Incidence of incisional hernia after laparoscopic liver resection.

BACKGROUND: Minimally invasive techniques have been broadly introduced to liver surgery during the last couple of years. In this study, we aimed to report the incidence and potential risk factors for incisional hernia (IH) as well as health-related quality of life (HRQoL) after laparoscopic liver resections (LLR). METHODS: All patients undergoing LLR between January 2014 and June 2017 were contacted for an outpatient hernia examination. In all eligible patients, photo documentation of the scar was performed and IH was evaluated by clinical examination and by ultrasound. Patients also completed a questionnaire to evaluate IH-specific symptoms and HRQoL. Obtained results were retrospectively analyzed with regard to patients' characteristics, perioperative outcomes and applied minimally invasive techniques, such as multi-incision laparoscopic liver surgery or hand-assisted/single-incision laparoscopic surgery (HALS/SILS). RESULTS: Of 184 patients undergoing surgery, 161 (87.5%) met the inclusion criteria and 49 patients (26.6%) participated in this study. After a median time of 26 months (range 19-50 months) after surgery, we observed an overall incidence of IH of 12%. Five of 6 patients were overweight or obese (BMI ≥ 25) and 5 of 6 hernias were located at the umbilical site. Univariate analysis suggested the performance status at time of operation (ASA score ≥ 3; HR 5.616, 95% CI 1.012-31.157, p = 0.048) and the approach (HALS/SILS, HR 6.571, 95% CI 1.097-39.379, p = 0.039) as potential risk factors for IH. A higher frequency of hernia-related physical restrictions (HRR; p = 0.058) and a decreased physical functioning (p = 0.17) were noted in patients with IH; however, both being short of statistical significance. CONCLUSION: Advantages of laparoscopic surgery with regard to low rates of IH can be translated to minimally invasive liver surgery. Even though there are low rates of IH, patients with poor performance status at the time of operation should be monitored closely. While patients' characteristics are hard to influence, it might be worth focusing on surgical factors such as the approach and the closure of the umbilical site to further minimize the rate of IH.

Willingness to pay for risky lifestyles: results from the Pay for Others (PAY4O) study, Italy.

OBJECTIVES: We assess the individual willingness to pay for diseases arising from risky lifestyles and investigate the personal factors that influence such willingness. STUDY DESIGN: We conducted an online survey with 821 respondents in Italy. The questionnaire was distributed via Facebook® in July and August 2016. The questionnaire covered sociodemographic characteristics, health status, behaviour and psychological attitudes, economic status, and opinion about covering the healthcare costs related to overeating, unhealthy diet, sedentary lifestyles, alcohol abuse, tobacco smoking, driving under the influence of alcohol, and illegal drug use by. METHODS: We performed the following: (1) the study of the patterns in the dependent variables by principal component analysis; (2) analysis of the determinants by Holdout Variable Importance measure obtained in Random Forest; and (3) we used ordered logit models. RESULTS: Participants agreed with the idea that public health care should be provided for problems arising from bad eating habits and sedentary lifestyle (50.4%), whereas the health care consequences of the other risky behaviours should not be publicly financed by the Italian National Health Service. CONCLUSIONS: Our study gives an overview of the willingness to pay of a population living in a country where financing of the Health Service is based on general taxation. So, these results may be generalized, with due caution, to all the countries where the Health Service offers universal coverage and is operated by the government, but of course not to scenarios related to market-based or social health insurance systems.

The genetic basis for most patients with pustular skin disease remains elusive.

BACKGROUND: Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause or contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP). OBJECTIVES: To better understand the disease relevance of these genes, we screened our cohorts of patients with pustular skin diseases [primarily GPP and palmoplantar pustular psoriasis (PPP)] for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN. METHODS: Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, two with acute generalized exanthematous pustulosis and four with acrodermatitis continua of Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number variants and 258 patients with PPP for coding changes in AP1S3. Eleven heterozygous IL36RN mutations carriers were analysed for a second noncoding IL36RN mutation. Genotype-phenotype correlations in carriers/noncarriers of IL36RN mutations were assessed within the GPP cohort. RESULTS: The majority of patients (GPP, 64%) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were identified in 15 and five patients with GPP, respectively. Noncoding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype correlation observed for IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers. CONCLUSIONS: The identification of IL36RN mutation carriers harbouring additional rare variants in CARD14 or AP1S3 indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest that, in heterozygous IL36RN mutation carriers, there are additional disease-causing genetic factors outside IL36RN.

