Targeted next-generation sequencing has incremental value in the diagnostic work-up of patients with suspect pancreatic masses; a multi-center prospective cross sectional study.

BACKGROUND: The diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions. METHODS: In this prospective cross-sectional cohort study, patients were screened for inclusion in four hospitals. NGS was performed with AmpliSeq Cancer Hotspot Panel v2 and v4b in patients with inconclusive cytology results or with an uncertain diagnosis. Diagnostic results were evaluated by the oncology pancreatic multidisciplinary team. The added value of NGS was determined by comparing diagnosis (malignancy, cystic lesion or benign condition) and proposed treatment plan (exploration/resection, neoadjuvant chemotherapy, follow-up, palliation or repeated FNA) before and after integration of NGS results. Final histopathological analysis or a 6-month follow-up period were used as the reference standard in case of surgical intervention or non-invasive treatment, respectively. RESULTS: In 50 of the 53 included patients, cytology material was sufficient for NGS analysis. Diagnosis before and after integration of NGS results differed in 24% of the patients. The treatment plan was changed in 32% and the diagnosis was substantiated by the NGS data in 44%. Repetition of FNA/brushing was prevented in 14% of patients. All changes in treatment plan were correctly made after integration of NGS. Integration of NGS increased overall diagnostic accuracy from 68% to 94%. INTERPRETATION: This study demonstrates the incremental diagnostic value of NGS in patients with an initial inconclusive diagnosis. Integration of NGS results can prevent repeated EUS/FNA, and can also rigorously change the final diagnosis and treatment plan.

Cumulative sum learning curves guiding multicenter multidisciplinary quality improvement of EUS-guided tissue acquisition of solid pancreatic lesions.

Background and study aims In this study, we evaluated the performance of community hospitals involved in the Dutch quality in endosonography team regarding yield of endoscopic ultrasound (EUS)-guided tissue acquisition (TA) of solid pancreatic lesions using cumulative sum (CUSUM) learning curves. The aims were to assess trends in quality over time and explore potential benefits of CUSUM as a feedback-tool. Patients and methods All consecutive EUS-guided TA procedures for solid pancreatic lesions were registered in five community hospitals between 2015 and  2018. CUSUM learning curves were plotted for overall performance and for performance per center. The American Society of Gastrointestinal Endoscopy-defined key performance indicators, rate of adequate sample (RAS), and diagnostic yield of malignancy (DYM) were used for this purpose. Feedback regarding performance was provided on multiple occasions at regional interest group meetings during the study period. Results A total of 431 EUS-guided TA procedures in 403 patients were included in this study. The overall and per center CUSUM curves for RAS improved over time. CUSUM curves for DYM revealed gradual improvement, reaching the predefined performance target (70 %) overall, and in three of five contributing centers in 2018. Analysis of a sudden downslope development in the CUSUM curve of DYM in one center revealed temporary absence of a senior cytopathologist to have had a temporary negative impact on performance. Conclusions CUSUM-derived learning curves allow for assessment of best practices by comparison among peers in a multidisciplinary multicenter quality improvement initiative and proved to be a valuable and easy-to-interpret means to evaluate EUS performance over time.

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.

Vaginal Myomectomy and Total Vaginal Hysterectomy on Large Prolapsed Cervical Myoma: A Case Report.

Cervical myomas are benign tumors originating from cervical muscle tissue with a very rare incidence of only about 8% of all myomas. The surgical approach depends on the position of cervical myoma. This case report discusses a 44-year-old woman who complained of a lump discharge from her birth canal 6 months ago, and currently discharging from her vagina. We performed vaginal myomectomy, and the cervical myoma measuring 8 × 8 × 6 cm with solid consistency was removed. We continued with total vaginal hysterectomy. Post-operative recovery was progressing well. The histopathology report was consistent with leiomyoma. Large prolapsed cervical myoma can be disturbing and discomforting for many patients. It is relatively rare and can be successfully removed vaginally with minimal morbidity.

The relationship between burnout, personality traits, and medical specialty. A national study among Dutch residents.

