CRISPR/Cas9-generated mutations in a sugar transporter gene reduce cassava susceptibility to bacterial blight.

Bacteria from the genus Xanthomonas are prolific phytopathogens that elicit disease in over 400 plant species. Xanthomonads carry a repertoire of specialized proteins called transcription activator-like (TAL) effectors that promote disease and pathogen virulence by inducing expression of host susceptibility (S) genes. Xanthomonas phaseoli pv. manihotis (Xpm) causes bacterial blight on the staple food crop cassava (Manihot esculenta Crantz). The Xpm effector TAL20 induces ectopic expression of the S gene Manihot esculenta Sugars Will Eventually be Exported Transporter 10a (MeSWEET10a), which encodes a sugar transporter that contributes to cassava bacterial blight susceptibility. We used CRISPR/Cas9 to generate multiple cassava lines with edits to the MeSWEET10a TAL20 effector binding site and/or coding sequence. In several of the regenerated lines, MeSWEET10a expression was no longer induced by Xpm, and in these cases, we observed reduced cassava bacterial blight (CBB) disease symptoms post Xpm infection. Because MeSWEET10a is expressed in cassava flowers, we further characterized the reproductive capability of the MeSWEET10a promoter and coding sequence mutants. Lines were crossed to themselves and to wild-type plants. The results indicated that expression of MeSWEET10a in female, but not male, flowers, is critical to produce viable F1 seed. In the case of promoter mutations that left the coding sequence intact, viable F1 progeny were recovered. Taken together, these results demonstrate that blocking MeSWEET10a induction is a viable strategy for decreasing cassava susceptibility to CBB and that ideal lines will contain promoter mutations that block TAL effector binding while leaving endogenous expression of MeSWEET10a unaltered.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Trauma and mental health in young adults who arrived in France as unaccompanied and separated migrant children.

OBJECTIVES: The mental health of unaccompanied and separated minors (UASC) has been widely studied but not their first years of adulthood, often characterised by uncertainty after leaving child protection. The aim of this study was to estimate the prevalence of psychiatric disorders using standardised and validated research instruments and examine the effect of exposure to trauma. METHODS: One hundred and ten youth (92.7% male, median age 19.7 [18.1-22.8]) from Chambery, Montpellier and La Rochelle were recruited to a cross-sectional exploratory study. During a face-to-face interview, somatoform disorder, anxiety, and depression were assessed using the Patient Health Questionnaire (score≥10) and post-traumatic stress disorder (PTSD) with the PTSD Checklist for DSM-5 (score≥33). Traumatic life events were assessed using the Life Events Checklist. RESULTS: Of the youth, 19.3% had a probable somatoform disorder, 17.6% anxiety, 28.7% depression, and 20% PTSD. The number of traumatic life events increased the risk of depression (multi-adjusted OR (95%CI): 1.56 (1.25-1.96)), PTSD (1.60 (1.23-2.08)), somatoform disorder (1.41 (1.10-1.82), and anxiety (1.33 (1.02-1.72)). Physical assault was the type of event positively associated with the most disorders (P≤0.01, except for anxiety), followed by witnessing sudden and violent death (P≤0.01 for depression and PTSD) and sexual assault (P=0.002 for PTSD). CONCLUSION: Our study highlights the high prevalence of psychiatric disorders in young adults who arrived as UASC and the impact on their mental health of cumulative trauma and exposure to interpersonal and violent traumatic life events. A greater focus on their mental health with regular assessments is needed in order to provide rapid and adapted care.

Association between uncertainty regarding right-to-stay and mental health in unaccompanied and separated migrant children (UASC) reaching adulthood: findings from France.