Effect of feed supplementation with kynurenic acid on the morphology of the liver, kidney and gills in rainbow trout (Oncorhynchus mykiss Walbaum, 1792), healthy and experimentally infected with Yersinia ruckeri.

Kynurenic acid (KYNA) is an endogenous substance produced on the kynurenine pathway which is primarily known for its neuroactive properties. Recently, it has been proven that KYNA is a selective ligand for G protein-coupled receptor (GPR 35), presented on immunocompetent cells such as T lymphocytes. This opens up new possibilities of its application as an immunostimulating substance in aquaculture. Thus far, no histopathological investigations in fish have been completed to evaluate influence of KYNA supplementation in feed. This study has been undertaken to determine the effect of feed supplementation with KYNA (2.5, 25, 250 mg kg-1 of feed) for 28 days on the liver, gills and kidney in healthy fish and experimentally infected with Yersinia ruckeri. In a control group were observed a fatty liver, which is natural for this fish species in the autumn and winter season. As the dose of the supplement was increased, the fat liver changed, it decreased or completely disappeared. Additionally, inflammatory changes occurred in all the analysed organs, and their intensification was dose dependent. In the fish experimentally infected, KYNA caused aggravation of the signs in the liver, kidneys and gills, and the effect was dose dependent. The results implicate that KYNA may be a stressor for fish.

Catalogue of Interactive Learning Objectives to improve an Integrated Medical and Dental Curriculum.

INTRODUCTION: Online learning media are increasingly being incorporated into medical and dental education. However, the coordination between obligatory and facultative teaching domains still remains unsatisfying. The Catalogue of Interactive Learning Objectives of the University Clinic of Mainz (ILKUM), aims to offer knowledge transfer for students while being mindful of their individual qualifications. Its hierarchical structure is designed according to the Association for Dental Education in Europe (ADEE) levels of competence. MATERIALS AND METHODS: The ILKUM was designed to establish a stronger interconnection between already existing and prospective learning strategies. All contents are linked to the current lectures as well as to e-learning modules, e.g., clinical case studies and OR videos. Students can conduct self-examinations regarding specific learning objectives. Since 2007, ILKUM has been developed and analyzed regarding its acceptance among dental students. RESULTS: These improved e-learning techniques foster time and location-independent access to study materials and allow an estimation of the knowledge achieved by students. Surveys of our students clearly show a large demand for upgrading ILKUM content (89%; n = 172) with integrated self-testing (89%; n = 174). In parallel to the advancement of our e-learning offering, a portion of internet-based learning is constantly rising among students. CONCLUSION: The broad acceptance and demand for the development of ILKUM show its potential. Moreover, ILKUM grants fast, topic-oriented querying of learning content without time and locale limitations as well as direct determination of the individually needed knowledge conditions. CLINICAL SIGNIFICANCE: The long-term goal of the ILKUM project is to be a sustainable, important additional modality of teaching and training for dental and medical students.

The proline TP53 variant stimulates likely lymphangiogenesis in an orthotopic mouse model of pancreatic cancer.

BACKGROUND: Pancreatic cancer is a deadly disease characterised by high incidence of TP53 mutations. Restoration of TP53 function is perceived as a highly attractive therapeutic strategy, whose effects are not well characterised. METHODS: The current work adapted an inducible strategy of stage-specific reexpression of wild-type (wt) TP53 in an in vivo orthotopic mouse model of pancreatic cancer. RESULTS: The reconstitution of wt TP53 function in TP53-mutant DanG and MiaPaCa-2 cells caused G1 cell cycle arrest but no evidence of apoptosis induction. Consistent with subcutaneous xenograft models, we found that wt TP53 reduced primary tumour growth. Wt TP53 reexpression during early tumour growth led to significant increase in vascularisation. This correlated with an unexpectedly high rate of micro-metastases in lymph nodes of animals with wt TP53 induction, despite the 90% decrease in median primary tumour weight. Reexpression of wt TP53 later in tumour development did not significantly affect the number of CD31-reactive vessels, but increased lymphatic vessel density. CONCLUSION: The increased number of lymphatic vessels and micro-metastases suggests that wt TP53 induction complexly affected the biology of different tumour constituents of pancreatic cancer. Our observation suggests that combination of the inducible system with an orthotopic model can yield important insights into in vivo pancreatic cancer biology.

Purification and biochemical characterization of functional complement factor H from human plasma fractions.

