To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Depressed patients with early traumatic experiences may represent a clinically distinct subtype with worse clinical outcome. Since early traumatic experiences alter the development of systems that regulate the stress response, certain personality features may influence coping strategies, putting individuals with depression and a history of early traumatic experiences at greater risk of suicidal behaviour.
To determine whether impulsivity mediates the relationship between early traumatic experiences and suicidal behaviour in patients with major depressive disorder (MDD).
The sample included 190 patients [mean age (SD)=53.71 (10.37); females: 66.3%], with current MDD. The Childhood Trauma Questionnaire-Short Form (CTQ-SF), the List of Threatening Experiences (LTE), and the Barratt Impulsiveness Scale-11 (BIS-11) were used to assess childhood and adulthood adverse life events and impulsivity. We developed mediation models by bootstrap sampling methods.
81 (42.6%) patients had previous suicide attempts (SA). CTQ-SF-Total and BIS-11-Total scores were higher in MDD patients with previous SA. Correlation analyses revealed significant correlations between the CTQ-SF-Total and BIS-11-Total, CTQ-SF-Total and HDRS-Total, and BIS-11-Total and HDRS-Total scores. Regression models found that CTQ-SF-Total, BIS-11-Total, and HDRS-Total scores were associated with SA. Mediation analyses further revealed the association between CTQ-SF-Total and SA was mediated by the indirect effect of the BIS-11-Total score (b=0.007, 95% CI=0.001, 0.015), after controlling for sex, HDRS-Total, and LTE-Total.
Impulsivity could mediate the influence of childhood trauma on suicidal behaviour. This will help understand the role of risk factors in suicidal behaviour and aid in the development of prevention interventions focused on modifiable mediators when risk factors are non-modifiable.
Suicidal behavior has a great impact on world public health. The literature describes the possible existence of an association between neurobiological, clinical and cognitive factors in suicidal behavior.
To determine the possible relationship between clinical variables (history of abuse/maltreatment in childhood), psychopathology (impulsivity traits) and cognitive (decision-making) with a history of suicide attempt and/or current suicidal idea in patients with major depressive disorder.
Cross-sectional study in a sample of adult patients with major depressive disorder in which two types of comparisons are made. In the first case, two groups were compared based on the presence or absence of history of suicide attempt. In the second case, two groups were compared based on the presence or absence of suicidal ideation in the same sample of patients. Finally, sociodemographic, clinical and cognitive variables were evaluated in that population sample.
When the joint influence of sociodemographic, clinical and cognitive characteristics are present, it can be said that being single/divorced/separated, a history of sexual abuse in childhood and an alteration in decision-making, specifically a lower number of choices of deck D in the IGT test, are associated with a higher probability of a personal history of suicide attempt. While a higher score on the Barrat impulsivity scale is associated with a greater probability of presenting current suicidal ideation once the influence of sociodemographic, clinical and cognitive variables has been taken into account.
Different sociodemographic, clinical and cognitive factors are associated with the presence of a history of suicide attempt and/or current suicidal ideation.
The design and performance quantification of four Vertical Take-Off and Landing (VTOL) architectures for a canard-type aircraft configuration are presented. The aero-structural sizing of the canard configuration and the sizing procedure for the proposed VTOL configurations are described and discussed. The proposed VTOL architectures are based on a range of rotor distances to the centre of gravity, quad- and tri-rotor configurations, retractable front rotors and tilt rear rotors. The aerodynamic performance, total installed power and VTOL system mass were modelled and experimentally validated. The results show that a fully exposed VTOL system penalises the Lift-over-Drag (L/D) ratio significantly relative to a clean configuration. The VTOL system mass can be reduced by up to 32% by using a tilt tri-rotor configuration when compared with an equidistant quad-rotor+pusher configuration. The fraction of installed power usable for forward flight can be increased by up to 80% with a tilt configuration. For the proposed mission, the range can be significantly increased if a tri-rotor tilt configuration is adopted in place of an equidistant quad-rotor+pusher configuration.
To investigate the frequency of environmental contamination in hospital areas outside patient rooms and in outpatient healthcare facilities.
This study was conducted across 4 hospitals, 4 outpatient clinics, and 1 surgery center.
