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Niemann–Pick disease type C (NPC) is an atypical, ultra-rare, lysosomal storage disease . In contrast to classic lysosomal storage diseases , the lysosomal storage of macromolecules is not caused by an enzyme deficiency, but rather by a deficiency of the protein products of two distinct genes, NPC1 and NPC2 [3, 4]. These two proteins are highly conserved across species; despite intense study for many years, their basic functions and the sequence of pathogenic events remains uncertain.
This article addresses recent advances in liquid phase transmission electron microscopy (LPTEM) for studying nanoscale synthetic processes of carbon-based materials that are independent of the electron beam—those driven by nonradiolytic chemical or thermal reactions. In particular, we focus on chemical/physical formations and the assembly of nanostructures composed of organic monomers/polymers, peptides/DNA, and biominerals. The synthesis of carbon-based nanomaterials generally only occurs at specific conditions, which cannot be mimicked by aqueous solution radiolysis. Carbon-based structures themselves are also acutely sensitive to the damaging effects of the irradiating beam, which make studying their synthesis using LPTEM a unique challenge that is possible when beam effects can be quantified and mitigated. With new direct sensing, high frame-rate cameras, and advances in liquid cell holder designs, combined with a growing understanding of irradiation effects and proper experimental controls, microscopists have been able to make strides in observing traditionally problematic carbon-based materials under conditions where synthesis can be controlled, and imaged free from beam effects, or with beam effects quantified and accounted for. These materials systems and LPTEM experimental techniques are discussed, focusing on nonradiolytic chemical and physical transformations relevant to materials synthesis.
Increased fruit and vegetable (FV) intake is associated with reduced blood pressure (BP). However, it is not clear whether the effect of FV on BP depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on BP. Baseline data from a prospective cohort study of 10 660 men aged 50–59 years examined not only the cross-sectional association between total FV intake but also specific types of FV and BP in France and Northern Ireland. BP was measured, and dietary intake assessed using FFQ. After adjusting for confounders, both systolic BP (SBP) and diastolic BP (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake; however, when examined according to fruit or vegetable sub-type (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on SBP >140 mmHg, the OR for total fruit, vegetable and fruit juice intake (per fourth) was 0·95 (95 % CI 0·91, 1·00), with the same estimates being 0·98 (95 % CI 0·94, 1·02) for citrus fruit (per fourth), 1·02 (95 % CI 0·98, 1·06) for fruit juice (per fourth), 0·93 (95 % CI 0·89, 0·98) for other fruit (per fourth), 1·05 (95 % CI 0·99, 1·10) for cooked vegetable (per fourth) and 0·86 (95 % CI 0·80, 0·91) for raw vegetable intakes (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP, DBP and risk of hypertension, but this differed by FV sub-type, suggesting that the strength of the association between FV sub-types and BP might be related to the type consumed, or to processing or cooking-related factors.
A large range of pulmonary and cardiac diseases may affect pregnant patients. The most common causes include acute viral respiratory infections, chronic pulmonary or cardiac conditions and bacterial pneumonia. Asthma is the most common pulmonary disease to complicate pregnancy, and a third of patients experience worsening of asthma control during pregnancy. In patients with chronic obstructive pulmonary disease, cystic fibrosis (CF), non-CF bronchiectasis or interstitial lung disease, and rarely in patients who have a history of lung transplantation, the physiological and biological conditions of pregnancy will not exacerbate the underlying pulmonary disease as much as reduce pulmonary reserve and disease tolerance. Pregnancy is associated with an increased risk of aspiration pneumonitis, pulmonary embolism, cardiomyopathy, acute myocardial infarction and aortic dissection. Often these occur in patients without other known risk factors.
Recognizing materials development was advancing slower than technological needs, the 2011 the Materials Genome Initiative (MGI) advocated interdisciplinary approaches employing an informatics framework in materials discovery and development. In response, an interdisciplinary graduate program, funded by the National Science Foundation, was designed at the intersection of materials science, materials informatics, and engineering design, aiming to equip the next generation of scientists and engineers with Material Data Science. Based on the 4- year implementation experience, this report demonstrates how intellectual communities bridge students interdisciplinary learning processes and support a transition from disciplinary grounding to interdisciplinary learning and research. We hope this training model can benefit other interdisciplinary graduate programs, and produce a more productive and interdisciplinary materials workforce.
Basic symptoms, defined as subjectively perceived disturbances in thought, perception and other essential mental processes, have been established as a predictor of psychotic disorders. However, the relationship between basic symptoms and family history of a transdiagnostic range of severe mental illness, including major depressive disorder, bipolar disorder and schizophrenia, has not been examined.
