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To assess the Framingham risk score as a prognostic tool for idiopathic sudden sensorineural hearing loss patients.
Medical records were reviewed for unilateral idiopathic sudden sensorineural hearing loss patients between January 2010 and October 2017. The 10-year risk of developing cardiovascular disease was calculated. Patients were subdivided into groups: group 1 – Framingham risk score of less than 10 per cent (n = 28); group 2 – score of 10 to less than 20 per cent (n = 6); and group 3 – score of 20 per cent or higher (n = 5).
Initial pure tone average and Framingham risk score were not significantly associated (p = 0.32). Thirteen patients in group 1 recovered completely (46.4 per cent), but none in groups 2 and 3 showed complete recovery. Initial pure tone average and Framingham risk score were significantly associated in multivariable linear regression analysis (R2 = 0.36). The regression coefficient was 0.33 (p = 0.003) for initial pure tone average and −0.67 (p = 0.005) for Framingham risk score.
Framingham risk score may be useful in predicting outcomes for idiopathic sudden sensorineural hearing loss patients, as those with a higher score showed poorer hearing recovery.
Introduction: Mild Traumatic Brain Injury (mTBI) is a common problem: each year in Canada, its incidence is estimated at 500-600 cases per 100 000. Between 10 and 56% of mTBI patients develop persistent post-concussion symptoms (PPCS) that can last for more than 90 days. It is therefore important for clinicians to identify patients who are at risk of developing PPCS. We hypothesized that blood biomarkers drawn upon patient arrival to the Emergency Department (ED) could help predict PPCS. The main objective of this project was to measure the association between four biomarkers and the incidence of PPCS 90 days post mTBI. Methods: Patients were recruited in seven Canadian ED. Non-hospitalized patients, aged ≥14 years old with a documented mTBI that occurred ≤24 hrs of ED consultation, with a GCS ≥13 at arrival were included. Sociodemographic and clinical data as well as blood samples were collected in the ED. A standardized telephone questionnaire was administered at 90 days post ED visit. The following biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA): S100B protein, Neuron Specific Enolase (NSE), cleaved-Tau (c-Tau) and Glial fibrillary acidic protein (GFAP). The primary outcome measure was the presence of persistent symptoms at 90 days after mTBI, as assessed using the Rivermead Post-Concussion symptoms Questionnaire (RPQ). A ROC curve was constructed for each biomarker. Results: 1276 patients were included in the study. The median age for this cohort was 39 (IQR 23-57) years old, 61% were male and 15% suffered PPCS. The median values (IQR) for patients with PPCS compared to those without were: 43 pg/mL (26-67) versus 42 pg/mL (24-70) for S100B protein, 50 pg/mL (50-223) versus 50 pg/mL (50-199) for NSE, 2929 pg/mL (1733-4744) versus 3180 pg/mL (1835-4761) for c-Tau and 1644 pg/mL (650-3215) versus 1894 pg/mL (700-3498) for GFAP. For each of these biomarkers, Areas Under the Curve (AUC) were 0.495, 0.495, 0.51 and 0.54, respectively. Conclusion: Among mTBI patients, S100B protein, NSE, c-Tau or GFAP during the first 24 hours after trauma do not seem to be able to predict PPCS. Future research testing of other biomarkers is needed in order to determine their usefulness in predicting PPCS when combined with relevant clinical data.
Introduction: Acute bloody diarrhea obligates rapid and accurate diagnostic evaluation; few studies have described such cohorts of children. Methods: We conducted a planned secondary analysis employing the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) acute gastroenteritis study cohort to describe the characteristics of children with acute bloody diarrhea, compared to a cohort of children without hematochezia. Children <18 years of age presenting to 2 pediatric tertiary care emergency departments (EDs) in Alberta, with ≥3 episodes of diarrhea and/or vomiting in the preceding 24 hours and <7 days of symptoms were consecutively recruited. Stools were tested for 17 viruses, bacteria and parasites. Primary outcomes were clinical characteristics and pathogens identified. Secondary outcomes included interventions and resource utilization. Results: Of 2257 children enrolled between October 2015 and August 2018, hematochezia before or at the index ED visit was reported in 122 (5.4%). Compared to children with nonbloody diarrhea, children with hematochezia had longer illness duration [59.5 vs. 41.5 hrs, difference 10.6, 95% CI 3.5, 19.9], more diarrheal episodes in a 24-hour period [8 vs. 5, difference 3, 95% CI 2, 4], and less vomiting [55.7% vs. 91.1%; difference -35.3%; 95% CI -44.7, -26.3]. They received more intravenous fluids [32.0% vs. 18.3%; difference 13.7%, 95% CI 5.5, 23.0], underwent non-study stool testing [53.7% vs. 4.8%; difference 49.0%, 95% CI 39.6, 58.0], experienced longer ED visits [4.1 vs. 3.3 hours, difference 0.9, 95% CI 0.3, 1.0] and were more likely to have repeat healthcare visits within 14 days [54.8% vs. 34.2%; difference 20.6%, 95% CI 10.8, 30.1]. A bacterial enteric pathogen was found in 31.9% of children with hematochezia versus 6.6% without bloody diarrhea (difference 25.4%, 95% CI 17.2, 34.7). In children with hematochezia, the most commonly detected bacteria were Salmonella spp. (N = 15), Shiga toxin-producing E. coli (N = 9), Campylobacter spp. (N = 7), and Shigella spp. (N = 5). Viruses were detected in 32.8% of children with bloody diarrhea, most commonly adenovirus (N = 15), norovirus (N = 14), sapovirus (N = 8) and rotavirus (N = 7). Conclusion: Children with hematochezia differed clinically from those without hematochezia and required more healthcare resources. While bacterial etiologies are common, several viruses were also detected.