PURPOSE: There is substantial evidence suggesting high levels of mental health problems in unaccompanied and separated children (UASC). However, there is less focus on the first years of adulthood characterised by increased vulnerability and fear of expulsion. We aimed to describe the mental health of UASC on reaching adulthood, and how this was affected by uncertainty regarding their right-to-stay in France. METHODS: One hundred and ten youth aged 18-22 were recruited via child protection reception centres. We administered the Patient Health Questionnaire somatic (PHQ-15), anxiety (GAD-7) and depression (PHQ-9) modules, the Post-Traumatic Stress Disorder Checklist (PCL-5) and Connor-Davidson Resilience Scale (CD-RISC-10). Logistic regression analysis was performed with the dependent variable, a secure (versus uncertain) situation, defined as (1) detaining a residence permit and being in school, an apprenticeship or a salaried job, or (2) waiting for residence permit whilst occupying a salaried job. RESULTS: Of the sample, 19.3% reached criteria for a probable somatic disorder, 17.6% for anxiety and 28.7% for depression (score  ≥ 10); 41.8% were in an uncertain situation regarding their right-to-stay. Uncertainty was associated with higher anxiety ((OR per Interquartile range (95% CI), 1.77 (1.05-2.98)) and post-traumatic stress symptoms (2.05 (1.06-4.00)), lower resilience (0.50 (0.27-0.91)), and participants rating their anxiety (p = 0.02) and depressive symptoms (p = 0.003) as more severe since reaching adulthood. CONCLUSIONS: Our findings suggest uncertainty regarding right-to-stay is associated with increased mental health symptoms, specifically anxiety and trauma-induced stress, thereby highlighting the vulnerability of UASC in their first years of adulthood. This calls for greater support during this transition period with regular symptom monitoring for timely psychological interventions.

Time-dependent depression and anxiety symptoms as risk factors for recurrent cardiac events: findings from the UPBEAT-UK study.

BACKGROUND: Depression is a well-known risk factor for recurrent cardiac events (RCEs) but findings are less consistent for anxiety, not previously reported on using a time-dependent approach. We aimed to study the prognostic effect of anxiety and depression symptom levels on RCEs. METHODS: Data (N = 595) were drawn from the UPBEAT-UK heart disease patient cohort with 6-monthly follow-ups over 3 years. Hospital Anxiety and Depression Scale symptoms were grouped into: agitation (three items), anxiety (four items), and depression (seven items) subscales. We performed two types of multivariate analyses using Cox proportional hazard models with delayed entry: with baseline variables (long-term analysis), and with variables measured 12-to-18 months prior to the event (short-term time-dependent analysis), as RCE risk factors. RESULTS: In the baseline analysis, both anxiety and depression, but not agitation, were separate RCE risk factors, with a moderating effect when considered jointly. In the short-term time-dependent analysis, elevated scores on the anxiety subscale were associated with increased RCE risk even when adjusted for depression [hazard ratio (95% confidence interval) 1.22 (1.05-1.41), p = 0.009]. Depression was no longer a significant predictor when adjusted for anxiety [1.05 (0.87-1.27), p = 0.61]. For anxiety, individual items associated with RCEs differed between the two approaches: item 5 'worrying thoughts' was the most significant long-term risk factor [1.52 (1.21-1.91), p = 0.0004] whereas item 13 'feelings of panic' was the most significant time-dependent short-term risk factor [1.52 (1.18-1.95), p = 0.001]. CONCLUSIONS: Anxiety is an important short-term preventable and potentially causal risk factor for RCEs, to be targeted in secondary cardiac disease prevention programmes.

11ß-Hydroxylase (CYP11B1) gene variants and new-onset depression in later life.

Background: Cumulative exposure to high glucocorticoid levels is detrimental for the brain and may have particular implications in later life. A feature of late-life depression is increased cortisol secretion. Variants in the CYP11B1 gene, which codes for the enzyme responsible for cortisol synthesis, could influence risk of late-life depression, but this hypothesis has not been examined. We investigated the associations between variants in the CYP11B1 gene and late-life depression, taking into account history of depression and potential sex-specific effects. Methods: We assessed depression in 1007 community-dwellers aged 65 years or older (60% women) at baseline and over a 14-year follow-up. A clinical level of depression was defined as a score of ≥ 16 on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). We examined incident and recurrent depression in participants without or with a history of major depression, respectively. We genotyped 5 single-nucleotide polymorphisms (SNPs) spanning CYP11B1. We used multivariable analyses to adjust for age, body mass index, cardiovascular ischemic pathologies, hypertension, cognitive impairment and anxiety. Results: In women, rs6471580 and rs7016924 were associated with a 50% lower rate of incident (new-onset) late-life depression, and rs11783855 was associated with a 2.4-fold higher rate of late-life depression. These associations remained after correction for multiple testing, but we found no associations for recurrent depression in women or men. Limitations: This study focused on the major gene involved in corticosteroid biosynthesis, but other genes may also be implicated in this pathway. Conclusion: Variants of the CYP11B1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner.

