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Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.
Several life-threatening diseases of the kidney have their origins in mutational events that occur during embryonic development. In this study, we investigate the role of the Wolffian duct (WD), the earliest embryonic epithelial progenitor of renal tubules, in the etiology of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is associated with a germline mutation of one of the two Pkd1 alleles. For the disease to occur, a second event that disrupts the expression of the other inherited Pkd1 allele must occur. We postulated that this secondary event can occur in the pronephric WD. Using Cre-Lox recombination, mice with WD-specific deletion of one or both Pkd1 alleles were generated. Homozygous Pkd1-targeted deletion in WD-derived tissues resulted in mice with large cystic kidneys and serologic evidence of renal failure. In contrast, heterozygous deletion of Pkd1 in the WD led to kidneys that were phenotypically indistinguishable from control in the early postnatal period. High-throughput sequencing, however, revealed underlying gene and microRNA (miRNA) changes in these heterozygous mutant kidneys that suggest a strong predisposition toward developing ADPKD. Bioinformatic analysis of this data demonstrated an upregulation of several miRNAs that have been previously associated with PKD; pathway analysis further demonstrated that the differentially expressed genes in the heterozygous mutant kidneys were overrepresented in signaling pathways associated with maintenance and function of the renal tubular epithelium. These results suggest that the WD may be an early epithelial target for the genetic or molecular signals that can lead to cyst formation in ADPKD.
Oxidative stress is implicated in the aetiology of schizophrenia, and the antioxidant defence system (AODS) may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain and its correlates with clinical and demographic variables in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r = −0.46, p = 0.015), and a trend-level positive relationship between GSH and duration of illness (r = 0.34, p = 0.076).
Our findings are consistent with a possible compensatory upregulation of the AODS with longer duration of illness and suggest that the AODS may play a role in schizophrenia.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Norovirus, a major cause of gastroenteritis in people of all ages worldwide, was first reported in South Korea in 1999. The most common causal agents of pediatric acute gastroenteritis are norovirus and rotavirus. While vaccination has reduced the pediatric rotavirus infection rate, norovirus vaccines have not been developed. Therefore, prediction and prevention of norovirus are very important. Norovirus is divided into genogroups GI–GVII, with GII.4 being the most prevalent. However, in 2012–2013, GII.17 showed a higher incidence than GII.4 and a novel variant, GII.P17-GII.17, appeared. In this study, 204 stool samples collected in 2013–2014 were screened by reverse transcriptase-polymerase chain reaction; 11 GI (5.39%) and 45 GII (22.06%) noroviruses were identified. GI.4, GI.5, GII.4, GII.6 and GII.17 were detected. The whole genomes of the three norovirus GII.17 were sequenced. The whole genome of GII.17 consists of three open reading frames of 5109, 1623 and 780 bp. Compared with 20 GII.17 strains isolated in other countries, we observed numerous changes in the protruding P2 domain of VP1 in the Korean GII.17 viruses. Our study provided genome information that might aid in epidemic prevention, epidemiology studies and vaccine development.
Introduction: Competence committees (CCs) struggle with incorporating professionalism issues into resident progression decisions. This study examined how professionalism concerns influence individual faculty decisions about resident progression using simulated CC reviews. Methods: In 2017, the investigators conducted a survey of 25 program directors of Royal College emergency medicine residency training programs in Canada and those faculty members who are members of the CCs (or equivalent) at their home institution. The survey contained twelve resident portfolios, each containing formative and summative information available to a CC for making progression decisions. Six portfolios outlined residents progressing as expected and six were not progressing as expected. Further, a professionalism variable (PV) was added to six portfolios, evenly split between those residents progressing as expected and not. Participants were asked to make progression decisions based on each portfolio. Results: Raters were able to consistently identify a resident needing an educational intervention versus those who did not. When a PV was added, the consistency among raters decreased by 34.2% in those residents progressing as expected, versus increasing by 3.8% in those not progressing as expected (p = 0.01). Conclusion: When using an unstructured review of a simulated resident portfolio, individual reviewers can better discriminate between trainees progressing as expected when professionalism concerns are added. Considering this, educators using a competence committee in a CBME program must have a system to acquire and document professionalism issues to make appropriate progress decisions.
