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Various psychological and biological pathways have been proposed as mediators between childhood adversity (CA) and psychosis. A systematic review of the evidence in this domain is needed. Our aim is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This review followed PRISMA guidelines. Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO, Medline and Embase) and Cochrane Libraries. The evidence by each analysis and each study is presented by group of mediator categories found. The percentage of total effect mediated was calculated. Forty-eight studies were included, 21 in clinical samples and 27 in the general population (GP) with a total of 82 352 subjects from GP and 3189 from clinical studies. The quality of studies was judged as ‘fair’. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world and others (NS); by dissociation and other post-traumatic stress disorder symptoms; and through an affective pathway in GP but not in subjects with disorder; (iii) lack of studies exploring biological mediators. We found evidence suggesting that various overlapping and not competing pathways involving post-traumatic and mood symptoms, as well as negative cognitions contribute partially to the link between CA and psychosis. Experiences of CA, along with relevant mediators should be routinely assessed in patients with psychosis. Evidence testing efficacy of interventions targeting such mediators through cognitive behavioural approaches and/or pharmacological means is needed in future.
The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
it is well established that adversities and GRIN2B genetic variants (encoding NMDAR GluN2B subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to risk have good, long-term outcomes.
for the first time, we explored how environmental adversities and GRIN2B genetic variants influence children's cognitive abilities and behavioral problems.
we adopted a gene-by-environment interaction (GxE) approach, to identify children with an unfavorable developmental outcome with the potential of better informing the understanding of susceptibility to developmental disorders.
6 SNPs of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interactive effect of GRIN2B variants with 4 measures of adversities (low socioeconomic status - SES, preterm delivery, maternal smoking, absence of breastfeeding) was investigated upon cognitive abilities (vocabulary, block design, forward/backward digit spans of Wechsler's Intelligence Scale, and Rey Figure test) and parents-rated behavioral problems (Child Behavior Checklist/6-18).
rs5796555 x gestational age interaction (p= .00145) influenced cognition, with lower IQ memory among children in the ‘A/A genotype and ≤ 36 gestational age’ group, compared to all other groups. Rs2268119 x SES interaction (p= .00008) influenced behavior, with more attention problems among children in the ‘either A/T or T/T genotype and low SES’ group, compared to all other groups.
GRIN2B targets children with the worst outcome in memory and attention functioning among children exposed to environmental adversities. Identification of children with the highest risk may prompt cost-effective preventive/treatment strategies.
The DCDC2/intron 2 deletion increases the risk to Developmental Dyslexia (DD) and DD-related phenotypes, and it is associated with brain functional and structural measures that are important for fluent reading. Illusory motion perception is specifically processed by the magnocellulardorsal (M-D) pathway, which is impaired in individuals with DD. We tested the performance in two psychophysical tasks, tapping the M-D and the parvocellular-ventral (P-V) streams, in normal readers grouped according to the presence/absence of the DCDC2/intron 2 deletion (‘at-risk’ and ‘not at-risk’ groups, respectively). The M-D stream was tested by the Rotating-Tilted-Lines Illusion (RTLI) sensitivity; the P-V pathway, by a grating orientation identification task. Our data showed that the ‘at-risk’ group needed more contrast to process the illusory rotation in the RTLI task, while they perform similarly to the ‘not at-risk’ group in the grating orientation identification task. By showing that the DCDC2/intron 2 deletion influenced the inter-individual variation in the RTLI task, our data demonstrated that the function of the M-D, but not of the P-V, pathway is impaired by this genetic variant. Moreover, our data showed a link between the M-D pathway and the dorsal-phonological reading route; importantly, this correlation is not a consequence of reduced exposure to print, as it might be the case if it was found in subjects with DD, being that it has been found in normal-reading adults. Our findings demonstrated, for the first time, that a specific neurocognitive dysfunction tapping the M-D pathway is related with well-defined genetic susceptibility in normal-reading subjects.
Previous studies reported that music therapy (MT) exerts a positive effect on many medical and neuropsychiatric disorders. The use of MT has been proposed also for patients with severe mental illnesse (SMI), altrough further studies are still needed. The aim of the present study was to evaluate the effects on a structured MT program on clinical and social functioning indices of patient with SMI, hospitalized in an psychiatric emergency ward.
