HCC is diagnosed in approximately half a million people per year, worldwide. Staging is a more complex issue than in most other cancer entities and, mainly due to unique geographic characteristics of the disease, no universally accepted staging system exists to date. Focusing on survival rates we analyzed demographic, etiological, clinical, laboratory and tumor characteristics of HCC-patients in our institution and applied the common staging systems. Furthermore we aimed at identifying the most suitable of the current staging systems for predicting survival.
Overall, 405 patients with HCC were identified from an electronic medical record database. The following seven staging systems were applied and ranked according to their ability to predict survival by using the Akaike information criterion (AIC) and the concordance-index (c-index): BCLC, CLIP, GETCH, JIS, Okuda, TNM and Child-Pugh. Separately, every single variable of each staging system was tested for prognostic meaning in uni- and multivariate analysis. Alcoholic cirrhosis (44.4%) was the leading etiological factor followed by viral hepatitis C (18.8%). Median survival was 18.1 months (95%-CI: 15.2–22.2). Ascites, bilirubin, alkaline phosphatase, AFP, number of tumor nodes and the BCLC tumor extension remained independent prognostic factors in multivariate analysis. Overall, all of the tested staging systems showed a reasonable discriminatory ability. CLIP (closely followed by JIS) was the top-ranked score in terms of prognostic capability with the best values of the AIC and c-index (AIC 2286, c-index 0.71), surpassing other established staging systems like BCLC (AIC 2343, c-index 0.66). The unidimensional scores TNM (AIC 2342, c-index 0.64) and Child-Pugh (AIC 2369, c-index 0.63) performed in an inferior fashion.
Compared with six other staging systems, the CLIP-score was identified as the most suitable staging system for predicting prognosis in a large German cohort of predominantly non-surgical HCC-patients.
Rates of self-reported psychotic experiences (SRPEs) in general population samples are high; however the reliability against interview-based assessments and the clinical significance of false-positive (FP) ratings remain unclear. Design: The second Netherlands Mental Health Survey and Incidence Study-2, a general population study.
Trained lay interviewers administered a structured interview assessing psychopathology and psychosocial characteristics in 6646 participants. Participants with at least one SRPE (N = 1084) were reassessed by clinical telephone interview.
Thirty-six percent of participants with SRPEs were confirmed by clinical interview as true positive (TP). SPREs not confirmed by clinical interview (FP group) generated less help-seeking behavior and occurred less frequently compared with TP experiences (TP group). However, compared with controls without psychotic experiences, the FP group more often displayed mood disorder (relative risk [RR] 1.7, 1.4–2.2), substance use disorder (RR 2.0, 1.6–2.6), cannabis use (RR 1.5, 1.2–1.9), higher levels of neuroticism (RR 1.8, 1.5–2.2), affective dysregulation, and social dysfunction. The FP group also experienced more sexual (RR 2.0, 1.5–2.8) and psychological childhood trauma (RR 2.1, 1.7–2.6) as well as peer victimization (RR 1.5, 1.2–2.0) and recent life events (RR 2.0, 1.6–2.4) than controls without psychotic experiences. Differences between the FP group and the TP group across these domains were much smaller and less conclusive.
SRPEs not confirmed by clinical interview may epresent the softest expression of an extended psychosis phenotype that is phenotypically continuous with clinical psychosis but discontinuous in need for care.
diagnosis; schizophrenia; trauma; cannabis; epidemiology; false positive
Understanding precursors to distress and emotional well-being (EWB) experienced in anticipation of radiotherapy would facilitate the ability to intervene with this emotional upset (i.e., higher distress, lower EWB). Thus the present study tested an expectancy-based model for explaining emotional upset in breast cancer patients prior to radiotherapy. Women affected by breast cancer (N=106) were recruited and participants completed questionnaires prior to commencing radiotherapy. Structural equation modeling was used test a cross-sectional model, which assessed the ability of dispositional optimism (Life Orientation Test-Revised - two factors), response expectancies (VAS items), medical (type of surgery, cancer stage, chemotherapy history) and demographic (age, race/ethnicity, education, marital status) variables to predict both EWB (Functional Assessment of Chronic Illness Therapy - Emotional Well-being Subscale) and distress (Profile of Mood States - Short Version). The model represented a good fit to the data accounting for 65% of the variance in EWB and 69% in Distress. Significant predictors of emotional upset were pessimism, response expectancies, Latina ethnicity, cancer stage, and having had a mastectomy. These variables explained a large portion of emotional upset experienced prior to radiotherapy for breast cancer and are important to consider when aiming to reduce distress and improve EWB in this context.
distress; quality of life; breast neoplasm; radiotherapy; optimism; response expectancies
Atrial fibrillation affects almost 2% of the population in the Western world. To preserve sinus rhythm, ablation is undertaken in symptomatic patients. Observational studies show that patients with atrial fibrillation often report a low quality of life and are less prone to be physically active due to fear of triggering fibrillation. Small trials indicate that exercise training has a positive effect on exercise capacity and mental health, and both patients with recurrent atrial fibrillation and in sinus rhythm may benefit from rehabilitation in managing life after ablation. No randomised trials have been published on cardiac rehabilitation for atrial fibrillation patients treated with ablation that includes exercise and psychoeducational components.
To test the effects of an integrated cardiac rehabilitation programme versus treatment as usual for patients with atrial fibrillation treated with ablation.
Methods and analysis design
The trial is a multicentre parallel arm design with 1:1 randomisation to the intervention and control group with blinded outcome assessment. 210 patients treated for atrial fibrillation with radiofrequency ablation will be included. The intervention consists of a rehabilitation programme including four psychoeducative consultations with a specially trained nurse and 12 weeks of individualised exercise training, plus the standard medical follow-up. Patients in the control group will receive the standard medical follow-up. The primary outcome measure is exercise capacity measured by the VO2 peak. The secondary outcome measure is self-rated mental health measured by the Short Form 36 questionnaire. Postintervention, qualitative interviews will be conducted in 10% of the intervention group.
Ethics and dissemination
The protocol is approved by the regional research ethics committee (number H-1-2011-135), the Danish Data Protection Agency (reg. nr. 2007-58-0015) and follows the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and may possibly impact on rehabilitation guidelines.
Clinicaltrials.gov identifier: NCT01523145.
Atrial Fibrillation ; QUALITATIVE RESEARCH
This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.
Methods and results
Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.
The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.
Heart failure; Anaemia
Degenerative aortic valve (AV) stenosis is the most prevalent heart valve disease in the western world. Surgical aortic valve replacement (SAVR) has until recently been the standard of treatment for patients with severe AV stenosis. Whether transcatheter aortic valve implantation (TAVI) can be offered with improved safety and similar effectiveness in a population including low-risk patients has yet to be examined in a randomised setting.
This randomised clinical trial will evaluate the benefits and risks of TAVI using the transarterial CoreValve System (Medtronic Inc., Minneapolis, MN, USA) (intervention group) compared with SAVR (control group) in patients with severe degenerative AV stenosis. Randomisation ratio is 1:1, enrolling a total of 280 patients aged 70 years or older without significant coronary artery disease and with a low, moderate, or high surgical risk profile. Trial outcomes include a primary composite outcome of myocardial infarction, stroke, or all-cause mortality within the first year after intervention (expected rates 5% for TAVI, 15% for SAVR). Exploratory safety outcomes include procedure complications, valve re-intervention, and cardiovascular death, as well as cardiac, cerebral, pulmonary, renal, and vascular complications. Exploratory efficacy outcomes include New York Heart Association functional status, quality of life, and valve prosthesis and cardiac performance. Enrolment began in December 2009, and 269 patients have been enrolled up to December 2012.
The trial is designed to evaluate the performance of TAVI in comparison with SAVR. The trial results may influence the choice of treatment modality for patients with severe degenerative AV stenosis.
Aortic valve stenosis; Aortic valve prosthesis; Transcatheter aortic valve implantation; Surgical aortic valve replacement; Randomised clinical trial design
Health-related quality of life (HRQoL) was found to improve in participants of weight management interventions. However, information on moderately overweight youth as well as on maintaining HRQoL improvements following treatment is sparse. We studied the HRQoL of 74 overweight, but not obese participants (32.4% male, mean age = 11.61 ± 1.70 SD) of a comprehensive and effective six-month outpatient training at four time-points up to 12 months after end of treatment.
