologic situations of the cells. Regular and pathologic situations often are intermingled, and experimental treatments by themselves change cell organizations. This review addresses physiologic and pathologic situations, tries to correlate results obtained by different cell biologic techniques, and asks questions, which may be the basis and starting point for further investigations

Thoracic spine pain in the general population: Prevalence, incidence and associated factors in children, adolescents and adults. A systematic review

<p>Abstract</p> <p>Background</p> <p>Thoracic spine pain (TSP) is experienced across the lifespan by healthy individuals and is a common presentation in primary healthcare clinical practice. However, the epidemiological characteristics of TSP are not well documented compared to neck and low back pain. A rigorous evaluation of the prevalence, incidence, correlates and risk factors needs to be undertaken in order for epidemiologic data to be meaningfully used to develop evidence-based prevention and treatment recommendations for TSP.</p> <p>Methods</p> <p>A systematic review method was followed to report the evidence describing prevalence, incidence, associated factors and risk factors for TSP among the general population. Nine electronic databases were systematically searched to identify studies that reported either prevalence, incidence, associated factors (cross-sectional study) or risk factors (prospective study) for TSP in healthy children, adolescents or adults. Studies were evaluated for level of evidence and method quality.</p> <p>Results</p> <p>Of the 1389 studies identified in the literature, 33 met the inclusion criteria for this systematic review. The mean (SD) quality score (out of 15) for the included studies was 10.5 (2.0). TSP prevalence data ranged from 4.0–72.0% (point), 0.5–51.4% (7-day), 1.4–34.8% (1-month), 4.8–7.0% (3-month), 3.5–34.8% (1-year) and 15.6–19.5% (lifetime). TSP prevalence varied according to the operational definition of TSP. Prevalence for any TSP ranged from 0.5–23.0%, 15.8–34.8%, 15.0–27.5% and 12.0–31.2% for 7-day, 1-month, 1-year and lifetime periods, respectively. TSP associated with backpack use varied from 6.0–72.0% and 22.9–51.4% for point and 7-day periods, respectively. TSP interfering with school or leisure ranged from 3.5–9.7% for 1-year prevalence. Generally, studies reported a higher prevalence for TSP in child and adolescent populations, and particularly for females. The 1 month, 6 month, 1 year and 25 year incidences were 0–0.9%, 10.3%, 3.8–35.3% and 9.8% respectively. TSP was significantly associated with: concurrent musculoskeletal pain; growth and physical; lifestyle and social; backpack; postural; psychological; and environmental factors. Risk factors identified for TSP in adolescents included age (being older) and poorer mental health.</p> <p>Conclusion</p> <p>TSP is a common condition in the general population. While there is some evidence for biopsychosocial associations it is limited and further prospectively designed research is required to inform prevention and management strategies.</p

Thoracic spine pain in the general population: Prevalence, incidence and associated factors in children, adolescents and adults. A systematic review

<p>Abstract</p> <p>Background</p> <p>Thoracic spine pain (TSP) is experienced across the lifespan by healthy individuals and is a common presentation in primary healthcare clinical practice. However, the epidemiological characteristics of TSP are not well documented compared to neck and low back pain. A rigorous evaluation of the prevalence, incidence, correlates and risk factors needs to be undertaken in order for epidemiologic data to be meaningfully used to develop evidence-based prevention and treatment recommendations for TSP.</p> <p>Methods</p> <p>A systematic review method was followed to report the evidence describing prevalence, incidence, associated factors and risk factors for TSP among the general population. Nine electronic databases were systematically searched to identify studies that reported either prevalence, incidence, associated factors (cross-sectional study) or risk factors (prospective study) for TSP in healthy children, adolescents or adults. Studies were evaluated for level of evidence and method quality.</p> <p>Results</p> <p>Of the 1389 studies identified in the literature, 33 met the inclusion criteria for this systematic review. The mean (SD) quality score (out of 15) for the included studies was 10.5 (2.0). TSP prevalence data ranged from 4.0–72.0% (point), 0.5–51.4% (7-day), 1.4–34.8% (1-month), 4.8–7.0% (3-month), 3.5–34.8% (1-year) and 15.6–19.5% (lifetime). TSP prevalence varied according to the operational definition of TSP. Prevalence for any TSP ranged from 0.5–23.0%, 15.8–34.8%, 15.0–27.5% and 12.0–31.2% for 7-day, 1-month, 1-year and lifetime periods, respectively. TSP associated with backpack use varied from 6.0–72.0% and 22.9–51.4% for point and 7-day periods, respectively. TSP interfering with school or leisure ranged from 3.5–9.7% for 1-year prevalence. Generally, studies reported a higher prevalence for TSP in child and adolescent populations, and particularly for females. The 1 month, 6 month, 1 year and 25 year incidences were 0–0.9%, 10.3%, 3.8–35.3% and 9.8% respectively. TSP was significantly associated with: concurrent musculoskeletal pain; growth and physical; lifestyle and social; backpack; postural; psychological; and environmental factors. Risk factors identified for TSP in adolescents included age (being older) and poorer mental health.</p> <p>Conclusion</p> <p>TSP is a common condition in the general population. While there is some evidence for biopsychosocial associations it is limited and further prospectively designed research is required to inform prevention and management strategies.</p

Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia

BACKGROUND: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. METHODS: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). RESULTS: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs =-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. CONCLUSION: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities