The effectiveness and safety of dialectical behavior therapy for suicidal ideation and behavior in autistic adults: a pragmatic randomized controlled trial.

BACKGROUNDS: Many autistic people in mental health are suicidal. This study evaluated the effectiveness of dialectical behavior therapy (DBT) v. treatment as usual (TAU) in reducing suicidal ideation and suicide attempts. METHODS: At six Dutch mental health centers, 123 outpatients (18-65 years) with DSM-5 diagnosed autism spectrum disorder (ASD) and suicidal behavior were randomly assigned to the DBT intervention group (n = 63) or TAU control group (n = 60). Assessments were conducted at baseline, post-treatment at 6 months and 12-month follow-up. The primary outcomes were severity of suicidal ideation and frequency of suicide attempts. The severity of depression and social anxiety were secondary outcomes. RESULTS: At end-of-treatment, DBT significantly reduced both suicidal ideation (z = -2.24; p = 0.025; b = -4.41; s.e. = 197.0) and suicide attempts (z = -3.15; p = 0.002; IRR = 0.046; s.e. = 0.045) compared to TAU, but lost statistical significance at the 12-month follow-up. Depression severity significantly decreased with DBT (z = -1.99; p = 0.046: b = -2.74; s.e. = 1.37) remaining so at 12 months (z = -2.46; p = 0.014; b = -3.37; s.e. = 1.37). No effects were observed on social anxiety. Severe adverse events included two suicides in the TAU condition. CONCLUSIONS: DBT is an acceptable, safe, and short-term effective intervention to reduce suicidal ideation and suicide attempts in autistic adults with suicidal behavior.

[Treatment of emotion regulation problems in people with neurofibromatosis type 1]. / Behandeling van emotieregulatieproblemen bij mensen met neurofibromatose type 1.

Individuals with the genetic disorder neurofibromatosis type 1 (NF1) are typically diagnosed in a medical hospital setting strongly relying on the presence of well-defined physical symptoms such as neurofibromas or pigmentary spots (known as café-au-lait spots). In mental health care settings, however, aside from a few highly specialized centres, the diagnosis and treatment of individuals with NF1 receives little attention, while the need for psychological treatment is increasingly identified, both in clinical practice and in the scientific literature. Occasional referrals of individuals with NF1 to the mental health services are often only targeted at psychological assessment. Subsequent treatment, however, is usually lacking. We describe two individuals with NF1 for whom by means of specialized clinical neuropsychological assessment, participation in a tailored dialectical behavior therapy (DBT) skills training was indicated. We exposit how they were able to develop their skills and how they themselves and their significant others experienced the treatment.

Necrosome-positive granulovacuolar degeneration is associated with TDP-43 pathological lesions in the hippocampus of ALS/FTLD cases.

AIM: Granulovacuolar degeneration (GVD) in Alzheimer's disease (AD) involves the necrosome, which is a protein complex consisting of phosphorylated receptor-interacting protein kinase 1 (pRIPK1), pRIPK3 and phosphorylated mixed lineage kinase domain-like protein (pMLKL). Necrosome-positive GVD was associated with neuron loss in AD. GVD was recently linked to the C9ORF72 mutation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with transactive response DNA-binding protein (TDP-43) pathology (FTLD-TDP). Therefore, we investigated whether GVD in cases of the ALS-FTLD-TDP spectrum (ALS/FTLD) shows a similar involvement of the necrosome as in AD, and whether it correlates with diagnosis, presence of protein aggregates and cell death in ALS/FTLD. METHODS: We analysed the presence and distribution of the necrosome in post-mortem brain and spinal cord of ALS and FTLD-TDP patients (n = 30) with and without the C9ORF72 mutation, and controls (n = 22). We investigated the association of the necrosome with diagnosis, the presence of pathological protein aggregates and neuronal loss. RESULTS: Necrosome-positive GVD was primarily observed in hippocampal regions of ALS/FTLD cases and was associated with hippocampal TDP-43 inclusions as the main predictor of the pMLKL-GVD stage, as well as with the Braak stage of neurofibrillary tangle pathology. The central cortex and spinal cord, showing motor neuron loss in ALS, were devoid of any accumulation of pRIPK1, pRIPK3 or pMLKL. CONCLUSIONS: Our findings suggest a role for hippocampal TDP-43 pathology as a contributor to necrosome-positive GVD in ALS/FTLD. The absence of necroptosis-related proteins in motor neurons in ALS argues against a role for necroptosis in ALS-related motor neuron death.

Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study.

BACKGROUND: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. METHODS/DESIGN: MEDOCC-CrEATE follows the 'trial within cohorts' (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. DISCUSSION: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. TRIAL REGISTRATION: Netherlands Trial Register: NL6281/NTR6455 . Registered 18 May 2017, https://www.trialregister.nl/trial/6281.

The effect of dialectical behaviour therapy in autism spectrum patients with suicidality and/ or self-destructive behaviour (DIASS): study protocol for a multicentre randomised controlled trial.

BACKGROUND: Many persons with autism spectrum disorder (ASD) are treated in long-term specialised care. In this population, suicidal behaviour troubles patients, families, and specialists in the field because it is difficult to treat. At present, there is no documented effective therapy for suicidal behaviour in ASD (Autism Research 7:507-521, 2014; Crisis 35:301-309, 2014). Dialectical Behaviour Therapy (DBT) is an efficacious treatment programme for chronically suicidal and/or self-harm behaviour in patients with Borderline Personality Disorder (J Psychiatry 166:1365-1374, 2014; Linehan MM. Cognitive behavioural therapy of borderline personality disorder. 1993). This study will evaluate the efficacy of DBT in persons with ASD and suicidal/ self- destructive behaviour in a multicentre randomised controlled clinical trial. METHOD: One hundred twenty-eight persons with autism and suicidal and/or self-harming behaviour will be recruited from specialised mental healthcare services and randomised into two conditions: 1) the DBT condition in which the participants have weekly individual cognitive behavioural therapy sessions and a 2.5 h skills training group session twice per week during 6 months, and 2) the treatment as usual condition which consists of weekly individual therapy sessions of 30-45 min with a psychotherapist or social worker. Assessments will take place at baseline, at post-treatment (6 months), and after a follow-up period of 12 months. The mediators will also be assessed at 3 months. The primary outcome is the level of suicidal ideation and behaviour. The secondary outcomes are anxiety and social performance, depression, core symptoms of ASD, quality of life, and cost-utility. Emotion regulation and therapeutic alliance are hypothesised to mediate the effects on the primary outcome. DISCUSSION: The results from this study will provide an evaluation of the efficacy of DBT treatment in persons with ASD on suicidal and self-harming behaviour. The study is conducted in routine mental health services which enhances the generalisability of the study results to clinical practice. TRIAL REGISTRATION: ISRCTN96632579. Registered 1 May 2019. Retrospectively registered.

Hemidiaphragmatic paralysis following ultrasound-guided anterior vs. posterior suprascapular nerve block: a double-blind, randomised control trial.

Interscalene brachial plexus block provides analgesia for shoulder surgery but is associated with hemidiaphragmatic paralysis. Before considering a combined suprascapular and axillary nerve block as an alternative to interscalene brachial plexus block, evaluation of the incidence of diaphragmatic dysfunction according to the approach to the suprascapular nerve is necessary. We randomly allocated 84 patients undergoing arthroscopic shoulder surgery to an anterior or a posterior approach to the suprascapular nerve block combined with an axillary nerve block using 10 ml ropivacaine 0.375% for each nerve. The primary outcome was the incidence of hemidiaphragmatic paralysis diagnosed by ultrasound. Secondary outcomes included: characterisation of the hemidiaphragmatic paralysis over time; numeric rating scale pain scores; oral morphine equivalent consumption; and patient satisfaction. The incidence of hemidiaphragmatic paralysis was 40% (n = 17) vs. 2% (n = 1) in the anterior and posterior groups, respectively (p < 0.001). In one third of patients with hemidiaphragmatic paralysis, it persisted beyond the eighth hour. The median (interquartile range [range]) oral morphine equivalent consumption was significantly higher in the posterior approach when compared with the anterior approach, whether in the recovery area (20 [5-31 (0-60)] mg vs. 7.5 [0-14 (0-52)] mg, respectively; p = 0.004) or during the first 24 h (82 [61-127 (12-360) mg] vs. 58 [30-86 (0-160)] mg, respectively; p = 0.01). Patient satisfaction was comparable between groups (p = 0.6). Compared with the anterior approach, diaphragmatic function is best preserved with the posterior needle approach to the suprascapular nerve block.

Multitarget Stool DNA Test Performance in an Average-Risk Colorectal Cancer Screening Population.