HRQoL was measured by self-report and proxy-report versions of the generic German KINDL-R, including six sub domains, and an obesity-specific additional module. Changes in original and z-standardized scores were analyzed by (2×4) doubly multivariate analysis of variance. This was done separately for self- and proxy-reported HRQoL, taking into account further socio-demographic background variables and social desirability. Additionally, correlations between changes in HRQoL scores and changes in zBMI were examined.
There were significant multivariate time effects for self-reported and proxy-reported HRQoL and a significant time-gender interaction in self-reports revealed (p < .05). Improvements in weight-specific HRQoL were evident during treatment (partial η2 = 0.14-0.19). Generic HRQoL further increased after end of treatment. The largest effects were found on the dimension self-esteem (partial η2 = 0.08-0.09 for proxy- and self-reported z-scores, respectively). Correlations with changes in weight were gender-specific, and weight reduction was only associated with HRQoL improvements in girls.
Positive effects of outpatient training on generic and weight-specific HRQoL of moderately overweight (not obese) children and adolescents could be demonstrated. Improvements in HRQoL were not consistently bound to weight reduction. While changes in weight-specific HRQoL were more immediate, generic HRQoL further increased after treatment ended. An extended follow-up may therefore be needed to scrutinize HRQoL improvements due to weight management.
Overweight; Health-related quality of life; Intervention; Weight reduction; Children and adolescents
coocidioidomycosis; meningitis; atypical lymphocytes; IRIS; immune reconstitution inflammatory syndrome; HIV/AIDS and other retroviruses; CD4+ T-cells; antiretroviral therapy; fungi
Most interventions for depression have shown small or no effects. ‘Third wave‘ cognitive therapy and mentalization-based therapy have both gained some ground as treatments of psychological problems. No randomised trial has compared the effects of these two interventions for patients with major depression.
We plan a randomised, parallel group, assessor-blinded superiority clinical trial. During two years we will include 84 consecutive adult participants diagnosed with major depressive disorder. The participants will be randomised to either ‘third wave‘ cognitive therapy versus mentalization-based therapy. The primary outcome will be the Hamilton Rating Scale for Depression at cessation of treatment at 18 weeks. Secondary outcomes will be the proportion of patients with remission, Symptom Checklist 90 Revised, Beck’s Depression Inventory, and The World Health Organisation-Five Well-being Index 1999.
Interventions for depression have until now shown relatively small effects. Our trial results will provide knowledge about the effects of two modern psychotherapeutic interventions.
Infective endocarditis (IE) is among the most serious infectious diseases in the western world. Treatment requires lengthy hospitalisation, high-dosage antibiotic therapy and possible valve replacement surgery. Despite advances in treatment, the 1-year mortality remains at 20–40%. Studies indicate that patients experience persisting physical symptoms, diminished quality of life and difficulties returning to work up to a year postdischarge. No studies investigating the effects of rehabilitation have been published. We present the rationale and design of the CopenHeartIE trial, which investigates the effect of comprehensive cardiac rehabilitation versus usual care for patients treated for IE.
Methods and analysis
We will conduct a randomised clinical trial to investigate the effects of comprehensive cardiac rehabilitation versus usual care on the physical and psychosocial functioning of patients treated for IE. The trial is a multicentre, parallel design trial with 1 : 1 individual randomisation to either the intervention or control group. The intervention consists of five psychoeducational consultations provided by specialised nurses and a 12-week exercise training programme. The primary outcome is mental health (MH) measured by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen uptake measured by the bicycle ergospirometry test. Furthermore, a number of exploratory analyses will be performed. Based on sample size calculation, 150 patients treated for left-sided (native or prosthetic valve) or cardiac device endocarditis will be included in the trial. A qualitative and a survey-based complementary study will be undertaken, to investigate postdischarge experiences of the patients. A qualitative postintervention study will explore rehabilitation participation experiences.