Purpose: To examine the associations between residents' personality traits, type of specialty, and symptoms of burnout. Method: A cross-sectional online survey among Dutch residents was conducted (see Supplementary Material ). The 20-item Dutch translation of the Maslach Burnout Inventory was used to ascertain burnout. Personality traits were assessed with the 44-item Dutch Big Five Inventory. Logistic regression analyses, including all five personality traits, were used to assess associations with burnout. Analyses were stratified by specialties. Results: One thousand two hundred thirty one residents participated, 185 (15.0%) of whom met the criteria for burnout. Neuroticism was significantly associated with resident burnout in all specialties, more strongly in supportive (odds ratio (OR) 6.19, 95% CI 2.12-18.12) and surgical (OR 4.37, 95% CI 1.76-10.86) than in medical residents (OR 1.99, 95% CI 1.22-3.24). Extraversion was significantly associated with less burnout in surgical residents (OR 0.26, 95% CI 0.13-0.58). These findings remained highly significant after controlling for gender, overtime, autonomy at work, satisfaction between work and private life, and the perceived quality of the learning environment. Conclusions: Burnout risk was associated with personality traits in residents. Consistently, residents scoring high on neuroticism reported more burnout. Extraverted surgical residents were less susceptible to burnout. Residents scoring high on neuroticism may require more intense monitoring during their training years.

The learning environment and resident burnout: a national study.

INTRODUCTION: Concerns exist about the negative impact of burnout on the professional and personal lives of residents. It is suggested that the origins of burnout among residents are rooted in the learning environment. We aimed to evaluate the association between the learning environment and burnout in a national sample of Dutch residents. METHODS: We conducted a cross-sectional online survey among all Dutch residents in September 2015. We measured the learning environment using the three domain scores on content, organization, and atmosphere from the Scan of Postgraduate Educational Environment Domains (SPEED) and burnout using the Dutch version of the Maslach Burnout Inventory (UBOS-C). RESULTS: Of 1,231 responding residents (33 specialties), 185 (15.0%) met criteria for burnout. After adjusting for demographic (age, gender and marital status) and work-related factors (year of training, type of teaching hospital and type of specialty), we found a consistent inverse association between SPEED scores and the risk of burnout (aOR 0.54, 95% CI 0.46 to 0.62, p < 0.001). DISCUSSION: We found a strong and consistent inverse association between the perceived quality of the learning environment and burnout among residents. This suggests that the learning environment is of key importance in preventing resident burnout.

The relationship between work and home characteristics and work engagement in medical residents.

INTRODUCTION: Work engagement is important for medical residents and the healthcare organizations they work for. However, relatively little is known about the specific predictors of work engagement in medical residents. Therefore, we examined the associations of work and home characteristics, and work-home interference with work engagement in male and female residents. METHODS: This study was conducted on a nationwide sample of medical residents. In 2005, all Dutch medical residents (n = 5245) received a self-report questionnaire. Path analysis was used to examine the associations between the potential predictors and work engagement. RESULTS: In total, 2115 (41.1%) residents completed the questionnaire. Job characteristics, home characteristics and work-home interference were associated with work engagement. Important positive contributing factors of work engagement were opportunities for job development, mental demands at work, positive work-home interference and positive home-work interference. Important negative contributing factors were emotional demands at work and negative home-work interference. The influence of these factors on work engagement was similar in male and female residents. DISCUSSION: Opportunities for job development and having challenging work are of high relevance in enhancing work engagement. Furthermore, interventions that teach how to deal skilfully with emotional demands at work and home-work interference are expected to be the most effective interventions to enhance work engagement in medical residents.

The contribution of work characteristics, home characteristics and gender to burnout in medical residents.

