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There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.
We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.
We used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.
Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).
These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.
Declaration of interest
W.v.d.B received fees in the past 3 years from Indivior, C&A Pharma, Opiant and Angelini. G.M.G. is a National Institute for Health Research (NIHR) Emeritus Senior Investigator, holds shares in P1vital and has served as consultant, advisor or CME speaker in the past 3 years for Allergan, Angelini, Compass Pathways, MSD, Lundbeck (/Otsuka and /Takeda), Medscape, Minervra, P1Vital, Pfizer, Sage, Servier, Shire and Sun Pharma.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
The study aims to evaluate the antiprotozoal activities of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Compounds 1–20 were obtained and identified by using chromatographic and spectroscopic techniques. The antiparasitic assays were performed on the intracellular form of T. cruzi and L. amazonensis using human leukaemic THP-1 cells as the host. The mechanism of action of the most active compounds was explored in silico by molecular docking using T. cruzi trypanothione reductase (TR) as a target, whereas the in vitro studies were performed by enzymatic assay using T. cruzi recombinant TR. In addition, the mitochondrial membrane potential was evaluated by flow cytometry. Two flavonoids, one triterpene and three acetogenins showed from high to moderate trypanocidal activities with IC50 values ranging 3.6–37.2 µm while three of the metabolites were moderately leishmanicidal. The molecular docking study revealed interactions between TR and the most trypanocidal compounds 1 (abyssinone IV) and 2 (atalantoflavone). In contrast, both showed no effect on TR in vitro. For the mitochondrial membrane potential assay, atalantoflavone (2) displayed a dose-dependent depolarization. On the basis of the aforementioned results, this compound's structure could be chemically explored in order to develop more potent trypanocidal derivatives.
The purpose of this paper is to present two concavity results for symmetric functions and apply these to obtain inequalities connecting the characteristic roots of the non-negative Hermitian (n.n.h.) matrices A, B and A + B.
The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite.
To test an obesity prevention strategy derived from behavioural economics (optimal defaults plus delay), focused on changing the college dining hall service method.
After a uniform pre-load, participants attended an experimental lunch in groups randomized to one of three conditions: a nutrient-dense, lower-fat/energy lunch as an optimal default (OD); a less-nutrient-dense, higher-fat/energy lunch as a suboptimal default (SD); or a free array (FA) lunch. In the OD condition, students were presented a menu depicting healthier vegetarian and omnivore foods as default, with opt-out alternatives (SD menu) available on request with a 15 min wait. In the SD condition, the same menu format was used with the positioning of food items switched. In the FA condition, all choices were presented in uniform fonts and were available immediately.
Private rooms designed to provide a small version of a college dining hall, on two campuses of a Northeastern US university.
First-year college students (n 129).
There was a significant main effect for condition on percentage of optimal choices selected, with 94 % of food choices in the OD condition optimal, 47 % in the FA condition optimal and none in the SD condition optimal. Similarly, energy intake for those in the SD condition significantly exceeded that in the FA condition, which exceeded that in the OD condition.
Presenting menu items as optimal defaults with a delay had a significant impact on choice and consumption, suggesting that further research into its long-term applicability is warranted.
This study aimed to investigate the prevalence of and risk factors for Eustachian tube dysfunction leading to middle-ear pathology in patients on chronic mechanical ventilation via tracheostomy tube.
A total of 40 patients on chronic ventilation were included in a prospective cohort study. Middle-ear status was determined by tympanometry. Tympanograms were categorised as types A, B or C; types B and C were defined as middle-ear pathology.
In all, 57 ears of 40 patients were examined. Disease was found in at least 1 ear in 26 out of 40 patients. Middle-ear pathology was found in 25 out of 34 patients who were tube fed (via nasogastric tube or percutaneous endoscopic gastrostomy) vs 1 patient out of the 6 fed orally (p = 0.014), and in 23 out of 31 with conscious or cognitive impairment vs 3 out of 9 cognitively intact patients (p = 0.044).
Middle-ear pathology is common in patients on chronic mechanical ventilation via tracheostomy tube. The highest prevalence was in those with impaired consciousness or cognition, and oral feeding appeared protective.
We describe three cases of newborns with complex CHD characterised by communication challenges. These communication challenges were categorised as patient, family, or system-related red flags. Strategies for addressing these red flags were proposed, for the goal of optimising care and improving quality of life in this vulnerable population.
Many technological applications of austenitic shape memory alloys (SMAs) involve cyclical mechanical loading and unloading in order to take advantage of pseudoelasticity. In this paper, we investigated the effect of mechanical bending of pseudoelastic NiTi SMA wires using high-energy synchrotron radiation X-ray diffraction (SR-XRD). Differential scanning calorimetry was performed to identify the phase transformation temperatures. Scanning electron microscopy images show that micro-cracks in compressive regions of the wire propagate with increasing bend angle, while tensile regions tend not to exhibit crack propagation. SR-XRD patterns were analyzed to study the phase transformation and investigate micromechanical properties. By observing the various diffraction peaks such as the austenite (200) and the martensite (
), and (101) planes, intensities and residual strain values exhibit strong anisotropy, depending upon whether the sample is in compression or tension during bending.