Ethics and dissemination
The study complies with the Declaration of Helsinki and was approved by the regional research ethics committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58-0015). Study findings will be disseminated widely through peer-reviewed publications and conference presentations.
Clinicaltrials.gov identifier: NCT01512615.
Infective Endocarditis; RCT; Mixed Method
Access procedures for alimentation have been performed both endoscopically and surgically. In patients in whom endoscopic gastrostomy feeding tubes cannot be placed, single-incision laparoscopic surgery gastrostomy is an alternative method. This minimally invasive approach is a new technique performed through a single umbilical incision and without the need for additional laparoscopic ports.
In this article we present a case of single-incision laparoscopic surgery gastrostomy performed with conventional laparoscopic instruments in a 10-year-old girl of Caucasian ethnicity who was not a candidate for a percutaneous endoscopic gastrostomy tube because of esophageal varices due to her advanced-stage cystic fibrosis with liver cirrhosis and portal hypertension. She also had an umbilical hernia, which was repaired during the same procedure through the same incision. Access and pneumoperitoneum were obtained through the umbilicus with the single-incision laparoscopic surgery port. The selected site for the feeding tube in the stomach was exteriorized through this incision and a feeding tube was placed. The stomach was returned into the abdomen. The fascial defect, and thus also the hernia, was repaired, and the 2cm umbilical incision was closed with endocutaneous sutures. The total operative time was 25 minutes. Our patient’s intra-operative and post-operative course was uneventful. We were able to use the feeding tube on the first post-operative day with good intestinal function. Our patient and her parents were pleased with the cosmetic result.
The single-incision laparoscopic surgery procedure seems to be a less invasive alternative to open placement of gastrostomy. This approach has the possible advantages of reduced post-operative pain, faster return to normal function, reduced port site complications, improved cosmesis and better patient satisfaction.
Gastrostomy; Single-incision laparoscopic surgery; Single-port; Transumbilical
Genetic variation in AKT1 may be associated with sensitivity to the psychotomimetic effects of cannabis as well as with increased risk for psychotic disorder following cannabis use. Investigation of the effect of this interaction on relevant intermediate phenotypes for psychosis, such as cognition, may help to clarify the underlying mechanism. Thus, verbal memory (visually presented Word Learning Task), sustained attention (Continuous Performance Test, CPT), AKT1 rs2494732 genotype, and cannabis use were examined in a large cohort of patients with psychotic disorder. No evidence was found for AKT1 × cannabis interaction on verbal memory. Cannabis use preceding onset of psychotic disorder did interact significantly with AKT1 rs2494732 genotype to affect CPT reaction time (β=8.0, SE 3.9, p=0.037) and CPT accuracy (β=−1.2, SE 0.4, p=0.003). Cannabis-using patients with the a priori vulnerability C/C genotype were slower and less accurate on the CPT, whereas cannabis-using patients with the T/T genotype had similar or better performance than non-using patients with psychotic disorder. The interaction was also apparent in patients with psychotic disorder who had not used cannabis in the 12 months preceding assessment, but was absent in the unaffected siblings of these patients and in healthy controls. In conclusion, cannabis use before onset of psychosis may have long-lasting effects on measures of sustained attention, even in the absence of current use, contingent on AKT1 rs2494732 genotype. The results suggest that long-term changes in cognition may mediate the risk-increasing effect of the AKT1 × cannabis interaction on psychotic disorder.
cannabinoids; cognition; schizophrenia/antipsychotics; neurogenetics; AKT1; cannabis; Cannabinoids; Cognition, Schizophrenia/Antipsychotics; Neurogenetics; AKT1; cannabis
Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10−9] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10−9).
The flavonoid pathway is a long-standing and important tool for plant genetics, biochemistry, and molecular biology. Numerous flavonoid mutants have been identified in Arabidopsis over the past several decades in a variety of ecotypes. Here we present an analysis of Arabidopsis lines of ecotype Columbia carrying T-DNA insertions in genes encoding enzymes of the central flavonoid pathway. We also provide a comprehensive summary of various mutant alleles for these structural genes that have been described in the literature to date in a wide variety of ecotypes.
