Personality traits, theory of mind and their relationship with multiple suicide attempts in a sample of first episode psychosis patients: One-year follow-up study

BACKGROUND: High rates of suicidal behaviour (SB) have been found in first episode psychosis (FEP) patients. It has been suggested that the presence of multiple suicide attempts (mSA) increases the risk of later SA and the risk of eventual death by suicide. OBJECTIVE: Our main objective was to study the baseline factors associated with the presence of mSA during the first year after FEP. In addition, a second aim was to find out whether there were any differences between single and multiple suicide attempters in the timing of the first SA after FEP. METHOD: A total of 65 FEP patients were evaluated. The presence of SAs were recorded at two different times after FEP. Bivariate and multivariate analyses were performed to explore the relationship between SA with sociodemographic and clinical variables. RESULTS: Multiple linear regression showed that mSA was associated with the presence of increased symptom severity (B?=?0.35; t?=?3.67; p < 0.01) and errors in first-order false-belief task (B?=?0.48; t?=?2.11; p?=?0.04). There were significant differences in the timing of first SA after FEP between multiple and single suicide attempters. CONCLUSIONS: Theory of mind impairments along with more severe symptoms during the first contact with mental health services for psychotic symptoms appeared to be important predictors of mSA. On the other hand, multiple suicide attempters tend to make a first SA after FEP earlier than single suicide attempters. These results could contribute to the implementation of preventive suicidal programs, however they must be confirmed by additional research.Funding: This study was funded by Ministry of Science and Innovation grant ISC PI11/0233

Reflectance anisotropy spectroscopy assessment of the MOVPE nucleation of GaInP on Germanium (100)

This work summarizes the observations made on the variation and time evolution of the reflectanceanisotropy signal during the MOVPE growth of GaInPnucleation layers on Germanium substrates. This in situ monitoring tool is used to assess the impact of different nucleation routines and reactor conditions on the quality of the layers grown. This comparison is carried out by establishing a correlation between reflectanceanisotropy signature at 2.1 eV and the morphology of the epilayers evaluated by atomic force microscopy (AFM). This paper outlines the potential of reflectanceanisotropy to predict, explore, and therefore optimize, the best growth conditions that lead to a high quality III–V epilayer on a Ge substrat

Aromatic L-amino acid decarboxylase deficiency: a patient-derived neuronal model for precision therapies

Aromatic L-amino acid decarboxylase (AADC) deficiency is a complex inherited neurological disorder of monoamine synthesis which results in dopamine and serotonin deficiency. The majority of affected individuals have variable, though often severe cognitive and motor delay, with a complex movement disorder and high risk of premature mortality. For most, standard pharmacological treatment provides only limited clinical benefit. Promising gene therapy approaches are emerging, though may not be either suitable or easily accessible for all patients. In order to better characterize the underlying disease pathophysiology and guide precision therapies, we generated a patient-derived midbrain dopaminergic (mDA) neuronal model of AADC deficiency from induced pluripotent stem cells (iPSCs). The neuronal model recapitulates key disease features, including absent AADC enzyme activity and dysregulated dopamine metabolism. We observed developmental defects affecting synaptic maturation and neuronal electrical properties, which were improved by lentiviral gene therapy. Bioinformatic and biochemical analyses on recombinant AADC predicted that the activity of one variant could be improved by L-3,4-dihydroxyphenylalanine (L-DOPA) administration; this hypothesis was corroborated in the patient-derived neuronal model, where L-DOPA treatment leads to amelioration of dopamine metabolites. Our study has shown that patient-derived disease modelling provides further insight into the neurodevelopmental sequelae of AADC deficiency, as well as a robust platform to investigate and develop personalised therapeutic approaches

Aromatic l-amino acid decarboxylase deficiency: a patient-derived neuronal model for precision therapies

Aromatic l-amino acid decarboxylase (AADC) deficiency is a complex inherited neurological disorder of monoamine synthesis which results in dopamine and serotonin deficiency. The majority of affected individuals have variable, though often severe cognitive and motor delay, with a complex movement disorder and high risk of premature mortality. For most, standard pharmacological treatment provides only limited clinical benefit. Promising gene therapy approaches are emerging, though may not be either suitable or easily accessible for all patients. To characterize the underlying disease pathophysiology and guide precision therapies, we generated a patient-derived midbrain dopaminergic neuronal model of AADC deficiency from induced pluripotent stem cells. The neuronal model recapitulates key disease features, including absent AADC enzyme activity and dysregulated dopamine metabolism. We observed developmental defects affecting synaptic maturation and neuronal electrical properties, which were improved by lentiviral gene therapy. Bioinformatic and biochemical analyses on recombinant AADC predicted that the activity of one variant could be improved by l-3,4-dihydroxyphenylalanine (l-DOPA) administration; this hypothesis was corroborated in the patient-derived neuronal model, where l-DOPA treatment leads to amelioration of dopamine metabolites. Our study has shown that patient-derived disease modelling provides further insight into the neurodevelopmental sequelae of AADC deficiency, as well as a robust platform to investigate and develop personalized therapeutic approaches

Primary refractory follicular lymphoma: a poor outcome entity with high risk of transformation to aggressive B cell lymphoma