Introduction: Although acute gastroenteritis is an extremely common childhood illness, there is a paucity of literature characterizing the associated pain and its management. Our primary objective was to quantify the pain experienced by children with acute gastroenteritis in the 24-hours prior to emergency department (ED) presentation. Secondary objectives included describing maximum pain, analgesic use, discharge recommendations, and factors that influenced analgesic use in the ED. Methods: Study participants were recruited into this prospective cohort study by the Alberta Provincial Pediatric EnTeric Infection TEam between January 2014 and September 2017. This study was conducted at two Canadian pediatric EDs; the Alberta Children's Hospital (Calgary) and the Stollery Children's Hospital (Edmonton). Eligibility criteria included < 18 years of age, acute gastroenteritis (□ 3 episodes of diarrhea or vomiting in the previous 24 hours), and symptom duration □ 7 days. The primary study outcome, caregiver-reported maximum pain in the 24-hours prior to presentation, was assessed using the 11-point Verbal Numerical Rating Scale. Results: We recruited 2136 patients, median age 20.8 months (IQR 10.4, 47.4); 45.8% (979/2136) female. In the 24-hours prior to enrolment, 28.6% (610/2136) of caregivers reported that their child experienced moderate (4-6) and 46.2% (986/2136) severe (7-10) pain in the preceding 24-hours. During the emergency visit, 31.1% (664/2136) described pain as moderate and 26.7% (571/2136) as severe. In the ED, analgesia was provided to 21.2% (452/2131) of children. The most commonly administered analgesics in the ED were ibuprofen (68.1%, 308/452) and acetaminophen (43.4%, 196/452); at home, acetaminophen was most commonly administered (77.7%, 700/901), followed by ibuprofen (37.5%, 338/901). Factors associated with analgesia use in the ED were greater pain scores during the visit, having a primary-care physician, shorter illness duration, fewer diarrheal episodes, presence of fever and hospitalization. Conclusion: Although children presenting to the ED with acute gastroenteritis experience moderate to severe pain, both prior to and during their emergency visit, analgesic use is limited. Future research should focus on appropriate pain management through the development of effective and safe pain treatment plans.
Introduction: According to WHO, one third of patients aged ≥65 fall every year. Those falls account for 25% of all geriatric emergency department (ED) visits. Fear of falling (FOF) is common in older patients who sustained a fall and is associated with a decline in mobility and health issues for patients. We hypothesized that there is an association between FOF and return to ED (RTED) and future falls. Objective: To assess the relation between FOF and RTED and subsequent falls in older ED patients Methods: This research was conducted as part of the Canadian Emergency Team Initiative in elderly (CETIe) multicenter prospective cohort study from 2011 to 2016. Participants: Patients 65 years or older were assessed and discharged from ED following a minor trauma. They had to be independent in all basic activities of daily living and being able to communicate in English or French. Measures: Primary outcome was RTED and secondary outcome was subsequent falls. Both were self-reported at 3 and 6 months. Patients were stratified according to Short Falls Efficacy Scale International (SFES-I) score, assessing FOF in different situations. A total score is calculated to determine the mild, moderate or severe level of FOF. Previous falls and TUG were used to evaluate patients’ mobility. OARS, ISAR and SOF were used to evaluated patient frailty. Descriptive statistical were performed and multiple regression were performed to show the association between SFES-1 score and outcomes. Results: FOF was measured in 2899 participants, of which 2214 participated at the 3 months follow-up and 2009 participated at the 6 months follow-up. Odds Ratio (OR) of return to ED at 3 months was 1.10 for moderate FOF and 1.52 for severe FOF (Type 3 test p = 0.11). At 6 months, OR was 1.03 for moderate FOF and 1.25 for severe FOF (Type 3 test p = 0.63). OR of subsequent fall at 3 months was 1.80 for moderate FOF and 2.18 for severe FOF (Type 3 test p < 0.001). At 6 months, OR of subsequent fall was 1.63 for moderate FOF and 2.37 for severe FOF (Type 3 test p < 0.001). Conclusion: The multicenter cohort study showed that severe fear of falling is strongly associated with subsequent falls over the next 6 months following ED discharge, but not significantly associated with return to ED episodes. Further research should be done to analyze the association between severe FOF and RTED.
Resonant optical dipole antennas, consisting either of two arms coupled by a small gap or of a single, uncoupled arm only, are fabricated by the application of electron beam lithography and gold evaporation. Using dark-field microscopy, scattering spectra of structures with varied antenna arm length and varied gap size are obtained. The results show not only a spectral redshift for coupled structures compared to single arm structures, but also that the far-field scattering intensity is significantly higher for two arm structures with gap. In addition to the dipole structures, first fabrication results on quadrupole antennas and split-ring antennas are presented, offering novel pathways for an enhancement of the optical response function.