The confirmed knockout lines present easily-scorable phenotypes due to altered pigmentation of the seed coat (or testa). Knockouts for seven alleles for six flavonoid biosynthetic genes were confirmed by PCR and characterized by UPLC for altered flavonol content.
Seven mutant lines for six genes of the central flavonoid pathway were characterized in ecotype, Columbia. These lines represent a useful resource for integrating biochemical and physiological studies with genomic, transcriptomic, and proteomic data, much of which has been, and continues to be, generated in the Columbia background.
Arabidopsis; Ecotype; Insertional inactivation lines; Flavonoid; Transparent testa
To investigate the effects of social-skills training and parental training programme for children with attention deficit hyperactivity disorder (ADHD).
We conducted a randomized two-armed, parallel group, assessor-blinded superiority trial consisting of social-skills training plus parental training and standard treatment versus standard treatment alone. A sample size calculation showed at least 52 children should be included for the trial with follow up three and six months after randomization. The primary outcome measure was ADHD symptoms and secondary outcomes were social skills and emotional competences.
children (39 boys, 17 girls, mean age 10.4 years, SD 1.31) with ADHD were randomized, 28 to the experimental group and 27 to the control group. Mixed-model analyses with repeated measures showed that the time course (y = a + bt + ct2) of ADHD symptoms (p = 0.40), social skills (p = 0.80), and emotional competences (p = 0.14) were not significantly influenced by the intervention.
Social skills training plus parental training did not show any significant benefit for children with attention deficit hyperactivity disorder when compared with standard treatment. More and larger randomized trials are needed.
Studies have consistently found a high incidence of neonatal medical problems, premature births and low birth weights in abused and neglected children. One of the explanations proposed for the relation between neonatal problems and adverse parenting is a possible delay or disturbance in the bonding process between the parent and infant. This hypothesis suggests that due to neonatal problems, the development of an affectionate bond between the parent and the infant is impeded. The disruption of an optimal parent-infant bond -on its turn- may predispose to distorted parent-infant interactions and thus facilitate abusive or neglectful behaviours. Video Interaction Guidance (VIG) is expected to promote the bond between parents and newborns and is expected to diminish non-optimal parenting behaviour.
This study is a multi-center randomised controlled trial to evaluate the effectiveness of Video Interaction Guidance in parents of premature infants. In this study 210 newborn infants with their parents will be included: n = 70 healthy term infants (>37 weeks GA), n = 70 moderate term infants (32–37 weeks GA) which are recruited from maternity wards of 6 general hospitals and n = 70 extremely preterm infants or very low birth weight infants (<32 weeks GA) recruited by the NICU of 2 specialized hospitals. The participating families will be divided into 3 groups: a reference group (i.e. full term infants and their parents, receiving care as usual), a control group (i.e. premature infants and their parents, receiving care as usual) and an intervention group (i.e. premature infants and their parents, receiving VIG). The data will be collected during the first six months after birth using observations of parent-infant interactions, questionnaires and semi-structured interviews. Primary outcomes are the quality of parental bonding and parent-infant interactive behaviour. Parental secondary outcomes are (posttraumatic) stress symptoms, depression, anxiety and feelings of anger and hostility. Infant secondary outcomes are behavioral aspects such as crying, eating, and sleeping.
This is the first prospective study to empirically evaluate the effect of VIG in parents of premature infants. Family recruitment is expected to be completed in January 2012. First results should be available by 2012.
Trail registration number
Few couple-focused interventions have been developed to improve distress and relationship outcomes among men diagnosed with localized prostate cancer and their partners.
We examined the effects of a five session Intimacy-Enhancing Therapy (IET) versus Usual Care (UC) on the psychological and relationship functioning of men diagnosed with localized prostate cancer and their partners. Pre-intervention levels of psychological and relationship functioning were evaluated as moderators of intervention effects.
Seventy one survivors and their partners completed a baseline survey and were subsequently randomly assigned to receive five sessions of IET or Usual Care (no treatment). Eight weeks after the baseline assessment, a follow-up survey was administered to survivor and partner.
Main outcome measures
Distress, well-being, relationship satisfaction, relationship intimacy, and communication were investigated as the main outcomes..