Aromatase (CYP19A1) gene variants, sex steroid levels, and late-life depression.

BACKGROUND: Sex differences in psychiatric disorders are common and could involve sex steroids. Aromatase, the product of the CYP19A1 gene, is the key enzyme in the conversion of androgen to estrogen. Whether CYP19A1 variants could be associated with depression differently in men and women has not been examined. METHODS: This population-based study included 405 men and 602 women aged ≥65 years. A clinical level of depression (DEP) was defined as having a score ≥16 on the Center for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) spanning the CYP19A1 gene were genotyped and circulating levels of estradiol and testosterone were determined. Multivariable analyses were adjusted for age, body mass index, ischemic pathologies, cognitive impairment, and anxiety. RESULTS: Five SNPs were associated with DEP in women specifically and this varied according to a history of major depression (p-values .01 to .0005). Three SNPs were associated with an increased risk of late-life DEP in women without a history of major depression, while two SNPs were associated with a decreased DEP risk in women with a history of major depression and were also associated with higher estradiol levels. CONCLUSIONS: Variants of the CYP19A1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner. The polymorphisms decreasing the risk of recurrent depression in postmenopausal women also influence estradiol levels.

Using a citizens' jury approach to determine a good nutrition resource for pregnant women.

OBJECTIVE: The development of user-friendly nutrition resources for pregnant women seldom involves end-users. This qualitative study used a citizens' jury approach to determine if our modification of a longstanding, frequently used dietitian-informed diet and diabetes booklet was deemed to be a good healthy eating resource for pregnant women. DESIGN: Midwives recruited thirteen first-time pregnant women not requiring specialist obstetric care or specialist dietetic advice for any reason. Participants were sent a copy of the modified healthy eating in pregnancy booklet prior to 'jury day'. Five women were unable to attend the citizens' jury citing reasons such as early labour. At the jury, five experts presented evidence. Participants adjourned, with an independent facilitator, to 'deliberate' as to whether the resource was suitable or not. The verdict was presented, and subsequent discussion was audio-recorded, transcribed and inductively content analysed. SETTING: Southland, New Zealand. PARTICIPANTS: Pregnant women aged 19-35 years (n 8), of whom half had a household income <$NZ30 000. RESULTS: The verdict was 'Yes'; the resource was good. Three themes were derived: communication of health information, resource content and harm reduction in pregnancy. Based on these data, ways to enhance the quality and usability of the booklet were evident. CONCLUSIONS: Citizens' juries can be used to obtain an independent assessment by end-users of health resources. Our modified diet and diabetes booklet was considered suitable for providing healthy eating advice to pregnant women. Inclusion of end-users' perspectives is critical for end-user relevant content, comprehension and resource credibility.

The cognitive, affective motivational and clinical longitudinal determinants of apathy in schizophrenia.

Apathy is a frequent and debilitating condition with few treatment options available in schizophrenia patients. Despite evidence of its multidimensional structure, most of past studies have explored apathy through a categorical approach. The main objective of this study was to identify the cognitive, emotional, motivational, and clinical factors at baseline that best predicted the three subtypes of apathy dimensions at follow-up. In a longitudinal study, 137 participants diagnosed with schizophrenia underwent different assessments including clinical, motivational, affective and cognitive measurements, at 1-month (referred to as baseline) and 12-month follow-ups. Data were analyzed using partial least squares variance-based structural equation modeling. Three latent variables representing the three previously described domains of apathy reaching consensus in the literature were extracted from the Lille Apathy Rating Scale. Results showed that in addition to baseline apathy, positive symptoms, anticipatory pleasure and sensibility to punishment at baseline predicted cognitive apathy at follow-up. Likewise, both baseline apathy and sensibility to punishment predicted emotional apathy at follow-up. Finally, baseline anhedonia and episodic memory were the main variables the predicted behavioral apathy at follow-up. This is the first study to show specific associations between apathy subtypes and clinical and cognitive motivational dysfunction in individual with schizophrenia, indicating possible distinct underlying mechanisms to these demotivational symptoms. Treatment for apathy should address both types of processes. Importantly, our results demonstrate the interest of multidimensional approaches in the understanding of apathy in schizophrenia.