Introduction: Clinical assessment of patients with mTBI is challenging and overuse of head CT in the emergency department (ED) is a major problem. During the last decades, studies have attempted to reduce unnecessary head CTs following a mTBI by identifying new tools aiming to predict intracranial bleeding. S100B serum protein level might be helpful reducing those imaging since a higher level of S-100B protein has been associated with intracranial hemorrhage following a mTBI in previous literature. The main objective of this study was to assess whether the S100B serum protein level is associated with clinically important brain injury and could be used to reduce the number of head CT following a mTBI. Methods: This prospective multicenter cohort study was conducted in five Canadian ED. MTBI patients with a Glasgow Coma Scale (GCS) score of 13-15 in the ED and a blood sample drawn within 24-hours after the injury were included. S-100B protein was analyzed using enzyme-linked immunosorbent assay (ELISA). All types of intracranial bleedings were reviewed by a radiologist who was blinded to the biomarker results. The main outcome was the presence of clinically important brain injury. Results: A total of 476 patients were included. Mean age was 41 ± 18 years old and 150 (31.5%) were female. Twenty-four (5.0%) patients had a clinically significant intracranial hemorrhage while 37 (7.8%) had any type of intracranial bleeding. S100B median value (Q1-Q3) of was: 0.043 ug/L (0.008-0.080) for patients with clinically important brain injury versus 0.039 μg/L (0.023-0.059) for patients without clinically important brain injury. Sensitivity and specificity of the S100B protein level, if used alone to detect clinically important brain injury, were 16.7% (95% CI 4.7-37.4) and 88.5% (95% CI 85.2-91.3), respectively. Conclusion: S100B serum protein level was not associated with clinically significant intracranial hemorrhage in mTBI patients. This protein did not appear to be useful to reduce the number of CT prescribed in the ED and would have missed many clinically important brain injuries. Future research should focus on different ways to assess mTBI patient and ultimately reduce unnecessary head CT.
Introduction: Each year, 3/1000 Canadians sustain a mild traumatic brain injury (mTBI). Many of those mTBI are accompanied by various co-injuries such as dislocations, sprains, fractures or internal injuries. A number of those patients, with or without co-injuries will suffer from persistent post-concussive symptoms (PPCS) more than 90 days post injury. However, little is known about the impact of co-injuries on mTBI outcome. This study aims to describe the impact of co-injuries on PPCS and on patient return to normal activities. Methods: This multicenter prospective cohort study took place in seven large Canadian Emergency Departments (ED). Inclusion criteria: patients aged ≥ 14 who had a documented mTBI that occurred within 24 hours of ED visit, with a Glasgow Coma Scale score of 13-15. Patients who were admitted following their ED visit or unable to consent were excluded. Clinical and sociodemographic information was collected during the initial ED visit. A research nurse then conducted three follow-up phone interviews at 7, 30 and 90 days post-injury, in which they assessed symptom evolution using the validated Rivermead Post-concussion Symptoms Questionnaire (RPQ). Adjusted risk ratios (RR) were calculated to estimate the influence of co-injuries. Results: A total of 1674 patients were included, of which 1023 (61.1%) had at least one co-injury. At 90 days, patients with co-injuries seemed to be at higher risk of having 3 symptoms ≥2 points according to the RPQ (RR: 1.28 95% CI 1.02-1.61) and of experiencing the following symptoms: dizziness (RR: 1.50 95% CI 1.03-2.20), fatigue (RR: 1.35 95% CI 1.05-1.74), headaches (RR: 1.53 95% CI 1.10-2.13), taking longer to think (RR: 1.50 95% CI 1.07-2.11) and feeling frustrated (RR: 1.45 95% CI 1.01-2.07). We also observed that patients with co-injuries were at higher risk of non-return to their normal activities (RR: 2.31 95% CI 1.37-3.90). Conclusion: Patients with co-injuries could be at higher risk of suffering from specific symptoms at 90 days post-injury and to be unable to return to normal activities 90 days post-injury. A better understanding of the impact of co-injuries on mTBI could improve patient management. However, further research is needed to determine if the differences shown in this study are due to the impact of co-injuries on mTBI recovery or to the co-injuries themselves.