Burnout is highly prevalent in medical residents. In order to prevent or reduce burnout in medical residents, we should gain a better understanding of contributing and protective factors of burnout. Therefore we examined the associations of job demands and resources, home demands and resources, and work-home interferences with burnout in male and female medical residents. This study was conducted on a nation-wide sample of medical residents. In 2005, all Dutch medical residents (n = 5245) received a self-report questionnaire on burnout, job and home demands and resources and work-home interference. Path analysis was used to examine the associations between job and home characteristics and work-home interference and burnout in both males and females. In total, 2115 (41.1 %) residents completed the questionnaire. In both sexes emotional demands at work and the interference between work and home were important contributors to burnout, especially when work interferes with home life. Opportunities for job development appeared to be an important protective factor. Other contributing and protective factors were different for male and female residents. In females, social support from family or partner seemed protective against burnout. In males, social support from colleagues and participation in decision-making at work seemed important. Effectively handling emotional demands at work, dealing with the interference between work and home, and having opportunities for job development are the most essential factors which should be addressed. However it is important to take gender differences into consideration when implementing preventive or therapeutic interventions for burnout in medical residents.

Effect of high salt diet on blood pressure and renal damage during vascular endothelial growth factor inhibition with sunitinib.

BACKGROUND: Antiangiogenic treatment with the multitargeted vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib associates with a blood pressure (BP) rise and glomerular renal injury. Recent evidence indicates that VEGF derived from tubular cells is required for maintenance of the peritubular vasculature. In the present study, we focussed on tubular and glomerular pathology induced by sunitinib and explored whether a high salt (HS) diet augments the BP rise and renal abnormalities. METHODS: Normotensive Wistar Kyoto (WKY) rats were exposed to a normal salt (NS) or HS diet for 2 weeks and subsequently for 8 days to sunitinib or vehicle administration after which the rats were euthanized and kidneys excised. Mean arterial pressure (MAP) was telemetrically measured. Urine was sampled for proteinuria and endothelinuria, and blood for measurement of endothelin-1, creatinine and cystatin C. RESULTS: Compared with the NS diet, MAP rapidly rose by 27 ± 3 mmHg with the HS diet. On sunitinib, MAP rose further by 15 ± 1 with the NS and by 23 ± 4 mmHg with the HS diet (P < 0.05). The HS diet itself had no effect on proteinuria, endothelinuria or the plasma levels of endothelin-1, creatinine and cystatin C. Only with the HS diet, sunitinib administration massively increased proteinuria and endothelinuria and these two parameters were related (r = 0.50, P < 0.01). Likewise, renal glomerular pathology was enhanced during sunitinib with the HS diet, whereas tubulointerstitial injury or reduced peritubular capillary density did not occur. CONCLUSIONS: An HS diet induces a marked BP rise in WKY rats and exacerbates both the magnitude of the BP rise and glomerular injury induced by sunitinib.

Relationship between plasma homovanillic acid and outcome in patients with psychosis spectrum disorders.

BACKGROUND: Psychosis spectrum disorders, especially schizophrenia, have been linked to disturbed dopaminergic activity in the brain. Plasma homovanillic acid (pHVA) levels partly represent dopaminergic metabolism in the central nervous system. In the present study associations between (changes in) pHVA levels, symptom severity and symptomatic improvement in patients with psychoses were investigated. METHODS: From a total of 80 patients, 58 fulfilled all inclusion criteria and their symptom profile and severity were assessed by means of the Comprehensive Assessment of Symptoms and History (CASH), the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale for Severity and Improvement (CGI-S/CGI-I) at baseline and after 6 weeks of antipsychotic treatment. After inclusion, all patients were prescribed first- or second-generation antipsychotics by their treating psychiatrist. A total of 12 patients had first-episode psychosis (FEP). At both time points, pHVA levels were measured. Subsequently, pHVA levels were compared with an age-matched control sample and changes in pHVA levels (ΔpHVA) after treatment were associated with clinical parameters. RESULTS: Before analyses, data were scrutinized for possible confounders, particularly gender, smoking, medication status (including antipsychotic class), and recent drug use. The pHVA levels in patients were not different from those in controls. Treatment resulted in a significant decrease of all parameters. Symptomatic improvement as well as ΔpHVA was most pronounced in FEP patients. CONCLUSION: These findings show that patients with FEP have a more favourable outcome than non-FEP patients and that greater ΔpHVA also suggests that FEP patients still have the capacity to adjust dopaminergic neurotransmission.