We conducted 3 point-prevalence culture surveys for methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Clostridioides difficile, Candida spp, and gram-negative bacilli including Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumanii, and Stenotrophomonas maltophilia in each facility. In hospitals, high-touch surfaces were sampled from radiology, physical therapy, and mobile equipment and in emergency departments, waiting rooms, clinics, and endoscopy facilities. In outpatient facilities, surfaces were sampled in exam rooms including patient and provider areas, patient bathrooms, and waiting rooms and from portable equipment. Fluorescent markers were placed on high-touch surfaces and removal was assessed 1 day later.
In the hospitals, 110 (9.4%) of 1,195 sites were positive for 1 or more bacterial pathogens (range, 5.3%–13.7% for the 4 hospitals) and 70 (5.9%) were positive for Candida spp (range, 3.7%–5.9%). In outpatient facilities, 31 of 485 (6.4%) sites were positive for 1 or more bacterial pathogens (range, 2% to 14.4% for the 5 outpatient facilities) and 50 (10.3%) were positive for Candida spp (range, 3.9%–23.3%). Fluorescent markers had been removed from 33% of sites in hospitals (range, 28.4%–39.7%) and 46.3% of sites in outpatient clinics (range, 7.4%–82.8%).
Surfaces in hospitals outside patient rooms and in outpatient facilities are frequently contaminated with healthcare-associated pathogens. Improvements in cleaning and disinfection practices are needed to reduce contamination.
In diagnosing dementia, estimating premorbid functioning is critical for accurate detection of the presence and severity of cognitive decline. However, which assessments of premorbid intelligence are most suitable for use in clinical practice is not well established. Here, we systematically evaluate the validity of instruments for measuring premorbid intelligence in people living with dementia.
Design and setting:
In this systematic review, electronic databases (EMBASE, PsycINFO, MEDLINE, CINAHL, and AMED) were searched to identify studies reporting on objective measures of premorbid intelligence in dementia. Participants from included studies were recruited from local communities and clinical settings.
A total of 1082 patients with dementia and 2587 healthy controls were included in the review.
The literature search resulted in 13 eligible studies describing 19 different instruments. The majority of instruments (n = 14) consisted of language-based measures, with versions of the National Adult Reading Test (NART) being most commonly investigated.
Preliminary evidence suggested comparable performance of patients with mild dementia and healthy controls on word reading tasks in English, Portuguese, Swedish, and Japanese. In moderate dementia, however, the performance was significantly impaired on most verbal tasks. There was a lack of reliability and validity testing of available instruments, with only one of the included studies reporting psychometric properties within the patient group.
The results demonstrate that there is a wide range of tools available for estimating premorbid intelligence in dementia, with cautious support for the potential of word reading tasks across different languages in individuals with mild dementia. However, the review highlights the urgent need for extensive assessments of the psychometric properties of these tasks in dementia. We propose that further longitudinal research and assessments of nonverbal measures are necessary to validate these instruments and enhance diagnostic procedures for people living with dementia worldwide.
To compare cognitive phenotypes of participants with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI), estimate progression to MCI/dementia by phenotype and assess classification error with machine learning.
Dataset consisted of 163 participants with SCD and 282 participants with aMCI from the Czech Brain Aging Study. Cognitive assessment included the Uniform Data Set battery and additional tests to ascertain executive function, language, immediate and delayed memory, visuospatial skills, and processing speed. Latent profile analyses were used to develop cognitive profiles, and Cox proportional hazards models were used to estimate risk of progression. Random forest machine learning algorithms reported cognitive phenotype classification error.
Latent profile analysis identified three phenotypes for SCD, with one phenotype performing worse across all domains but not progressing more quickly to MCI/dementia after controlling for age, sex, and education. Three aMCI phenotypes were characterized by mild deficits, memory and language impairment (dysnomic aMCI), and severe multi-domain aMCI (i.e., deficits across all domains). A dose–response relationship between baseline level of impairment and subsequent risk of progression to dementia was evident for aMCI profiles after controlling for age, sex, and education. Machine learning more easily classified participants with aMCI in comparison to SCD (8% vs. 21% misclassified).