Antidepressant use and cognitive decline in community-dwelling elderly people - The Three-City Cohort.

BACKGROUND: Cognitive impairment is very common in late-life depression, principally affecting executive skills and information processing speed. The aim of the study was to examine the effect of antidepressant treatment on cognitive performances over a 10-year period. METHODS: The community-based cohort included 7381 participants aged 65 years and above. Five cognitive domains (verbal fluency, psychomotor speed, executive function, visuospatial skills and global cognition) were assessed up to five times over 10 years of follow-up. Treatment groups included participants under a specific antidepressant class at both baseline and the first follow-up and their follow-up cognitive data were considered until the last consecutive follow-up with a report of antidepressant use of the same class. Linear mixed models were used to compare baseline cognitive performance and cognitive decline over time according to antidepressant treatment. The models were adjusted for multiple confounders including residual depressive symptoms assessed by the Center for Epidemiologic Studies-Depression scale. RESULTS: At baseline, 4.0% of participants were taking antidepressants. Compared to non-users, tricyclic antidepressant users had lower baseline performances in verbal fluency, visual memory and psychomotor speed, and selective serotonin reuptake inhibitor users in verbal fluency and psychomotor speed. For the two other cognitive abilities, executive function and global cognition, no significant differences were found at baseline irrespective of the antidepressant class. Regarding changes over time, no significant differences were observed in comparison with non-users whatever the cognitive domain, except for a slight additional improvement over the follow-up in verbal fluency skills for tricyclic antidepressant users. CONCLUSIONS: In this large elderly general population cohort, we found no evidence for an association between antidepressant use and post-treatment cognitive decline over 10 years of follow-up in various cognitive domains.

Is there a link between biological parents' insight into their offspring's schizophrenia and their cognitive functioning, expressed emotion and knowledge about disorder?

BACKGROUND: Recent studies suggest that parents' awareness of their offspring's schizophrenia could influence their offspring's insight. Low patient insight is linked to impairment of specific cognitive abilities, and biological parents of schizophrenia patients have impaired capacities in these same domains. However, little is known about what specific socio-demographic, affective or cognitive factors may influence biological parents' awareness of their offspring's disease. METHOD: Data were drawn from 41 patient-parent dyads. Insight was assessed with a modified version of Amador's Scale to assess Unawareness of Mental Disorders, exploring dimensions of parents' awareness and attribution of their offspring's illness and symptoms. RESULTS: Higher educational levels, better working memory and executive functioning of parents were associated with better attribution of their offspring's symptoms to schizophrenia. CONCLUSIONS: Parents' insight into their offspring's schizophrenia is associated with cognitive abilities. This must be taken into account when developing family interventions.

Health Service Utilisation, Detection Rates by Family Practitioners, and Management of Patients with Common Mental Disorders in French Family Practice.

OBJECTIVE: Provide up-to-date detection rates for common mental disorders (CMD) and examine patient service-use since the Preferred Doctor scheme was introduced to France in 2005, with patients encouraged to register with and consult a family practitioner (FP) of their choice. METHODS: Study of 1133 consecutive patients consulting 38 FPs in the Montpellier region, replicating a study performed before the scheme. Patients in the waiting room completed the self-report Patient Health Questionnaire (PHQ) and Client Service-Receipt Inventory with questions on registration with a Preferred Doctor and doctor-shopping. CMD was defined as reaching PHQ criteria for depression, somatoform, panic or anxiety disorder. For each patient, FPs completed a questionnaire capturing psychiatric caseness. RESULTS: 81.2% of patients were seeing their Preferred Doctor on the survey-day. Of those with a CMD, 52.6% were detected by the FP. This increased with CMD severity and comorbidity. Detected cases were more likely to be consulting their Preferred Doctor (84.7% versus 79.4% for non-detected cases, p = 0.05) rather than another FP. They declared more visits to psychiatrists (17.2% versus 6.7%, p = 0.002). There was no association with consultation frequency or doctor-shopping, which both declined between the two studies. CONCLUSION: The CMD detection rate is relatively high, with no increase compared to our previous study, despite a decline in doctor-shopping. An explanation is the same high proportion of patients visiting their usual FP on the survey-day at both periods, suggesting a limited impact of the scheme on care continuity. FP action taken highlights the importance of improving detection for providing care to patients with CMDs.