Greater Sensitivity of Blood Pressure Than Renal Toxicity to Tyrosine Kinase Receptor Inhibition With Sunitinib.

Hypertension and renal injury are off-target effects of sunitinib, a tyrosine kinase receptor inhibitor used for the treatment of various tumor types. Importantly, these untoward effects are accompanied by activation of the endothelin system. Here, we set up a study to explore the dose dependency of these side effects. Normotensive Wistar Kyoto rats were exposed to 3 different doses of sunitinib or vehicle. After 8 days, rats were euthanized. Telemetrically measured blood pressure rose dose dependently, from 13 to 30 mm Hg. Proteinuria was present at all doses, but a rise in cystatin C occurred only at the intermediate and high doses. Compared with vehicle circulating endothelin-1 increased dose dependently, whereas 24-hour urinary endothelin excretion decreased. Light and electron microscopy revealed glomerular endotheliosis and ischemia with the intermediate and high doses of sunitinib but completely absent histological abnormalities with the low dose. Podocyte number per glomerular circumference did not change. Glomerular nephrin, Neph1, podocin, and endothelin-converting enzyme gene expression were downregulated in a dose-dependent manner. We conclude that the sunitinib-induced rise in blood pressure requires lower doses than its induction of renal function impairment and that functional changes in glomerular filtration barrier contribute to the occurrence of proteinuria, given the lack of histopathologic changes with the low dose of sunitinib.

Treatment of hypertension and renal injury induced by the angiogenesis inhibitor sunitinib: preclinical study.

Common adverse effects of angiogenesis inhibition are hypertension and renal injury. To determine the most optimal way to prevent these adverse effects and to explore their interdependency, the following drugs were investigated in unrestrained Wistar Kyoto rats exposed to the angiogenesis inhibitor sunitinib: the dual endothelin receptor antagonist macitentan; the calcium channel blocker amlodipine; the angiotensin-converting enzyme inhibitor captopril; and the phosphodiesterase type 5 inhibitor sildenafil. Mean arterial pressure was monitored telemetrically. After 8 days, rats were euthanized and blood samples and kidneys were collected. In addition, 24-hour urine samples were collected. After sunitinib start, mean arterial pressure increased rapidly by ≈30 mm Hg. Coadministration of macitentan or amlodipine largely prevented this rise, whereas captopril or sildenafil did not. Macitentan, captopril, and sildenafil diminished the sunitinib-induced proteinuria and endothelinuria and glomerular intraepithelial protein deposition, whereas amlodipine did not. Changes in proteinuria and endothelinuria were unrelated. We conclude that in our experimental model, dual endothelin receptor antagonism and calcium channel blockade are suitable to prevent angiogenesis inhibition-induced hypertension, whereas dual endothelin receptor antagonism, angiotensin-converting enzyme inhibitor, and phosphodiesterase type 5 inhibition can prevent angiogenesis inhibition-induced proteinuria. Moreover, the variable response of hypertension and renal injury to different antihypertensive agents suggests that these side effects are, at least in part, unrelated.

BDNF and S100B in psychotic disorders: evidence for an association with treatment responsiveness.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) and S100B are involved in brain plasticity processes and their serum levels have been demonstrated to be altered in patients with psychoses. This study aimed to identify subgroups of patients with psychotic disorders across diagnostic boundaries that show a specific symptom profile or response to treatment with antipsychotics, by measuring serum levels of BDNF and S100B. METHODS: The study sample consisted of 58 patients with DSM-IV psychotic disorders. Comprehensive Assessment of Symptoms and History (CASH), Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression scale for severity and improvement (CGI-S/CGI-I) were applied at baseline and after 6 weeks of antipsychotic treatment. At both time points, serum levels of BDNF and S100B were measured and compared with a matched control sample. RESULTS: Baseline BDNF and S100B levels were significantly lower in patients as compared with controls and did not change significantly during treatment. Dividing the patient sample according to baseline biochemical parameters (low and high 25% and middle 50%), no differences in symptom profiles or outcome were found with respect to BDNF. However, the subgroups with low and high S100B levels had higher PANSS scores than the middle subgroup. In addition, the high subgroup still showed significantly more negative symptoms after treatment, whereas the low subgroup showed more positive symptoms compared with the other subgroups. CONCLUSION: Serum levels of BDNF and S100B are lowered in patients with psychotic disorders across diagnostic boundaries. The differences between high and low S100B subgroups suggest a relationship between S100B, symptom dimensions and treatment response, irrespective of diagnostic categories.

Cardiometabolic comorbidity in antipsychotic treated patients: need for systematic evaluation and treatment.

OBJECTIVE: The aim of the study was to determine the prevalence of cardiometabolic dysregulations and their somatic treatment regimens in a group of psychiatric patients treated with antipsychotics. METHODS: In a naturalistic cohort study, baseline cardiometabolic parameters were measured in 543 outpatients. After one year, a second assessment was performed in 220 patients out of the total sample. In addition, it was investigated whether in patients with somatic comorbidities adequate treatment was prescribed. RESULTS: In this cohort, about half of the patients fulfilled the criteria for metabolic syndrome. Only a limited number of patients, however, received pharmacologic treatment for individual risk factors: About 19% for hypercholesterolemia, 26% for hypertension, and 52% for diabetes. Non-treated patients were significantly younger than treated patients. Follow-up data show that the course of the cardiometabolic parameters can be dynamic. CONCLUSIONS: Cardiometabolic risk factors are highly prevalent in psychiatric patients treated with antipsychotic drugs. Unfortunately, adequate treatment of cardiometabolic comorbidity in these relatively young patients is seriously hampered. Thus, specific guidelines for psychiatric patients have to be developed taking into account the high cardiovascular risk at a relatively young age and potential pharmacokinetic interactions between psychotropics and somatic compounds. Moreover, integration of psychiatric and physical health care systems for patients with mental disorders is urgently needed.

Sunitinib-induced hypothyroidism is due to induction of type 3 deiodinase activity and thyroidal capillary regression.

CONTEXT: Anticancer treatment with the tyrosine kinase inhibitor sunitinib causes thyroid dysfunction. OBJECTIVE: Our objective was to investigate the time course and underlying mechanisms of sunitinib-induced thyroid dysfunction. DESIGN: Thyroid function tests of 83 patients on sunitinib were collected retrospectively for their total treatment duration between January 2006 and November 2009 and prospectively in 15 patients on sunitinib for 10 wk. Additionally, thyroid function and histology were assessed in rats on sunitinib (8 d; n = 10) and after sunitinib withdrawal (11 d; n = 7) and compared with controls (n = 7). SETTING: Patients were seen at a university outpatient oncology clinic. Patients and Animals: Patients with metastatic renal cell carcinoma or gastrointestinal stromal tumors participated in the clinical study and Wistar Kyoto rats were used in the rat study. INTERVENTION: Sunitinib was taken according to a 4 wk "on," 2 wk "off" treatment regimen. Blood samples for measurement of thyroid function were collected at baseline and at wk 4 and 10. In rats, blood, liver, and thyroid were collected to assess thyroid hormones, deiodinase activity, and thyroid histology. MAIN OUTCOME MEASURES: TSH and free T(4) levels, deiodinase activity, and thyroid histology were assessed. RESULTS: Forty-two percent of patients in the retrospective study developed elevated TSH levels. Prospective analysis showed increased TSH levels within 10 wk of treatment, accompanied by a decreased T(3)/rT(3) ratio. In rats, serum T(4) and T(3) decreased, hepatic type 3 deiodinase activity increased, and thyroid histology showed marked capillary regression, which all but thyroid hormones reversed after sunitinib withdrawal. CONCLUSION: Sunitinib induces hypothyroidism due to alterations in T(4)/T(3) metabolism as well as thyroid capillary regression.

The vascular endothelial growth factor receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin system.