In this study, an improved fluid–structure interaction (FSI) analysis method is developed for a flapping wing. A co-rotational (CR) shell element is developed for its structural analysis. Further, a relevant non-linear dynamic formulation is developed based on the CR framework. Three-dimensional preconditioned Navier–Stokes equations are employed for its fluid analysis. An implicit coupling scheme is employed to combine the structural and fluid analyses. An explicit investigation of a 3D plunging wing is conducted using this FSI analysis method. A further investigation of this plunging wing is performed in relation to its operating condition. In addition, the relation between the wing’s aerodynamic performance and plunging motion is investigated.
The effect of temperature change on LiF, ADP, and EDDT analyzing crystals was studied by measuring the change In intensity of a selected X-ray spectral line while maintaining a constant 2θ position on the spectrometer. A change in interplanar spacing due to thermal expansion and contraction satisfactorily account for experimentally observed line shifts for LiF and ADP. EDDT showed a large unexplained decrease in reflectivity with increasing ambient temperature.
An equation was developed to express the change in intensity at a constant 2θ position as an exponential function of temperature. In this equation the thermal expansion coefficients of the principal axes of the crystal, the width of the spectral line at half-height, and the Bragg angle appear as factors. Intensity changes due to peak shift were tabulated for LiF, ADP, NaCl, silicon, germanium, quartz, calcite, fiuorite, and topaz.
Reciprocal space mapping can be efficiently carried out using a position-sensitive x-ray detector (PSD) coupled to a traditional double-axis diffractometer. The PSD offers parallel measurement of the total scattering angle of all diffracted x-rays during a single rocking-curve scan. As a result, a two-dimensional reciprocal space map can be made in a very short time similar to that of a one-dimensional rocking-curve scan. Fast, efficient reciprocal space mapping offers numerous routine advantages to the x-ray diffraction analyst. Some of these advantages arc the explicit differentiation of lattice strain from crystal orientation effects in strain-relaxed heteroepitaxial layers; the nondestructive characterization of the size, shape and orientation of nanocrystalline domains in ordered-alloy epilayers; and the ability to measure the average size and shape of voids in porous epilayers. Here, the PSD-based diffractometer is described, and specific examples clearly illustrating the advantages of complete reciprocal space analysis are presented.
Porphyrins absorb light to initiate photocatalytic activity. The complex, asymmetric structures of natural porphyrins such as heme, chlorophyll, and their derivatives hold unique interest. A platform for biosynthesis of porphyrins in Escherichia coli is developed with the aim of producing a variety of porphyrins for examining their photocatalytic properties within a porous material. Bioderived protoporphyrin IX is tethered inside the highly porous metal-organic framework (MOF) NU-1000 via solvent-assisted ligand incorporation. This MOF catalyzes the photocatalytic oxidation of 2-chloroethyl ethyl sulfide with improved performance over an expanded range of the visible spectrum when compared to unmodified NU-1000.
The impact of dementia-related stressors and strains have been examined for their potential to threaten the well-being of either the person with dementia or the family care partner, but rarely have studies considered the dyadic nature of well-being in dementia. The purpose of this study was to examine the dyadic effects of multiple dimensions of strain on the well-being of dementia care dyads.
Using multilevel modeling to account for the inter-relatedness of individual well-being within dementia care dyads, we examined cross-sectional responses collected from 42 dyads comprised of a hospitalized patient diagnosed with a primary progressive dementia (PWD) and their family care partner (CP). Both PWDs and CPs self-reported on their own well-being using measures of quality of life (QOL-Alzheimer’s Disease scale) and depressive symptoms (Center for Epidemiological Studies Depression Scale).
In adjusted models, the PWD’s well-being (higher QOL and lower depressive symptoms) was associated with significantly less strain in the dyad’s relationship. The CP’s well-being was associated with significantly less care-related strain and (for QOL scale) less relationship strain.
Understanding the impact of dementia on the well-being of PWDs or CPs may require an assessment of both members of the dementia care dyad in order to gain a complete picture of how dementia-related stressors and strains impact individual well-being. These results underscore the need to assess and manage dementia-related strain as a multi-dimensional construct that may include strain related to the progression of the disease, strain from providing care, and strain on the dyad’s relationship quality.
This study evaluated tumour necrosis factor-α, interleukins 10 and 12, and interferon-γ levels, peripheral blood mononuclear cells, and clusters of differentiation 17c and 86 expression in unilateral sudden sensorineural hearing loss.