Patient-centeredness to anticipate and organize an end-of-life project for patients receiving at-home palliative care: a phenomenological study.

BACKGROUND: The development of end-of-life primary care is a socio-medical and ethical challenge. However, general practitioners (GPs) face many difficulties when initiating appropriate discussion on proactive shared palliative care. Anticipating palliative care is increasingly important given the ageing population and is an aim shared by many countries. We aimed to examine how French GPs approached and provided at-home palliative care. We inquired about their strategy for delivering care, and the skills and resources they used to devise new care strategies. METHODS: Twenty-one GPs from the South of France recruited by phone according to their various experiences of palliative care agreed to participate. Semi-structured interview transcripts were examined using a phenomenological approach inspired by Grounded theory, and further studied with semiopragmatic analysis. RESULTS: Offering palliative care was perceived by GPs as a moral obligation. They felt vindicated in a process rooted in the paradigm values of their profession. This study results in two key findings: firstly, their patient-centred approach facilitated the anticipatory discussions of any potential event or intervention, which the GPs openly discussed with patients and their relatives; secondly, this approach contributed to build an "end-of-life project" meeting patients' wishes and needs. The GPs all shared the idea that the end-of-life process required human presence and recommended that at-home care be coordinated and shared by multi-professional referring teams. CONCLUSIONS: The main tenets of palliative care as provided by GPs are a patient-centred approach in the anticipatory discussion of potential events, personalized follow-up with referring multi-professional teams, and the collaborative design of an end-of-life project meeting the aspirations of the patient and his or her family. Consequently, coordination strategies involving specialized teams, GPs and families should be modelled according to the specificities of each care system.

The effectiveness of a primary care nursing-led dietary intervention for prediabetes: a mixed methods pilot study.

BACKGROUND: Primary care nurse-led prediabetes interventions are seldom reported. We examined the implementation and feasibility of a 6-month multilevel primary care nurse-led prediabetes lifestyle intervention compared with current practice in patients with prediabetes, with weight and glycated haemoglobin (HbA1c) as outcomes. METHODS: This study used a convergent mixed methods design involving a 6-month pragmatic non-randomised pilot study with a qualitative process evaluation, and was conducted in two neighbouring provincial cities in New Zealand, with indigenous Maori populations comprising 18.2% and 23.0%, respectively. Participants were non-pregnant adults aged ≤ 70 years with newly diagnosed prediabetes (HbA1c 41-49 mmol/mol), body mass index (BMI) ≥ 25 kg/m2 and not prescribed Metformin. A structured dietary intervention tool delivered by primary care nurses with visits at baseline, 2-3 weeks, 3 months and 6 months was implemented in four intervention practices. Four control practices continued to provide usual care. Primary quantitative outcome measures were weight and HbA1c. Linear and quantile regression models were used to compare each outcome between the two groups at follow-up. Qualitative data included: observations of nurse training sessions and steering group meetings; document review; semi-structured interviews with a purposive sample of key informants (n = 17) and intervention patients (n = 20). Thematic analysis was used. RESULTS: One hundred fifty-seven patients with prediabetes enrolled (85 intervention, 72 control), 47.8% female and 31.2% Maori. Co-morbidities were common, particularly hypertension (49.7%), dyslipidaemia (40.1%) and gout (15.9%). Baseline and 6 month measures were available for 91% control and 79% intervention participants. After adjustment, the intervention group lost a mean 1.3 kg more than the control group (p < 0.001). Mean HbA1c, BMI and waist circumference decreased in the intervention group and increased in the control group, but differences were not statistically significant. Implementation fidelity was high, and it was feasible to implement the intervention in busy general practice settings. The intervention was highly acceptable to both patients and key stakeholders, especially primary care nurses. CONCLUSIONS: Study findings confirm the feasibility and acceptability of primary care nurses providing structured dietary advice to patients with prediabetes in busy general practice settings. The small but potentially beneficial mean weight loss among the intervention group supports further investigation. TRIAL REGISTRATION: ANZCTR ACTRN12615000806561 . Registered 3 August 2015 (Retrospectively registered).