INTRODUCTION: We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics. METHODS: Whole stool samples (n = 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n = 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n = 119), and non-AAs (n = 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing. RESULTS: The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27% (32/119), respectively, P < 0.001). Specificities among individuals with nonadvanced or negative findings (controls) were 89% (791/888) and 93% (828/888) for MT-sDNA and FIT testing, respectively. A positive MT-sDNA test was associated with multiple lesions (P = 0.005), larger lesions (P = 0.03), and lesions with tubulovillous architecture (P = 0.04). The sensitivity of the MT-sDNA test or FIT in detecting individuals with high-risk AAs (n = 19) from individuals with low-risk AAs (n = 52) was not significantly different. DISCUSSION: In an average-risk screening population, the MT-sDNA test has an increased sensitivity for detecting advanced precancerous lesions compared with FIT alone. AAs with a high risk of progression were not detected with significantly higher sensitivity by MT-sDNA or FIT.

Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis.

AIMS: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about 1 year after symptoms onset. In ALS, blood neurofilament light chain (NfL) levels are elevated, but it is not entirely clear what drives this increase and what the diagnostic performance of serum NfL is in terms of predictive values and likelihood ratios. The aims of this study were to further explore the prognostic and diagnostic performances of serum NfL to discriminate between patients with ALS and ALS mimics, and to investigate the relationship between serum NfL with motor neuron degeneration. METHODS: The diagnostic performances of serum NfL were based on a cohort of 149 serum samples of patients with ALS, 19 serum samples of patients with a disease mimicking ALS and 82 serum samples of disease control patients. The serum NfL levels were correlated with the number of regions (thoracic, bulbar, upper limb and lower limb) displaying upper and/or lower motor neuron degeneration. The prognostic performances of serum NfL were investigated based on a Cox regression analysis. RESULTS: The associated predictive values and likelihood ratio to discriminate patients with ALS and ALS mimics were established. Serum NfL was associated with motor neuron degeneration driven by upper motor neuron (UMN) degeneration and was independently associated with survival in patients with ALS. CONCLUSIONS: Altogether, these findings suggest that elevated serum NfL levels in ALS are driven by UMN degeneration and the disease progression rate and are independently associated with survival at time of diagnosis.

Prognostic value of BRAF and KRAS mutation status in stage II and III microsatellite instable colon cancers.

Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear whether it confers worse survival in this setting. The prognostic value of KRAS mutations in both MSS and MSI CRC remains unclear. We examined the effect of BRAF and KRAS mutations on survival in stage II and III MSI colon cancer patients. BRAF exon 15 and KRAS exon 2-3 mutation status was assessed in 143 stage II (n = 85) and III (n = 58) MSI colon cancers by high resolution melting analysis and sequencing. The relation between mutation status and cancer-specific (CSS) and overall survival (OS) was analyzed using Kaplan-Meier and Cox regression analysis. BRAF V600E mutations were observed in 51% (n = 73) and KRAS mutations in 16% of cases (n = 23). Patients with double wild-type cancers (dWT; i.e., BRAF and KRAS wild-type) had a highly favourable survival with 5-year CSS of 93% (95% CI 84-100%), while patients with cancers harbouring mutations in either BRAF or KRAS, had 5-year CSS of 76% (95% CI 67-85%). In the subgroup of stage II patients with dWT cancers no cancer-specific deaths were observed. On multivariate analysis, mutation in either BRAF or KRAS vs. dWT remained significantly prognostic. Mutations in BRAF as well as KRAS should be analyzed when considering these genes as prognostic markers in MSI colon cancers.

Elevated mean neutrophil volume represents altered neutrophil composition and reflects damage after myocardial infarction.

Myocardial infarction (MI) induces an inflammatory response in which neutrophils fulfill a prominent role. Mean neutrophil volume (MNV) represents the average size of the circulating neutrophil population. Our goal was to determine the effect of MI on MNV and investigate the mechanisms behind MNV elevation. MNV of 84 MI patients was compared with the MNV of 209 stable angina patients and correlated to simultaneously measured CK levels. Fourteen pigs were subjected to temporary coronary balloon occlusion and blood was sampled at multiple time points to measure MNV. Echocardiography was performed followed by ex vivo infarct size assessment after 72 h. MNV was higher in MI patients compared to stable angina patients (602 SD26 AU vs. 580 SD20 AU, p < 0.0001) and correlated with simultaneously measured CK levels (R = 0.357, p < 0.0001). In pigs, MNV was elevated post-MI (451 SD11 AU vs. 469 SD12 AU), p < 0.0001). MNV correlated with infarct size (R = 0.705, p = 0.007) and inversely correlated with left ventricular ejection fraction (R = -0.718, p = 0.009). Cell sorting revealed an increased presence of banded neutrophils after MI, which have a higher MNV compared to mature neutrophils post-MI (495 SD14 AU vs. 478 SD11 AU, p = 0.012). MNV from coronary sinus blood was higher than MNV of neutrophils from simultaneously sampled arterial blood (463 SD7.6 AU vs. 461 SD8.6 AU, p = 0.013) post-MI. The current study shows MNV is elevated and reflects cardiac damage post-MI. MNV increases due to altered neutrophil composition and systemic neutrophil activation. MNV may be an interesting parameter for prognostic assessment in MI and provide new insights into pathological innate immune responses evoked by ischemia-reperfusion.