Angiogenesis inhibition is an established treatment for several tumor types. Unfortunately, this therapy is associated with adverse effects, including hypertension and renal toxicity, referred to as "preeclampsia." Recently, we demonstrated in patients and in rats that the multitarget tyrosine kinase inhibitor sunitinib induces a rise in blood pressure (BP), renal dysfunction, and proteinuria associated with activation of the endothelin system. In the current study we investigated the effects of sunitinib on rat renal histology, including the resemblance with preeclampsia, as well as the roles of endothelin 1, decreased nitric oxide (NO) bioavailability, and increased oxidative stress in the development of sunitinib-induced hypertension and renal toxicity. In rats on sunitinib, light and electron microscopic examination revealed marked glomerular endotheliosis, a characteristic histological feature of preeclampsia, which was partly reversible after sunitinib discontinuation. The histological abnormalities were accompanied by an increase in urinary excretion of endothelin 1 and diminished NO metabolite excretion. In rats on sunitinib alone, BP increased (ΔBP: 31.6±0.9 mm Hg). This rise could largely be prevented with the endothelin receptor antagonist macitentan (ΔBP: 12.3±1.5 mm Hg) and only mildly with Tempol, a superoxide dismutase mimetic (ΔBP: 25.9±2.3 mm Hg). Both compounds could not prevent the sunitinib-induced rise in serum creatinine or renal histological abnormalities and had no effect on urine nitrates but decreased proteinuria and urinary endothelin 1 excretion. Our findings indicate that both the endothelin system and oxidative stress play important roles in the development of sunitinib-induced proteinuria and that the endothelin system rather than oxidative stress is important for the development of sunitinib-induced hypertension.

A man who wanted to commit suicide by hanging himself: an adverse effect of ciprofloxacin.

In this case report, we describe a man who developed recurrent depression and suicidal ideation with a serious plan to commit suicide as definite adverse effect of ciprofloxacin, which had been prescribed for recurrent prostatitis.

Bioengineering of living renal membranes consisting of hierarchical, bioactive supramolecular meshes and human tubular cells.

Maintenance of polarisation of epithelial cells and preservation of their specialized phenotype are great challenges for bioengineering of epithelial tissues. Mimicking the basement membrane and underlying extracellular matrix (ECM) with respect to its hierarchical fiber-like morphology and display of bioactive signals is prerequisite for optimal epithelial cell function in vitro. We report here on a bottom-up approach based on hydrogen-bonded supramolecular polymers and ECM-peptides to make an electro-spun, bioactive supramolecular mesh which can be applied as synthetic basement membrane. The supramolecular polymers used, self-assembled into nano-meter scale fibers, while at micro-meter scale fibers were formed by electro-spinning. We introduced bioactivity into these nano-fibers by intercalation of different ECM-peptides designed for stable binding. Living kidney membranes were shown to be bioengineered through culture of primary human renal tubular epithelial cells on these bioactive meshes. Even after a long-term culturing period of 19 days, we found that the cells on bioactive membranes formed tight monolayers, while cells on non-active membranes lost their monolayer integrity. Furthermore, the bioactive membranes helped to support and maintain renal epithelial phenotype and function. Thus, incorporation of ECM-peptides into electro-spun meshes via a hierarchical, supramolecular method is a promising approach to engineer bioactive synthetic membranes with an unprecedented structure. This approach may in future be applied to produce living bioactive membranes for a bio-artificial kidney.

Working memory in schizophrenia: a systematic study of specific modalities and processes.

Although many researchers agree that working memory (WM) impairments are a core symptom of schizophrenia, it remains unclear how the disturbances on specific WM components relate to one another. In this study, we presented a Delayed-Matching-To-Sample task to 24 schizophrenia patients and 24 healthy controls, matched on demographical variables. Verbal and visuospatial WM performance was investigated with pseudowords and Chinese characters as stimuli, respectively. Processing demands (maintenance and manipulation, measured with delay and mental rotation) were low or high. Reaction time and accuracy were recorded. All experimental factors had significant effects. In general, patients were slower and less accurate than controls. Patients were especially slower on verbal tasks but they were not less accurate. Accuracy differences did not increase when either maintenance or manipulation demands increased alone but they did when both maintenance and manipulation demands increased simultaneously. These findings indicate that performance impairment in patients was non-specific and that no specific deficit of any WM component was observed.