Twenty-four patients with unilateral sudden sensorineural hearing loss, and 24 individuals with normal hearing and no history of sudden sensorineural hearing loss (who were attending the clinic for other problems), were enrolled. Peripheral blood mononuclear cells, and clusters of differentiation 11c and 86 were isolated and analysed. Plasma and supernatant levels of tumour necrosis factor-α, interferon-γ, and interleukins 10 and 12 were measured.
There were no significant differences with respect to age and gender. Monocyte population, mean tumour necrosis factor-α level and cluster of differentiation 86 expression were significantly increased in the study group compared to the control group. However, interferon-γ and interleukin 12 levels were significantly decreased. The difference in mean interleukin 10 level was not significant.
Increases in tumour necrosis factor-α level and monocyte population might play critical roles in sudden sensorineural hearing loss. This warrants detailed investigation and further studies on the role of dendritic cells in sudden sensorineural hearing loss.
In this study, the combustion instability and emission characteristics of flames of different H2/CH4 compositions were investigated in a partially premixed model gas turbine combustor. A mode shift in the frequency of instability occurred under varying experimental conditions from the first to the seventh mode of longitudinal frequency in the combustor, and a parametric study was conducted to determine the reasons for this shift by using the length of the combustor, a factor that determines the mode frequency of longitudinal instability, as the main parameter. Furthermore, heat load and fuel composition (H2 ratio) were considered as parameters to compare the phenomenon under different conditions. The GRI-3.0 CANTERA code, OH chemiluminescence and the Abel inversion process were applied to analyse the frequency mode shift. NOx emissions, which occurred through the thermal NOx mechanism, increased with increasing heat load and H2 ratio. The instability frequency shifted from the first to the seventh mode as the H2 ratio increased in the H2/CH4 mixture. However, 100% H2 as fuel did not cause combustion instability because it has a higher burning velocity and extinction stretch rate than CH4. Furthermore, the laminar flame speed influenced the frequency mode shift. These phenomena were confirmed by the flame shapes. The Abel inversion process was applied to obtain the cross section of the flames from averaged OH chemiluminescence images. Stable and unstable flames were identified from the radial profile of OH concentration. The combustor length was found to not influence frequency mode shift, whereas the H2 ratio significantly influenced it as well as the flame shape. The results of this experimental study can help in the reliable operation of gas turbine systems in SNG plants.
Polyphenol oxidase (PPO) in red clover (RC) has been shown to reduce both lipolysis and proteolysis in silo and implicated (in vitro) in the rumen. However, all in vivo comparisons have compared RC with other forages, typically with lower levels of PPO, which brings in other confounding factors as to the cause for the greater protection of dietary nitrogen (N) and C18 polyunsaturated fatty acids (PUFA) on RC silage. This study compared two RC silages which when ensiled had contrasting PPO activities (RC+ and RC−) against a control of perennial ryegrass silage (PRG) to ascertain the effect of PPO activity on dietary N digestibility and PUFA biohydrogenation. Two studies were performed the first to investigate rumen and duodenal flow with six Hereford×Friesian steers, prepared with rumen and duodenal cannulae, and the second investigating whole tract N balance using six Holstein-Friesian non-lactating dairy cows. All diets were offered at a restricted level based on animal live weight with each experiment consisting of two 3×3 Latin squares using big bale silages ensiled in 2010 and 2011, respectively. For the first experiment digesta flow at the duodenum was estimated using a dual-phase marker system with ytterbium acetate and chromium ethylenediaminetetraacetic acid as particulate and liquid phase markers, respectively. Total N intake was higher on the RC silages in both experiments and higher on RC− than RC+. Rumen ammonia-N reflected intake with ammonia-N per unit of N intake lower on RC+ than RC−. Microbial N duodenal flow was comparable across all silage diets with non-microbial N higher on RC than the PRG with no difference between RC+ and RC−, even when reported on a N intake basis. C18 PUFA biohydrogenation was lower on RC silage diets than PRG but with no difference between RC+ and RC−. The N balance trial showed a greater retention of N on RC+ over RC−; however, this response is likely related to the difference in N intake over any PPO driven protection. The lack of difference between RC silages, despite contrasting levels of PPO, may reflect a similar level of protein-bound-phenol complexing determined in each RC silage. Previously this complexing has been associated with PPOs protection mechanism; however, this study has shown that protection is not related to total PPO activity.