Elderly benzodiazepine users at increased risk of activity limitations: influence of chronicity, indications, and duration of action--the three-city cohort.

OBJECTIVE: To examine the cross-sectional and longitudinal associations between benzodiazepine use and daily activity limitations, according to drug indications and duration of action. DESIGN: Prospective cohort study. SETTING: Population-based three-city study. PARTICIPANTS: 6,600 participants aged 65 years and over included between 1999 and 2001 and followed after 2, 4, and 7 years. MEASUREMENTS: Benzodiazepine users were separated into hypnotic, short-acting anxiolytic, and long-acting anxiolytic users and compared with non users. Three outcomes were examined assessing restrictions in mobility, instrumental activities of daily living (IADLs) and social participation. RESULTS: In multivariate simple or mixed logistic models adjusted for sociodemographic variables, impairments and comorbidity, and for anxiety, insomnia, and depression, hypnotic benzodiazepines were moderately associated with mobility limitation prevalence and IADL limitation incidence. Short-acting and long-acting anxiolytics were associated with IADL limitation prevalence and with mobility limitation prevalence and incidence and long-acting anxiolytics were also associated with IADL limitation incidence. Chronic benzodiazepines users were at a marked risk of developing restrictions for the three outcomes; odds ratio: 1.71 (95% CI: 1.23-2.39) for mobility, 1.54 (95% CI: 1.14-2.10) for IADL, and 1.74 (95% CI: 1.23-2.47) for participation limitations. CONCLUSIONS: Benzodiazepine users are at increased risk of activity limitations regardless of the duration of action or indication. Chronic use of benzodiazepines should be avoided in order to extend disability-free survival.

Mapping Cognitive Trajectories and Detecting Early Dementia Using the Mini-Mental State Examination Cognitive Charts: Application to the French Three-City Cohort.

The Cognitive Quotient (QuoCo) classification algorithm monitoring decline on age- and education-adjusted Mini-Mental State Examination (MMSE)-derived cognitive charts has proved superior to the conventionally-used cut-off for identifying incident dementia; however, it remains to be tested in different settings. Data were drawn from the Three-City Cohort to 1) assess the screening accuracy of the QuoCo, and 2) compare its performance to that of serial MMSE tests applying different cut-offs. For the QuoCo, sensitivity was 74.2 (95% CI: 71.4-76.8) and specificity 84.1 (83.6-84.7) and for the MMSE < 24, 64.1 (61.1-67.0) and 94.8 (94.4-95.1), respectively; whereas overall accuracy and sensitivity was highest for MMSE cut-offs <25 and <26. User-friendly charts for mapping cognitive trajectories over visits with an alert for potentially 'abnormal' decline can be of practical use and encourage regular monitoring in primary care where the <24 cut-off is still widely used despite its poor sensitivity.

Anxiety and mortality risk in community-dwelling elderly people.

BACKGROUND: There are conflicting data on the role of anxiety in predicting mortality. AIMS: To evaluate the 10-year mortality risk associated with anxiety in community-dwelling elderly people. METHOD: Using data from 718 men and 1046 women aged 65 years and over, gender-stratified associations of anxiety symptoms (Spielberger State-Trait Anxiety Inventory, third tertile) and current DSM-IV anxiety disorder including generalised anxiety disorder (GAD) and phobia with all-cause and cardiovascular mortality were determined. RESULTS: In women, mortality risk was increased for anxiety disorder and GAD in multivariate Cox models (hazard ratio (HR) = 1.53, 95% CI 1.02-2.27 and HR = 2.04, 95% CI 1.08-3.86 respectively), whereas for phobia it was nearly significant (HR = 1.52, 95% CI 0.94-2.47). Anxiety trait symptoms became non-significant as a result of the confounding effect of depressive symptoms. Anxiety disorder was associated with cardiovascular mortality in univariate analysis (HR = 2.42, 95% CI 1.16-5.07). No significant associations were found in men. CONCLUSIONS: Our study suggests a gender-specific association of anxiety and mortality.

Improving cassava bacterial blight resistance by editing the epigenome.