IET effects were largely moderated by pre-intervention psychosocial and relationship factors. Those survivors who had higher levels of cancer concerns at pre-treatment had significantly reduced concerns following IET. Similar moderating effects for pre-intervention levels were reported for the effects of IET on self-disclosure, perceived partner disclosure, and perceived partner responsiveness. Among partners beginning the intervention with higher cancer-specific distress, lower marital satisfaction, lower intimacy, and poorer communication, IET improved these outcomes.
IET had a marginally significant main effect upon survivor well-being but was effective among couples with fewer personal and relationship resources. Subsequent research is needed to replicate these findings with a larger sample and a longer follow-up.
Prostate cancer; Cancer and Sexual Quality of Life; Psychological Intervention; Intimacy-enhancing treatment
Despite longstanding concern that the presence of children deters drug-dependent women from entering treatment, there have been few empirical tests of the relationship between parenting responsibilities and treatment-seeking behavior. In this study, the relationship between number of biological children and treatment history was examined in a cohort of 153 women seeking methadone maintenance treatment. In a standard multiple regression analysis that also allowed for the potential influence of (a) age, (b) education, (c) ethnic minority status, (d) cohabitation with a sexual partner, (e) chronicity of opioid use, and (f) knowledge of HIV infection, there was a significant, negative relationship between number of children and number of earlier contacts for drug abuse treatment. Ethnic minority status and cohabitation with a sexual partner were also associated with fewer earlier contacts; greater chronicity and knowledge of HIV infection were associated with more earlier contacts. Moreover, there was significant moderation of the negative relationship between parenting responsibilities and treatment history by (a) ethnic minority status, (b) cohabitation, and (c) chronicity of use. Within a cross-sectional research design, the findings highlight ways parenting responsibilities may interact with other factors over time to influence the treatment-seeking behavior of drug-dependent women.
Opioid dependence; Methadone maintenance; Women; Parenting; Drug treatment history; Pharmacotherapy
Oncogenic KRAS mutations in colorectal cancer (CRC) are associated with lack of benefit from epidermal growth factor receptor (EGFR)-directed antibody (Ab) therapy. However, the mechanisms by which constitutively activated KRAS (KRASG12V) impairs effector mechanisms of EGFR-Abs are incompletely understood. Here, we established isogenic cell line models to systematically investigate the impact of KRASG12V on tumor growth in mouse A431 xenograft models as well as on various modes of action triggered by EGFR-Abs in vitro. KRASG12V impaired EGFR-Ab-mediated growth inhibition by stimulating receptor-independent downstream signaling. KRASG12V also rendered tumor cells less responsive to Fc-mediated effector mechanisms of EGFR-Abs—such as complement-dependent cytotoxicity (CDC) and Ab-dependent cell-mediated cytotoxicity (ADCC). Impaired CDC and ADCC activities could be linked to reduced EGFR expression in KRAS-mutated versus wild-type (wt) cells, which was restored by small interfering RNA (siRNA)-mediated knockdown of KRAS4b. Immunohistochemistry experiments also revealed lower EGFR expression in KRAS-mutated versus KRAS-wt harboring CRC samples. Analyses of potential mechanisms by which KRASG12V downregulated EGFR expression demonstrated significantly decreased activity of six distinct transcription factors. Additional experiments suggested the CCAAT/enhancer-binding protein (C/EBP) family to be implicated in the regulation of EGFR promoter activity in KRAS-mutated tumor cells by suppressing EGFR transcription through up-regulation of the inhibitory family member C/EBPβ-LIP. Thus, siRNA-mediated knockdown of C/EBPβ led to enhanced EGFR expression and Ab-mediated cytotoxicity against KRAS-mutated cells. Together, these results demonstrate that KRASG12V signaling induced C/EBPβ-dependent suppression of EGFR expression, thereby impairing Fc-mediated effector mechanisms of EGFR-Abs and rendering KRAS-mutated tumor cells less sensitive to these therapeutic agents.