Introduction: Mild traumatic brain injury (mTBI) is a serious public health issue and as much as one third of mTBI patients could be affected by persistent post-concussion symptoms (PPCS) three months after their injury. Even though a significant proportion of all mTBIs are sports-related (SR), little is known on the recovery process of SR mTBI patients and the potential differences between SR mTBI and patients who suffered non-sports-related mTBI. The objective of this study was to describe the evolution of PPCS among patients who sustained a SR mTBI compared to those who sustained non sport-related mTBI. Methods: This Canadian multicenter prospective cohort study included patients aged ≥ 14 who had a documented mTBI that occurred within 24 hours of Emergency Department (ED) visit, with a Glasgow Coma Scale score of 13-15. Patients who were hospitalized following their ED visit or unable to consent were excluded. Clinical and sociodemographic information was collected during the initial ED visit. Three follow-up phone interviews were conducted by a research nurse at 7, 30 and 90 days post-injury to assess symptom evolution using the validated Rivermead Post-concussion Symptoms Questionnaire (RPQ). Adjusted risk ratios (RR) were calculated to demonstrate the impact of the mechanism of injury (sports vs non-sports) on the presence and severity of PPCS. Results: A total of 1676 mTBI patients were included, 358 (21.4%) of which sustained a SR mTBI. At 90 days post-injury, patients who suffered a SR mTBI seemed to be significantly less affected by fatigue (RR: 0.70 (95% CI: 0.50-0.97)) and irritability (RR: 0.60 (95% CI: 0.38-0.94)). However, no difference was observed between the two groups regarding each other symptom evaluated in the RPQ. Moreover, the proportion of patients with three symptoms or more, a score ≥21 on the RPQ and those who did return to their normal activities were also comparable. Conclusion: Although persistent post-concussion symptoms are slightly different depending on the mechanism of trauma, our results show that patients who sustained SR-mTBI could be at lower risk of experiencing some types of symptoms 90 days post-injury, in particular, fatigue and irritability.
Introduction: Crowding is associated with poor patient outcomes in emergency departments (ED). Measures of crowding are often complex and resource-intensive to score and use in real-time. We evaluated single easily obtained variables to establish the presence of crowding compared to more complex crowding scores. Methods: Serial observations of patient flow were recorded in a tertiary Canadian ED. Single variables were evaluated including total number of patients in the ED (census), in beds, in the waiting room, in the treatment area waiting to be assessed, and total inpatient admissions. These were compared with Crowding scores (NEDOCS, EDWIN, ICMED, three regional hospital modifications of NEDOCS) as predictors of crowding. Predictive validity was compared to the reference standard of physician perception of crowding, using receiver operator curve analysis. Results: 144 of 169 potential events were recorded over 2 weeks. Crowding was present in 63.9% of the events. ED census (total number of patients in the ED) was strongly correlated with crowding (AUC = 0.82 with 95% CI = 0.76 - 0.89) and its performance was similar to that of NEDOCS (AUC = 0.80 with 95% CI = 0.76 - 0.90) and a more complex local modification of NEDOCS, the S-SAT (AUC = 0.83, 95% CI = 0.74 - 0.89). Conclusion: The single indicator, ED census was as predictive for the presence of crowding as more complex crowding scores. A two-stage approach to crowding intervention is proposed that first identifies crowding with a real-time ED census statistic followed by investigation of precipitating and modifiable factors. Real time signalling may permit more standardized and effective approaches to manage ED flow.