The MT intervention followed the Benenzon model of MT and was delivered biweekly to 61 patients consecutively admittted to the psychiatric emergency ward. Subjects who did not complete the two-week MT intervention (N=45) were considered as the control group. all subjects were administred the Brief Psychiatric Rating Scale (BPRS) to evaluate the general psychopatology, the Hospital Anxiety And Depression Scale (HADS) for affective symptomatology, the Clinical Global Impression Scale (CGI-S) for severity of symptoms and the Global Assestment of Functioning (GAF) for psychosocial functioning.
A repeated measures analysis of variance revealed that patients who unerwent the MT intervention had a statistically significant reduction of general and affective psychopatology scores and of symptoms severity with respect to the control group, after observation period.
Our result are in line with previous studies confirming that MT may exert positive effects on psychopatology (in particular, on affective symptomatology) of patient with SMI, and extend this observation to an emergency setting, with short period of hospital stay.
Some inconsistent evidence indicates experiences of trauma and the presence of symptoms of PTSD are associated with increased risk of cardiovascular diseases. This relation has rarely been explored with community samples including participants with PTSD symptoms or who fulfill criteria for PTSD disorders.
We identify those with a high number of PTSD symptoms and those fulfilling criteria for PTSD are more likely to have CVD than those without a PTSD syndrome or diagnosis. We examine rates of mental health access for those with PTSD and CVD.
We use Collaborative Psychiatric Epidemiology Surveys (CPES) to examine differences in trauma/PTSD prevalence and the association of prior trauma exposure and PTSD diagnoses with CVD (n = 13,286). CIDI was used to make psychiatric diagnoses and medical data was acquired regarding onset and severity of CVD.
Individuals with prior exposure to trauma and PTSD diagnoses had twice the likelihood of developing a cardiovascular disease as those without trauma exposure [OR = 1.77, 95% CI (1.0, 2.94)]. Having a PTSD diagnosis is a significant predictor of having a CVD for individuals who experienced a traumatic event.
The probability of developing a CVD was higher when patients had prior diagnosis of substance abuse [OR = 1.36, 95% CI (1.11, 1.65)] or mental health disorders [OR = 1.43, 95% CI (1.10, 1.87) for depression; OR = 1.33, 95% CI (1.04, 1.69) for anxiety]. Men were almost twice as likely as women to be diagnosed with a CVD [OR = 1.67, 95% CI (1.37, 2.00)].
Exposure to trauma and the presence of PTSD symptoms are significantly associated with CVD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Clinical evidences suggests that cerebral inflammatory processes are involved in the development of major affective disorders .
Obvious correlations exist between changes of inflammatory markers such as acute-phase protein C (PCR) and VES, in patients with bipolar spectrum diagnosis .
Our aim is demonstrating the correlations between changes of PCR and VES and pharmacological treatment with atypical antipsychotics in patients with acute bipolar disorder, highlighting a trend.
Twenty patients with bipolar disorder were assessed at the entrance (T0), after three weeks (T1) and after six weeks (T2) of hospitalization using specific rating scales and blood tests routines include PCR and VES.
Is possible to appreciate a correlation between the affective phase of bipolar disorder and inflammatory markers with a proportional trend (Table 1).
Discussion and conclusion
The scores obtained seem to confirm the effect of antipsychotic in both sense of psychiatric symptomatology reduction and in anti-inflammatory action.
A confirmation of a correlation between the resolution of affective disorders and normalization of inflammatory markers confirm the intrinsic anti-inflammatory activity of such drug compounds .
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
The internal dynamics of multiple stellar populations in Globular Clusters (GCs) provides unique constraints on the physical processes responsible for their formation. Specifically, the present-day kinematics of cluster stars, such as rotation and velocity dispersion, seems to be related to the initial configuration of the system. In recent work (Milone et al. 2018), we analyzed for the first time the kinematics of the different stellar populations in NGC 0104 (47 Tucanae) over a large field of view, exploiting the Gaia Data Release 2 proper motions combined with multi-band ground-based photometry. In this paper, based on the work by Cordoni et al. (2019), we extend this analysis to six GCs, namely NGC 0288, NGC 5904 (M 5), NGC 6121 (M 4), NGC 6752, NGC 6838 (M 71) and further explore NGC 0104. Among the analyzed clusters only NGC 0104 and NGC 5904 show significant rotation on the plane of the sky. Interestingly, multiple stellar populations in NGC 5904 exhibit different rotation curves.
Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
Diet supplementation with oilseeds is known to improve the fatty acid profile of meat, but few studies have been carried out to determine the time required for the incorporation of a significant quantity of n-3 polyunsaturated fatty acids (PUFA) into meat from steers. Therefore, the present study aimed to assess the effects of linseed supplementation and feeding duration on the fatty acid profile, cholesterol and bioactive compounds of bovine meat. In total, 54 Friesian steers were randomly allocated during the finishing period into six experimental treatments following a 2×3 factorial design. The six treatments consisted of two diets, the control diet (CO) with no supplemental fat and the linseed diet (LS) containing 10% whole linseed, fed 40, 75 or 120 days before slaughter. At the end of each finishing period, steers from the CO and LS groups were slaughtered. After 8 days of ageing chemical analysis, the fatty acid profile, cholesterol content and bioactive compounds were determined from the longissimus thoracis muscle. Including linseed in the diet increased the content of monounsaturated fatty acids, CLA and n-3 PUFA, and reduced the proportion of saturated fatty acids and n-6 PUFA. The percentage of myristic fatty acid increased with the duration of feeding, regardless of diet and a decrease in PUFA and n-6 PUFA was observed in the CO and LS diets, respectively. Furthermore, meat from steers fed linseed showed an increased percentage of n-3 PUFA, linolenic acid, and EPA from 40 to 75 days of feeding, whereas vaccenic acid, CLA 9c,11t, and total CLA increased from 40 and 75 days but declined at 120 days. Beef from the linseed group had a higher content of bioactive substances such as creatine, carnosine and anserine than beef from the control group. The duration of feeding significantly affected the creatine concentrations, with an increase in the LS group from 40 to 75 days of feeding. Feeding linseed did not modify the cholesterol content, on average and the lowest cholesterol content was found in meat after 75 days of linseed administration. This study demonstrates that a short-term diet manipulation is sufficient to improve the nutritional properties of meat, including n-3 PUFA and bioactive compounds.
Approximately 32,000 infants are born with CHDs each year in the United States of America. Of every 1000 live births, 2.3 require surgical or transcatheter intervention in the first year of life. There are few more stressful times for parents than when their neonate receives a diagnosis of complex CHD requiring surgery. The stress of caring for these infants is often unrelenting and may last for weeks, months, and often years, placing parents at risk for developing post-traumatic stress disorder, as well as a drastic decrease in quality of life. Anxiety often peaks in the days and weeks after discharge from the hospital as families no longer have immediate access to nursing and medical staff. The purpose of this paper is to describe the methods of a randomised controlled trial that was designed to determine whether REACH would favourably affect parental and infant outcomes by decreasing parental stress, improve parental quality of life, increase infant stability, and decrease resource utilisation in infants with complex CHD.
Jan-Marino Ramirez, Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, USA Departments of Neurological Surgery, Pediatrics, University of Washington, Seattle, USA,
Sanja C Ramirez, Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, USA,
Tatiana M Anderson, Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, USA
The identification of risk factors associated with sudden infant death syndrome (SIDS) has led to significant advances in the prevention of this tragic outcome. The discovery of the prone sleeping position and smoking as two of the major risk factors (1-5) led to worldwide awareness campaigns, such as, for example, the “Back to Sleep” campaign launched in the United States in 1996, and various smoking cessation campaigns (6, 7). These initiatives resulted in a dramatic reduction in the number of children succumbing to SIDS (5, 8). Unfortunately, SIDS still remains the number-one cause of death in infants under 1 year of age in many countries, despite epidemiological and pathological studies that continue to identify additional risk factors, such as hearing deficiencies, or various genetic alterations associated with SIDS (9-11, 12, 13). To parents and families, as well as some health professionals and researchers, the sheer number of suggested risk factors and gene mutations can also be bewildering.
The Triple Risk hypothesis by Dr Hannah Kinney and collaborators (14) can partly resolve this confusion. This hypothesis states that SIDS is caused by an incident in which not just one but three risk factors come together to bring an infant into a situation that leads to the sudden death. Specifically, it was proposed that those factors include  a vulnerable infant;  a critical period of development in homeostatic control; and  an exogenous stressor (14, 15). In other words, in the presence of two risk factors, namely being a vulnerable infant in a critical period of development, a third risk factor (e.g. an exogenous stressor) can become the ultimate cause that triggers an irreversible cascade of events leading to the sudden death.