Cognitive performance follows distinct patterns, especially within aMCI. The patterns map onto risk of progression to dementia.
Aim of the study: to examine the role of endocannabinoids and CB1 receptors in psychosocial (PS) stress in mice. PS stress was induced in C57Bl/6 mice by resident-intruder paradigm (Brzózka et al. 2010). After 3 weeks PS stress anandamide (AEA), 2-arachidonoylglycerol (2-AG), N-oleoylethanolamine (OEA) and palmitoylethanolamide (PEA) were estimated in hippocampus, prefrontal cortex, striatum and cerebellum. Identically stressed and control mice (N = 15) were injected with WIN55212.2 (3 mg/kg) ± Rimonabant (3 mg/kg). Functional Observational Battery (FOB) (Golub et al., 2004), Open Field (OF), Prepulse Inhibition test (PPI) were studied. All behavioral recordings were done at night. Stressed mice showed significantly lowered AEA and OEA in Hippocampus, significant increase of 2-AG in Cortex, decrease of OEA in Striatum and increase of 2-AG in Cerebellum. Stressed mice displayed significantly lowered body weight gain, higher scratching activity, decrease of righting reflex time in FOB, higher distance travelled, time moving and hyperactivity in OF. In stressed mice WIN55212.2 significantly lowered rearings, increased righting reflex time, reduced distance travelled, time moving and hyperactivity in OF. Rimonabant did not significantly antagonize the effect of WIN55212.2 in stressed mice, but in controls. In controls WIN55212.2 significantly increased the number of scratches, reduced distance travelled, time moving and climbing and increased the startle response amplitude in PPI. The latter effect was significantly antagonized by Rimonabant. To sum up significant stress effects could be recorded in behavior, but less in PPI. PPI seems to be dependent on CB1-receptor processes but in case of stress endocannabinoids-activities may contribute.
to investigate the consequences of chronic psychosocial stress on behavior, endocannabinoids and CBR expression in prefrontal cortex (PFC) and striatum of mice.
Materials and Methods
Psychosocial stress was induced in adult C57Bl/6 mice by resident-intruder paradigm (Brzózka et al. 2011). After 3 weeks daily exposure to psychosocial stress for 1 hour, animals were studied during the rodent active phase (night) by behavioral tests such as Functional Observational Battery (FOB), Rota-Rod (R-R), Open Field (OF), Prepulse Inhibition test (PPI). After behavioral testing, mice were sacrificed. 4 mice brains (prefrontal cortex, dorsal striatum) were studied by LC-MS to estimate the concentration of anandamide (AEA), 2- arachidonoylglycerol (2-AG), N-oleoylethanolamine (OEA), palmitoylethanolamide (PEA) (coll. di Marzo). In Situ Hybridization (ISH)and Immunohistochemistry (IHCH) against CB1 receptor were performed on free floating brain coronal sections fixed by 4% paraformaldehyde (coll del Río).
1. After psychosocial stress, mice displayed lower body weight (p<0.01), higher scratching and miccions activity compared to controls (p<0.05), decreased number of falls (p<0.01) and increased latency (p<0.05) in Rotarod. No effects in PPI were found. 2. In the same mice psychosocial stress reduced AEA levels in dorsal striatum and PFC (p<0.05). Endocannabinoids significantly showed an inverse relationship in PFC compared to striatum in control mice (AEA, p<0.001; 2-AG, p<0.001; OEA, p<0.001) and in psychosocially stressed mice (PEA, p<0.001; OEA, p<0.001). 3. Psychosocial stress increased the protein CBR1 expression in striatum (p<0.05) but not in prefrontal cortex.
Chronic psychosocial stress significantly changes behavior, endocannabinoids, CB receptor function and the striatal-cortical connectivity. These changes may contribute to vulnerability for psychosis and addiction.
A First Manic Episode (FME) can evolve differently and some patients remain chronically ill (Poor Outcome Manic Syndrome = POMS). Even, the majority of subsequent episodes reoccur over the time; few studies have looked at the long-term course of a FME. The aim is therefore to look at the longitudinal clinical characteristics of FME in a hospital setting.