Introduction: The elderly (65 yo and more) increase in Canada is well documented along with a disproportionate use of Emergency Departments after a minor injury. These patients requires specific care given a 16% risk of functional decline following a visit to ED. To prevent functional decline, a multidimensional assessment of the elderly is recommended in the emergency department. Objective: To determine if ED grip strength can predict functional decline at 3 or 6 months post-injury. Methods: A multicentre prospective study in 5 ED across Canada was realized between 2013 and 16. Patients 65 years old and over, autonomous in daily living activities and consulting the emergency department for minor trauma were recruited 7 days a week. Clinical-demographic data, functional status, fear of falling, number of falls in the last month, grip strength measurement were collected in the ED. Functional decline (loss of at least points to functional status) was calculated at 3 and 6 months. Descriptive statistics and linear regression model with repeated measurements were used to determine if the grip strength was predictive of functional decline at 3 or 6 months. Results: 387 patient were recruited. Mean age was 74 ± 7 years old, 52% were male. XXX experienced a fall in the last month. The initial maximum grip strength was (24 ± 10 intervention vs. 28 ± 13 control; p ≤ 0.05). grip strength is associated with pre-injury functional status (p < 0.0001) and fear of falling (p = 0.0001) but does not predict 3 or 6 month functional decline. Conclusion: Given the strong association with fear of falling and functional status at initial ED evaluation, we recommend that grip strength measurement could be included in a multidisciplinary geriatric emergency department assessment as needed.
Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries.
To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course.
Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder.
Cluster analysis of neurocognitive test scores derived three subgroups described as ‘normal range’ (n = 243, 38.6%), ‘intermediate impairment’ (n = 252, 40.1%), and ‘global impairment’ (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI −0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI −0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time.
Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.
Heat shock proteins (HSPs) consist of highly preserved stress proteins that are expressed in response to stress. Two studies were carried out to investigate whether HSP genes in hair follicles from beef calves can be suggested as indicators of heat stress (HS). In study 1, hair follicles were harvested from three male Hanwoo calves (aged 172.2 ± 7.20 days) on six dates over the period of 10 April to 9 August 2017. These days provided varying temperature–humidity indices (THIs). In study 2, 16 Hanwoo male calves (aged 169.6 ± 4.60 days, with a BW of 136.9 ± 6.23 kg) were maintained (4 calves per experiment) in environmentally controlled chambers. A completely randomized design with a 2 × 4 factorial arrangement involving two periods (thermoneutral: TN; HS) and four THI treatment groups (threshold: THI = 68 to 70; mild: THI = 74 to 76; moderate THI = 81 to 83; severe: THI = 88 to 90). The calves in the different group were subjected to ambient temperature (22°C) for 7 days (TN) and subsequently to the temperature and humidity corresponding to the target THI level for 21 days (HS). Every three days (at 1400 h) during both the TN and HS periods, the heart rate (HR) and rectal temperature (RT) of each individual were measured, and hair follicles were subsequently collected from the tails of each individual. In study 1, the high variation (P < 0.0001) in THI indicated that the external environment influenced the HS to different extents. The expression levels of the HSP70 and HSP90 genes at the high-THI level were higher (P = 0.0120, P = 0.0002) than those at the low-THI level. In study 2, no differences in the THI (P = 0.2638), HR (P = 0.2181) or RT (P = 0.3846) were found among the groups during the TN period, whereas differences in these indices (P < 0.0001, P < 0.0001 and P < 0.0001, respectively) were observed during the HS period. The expression levels of the HSP70 (P = 0.0010, moderate; P = 0.0065, severe) and HSP90 (P = 0.0040, severe) genes were increased after rapid exposure to heat-stress conditions (moderate and severe levels). We conclude that HSP gene expression in hair follicles provides precise and accurate data for evaluating HS and can be considered a novel indicator of HS in Hanwoo calves maintained in both external and climatic chambers.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
To analyse the results of treatment for nasolabial cysts according to whether an intraoral sublabial or endoscopic transnasal approach was used, and to determine the recent surgical trend in our hospital.
Twenty-four patients with a histopathologically and radiologically confirmed nasolabial cyst between January 2010 and December 2017 were enrolled in this study.
Nasolabial cysts were predominant in females (91.7 per cent) and on the left side (54.2 per cent). Treatment involved an intraoral sublabial approach in 12 cases (48.0 per cent) and a transnasal endoscopic approach in 13 cases (52.0 per cent). In 13 cases (52.0 per cent) surgery was performed under local anaesthesia, while in 12 cases (48.0 per cent) it was conducted under general anaesthesia. The most common post-operative complications were numbness of the upper lip or teeth (n = 9, 36.0 per cent). Only one patient (4.0 per cent), who underwent a transnasal endoscopic approach, experienced a reoccurrence.
Surgical resection through an intraoral sublabial or transnasal endoscopic approach is the best treatment for a nasolabial cyst, showing very good results and a low recurrence rate. The recent surgical trend in our hospital is to treat nasolabial cysts using a transnasal endoscopic approach under local anaesthesia.
Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.
Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.
Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.
These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.
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.
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.
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.
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.