[Dialectical behaviour theory in the Netherlands: implementation and consolidation]. / Dialectische gedragstherapie in Nederland: implementatie en consolidatie.

BACKGROUND: More and more evidence-based treatments for severe personality disorders are becoming available. Nevertheless, there are problems with the implementation of these treatments and it is proving difficult to keep the treatment programmes running. However, teams which offer dialectical behavior therapy (DBT) seem to survive. AIM: To find out which factors enable dbt teams to survive. METHOD: Twenty-five Dutch DBT teams received a questionnaire about factors that could be influencing the continuation of the DBT treatment programmes. The questionnaire consisted of 9 open questions, 2 multiple-choice questions and 26 closed questions. RESULTS: The results show that the continued existence of the treatment programmes is due largely to the commitment of both the team and its managers. They all feel embedded in the organisation as a whole, feel connected with one another and are supportive of the method. CONCLUSION: A well-functioning consultation team seems to be of crucial importance for the continued existence of the DBT programme. We believe that independent external supervision is essential to keep the dbt teams alert and aware of current trends and developments.

Presumptive spontaneous hemothorax associated to thymic involution in a dog with steroid responsive meningitis-arteritis (SRMA).

OBJECTIVE: To describe an unusual case of spontaneous hemothorax resulting from thymic involution in a dog with suspected acquired bleeding dyscrasia associated with steroid-responsive meningitis-arteritis (SRMA). CASE DESCRIPTION: A 6-month-old spayed female Golden Retriever was referred due to the sudden onset of lethargy, fever (pyrexia), loss of appetite (anorexia), and moderate neck pain. These symptoms emerged six days after an ovariohysterectomy performed by the primary veterinarian. Upon admission, the patient exhibited pale mucous membranes, tachycardia (180 bpm), bilateral muffled heart sounds and tachypnea. Abdominal and thoracic point-of-care ultrasound (POCUS) were performed and revealed bilateral pleural effusion. Due to the patient's unstable condition, emergent thoracocentesis and transfusion of packed red blood cells was required. The initial work-up performed included a complete blood cell count (CBC), biochemistry profile, venous blood gas and coagulation panel (PT, APTT, fibrinogen). Pleural effusion analysis was compatible with hemothorax. Bloodwork was unremarkable including the initial coagulation panel. Further coagulation test was performed including buccal mucosal bleeding time, viscoelastic-based clot detection tests (TEG) and Von Willebrand factor antigen measurement. TEG revealed marked hyperfibrinolysis. Angiostrongylus vasorum and 4DX snap test were performed and yielded a negative result. Thoracic CT scan revealed the presence of a soft tissue-attenuating mass in the ventral mediastinum, thymic involution, and enlargement of the sternal and mediastinal lymph nodes. Therapy with tranexamic acid and corticosteroids at anti-inflammatory doses was initiated. Marked clinical improvement was observed within 24 hours, and after three days of hospitalization the patient was discharged. One month later, the dog was referred again for acute pyrexia, hyporexia, and neck pain which progressed to non-ambulatory tetraparesis. Neurological examination was compatible with C6-T2 lesion. MRI and cerebrospinal fluid analysis were performed and revealed a final diagnosis of steroid-responsive meningitis-arteritis (SRMA) with associated intramedullary hemorrhage. Corticosteroids were started again, and the patient showed a dramatic improvement over the next 24 hours. Three weeks after the diagnosis, the dog returned to a clinically normal state. The treatment was gradually tapered over the following months, guided by regular neurological and clinical examinations and CRP measurements, without any relapses. NEW OR UNIQUE INFORMATION: To the best of the author's knowledge, this is the first documented case of a dog experiencing spontaneous hemothorax as a result of thymic hemorrhage/involution which, in the absence of other identifiable diseases, was attributed to a hyperfibrinolytic state induced by a severe inflammatory disease such as SRMA.