The subjects, developing POMS, were patients admitted to hospital with at least 2 hospitalizations for mania and having received continuing psychiatric care for ≥ 5 years. The control group subjects were FME patients with only one admission. The data was gathered from hospital discharge summaries for all 472 subjects with FME (age 14–64) admitted to a Quebec regional psychiatric hospital for the first time during a 30 year period (1980-2011).
Amongst all first admitted FME patients, 27% ended up with POMS. A logistic regression analysis indicates the subsequent development of POMS was correlated with younger age, male gender and alcohol misuse at the time of the initial admission to hospital. The historical data available (median=11 years) shows that the diagnosis evolved towards bipolar disorder (76%), schizoaffective disorder (17%) and schizophrenia (6%).
The results indicate that development of POMS is an inevitable clinical reality. The influence of alcoholism on the evolution of FME is clearly adverse. It is particularly associated with more manic episodes. The results underline the necessity for concomitant intervention for alcoholism in the presence of FME.
The aim of the present poster is to describe an initial complex case of schizoaffective disorder with other clinical adverse conditions (metabolic disorders) in a young adult male, which gradually went into a positive treatment way from polipharmacy to monoteraphy. His psychiatric history started when he was 25-year-old, he was diagnosed of heroine dependence, hypercholesterolemia and hypertrigliceridemia. In 2000 he had a suicide attempt in a context of depressive mood and delusions. He needed a psychiatric hospitalization for the first time in his life and he received anti-psychotics for the first time too. Drug abuse was detected in that hospitalization (cannabis and alcohol). In 2001 was diagnosed of paranoid schizophrenia. In 2007 the diagnosis was modified to schizoaffective disorder and also was detected high blood pressure, Diabetes Mellitus II and overweight. From 2007 to the present he passed from a scheme treatment composed by four or more psychotropic drugs to monotherapy (only one psychotropic drug, an anti-psychotic), he stayed clinically stable and all his metabolic parameters remained equal or improved.
Multimorbidity (MM) refers to the coexistence of two or more chronic diseases in the same individual; it encompasses medical comorbidity (MC) and psychiatric comorbidity (PC). Hypothesis: MM is prevalent amongst in-patients suffering from affective disorders (AD) and also impacted on length of stay.
To determine the prevalence of MM and its impact on duration of hospitalization in AD admissions.
This cross-sectional study was conducted using secondary data taken from discharge records of 1056 adults admitted for AD to a Quebec-based facility, between 2006 and 2014. Distribution of AD cases: 47% depression, 53% bipolar disorders.
The prevalence rate of MM: 85%. PC was present in 70% of sample whereas MC was present in 62%. The median number of comorbid illnesses was 2.7 for each study subject. The rate of MM was not related to age or gender. Metabolic syndrome (54%), cardiovascular diseases and chronic pain syndrome (17%) were the most prevalent MC in both depressed and bipolar populations. Personality disorder (65%) was highest in the depression population, whereas substance misuse (55%) was the most prevalent PC in the bipolar subjects. A longer length of stay was correlated with MM. However, a logistic regression analysis indicated that duration of hospitalization was only correlated with MC.
The observation that MM is the norm, even in this relatively young population with AD. The results confirmed that MC prolongs hospital stay. These findings advocate strongly for integrated management of psychiatric and physical health problems in clinical practice.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
A primary barrier to translation of clinical research discoveries into care delivery and population health is the lack of sustainable infrastructure bringing researchers, policymakers, practitioners, and communities together to reduce silos in knowledge and action. As National Institutes of Healthʼs (NIH) mechanism to advance translational research, Clinical and Translational Science Award (CTSA) awardees are uniquely positioned to bridge this gap. Delivering on this promise requires sustained collaboration and alignment between research institutions and public health and healthcare programs and services. We describe the collaboration of seven CTSA hubs with city, county, and state healthcare and public health organizations striving to realize this vision together. Partnership representatives convened monthly to identify key components, common and unique themes, and barriers in academic–public collaborations. All partnerships aligned the activities of the CTSA programs with the needs of the city/county/state partners, by sharing resources, responding to real-time policy questions and training needs, promoting best practices, and advancing community-engaged research, and dissemination and implementation science to narrow the knowledge-to-practice gap. Barriers included competing priorities, differing timelines, bureaucratic hurdles, and unstable funding. Academic–public health/health system partnerships represent a unique and underutilized model with potential to enhance community and population health.