The Triple Risk hypothesis also has important practical implications. The awareness campaigns have shown that it is possible to significantly reduce the risk of an infant being exposed to exogenous stressors. A potentially more challenging task is to identify the infant who is particularly vulnerable, which is clearly one of the major tasks for research. A better understanding of the characteristics of a vulnerable infant would facilitate the development of strategies that target a specific vulnerability.
Despite improvements in the medical and surgical management of infants with CHD, growth failure before surgery in many infants continues to be a significant concern. A nutritional pathway was developed, the aim of which was to provide a structured approach to nutritional care for infants with CHD awaiting surgery.
Materials and methods
The modified Delphi process was development of a nutritional pathway; initial stakeholder meeting to finalise draft guidelines and develop questions; round 1 anonymous online survey; round 2 online survey; regional cardiac conference and pathway revision; and final expert meeting and pathway finalisation.
Paediatric Dietitians from all 11 of the paediatric cardiology surgical centres in the United Kingdom contributed to the guideline development. In all, 33% of participants had 9 or more years of experience working with infants with CHD. By the end of rounds 1 and 2, 76 and 96% of participants, respectively, were in agreement with the statements. Three statements where consensus was not achieved by the end of round 2 were discussed and agreed at the final expert group meeting.
Nutrition guidelines were developed for infants with CHD awaiting surgery, using a modified Delphi process, incorporating the best available evidence and expert opinion with regard to nutritional support in this group.
In May 2016 a Norovirus (NoV) gastroenteritis outbreak involved a high school class visiting a seaside resort near Taormina (Mascali, Sicily). Twenty-four students and a teacher were affected and 17 of them showed symptoms on the second day of the journey, while the others got ill within the following 2 days. Symptoms included vomiting, diarrhoea and fever, and 12 students required hospitalisation. Stool samples tested positive for NoV genome by Real-Time polymerase chain reaction assay in all 25 symptomatic subjects. The GII.P2/GII.2 NoV genotype was linked to the outbreak by ORF1/ORF2 sequence analysis. The epidemiological features of the outbreak were consistent with food/waterborne followed by person-to-person and/or vomit transmission. Food consumed at a shared lunch on the first day of the trip was associated to illness and drinking un-bottled tap water was also considered as a risk factor. The analysis of water samples revealed the presence of bacterial indicators of faecal contamination in the water used in the resort as well as in other areas of the municipal water network, linking the NoV gastroenteritis outbreak to tap water pollution from sewage leakage. From a single water sample, an amplicon whose sequence corresponded to the capsid genotype recovered from patients could be obtained.
Accurate quantification of rates of glacier mass loss is critical for managing water resources and for assessing hazards at ice-clad volcanoes, especially in arid regions like southern Peru. In these regions, glacier and snow melt are crucial dry season water resources. In order to verify previously reported rates of ice area decline at Nevado Coropuna in Peru, which are anomalously rapid for tropical glaciers, we measured changes in ice cap area using 259 Landsat images acquired from 1980 to 2014. We find that Coropuna Ice Cap is presently the most extensive ice mass in the tropics, with an area of 44.1 km2, and has been shrinking at an average area loss rate of 0.409 km2 a−1 (~0.71% a−1) since 1980. Our estimated rate of change is considerably lower than previous studies (1.4 km2 a−1 or ~2.43% a−1), but is consistent with other tropical regions, such as the Cordillera Blanca located ~850 km to the NW (~0.68% a−1). Thus, if glacier recession continues at its present rate, our results suggest that Coropuna Ice Cap will likely continue to contribute to water supply for agricultural and domestic uses until ~2120, which is nearly 100 years longer than previously predicted.
Although the right jugular vein approach for percutaneous pulmonary valve implantation is well described, there are no reports that describe a percutaneous pulmonary valve implantation through a left superior caval vein to coronary sinus pathway.