Background: Primary refractory (PREF) follicular lymphoma (FL) has a completely different clinical course from that of FL that responds to front-line treatments. In addition to having poor responses to salvage therapies, it seems that patients with PREF are at increased risk of histological transformation (HT). The Aristotle consortium presented the opportunity of investigating the risk of HT in a very large series of cases. Thus, we investigated the risk of HT in patients with PREF FL compared with that of responding patients or in stable disease and ultimately their outcome. Methods: Six thousand three hundred thirty-nine patients from the Aristotle database were included in the analysis. These patients had a histologically confirmed grade 1, 2 or 3a FL diagnosed between 1997 and 2013. The primary end-points were the cumulative incidence (CI) of HT at the first progression or relapse and the survival after transformation. Findings.: The 5-year CI of HT among patients with PREF was 34% (95% confidence interval (CI): 27–43), whilst it was 7.1% (95% CI: 6.0–8.5) in the group of patients with partial response (PR) or stable disease (SD) (PR + SD) and 3.5% (95% CI: 3.0–4.2) in the group of patients achieving complete response (CR). The 5-year survival after relapse (SAR) was 33% (95% CI: 28–39) for the PREF group, 57% (95% CI 54–61) in patients with PR, 51% (95% CI 43–58) in the SD group after first-line therapy and 63% (95% CI: 66–72) in patients with CR after initial treatment (p-value &lt;0.001). The 5-year SAR for those patients with PREF who developed HT was 21% (95% CI: 12–31), clearly diminished when compared with those patients with PREF who did not experience HT (38% [95% CI: 31–44]) (p-value = 0.001). Interpretation.: Patients with PREF FL have a dismal outcome and an associated very high rate of HT that further worsens their poor prognosis

Gene therapy restores dopamine transporter expression and ameliorates pathology in iPSC and mouse models of infantile parkinsonism

Most inherited neurodegenerative disorders are incurable, and often only palliative treatment is available. Precision medicine has great potential to address this unmet clinical need. We explored this paradigm in dopamine transporter deficiency syndrome (DTDS), caused by biallelic loss-of-function mutations in SLC6A3, encoding the dopamine transporter (DAT). Patients present with early infantile hyperkinesia, severe progressive childhood parkinsonism, and raised cerebrospinal fluid dopamine metabolites. The absence of effective treatments and relentless disease course frequently leads to death in childhood. Using patient-derived induced pluripotent stem cells (iPSCs), we generated a midbrain dopaminergic (mDA) neuron model of DTDS that exhibited marked impairment of DAT activity, apoptotic neurodegeneration associated with TNFα-mediated inflammation, and dopamine toxicity. Partial restoration of DAT activity by the pharmacochaperone pifithrin-μ was mutation-specific. In contrast, lentiviral gene transfer of wild-type human SLC6A3 complementary DNA restored DAT activity and prevented neurodegeneration in all patient-derived mDA lines. To progress toward clinical translation, we used the knockout mouse model of DTDS that recapitulates human disease, exhibiting parkinsonism features, including tremor, bradykinesia, and premature death. Neonatal intracerebroventricular injection of human SLC6A3 using an adeno-associated virus (AAV) vector provided neuronal expression of human DAT, which ameliorated motor phenotype, life span, and neuronal survival in the substantia nigra and striatum, although off-target neurotoxic effects were seen at higher dosage. These were avoided with stereotactic delivery of AAV2.SLC6A3 gene therapy targeted to the midbrain of adult knockout mice, which rescued both motor phenotype and neurodegeneration, suggesting that targeted AAV gene therapy might be effective for patients with DTDS

Recent advances in Pichia pastoris as host for heterologous expression system for lipases : a review

The production of heterologous lipases is one of the most promising strategies to increase the productivity of the bioprocesses and to reduce costs, with the final objective that more industrial lipase applications could be implemented. In this chapter, an overview of the new success in synthetic biology, with traditional molecular genetic techniques and bioprocess engineering in the last 5 years in the cell factory Pichia pastoris, the most promising host system for heterologous lipase production, is presented. The goals get on heterologous Candida antarctica, Rhizopus oryzae, and Candida rugosa lipases, three of the most common lipases used in biocatalysis, are showed. Finally, new cell factories producing heterologous lipases are presented

Universal mental health screening with a focus on suicidal behaviour using smartphones in a Mexican rural community: Protocol for the SMART-SCREEN population-based survey

Introduction Mental disorders represent the second cause of years lived with disability worldwide. Suicide mortality has been targeted as a key public health concern by the WHO. Smartphone technology provides a huge potential to develop massive and fast surveys. Given the vast cultural diversity of Mexico and its abrupt orography, smartphone-based resources are invaluable in order to adequately manage resources, services and preventive measures in the population. The objective of this study is to conduct a universal suicide risk screening in a rural area of Mexico, measuring also other mental health outcomes such as depression, anxiety and alcohol and substance use disorders. Methods and analysis A population-based cross-sectional study with a temporary sampling space of 9 months will be performed between September 2019 and June 2020. We expect to recruit a large percentage of the target population (at least 70%) in a short-term survey of Milpa Alta Delegation, which accounts for 137 927 inhabitants in a territorial extension of 288 km 2. They will be recruited via an institutional call and a massive public campaign to fill in an online questionnaire through mobile-assisted or computer-assisted web app. This questionnaire will include data on general health, validated questionnaires including Well-being Index 5, Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale 2, Alcohol Use Disorders Identification Test, selected questions of the Drug Abuse Screening Test and Columbia-Suicide Severity Rating Scales and Diagnostic and statistical manual of mental disorders (DSM-5) questions about self-harm. We will take into account information regarding time to mobile app response and geo-spatial location, and aggregated data on social, demographical and environmental variables. Traditional regression modelling, multilevel mixed methods and data-driven machine learning approaches will be used to test hypotheses regarding suicide risk factors at the individual and the population level. Ethics and dissemination Ethical approval (002/2019) was granted by the Ethics Review Board of the Hospital Psiquiátrico Yucatán, Yucatán (Mexico). This protocol has been registered in ClinicalTrials.gov. The starting date of the study is 3 September 2019. Results will serve for the planning and healthcare of groups with greater mental health needs and will be disseminated via publications in peer-reviewed journal and presented at relevant mental health conferences. Trial registration number NCT04067063