The objectives of this study were: to assess the efficiency of high hydrostatic pressure or ultra-high pressure homogenization against Mycobacterium smegmatis in milk and to discuss whether M. smegmatis can be considered a suitable surrogate for other Mycobacterium spp. in high pressure inactivation trials using milk. Three strains of this specie (CECT 3017, 3020 and 3032) were independently inoculated into both skimmed (0.2% fat) and whole milk (3.4% fat) at an approximate load of 6.5 Log CFU/ml and submitted to HHP treatments at 300, 400 or 500 MPa for 10 m at 6°C and 20°C. Evolution of the surviving cells of the inoculated strains was evaluated analysing milk immediately after the treatments and after 5 and 8 d of storage at 6°C. HHP treatments at 300 MPa were seldom efficient at inactivating M. smegmatis strains, but lethality increased with pressure applied in all cases. Generation of sub-lethal injured cells was observed only after 400 MPa treatments since inactivation at 500 MPa was shown to be complete. Significant differences were not observed due to either temperature of treatment or fat content of milk, except for strain CECT3032, which was shown to be the most sensitive to HHP treatments. Milk inoculated with strain CECT3017 was submitted to ultra-high pressure homogenization (UHPH) treatments at 200, 300 and 400 MPa. Maximum reductions were obtained after 300 and 400 MPa treatments, although less than 3.50 Log CFU/ml were inactivated. UHPH did not cause significant number of injured cells. The usefulness of this species as a marker for pressure-based processing seems limited since it showed greater sensitivity than some pathogenic species including other Mycobacteria reported in previous studies.
Immune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear.
To identify potential differential intra-/intercellular biochemical pathways controlling immune-inflammatory response and their oxidative-nitrosative impact on SCH patients, compared with bipolar disorder (BD) patients and healthy controls (HC).
Cross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)].
ANCOVA (or Quade test) controlling for age and gender when comparing the three groups, and controlling for age, gender, length of illness, cigarettes per day, and body mass index (BMI) when comparing SCH and BD.
Pro-inflammatory biomarkers: Expression of COX-1 was statistically higher in SCH and BD than HC (P<0.0001; P<0.0001); NFκB and PGE2 were statistically higher in SCH compared with BD (P=0.001; P<0.0001) and HC (P=0.003; P<0.0001); NLRP3 was higher in BD than HC (P=0.005); and CPR showed a gradient among the three groups. Anti-inflammatory biomarkers: BD patients had lower PPARγ and higher 15d-PGJ2 levels than SCH (P=0.005; P=0.008) and HC (P=0.001; P=0.001). Differences between SCH and BD: previous markers of SCH (NFκB and PGE2) and BD (PPARγ and 15d-PGJ2) remained statistically significant and, interestingly, iNOS and COX-2 (pro-inflammatory biomarkers) levels were statistically higher in SCH than BD (P=0.019; P=0.040).
This study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.
The indications for expanded endoscopic transnasal approaches continue to increase, with more complex skull base defects needing to be repaired. This study reviews the management of large anterior skull base defects with opening of the sellar diaphragm.
A prospective analysis of endonasal endoscopic surgery carried out at Son Espases University Hospital between January 2013 and December 2018 was performed. The analysis included only the cases with a significative intra-operative cerebrospinal fluid leak. In all cases, reconstruction was performed by combining the gasket seal technique with a pedicled mucosal endonasal flap.
Twenty-eight patients were included. The mucoperiosteal nasoseptal flap, the lateral wall flap and the middle turbinate flap were used in 13, 8 and 7 patients, respectively, combined with the gasket seal technique. One case of post-operative cerebrospinal fluid leak was observed (3.57 per cent).
The combination of a gasket seal with an endonasal mucosal flap is an excellent technique for repairing large anterior skull base defects.
In a crossover trial, a gown designed to increase skin coverage at the hands and wrists significantly reduced contamination of personnel during personal protective equipment (PPE) removal, and education on donning and doffing technique further reduced contamination. Simple modifications of PPE and education can reduce contamination during PPE removal.