The serotonergic neurotransmitter system is closely linked to depression and personality traits. It is not known if selective serotonin reuptake inhibitors (SSRI) have an effect on neuroticism that is independent of their effect on depression. Healthy individuals with a genetic liability for depression represent a group of particular interest when investigating if intervention with SSRIs affects personality. The present trial is the first to test the hypothesis that escitalopram may reduce neuroticism in healthy first-degree relatives of patients with major depressive disorder (MD).
The trial used a randomized, blinded, placebo-controlled parallel-group design. We examined the effect of four weeks escitalopram 10 mg daily versus matching placebo on personality in 80 people who had a biological parent or sibling with a history of MD. The outcome measure on personality traits was change in self-reported neuroticism scores on the Revised Neuroticism-Extroversion-Openness-Personality Inventory (NEO-PI-R) and the Eysenck Personality Inventory (EPQ) from entry until end of four weeks of intervention.
When compared with placebo, escitalopram did not significantly affect self-reported NEO-PI-R and EPQ neuroticism and extroversion, EPQ psychoticism, NEO-PI-R openness, or NEO-PI-R conscientiousness (p all above 0.05). However, escitalopram increased NEO-PI-R agreeableness scores significantly compared with placebo (mean; SD) (2.38; 8.09) versus (−1.32; 7.94), p = 0.046), but not following correction for multiplicity. A trend was shown for increased conscientiousness (p = 0.07). There was no significant effect on subclinical depressive symptoms (p = 0.6).
In healthy first-degree relatives of patients with MD, there is no effect of escitalopram on neuroticism, but it is possible that escitalopram may increase the personality traits of agreeableness and conscientiousness.
Several studies have found a positive effect on the learning curve as well as the improvement of basic psychomotor skills in the operating room after virtual reality training. Despite this, the majority of surgical and gynecological departments encounter hurdles when implementing this form of training. This is mainly due to lack of knowledge concerning the time and human resources needed to train novice surgeons to an adequate level. The purpose of this trial is to investigate the impact of instructor feedback regarding time, repetitions and self-perception when training complex operational tasks on a virtual reality simulator.
The study population consists of medical students on their 4th to 6th year without prior laparoscopic experience. The study is conducted in a skills laboratory at a centralized university hospital. Based on a sample size estimation 98 participants will be randomized to an intervention group or a control group. Both groups have to achieve a predefined proficiency level when conducting a laparoscopic salpingectomy using a surgical virtual reality simulator. The intervention group receives standardized instructor feedback of 10 to 12 min a maximum of three times. The control group receives no instructor feedback. Both groups receive the automated feedback generated by the virtual reality simulator. The study follows the CONSORT Statement for randomized trials. Main outcome measures are time and repetitions to reach the predefined proficiency level on the simulator. We include focus on potential sex differences, computer gaming experience and self-perception.
The findings will contribute to a better understanding of optimal training methods in surgical education.
Virtual reality simulation; Laparoscopy; Training; Salpingectomy; Feedback
Ischemic bowel disease comprises both mesenteric ischemia and colonic ischemia. Mesenteric ischemia can be divided into acute and chronic ischemia. These are two separate entities, each with their specific clinical presentation and diagnostic and therapeutic modalities. However, diagnosis may be difficult due to the vague symptomatology and subtle signs.
We report the case of a 68-year-old Caucasian woman who presented with abdominal discomfort, anorexia, melena and fever. A physical examination revealed left lower quadrant tenderness and an irregular pulse. Computed tomography of her abdomen as well as computed tomography enterography, enteroscopy, angiography and small bowel enteroclysis demonstrated an ischemic jejunal segment caused by occlusion of a branch of the superior mesenteric artery. The ischemic segment was resected and an end-to-end anastomosis was performed. The diagnosis of segmental small bowel ischemia was confirmed by histopathological study.
Mesenteric ischemia is a pathology well-known by surgeons, gastroenterologists and radiologists. Acute and chronic mesenteric ischemia are two separate entities with their own specific clinical presentation, radiological signs and therapeutic modalities. We present the case of a patient with symptoms and signs of chronic mesenteric ischemia despite an acute etiology. To the best of our knowledge, this is the first report presenting a case of acute mesenteric ischemia with segmental superior mesenteric artery occlusion.