BACKGROUND AND OBJECTIVES: Complement factor H (CFH) acts as major regulator of the alternative pathway of complement and its mutations and polymorphisms predispose to various human diseases. We aimed to develop a scalable purification process of CFH from human plasma fractions to supply a pathogen-safe and functional CFH concentrate. MATERIALS AND METHODS: Starting with intermediates of cold ethanol fractionation of plasma, CFH purification was performed with three chromatographic steps including solvent detergent treatment and nanofiltration. CFH functionality was tested by a haemolysis assay using sheep erythrocytes, by determining decay acceleration activity on C3 convertases and cofactor activity of C3b cleavage. CFH identity was confirmed by Western blot and mass spectrometry. RESULTS: Three scalable chromatographic steps highly purified full-length and native CFH from human plasma fractions. The purification process enabled the removal of truncated and dysfunctional CFH species, yielding a native CFH concentrate as demonstrated in sensitive functional in vitro assays. CONCLUSION: This novel process provides a pathogen-safe and functional CFH concentrate that can be produced on an industrial scale and is suitable for pre-/clinical studies.

Reliability and validity of the cross-culturally adapted Italian version of the Core Outcome Measures Index.

Patient-orientated outcome questionnaires are essential for the assessment of treatment success in spine care. Standardisation of the instruments used is necessary for comparison across studies and in registries. The Core Outcome Measures Index (COMI) is a short, multidimensional outcome instrument validated for patients with spinal disorders and is the recommended outcome instrument in the Spine Society of Europe Spine Tango Registry; currently, no validated Italian version exists. A cross-cultural adaptation of the COMI into Italian was carried out using established guidelines. 96 outpatients with chronic back problems (>3 months) were recruited from five practices in Switzerland and Italy. They completed the newly translated COMI, the Roland Morris disability (RM), adjectival pain rating, WHO Quality of Life (WHOQoL), EuroQoL-5D, and EuroQoL-VAS scales. Reproducibility was assessed in a subgroup of 63 patients who returned a second questionnaire within 1 month and indicated no change in back status on a 5-point Likert-scale transition question. The COMI scores displayed no floor or ceiling effects. On re-test, the responses for each individual domain of the COMI were within one category in 100% patients for "function", 92% for "symptom-specific well-being", 100% for "general quality of life", 90% for "social disability", and 98% for "work disability". The intraclass correlation coefficients (ICC(2,1)) for the COMI back and leg pain items were 0.78 and 0.82, respectively, and for the COMI summary index, 0.92 (95% CI 0.86-0.95); this compared well with 0.84 for RM, 0.87 for WHOQoL, 0.79 for EQ-5D, and 0.77 for EQ-VAS. The standard error of measurement (SEM) for COMI was 0.54 points, giving a ''minimum detectable change'' for the COMI of 1.5 points. The scores for most of the individual COMI domains and the COMI summary index correlated to the expected extent (0.4-0.8) with the corresponding full-length reference questionnaires (r = 0.45-0.72). The reproducibility of the Italian version of the COMI was comparable to that published for the German and Spanish versions. The COMI scores correlated in the expected manner with existing but considerably longer questionnaires suggesting adequate convergent validity for the COMI. The Italian COMI represents a practical, reliable, and valid tool for use with Italian-speaking patients and will be of value for international studies and surgical registries.

'Too withdrawn' or 'too friendly': considering social vulnerability in two neuro-developmental disorders.

In some neuro-developmental disorders, the combined effect of intellectual disability and atypicalities of social cognition may put individuals at increased vulnerability in their social environment. The neuro-developmental disorders Williams syndrome, characterised by 'hypersociability', and autism spectrum disorders, characterised by 'social withdrawal', are at two extremes of atypical social functioning in humans. In this article, we use Williams syndrome and autism spectrum disorders as exemplars to demonstrate how atypicalities of social cognition may contribute to social vulnerability in these populations. The lives of individuals with both these disorders are marred by an increased risk of social isolation, bullying, unsteady relationships, employment difficulties and abuse. While different behavioural interventions have been tried to improve social functioning in these populations, there has been great variability in their success. Finally, we discuss different issues regarding social independence of these individuals; including employment, safety and decision making.

Photocatalytic degradation of acridine dyes using anatase and rutile TiO2.