The combined association of dietary fat, glycaemic index (GI) and fibre with type 2 diabetes has rarely been investigated. The objective was to examine the relationship between a high-fat, high-GI, low-fibre dietary pattern across adult life and type 2 diabetes risk using reduced rank regression. Data were from the MRC National Survey of Health and Development. Repeated measures of dietary intake estimated using 5-d diet diaries were available at the age of 36, 43 and 53 years for 1180 study members. Associations between dietary pattern scores at each age, as well as longitudinal changes in dietary pattern z-scores, and type 2 diabetes incidence (n 106) from 53 to 60–64 years were analysed. The high-fat, high-GI, low-fibre dietary pattern was characterised by low intakes of fruit, vegetables, low-fat dairy products and whole-grain cereals, and high intakes of white bread, fried potatoes, processed meat and animal fats. There was an increasing trend in OR for type 2 diabetes with increasing quintile of dietary pattern z-scores at the age of 43 years among women but not among men. Women in the highest z-score quintile at the age of 43 years had an OR for type 2 diabetes of 5·45 (95 % CI 2·01, 14·79). Long-term increases in this dietary pattern, independently of BMI and waist circumference, were also detrimental among women: for each 1 sd unit increase in dietary pattern z-score between 36 and 53 years, the OR for type 2 diabetes was 1·67 (95 % CI 1·20, 2·43) independently of changes in BMI and waist circumference in the same periods. A high-fat, high-GI, low-fibre dietary pattern was associated with increased type 2 diabetes risk in middle-aged British women but not in men.
Some inconsistency is observed in the results from studies of reading development regarding the role of the syllable in visual word recognition, perhaps due to a disparity between the tasks used. We adopted a word-spotting paradigm, with Spanish children of second grade (mean age: 7 years) and sixth grade (mean age: 11 years). The children were asked to detect one-syllable words that could be found at the beginning of pseudo-words, with the boundary between the word and the remaining letters being manipulated. The end of the embedded word could either match the syllabic boundary (e.g. the word FIN in the pseudo-word FINLO, where the syllable boundary is between N and L) or not (e.g. FINUS, where the syllable boundary is located between I and N). The results showed that children of both grades were faster in the syllabic than the non-syllabic condition, and that the magnitude of this effect was the same regardless of reading ability. The results suggest an early universality in the use of syllables in Spanish, regardless of reading level.
Previous studies have suggested that prenatal maternal folate deficiency is associated with reduced prenatal brain growth and psychological problems in offspring. However, little is known about the longer-term impact. The aims of this study were to investigate whether prenatal maternal folate insufficiency, high total homocysteine levels and low vitamin B12 levels are associated with altered brain morphology, cognitive and/or psychological problems in school-aged children. This study was embedded in Generation R, a prospective population-based cohort study. The study sample consisted of 256 Dutch children aged between 6 and 8 years from whom structural brain scans were collected using MRI. The mothers of sixty-two children had insufficient (<8 nmol/l) plasma folate concentrations in early pregnancy. Cognitive development was assessed by the Snijders-Oomen Niet-verbale intelligentietest – Revisie and the NEPSY-II-NL. Psychological problems were assessed at age 6 years using the parent report of the Child Behavior Checklist. Low prenatal folate levels were associated with a smaller total brain volume (B –33·34; 95 % CI –66·7, 0·02; P=050) and predicted poorer performance on the language (B –0·28; 95 % CI –0·52, –0·04; P=0·020) and visuo-spatial domains (B –0·27; 95 % CI –0·50, –0·04; P=0·021). High homocysteine levels (>9·1 µmol/l) predicted poorer performance on the language (B –0·31; 95 % CI –0·56, –0·06; P=0·014) and visuo-spatial domains (B –0·36; 95 % CI –0·60, –0·11; P=0·004). No associations with psychological problems were found. Our findings suggest that folate insufficiency in early pregnancy has a long-lasting, global effect on brain development and is, together with homocysteine levels, associated with poorer cognitive performance.
Knowledge of the composition of many cultural heritage objects is limited, resulting in many unanswered questions in regards to the provenance, composition, and production methods. In this paper, our objective is to show that dual beam scanning electron microscope (SEM) and focused ion beam (FIB) can be used rapidly and non-destructively to determine the surface and bulk metal compositions in small cultural heritage objects. We show, for the first time, that this novel FIB technique can be successfully applied non-destructively to cultural heritage objects by examining three representative silver plated objects (Candelabra, “Century” spoon, and New York World’s Fair spoon) from the Dallas Museum of Art’s unparalleled collection of modern American silver. In each case, we successfully reveal and characterize the bulk metal as well as the Ag-plating, up to ∼80 µm deep and show that there is no visual damage resulting from the milling process of the FIB. This novel characterization technique can be applied, due to its ease of availability and rapid use, to many other problems in addition to silver plated objects, making dual beam SEM/FIB a possible cornerstone technique in the study of cultural heritage objects.