We sought to test whether non-severe mood disorders and severe mood and psychotic disorders in parents is associated with increased basic symptoms in their biological offspring.
We measured basic symptoms using the Schizophrenia Proneness Instrument – Child and Youth Version in 332 youth aged 8–26 years, including 93 offspring of control parents, 92 offspring of a parent with non-severe mood disorders, and 147 offspring of a parent with severe mood and psychotic disorders. We tested the relationships between parent mental illness and offspring basic symptoms in mixed-effects linear regression models.
Offspring of a parent with severe mood and psychotic disorders (B = 0.69, 95% CI 0.22–1.16, P = 0.004) or illness with psychotic features (B = 0.68, 95% CI 0.09–1.27, P = 0.023) had significantly higher basic symptom scores than control offspring. Offspring of a parent with non-severe mood disorders reported intermediate levels of basic symptoms, that did not significantly differ from control offspring.
Basic symptoms during childhood are a marker of familial risk of psychopathology that is related to severity and is not specific to psychotic illness.
Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.
Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.
Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.
Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.
We compared antibiotic prescribing to older people in different settings to inform antibiotic stewardship interventions. We used data linkage to stratify individuals aged 65 years and over in Northern Ireland, 1st January 2012–31st December 2013, by residence: community dwelling, care home dwelling or ‘transitioned’ if admitted to a care home. The odds of being prescribed an antibiotic by residence were analysed using logistic regression, adjusting for patient demographics and selected medication use (proxy for co-morbidities). Trends in monthly antibiotic prescribing were examined in the 6 months pre- and post-admission to the care home. The odds of being prescribed at least one antibiotic were twofold higher in care homes compared with community dwellers (adjusted odds ratio 2.05, 95% CI 1.93–2.17). There was a proportionate increase of 51.5% in the percentage prescribed an antibiotic on admission, with a monthly average of 23% receiving an antibiotic in the 6 months post admission. While clinical need likely accounts for some of the observed antibiotic prescribing in care homes we cannot rule out more liberal prescribing, given the twofold difference between care home residents and their community dwelling peers having accounted for co-morbidities. The appropriateness of antibiotic prescribing in the care home setting should be examined.
Tools applied at the point of care can provide valuable prognostic information for practitioners. In this one-year, prospective observational study, we examined the association of the short performance physical battery (SPPB) and one-year emergency department (ED) visits and hospitalizations. Overall, 191 new referrals attending an outpatient geriatric clinic in Hamilton, Ontario, were approached, and 120 were enrolled. SPPB and other assessments were completed during the routine clinical visit. ED visits and hospitalizations within one year of the baseline assessment were abstracted from electronic medical records. Logistic regression analyses were used to determine ED visits and hospitalization predictors. The mean SPPB score in the study cohort (mean age 80.6, SD 6.3 years; 53% female) was 6.3 (SD 3.2). SPPB score was associated with a one-year ED visit (OR = 0.90 [0.78–1.03]) and hospitalization (OR = 0.84 [0.72–0.97]) after adjusting for age, sex, and co-morbidities.
It is recognised that a limited cohort of patients receive open partial laryngeal surgery in specific centres within the UK, so sharing information around key clinical issues and recommendations for practice is necessary to improve outcomes.
This position statement provides practice recommendations based on a synthesis of the available evidence presented at the 12th Evidence Based Management day on ‘Laryngeal Cancer’ and the ensuing discussions. Literature searches and critical analysis of available evidence were undertaken and triangulated with the clinical experience of the authors to develop these recommendations.
Results and conclusion
This paper presents a comprehensive overview of challenges that the multidisciplinary team may encounter. It provides recommendations for swallow and speech rehabilitation after open partial laryngectomy, and suggests practical ways that these issues may be addressed pre- and post-operatively.