The adsorption and photodegradation of acridine orange (AO) and acriflavine (AF) dyes on two mesoporous titania crystalline phases, anatase and rutile, were experimentally studied. Anatase and rutile were characterized by nitrogen adsorption, electron scanning and transmission microscopy, and X-ray diffraction. The adsorption capacity of rutile was higher than that of anatase, while the reverse is observed for photodegradation of both dyes. The adsorption of AF on both adsorbents was higher than that of AO, which was related with the smaller size of AF molecules compared with those of AO, therefore the access of AF to the adsorption sites is favored.

Does apolipoprotein E genotype modify the clinical expression of ALS?

BACKGROUND: The presence of the apolipoprotein E (ApoE) 4 genotype is associated with an earlier age of onset for Alzheimer's disease (AD) and several other neurodegenerative disorders. The objective of this study was to investigate the effect of ApoE genotypes on the clinical course of amyotrophic lateral sclerosis (ALS). METHODS: Eight hundred and fifty-two consecutive patients with sporadic ALS evaluated at a tertiary care center were investigated for the effect of ApoE genotype on age of onset, rate of motor disease progression, cognitive functioning, and survival in ALS. RESULTS: The frequencies of individual ApoE genotypes did not differ between patients with ALS and ALS-free Caucasian populations. Patients with different ApoE genotypes did not differ in the age of onset for ALS (years) (ApoE2 = 57.8 ± 13.7, ApoE3 = 57.3 ± 13.7, ApoE4 = 57.7 ± 13.2; P = 0.97), the rate of disease progression (Appel ALS score/month) (ApoE2 = 2.91 ± 2.66, ApoE3 = 2.67 ± 2.66, ApoE4 = 2.61 ± 2.47; P = 0.89), cognitive status (% cognitively impaired) (ApoE2 = 31.7, ApoE3 = 26.8, ApoE4 = 34.3, P = 0.28), or survival in years (ApoE2 = 3.79 ± 3.70, ApoE3 = 3.17 ± 2.27, ApoE4 = 3.05 ± 1.75; P = 0.85). CONCLUSIONS: Our results suggest that ApoE genotype does not modify clinical course of sporadic ALS, in stark contrast to the influence of ApoE genotype on the disease course of AD and other neurodegenerative disorders.

Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI): a modified outcome instrument for cutaneous lupus erythematosus.

BACKGROUND: In 2005, a scoring system (CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index) was developed for patients with cutaneous lupus erythematosus (CLE) to assess disease 'activity' and 'damage'. However, the CLASI does not give an accurate assessment of the severity in all disease subtypes. OBJECTIVES: The main objective of this study was to analyse critically the included parameters of the CLASI and to revise the activity and damage score taking into account various clinical features of the different subtypes of CLE. The revised CLASI (RCLASI) was also validated for use in clinical trials. Patients and methods A RCLASI was designed with regard to the anatomical region (i.e. face, chest, arms) and morphological aspects (i.e. erythema, scaling/hyperkeratosis, oedema/infiltration, scarring/atrophy) of skin lesions and evaluated by nine dermatologists who scored 12 patients with different subtypes of CLE to estimate inter- and intrarater reliability. RESULTS: Reliability studies demonstrated an intraclass correlation coefficient (ICC) for an inter-rater reliability of 0.89 for the activity score [95% confidence interval (CI) 0.79-0.96] and of 0.79 for the damage score (95% CI 0.62-0.92). The ICC for intrarater reliability for the activity score was 0.92 (95% CI 0.89-0.95) and the ICC for the damage score was 0.95 (95% CI 0.92-0.98). CONCLUSIONS: In the present study, a RCLASI was developed by experts, and reliability studies supported the validity and applicability of the revised scoring instrument for CLE. Thus, the RCLASI is a valuable instrument in multicentre studies and for the clinical evaluation of activity and damage in different disease subtypes.

ALS disease onset may occur later in patients with pre-morbid diabetes mellitus.

BACKGROUND: Several metabolic derangements associated with diabetes mellitus type 2 (DM) have been associated with a better outcome in amyotrophic lateral sclerosis (ALS), including hyperlipidemia and obesity. Here, we tested the hypothesis that DM would have a positive effect on the motor and cognitive findings of ALS. METHODS: We compared data from ALS patients with pre-morbid DM (ALS-DM; n = 175) versus without DM (ALS; n = 2196) with regard to the age of onset, rate of motor progression, survival, and neuropsychological test performance. RESULTS: The age of onset was later for women, Caucasians and patients with bulbar-onset ALS. However, we also found that after adjusting for gender, ethnicity and site of onset, DM was associated with a 4-year later onset of ALS (ALS = 56.3, ALS-DM = 60.3, P < 0.05). CONCLUSION: Diabetes mellitus type 2 may delay the onset of motor symptoms in ALS. These findings support other studies suggesting a relationship between the pathophysiology of ALS and metabolic derangements. Further investigations are needed to ascertain whether manipulating metabolic parameters would improve outcomes in ALS.