Pathogens rely on expression of host susceptibility (S) genes to promote infection and disease. As DNA methylation is an epigenetic modification that affects gene expression, blocking access to S genes through targeted methylation could increase disease resistance. Xanthomonas phaseoli pv. manihotis, the causal agent of cassava bacterial blight (CBB), uses transcription activator-like20 (TAL20) to induce expression of the S gene MeSWEET10a. In this work, we direct methylation to the TAL20 effector binding element within the MeSWEET10a promoter using a synthetic zinc-finger DNA binding domain fused to a component of the RNA-directed DNA methylation pathway. We demonstrate that this methylation prevents TAL20 binding, blocks transcriptional activation of MeSWEET10a in vivo and that these plants display decreased CBB symptoms while maintaining normal growth and development. This work therefore presents an epigenome editing approach useful for crop improvement.

Psychometric properties of the BIRT Motivation Questionnaire (BMQ), a self-measure of avolition in individuals with schizophrenia.

AIMS: Avolition defined as a lack of interest or engagement in goal-directed behavior plays a key role in everyday functioning in schizophrenia and is considered as one of the main contributors to the burden of disease. The aim of this study was to 1) validate the self-report BIRT Motivation Questionnaire (BMQ-S) seldom used before in schizophrenia 2) examine the degree of agreement between the BMQ-S and its informant-report version 3) to assess its ability to predict real-world outcome at 12 month follow-up. METHODS: One hundred and twenty-two (51.9% inpatients) adults with a diagnosis of schizophrenia were included. Exploratory Factor analysis was performed on the BMQ-S to identify the underlying structure. Real life functioning was measured with the Global Assessment of Functioning scale (GAF). Convergent validity was assessed with the Scale for Assessment of Negative Symptom (SANS) and the Lille Apathy Rating Scale (LARS). RESULTS: The main psychometric properties of the BMQ-S (internal consistency, test-retest reliability) were satisfactory. Exploratory factorial analysis revealed a 4-factor model which explained 76% of the overall variance. The BMQ-S correlated significantly with the LARS and the SANS avolition subscore suggesting adequate convergent validity. The correlation between the BMQ-S and the clinician-report version was 0.48. The global score and in particular the Initiation/disorganisation dimension was a significant predictor of global functioning at 12-months even when adjusted for age, chlorpromazine intake and depression. CONCLUSION: Our findings indicate that the BMQ-S has satisfactory psychometric properties and that schizophrenia patients can reliably assess their lack of motivation. Self-evaluation of avolition should be considered in the overall prediction of real-world functioning in schizophrenia.

Validation of KASP-SNP markers in cassava germplasm for marker-assisted selection of increased carotenoid content and dry matter content.

Provitamin A biofortification and increased dry matter content are important breeding targets in cassava improvement programs worldwide. Biofortified varieties contribute to the alleviation of provitamin A deficiency, a leading cause of preventable blindness common among pre-school children and pregnant women in developing countries particularly Africa. Dry matter content is a major component of dry yield and thus underlies overall variety performance and acceptability by growers, processors, and consumers. Single nucleotide polymorphism (SNP) markers linked to these traits have recently been discovered through several genome-wide association studies but have not been deployed for routine marker-assisted selection (MAS). This is due to the lack of useful information on markers' performances in diverse genetic backgrounds. To overcome this bottleneck, technical and biological validation of the loci associated with increased carotenoid content and dry matter content were carried out using populations independent of the marker discovery population. In the present study, seven previously identified markers for these traits were converted to a robust set of uniplex allele-specific polymerase chain reaction (PCR) assays and validated in two independent pre-breeding and breeding populations. These assays were efficient in discriminating marker genotypic classes and had an average call rate greater than 98%. A high correlation was observed between the predicted and observed carotenoid content as inferred by root yellowness intensity in the breeding (r = 0.92) and pre-breeding (r = 0.95) populations. On the other hand, dry matter content-markers had moderately low predictive accuracy in both populations (r< 0.40) due to the more quantitative nature of the trait. This work confirmed the markers' effectiveness in multiple backgrounds, therefore, further strengthening their value in cassava biofortification to ensure nutritional security as well as dry matter content productivity. Our study provides a framework to guide future marker validation, thus leading to the more routine use of markers in MAS in cassava improvement programs.