Acid-base and electrolyte changes in dogs after packed red blood cell transfusion.

BACKGROUND: Packed RBC (pRBC) transfusions are often necessary to enhance organ perfusion and tissue oxygenation in cases of severe anemia. OBJECTIVES: We aimed to describe changes in acid-base and biochemical parameters in dogs after transfusion of pRBC and potential effects on the outcome. METHODS: The prospective observational study included anemic dogs requiring pRBC transfusions. Venous blood gas and electrolytes were measured pre-transfusion and repeated within 1 h post-transfusion. Signalment, pre-existing conditions and underlying disease(s), number of days spent of hospitalization, the quantity of transfused pRBC units, and the outcome were also recorded. Associations between analytical values and all other parameters before and after transfusion were assessed using the Wilcoxon test. A generalized linear model was generated for each of the blood gas parameters post-transfusion, including the pre-transfusion values and the characteristics of the animal as fixed effects. The effect of the blood gas parameters on the mortality and hospitalization length was assessed using logistic regression and generalized linear models, respectively. RESULTS: Twenty-six dogs with different causes of anemia were included in the study, with dogs remaining hospitalized for a median of 3 days (range: 0-11). Pre-transfusion heart rate, respiratory rate, Angap, base excess, and lactate were higher than post-transfusion values. Post-transfusion results showed an increase in hematocrit, hemoglobin, HCO3-, PCO2, tCO2, and chloride. Pre-transfusion hypophosphatemia and receiving an increased volume of transfused pRBC were associated with a longer hospital stay, while higher pre-transfusion lactate values were associated with higher mortality. CONCLUSIONS: pRBC transfusion in anemic dogs was associated with an improvement in perfusion and acid-base parameters. Pre-transfusion lactate may be an indicator of mortality in dogs.

A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome.

Wolfram syndrome (WS) is a rare childhood disease characterized by diabetes mellitus, diabetes insipidus, blindness, deafness, neurodegeneration and eventually early death, due to autosomal recessive mutations in the WFS1 (and WFS2) gene. While it is categorized as a neurodegenerative disease, it is increasingly becoming clear that other cell types besides neurons may be affected and contribute to the pathogenesis. MRI studies in patients and phenotyping studies in WS rodent models indicate white matter/myelin loss, implicating a role for oligodendroglia in WS-associated neurodegeneration. In this study, we sought to determine if oligodendroglia are affected in WS and whether their dysfunction may be the primary cause of the observed optic neuropathy and brain neurodegeneration. We demonstrate that 7.5-month-old Wfs1∆exon8 mice display signs of abnormal myelination and a reduced number of oligodendrocyte precursor cells (OPCs) as well as abnormal axonal conduction in the optic nerve. An MRI study of the brain furthermore revealed grey and white matter loss in the cerebellum, brainstem, and superior colliculus, as is seen in WS patients. To further dissect the role of oligodendroglia in WS, we performed a transcriptomics study of WS patient iPSC-derived OPCs and pre-myelinating oligodendrocytes. Transcriptional changes compared to isogenic control cells were found for genes with a role in ER function. However, a deep phenotyping study of these WS patient iPSC-derived oligodendroglia unveiled normal differentiation, mitochondria-associated endoplasmic reticulum (ER) membrane interactions and mitochondrial function, and no overt signs of ER stress. Overall, the current study indicates that oligodendroglia functions are largely preserved in the WS mouse and patient iPSC-derived models used in this study. These findings do not support a major defect in oligodendroglia function as the primary cause of WS, and warrant further investigation of neurons and neuron-oligodendroglia interactions as a target for future neuroprotective or -restorative treatments for WS.

Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration.

Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis. The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition, Vegf165 promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons.

[Short-term dialectical behaviour therapy for borderline personality disorder]. / Kortdurende klinische dialectische gedragstherapie voor de borderlinepersoonlijkheidsstoornis: ontwerp van programma en resultaten pilotstudie.