The consumption of nitrate-rich vegetables can acutely lower blood pressure and improve mediators shown to optimise vascular health. However, we do not yet understand the impact of long-term habitual dietary nitrate intake and its association with CVD. Therefore, the aim of this investigation was to examine the relationship between habitual dietary nitrate intakes and risk of CHD in women from the Nurses’ Health Study. We prospectively followed 62 535 women who were free from diabetes, CVD and cancer at baseline in 1986. Information on diet was updated every 4 years with validated FFQ. The main outcome was CHD defined by the occurrence of non-fatal myocardial infarction or fatal CHD. Cox proportional hazard regression models were used to estimate the relative risks (RR) and 95 % CI. During 26 years of follow-up, 2257 cases of CHD were identified. When comparing the highest quintile of nitrate intake with the lowest quintile, in aged-adjusted analysis there was a protective association for CHD (RR=0·77, 95 % CI 0·68, 0·97; P=0·0002) which dissipated after further adjustment for smoking, physical activity, BMI and race (RR=0·91; 95 % CI 0·80, 1·04; P=0·27). This magnitude of association was further attenuated once we adjusted for the Alternative Healthy Eating Index excluding vegetable and fruit consumption (RR=1·04, 95 % CI 0·91, 1·20; P=0·34). Dietary nitrate intake was not related to the risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors in a large group of US women.
The association between dietary patterns (DP) and prevalence of hearing loss in men enrolled in the Caerphilly Prospective Study was investigated. During 1979–1983, the study recruited 2512 men aged 45–59 years. At baseline, dietary data were collected using a semi-quantitative FFQ, and a 7-d weighed food intake (WI) in a 30 % subsample. Five years later, pure-tone unaided audiometric threshold was assessed at 0·5, 1, 2 and 4 kHz. Principal component analysis (PCA) identified three DP and multiple logistic and ordinal logistic regression models examined the association with hearing loss (defined as pure-tone average of frequencies 0·5, 1, 2 and 4 kHz >25 dB). Traditional, healthy and high-sugar/low-alcohol DP were found with both FFQ and WI data. With the FFQ data, fully adjusted models demonstrated significant inverse association between the healthy DP and hearing loss both as a dichotomous variable (OR=0·83; 95 % CI 0·77, 0·90; P<0·001) and as an ordinal variable (OR=0·87; 95 % CI 0·81, 0·94; P<0·001). With the WI data, fully adjusted models showed a significant and inverse association between the healthy DP and hearing loss (OR=0·85; 95 % CI 0·73, 0·99; P<0·03), and a significant association between the traditional DP (per fifth increase) and hearing loss both as a dichotomous variable (OR=1·18; 95 % CI 1·02, 1·35; P=0·02) and as an ordinal variable (OR=1·17; 95 % CI 1·03, 1·33; P=0·02). A healthy DP was significantly and inversely associated with hearing loss in older men. The role of diet in age-related hearing loss warrants further investigation.
Vitamin D deficiency is a common occurrence globally, and particularly so in pregnancy. There is conflicting evidence regarding the role of vitamin D during pregnancy in non-skeletal health outcomes for both the mother and the neonate. The aim of this study was to investigate the associations of maternal total 25-hydroxy vitamin D (25OHD) with neonatal anthropometrics and markers of neonatal glycaemia in the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Serological samples (n 1585) were obtained from pregnant women in the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, between 24 and 32 weeks’ gestation as part of the HAPO study. 25OHD concentrations were measured by liquid chromatography tandem-MS. Cord blood and neonatal anthropometric measurements were obtained within 72 h of birth. Statistical analysis was performed. After adjustment for confounders, birth weight standard deviation scores (SDS) and birth length SDS were significantly associated with maternal total 25OHD. A doubling of maternal 25OHD at 28 weeks’ gestation was associated with mean birth weight SDS and mean birth length SDS higher by 0·05 and 0·07, respectively (both, P=0·03). There were no significant associations with maternal 25OHD and other measures of neonatal anthropometrics or markers of neonatal glycaemia. In conclusion, maternal total 25OHD during pregnancy was independently associated with several neonatal anthropometric measurements; however, this association was relatively weak.
We aimed to quantify the proportion of people receiving care for HIV-infection that are 50 years or older (older HIV patients) in Latin America and the Caribbean between 2000 and 2015 and to estimate the contribution to the growth of this population of people enrolled before (<50yo) and after 50 years old (yo) (⩾50yo). We used a series of repeated, cross-sectional measurements over time in the Caribbean, Central and South American network (CCASAnet) cohort. We estimated the percentage of patients retained in care each year that were older HIV patients. For every calendar year, we divided patients into two groups: those who enrolled before age 50 and after age 50. We used logistic regression models to estimate the change in the proportion of older HIV patients between 2000 and 2015. The percentage of CCASAnet HIV patients over 50 years had a threefold increase (8% to 24%) between 2000 and 2015. Most of the growth of this population can be explained by the increasing proportion of people that enrolled before 50 years and aged in care. These changes will impact needs of care for people living with HIV, due to multiple comorbidities and high risk of disability associated with aging.