A 14-year-old female with tetralogy of Fallot, mesocardia, left superior caval vein draining into the coronary sinus, and hemiazygos continuation of the inferior caval vein underwent ventricular septal defect closure, with homograft insertion from the right ventricle to the pulmonary artery, patch augmentation of the left pulmonary artery, and creation of an atrial communication. Thereafter followed numerous catheterisations and interventions with stent implantation for stenosis of the left pulmonary artery and the homograft, as did device closure of the atrial communication. When she was a 12-year-old, the indications for a percutaneous pulmonary valve implantation were fulfilled and she underwent implantation of a 22 mm Melody® valve through the left superior caval vein. The extra-stiff exchange wire was pre-formed into a “U-spiral”-type configuration, according to the underlying anatomy, in order to provide a smooth route for the delivery of stents, to create the landing zone, and for the implantation of the Melody “ensemble”. The procedure was performed under deep sedation according to our standard protocol. The duration of the procedure was 172 min and the radiation time was 24.9 min.
On the basis of this unique experience, percutaneous pulmonary valve implantation is safe and feasible even in patients with unusual anatomy. Crucial is the “U-spiral” shaped configuration of the guide wire.
Norwood palliation for patients with single ventricle heart disease is associated with a significant risk for acute kidney injury, which portends a worse prognosis. We sought to investigate the impact of hybrid stage I palliation (Hybrid) on acute kidney injury risk.
This study is a single-centre prospective case–control study of seven consecutive neonates with single ventricle undergoing Hybrid palliation. Levels of serum creatinine and four novel urinary biomarkers, namely neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, and kidney injury molecule-1, were obtained before and after palliation. Acute kidney injury was defined as a ⩾50% increase in serum creatinine within 48 hours after the procedure. Data were compared with a contemporary cohort of 12 neonates with single ventricle who underwent Norwood palliation.
Patients who underwent Hybrid were more likely to be high-risk candidates (86 versus 25%, p=0.01) compared with those who underwent Norwood. Despite similar preoperative serum creatinine levels, there was a trend towards higher levels of postoperative peak serum creatinine (0.7 [0.63, 0.94] versus 0.56 [0.47, 0.74], p=0.06) and rate of acute kidney injury (67 versus 29%, p=0.17) in the Norwood cohort. Preoperative neutrophil gelatinase-associated lipocalin (58.4 [11, 86.3] versus 6.3 [5, 16.2], p=0.07) and interleukin-18 (30.6 [9.6, 167.2] versus 6.3 [6.3, 16.4], p=0.03) levels were higher in the Hybrid cohort. Nevertheless, longitudinal mixed-effect models demonstrated Hybrid palliation to be a protective factor against increased postoperative levels of neutrophil gelatinase-associated lipocalin (estimate −1.8 [−3.0, −9.0], p<0.001) and liver fatty acid-binding protein (−49.3 [−89.7, −8.8], p=0.018).
In this single-centre case–control study, postoperative acute kidney injury risk did not differ significantly by single ventricle stage I treatment strategy; however, postoperative elevation in novel urinary biomarkers, consistent with subclinical kidney injury, was encountered in the Norwood cohort but not in the Hybrid cohort.
Children with hypoplastic left heart syndrome are at a risk for neurodevelopmental delays. Current guidelines recommend systematic evaluation and management of neurodevelopmental outcomes with referral for early intervention services. The Single Ventricle Reconstruction Trial represents the largest cohort of children with hypoplastic left heart syndrome ever assembled. Data on life events and resource utilisation have been collected annually. We sought to determine the type and prevalence of early intervention services used from age 1 to 4 years and factors associated with utilisation of services.
Data from 14-month neurodevelopmental assessment and annual medical history forms were used. We assessed the impact of social risk and geographic differences. Fisher exact tests and logistic regression were used to evaluate associations.
Annual medical history forms were available for 302 of 314 children. Greater than half of the children (52–69%) were not receiving services at any age assessed, whereas 20–32% were receiving two or more therapies each year. Utilisation was significantly lower in year 4 (31%) compared with years 1–3 (with a range from 40 to 48%) (p<0.001). Social risk factors were not associated with the use of services at any age but there were significant geographic differences. Significant delay was reported by parents in 18–43% of children at ages 3 and 4.
Despite significant neurodevelopmental delays, early intervention service utilisation was low in this cohort. As survival has improved for children with hypoplastic left heart syndrome, attention must shift to strategies to optimise developmental outcomes, including enrolment in early intervention when merited.