BACKGROUND: Outpatient dialectical behaviour therapy (DBT) reduces severe suicidal and self-injurious behaviour in patients with borderline personality disorder. The Jelgersma center for personality disorders has developed an intensive inpatient dbt programme that lasts for 14 weeks and is designed to achieve a faster reduction in these borderline symptoms. AIM: To examine the effect of the Jelgersma programme by means of a pilot study in order to prepare a randomised clinical trial in which a short intensive course of DBT will be compared with standard outpatient DBT. METHOD: We compared the starting data and the final data for 39 female patients with borderline problems (DBT). We participated in 3½-month-long inpatient DBT programme. The collected data referred to (para)suicidal behaviour, drop-out, severity of borderline problems and the quality of life. RESULTS: The severity of borderline problems, particularly in the field of interpersonal problems, was significantly reduced. There was no significant reduction in (para) suicidal behaviours. The drop-out percentage was higher than in comparable studies. CONCLUSION: Short-term inpatient DBT had a positive effect on borderline problems. (Para)suicidal behaviour, however, was not reduced significantly. The randomised trial that began in 2012 should reveal whether the use of short-term inpatient DBT can lead to a faster decline of suicidal and self-injurious behaviour than does standard outpatient DBT.

Dialectical behavior therapy: is outpatient group psychotherapy an effective alternative to individual psychotherapy?: Preliminary conclusions.

OBJECTIVES: This study evaluates a 12-month-duration adapted outpatient group dialectical behavior therapy (DBT) program for patients with a borderline personality disorder in an unselected, comorbid population. If the results of this approach are comparable with the outcome rates of a standard DBT program, the group approach can have several advantages over individual treatment. One advantage is the possibility of treating more patients per therapist. METHOD: A pre-post design was used to measure the effectiveness of an outpatient group DBT. Data from the Beck Depression Inventory II, the Symptom Checklist 90-Revised, the State-Trait Anger Inventory, the State and Trait Anxiety Inventory, of 34 female patients (mean age, 32.65 years) were collected before and after a treatment period of 1 year. RESULTS: Overall, a significant reduction (P < .05) of depressive symptoms, suicidal thoughts, anxiety, and anger was experienced by the patients. CONCLUSIONS: This study is a first attempt in showing that DBT in an outpatient group setting can be effective in reducing psychiatric complaints and therefore has several advantages, such as the opportunity to treat more patients at once.

The experiences of Latino siblings of children with developmental disabilities.

OBJECTIVE: This qualitative study explored the experiences of Latino siblings of children with developmental disabilities. METHODS: Parents and typically developing siblings from 15 Latino families with a child with a developmental disability participated in separate interviews. RESULTS: Using consensual qualitative research methodology, domains reflecting siblings' relationships, emotional experiences and communication about the disability were identified. The child's need for caregiving was a prominent topic in the sibling and parent narratives. Parents reported concerns about siblings' experience of differential treatment, whereas siblings reported concerns about restricted social activities because of their brother/sister. CONCLUSIONS: Including multiple informants revealed commonalities and differences in parents' and siblings' perspectives on the impact of a child's disability. The importance of considering sibling adaptation in sociocultural context is discussed.

[Acute illness and depression in the elderly and the influence of cognitive impairment : AIDE-cog trial]. / Komorbidität von Depression und Demenz bei geriatrischen Patienten mit akuter körperlicher Erkrankung: AIDE-cog-Studie.

Geriatric patients with acute somatic illness have a high comorbidity of depression and dementia. The following differential diagnoses have to be discerned: pseudodementia in acute depressive states, depression as a risk factor for dementia, and a depressive episode in the early stage of dementia. For both the symptoms and the trigger factors of these differential diagnoses the overlap and the particularities were qualitatively examined in the AIDE-cog (Acute Illness and Depression in Elderly cognition) trial. A second prospective randomized controlled part of the AIDE-cog trial quantitatively evaluated the influence of cognitive impairment in geriatric patients with an acute somatic illness and comorbid depression on the therapeutic effect of cognitive behavioral therapy. A preliminary analysis shows that already in early dementia the therapeutic effects are inferior. Other psychotherapeutic methods that address the remaining cognitive and emotional functions in dementia must be evaluated.

Speech register influences listeners' word expectations.

We utilized the N400 effect to investigate the influence of speech register on predictive language processing. Participants listened to long stretches (4 - 15 min) of naturalistic speech from different registers (dialogues, news broadcasts, and read-aloud books), totalling approximately 50,000 words, while the EEG signal was recorded. We estimated the surprisal of words in the speech materials with the aid of a statistical language model in such a manner that it reflected different predictive processing strategies; generic, register-specific, or recency-based. The N400 amplitude was best predicted with register-specific word surprisal, indicating that the statistics of the wider context (i.e., register) influences predictive language processing. Furthermore, adaptation to speech register cannot merely be explained by recency effects; instead, listeners adapt their word anticipations to the presented speech register.