Frontal-lobe mediated behavioral dysfunction in amyotrophic lateral sclerosis.

BACKGROUND: Cognitive impairment secondary to frontal lobe atrophy exists in 40-60% of Amyotrophic Lateral Sclerosis (ALS) cases. We aimed to determine the prevalence of frontal-lobe mediated behavioral impairment in (ALS) and to ascertain its relationship to cognitive impairment. METHODS: Two-hundred and twenty five patients diagnosed with sporadic ALS were evaluated for behavioral dysfunction using the Frontal Systems Behavior Scale (FrSBe), a validated measure used to examine frontal-lobe mediated behaviors, specifically apathy, executive dysfunction and disinhibition; a total behavior score is also provided. Additionally, a subset of patients also underwent a comprehensive neuropsychological evaluation. RESULTS: Changes in the total FrSBe scores were observed in 24.4% of the patients and 39.6% of the patients had impairment in at least one behavioral domain with symptoms of Apathy being the most common (31.1%). Cognitively impaired ALS patients had worse total (P = 0.05) and apathy scores (P < 0.01); however, behavioral dysfunction was also present in 16% of the cognitively intact patients. Half of the behaviorally intact patients exhibited cognitive impairment. Significant correlations were observed for performance on certain neuropsychological tests (Animal fluency, Block Design, Logical Memory I and Verbal Series Attention Test) and severity of behavioral dysfunction on certain FrSBe sub scores. CONCLUSIONS: Frontal-lobe mediated behavioral dysfunction appears to be common in ALS. Cognitively impaired ALS patients had greater behavioral dysfunction. Recognition of behavioral and cognitive dysfunction may assist health-care providers and care-givers recognize changes in decision-making capacity and treatment compliance of patients with ALS.

Insights into the surface composition and enrichment effects of ionic liquids and ionic liquid mixtures.

A systematic study of ionic liquid surfaces by angle resolved X-ray photoelectron spectroscopy (ARXPS) is presented. By reviewing recent and presenting new results for imidazolium-based ionic liquids (ILs), we discuss the impact of chemical differences on surface composition and on surface enrichment effects. (1) For the hydrophilic ethylene glycol (EG) functionalised ILs [Me(EG)MIm][Tf(2)N], [Et(EG)(2)MIm][Tf(2)N] and [Me(EG)(3)MIm][Tf(2)N], which vary in the number of ethylene glycol units (from 1 to 3), we find that the surface composition of the near-surface region is in excellent agreement with the bulk composition, which is attributed to attractive interactions between the oxygen atoms on the cation to the hydrogen atoms on the imidazolium ring. (2) For [C(n)C(1)Im][Tf(2)N] (where n = 1-16), i.e. ILs with an alkyl chain of increasing length, an enrichment of the aliphatic carbons is observed for longer chains (n > 2), at the expense of the polar cation head groups and the anions in the first molecular layer, both of which are located approximately at the same distance from the outer surface. (3) To study the influence of the anion on the surface enrichment, we investigated ten ILs [C(8)C(1)Im][X] with the same cation, but very different anions [X](-). In all cases, surface enrichment of the cation alkyl chains is found, with the degree of enrichment decreasing with increasing size of the anion, i.e., it is most pronounced for the smallest anions and least pronounced for the largest anions. (4) For the IL mixture [C(2)C(1)Im][Tf(2)N] and [C(12)C(1)Im][Tf(2)N] we find a homogeneous distribution in the outermost surface region with no specific enrichment of the [C(12)C(1)Im](+) cation.

Influence of different substituents on the surface composition of ionic liquids studied using ARXPS.

Angle resolved X-ray photoelectron spectroscopy has been used to study the surface composition of various nonfunctionalized and functionalized 1,3-dialkylimidazolium ionic liquids. For [CnC1Im][Tf2N] (where n = 2-16), an enrichment of the aliphatic carbon was observed for longer chains (n > or = 4). Enrichment of the aliphatic carbon also occurs for alkyl chains attached to the anion, as observed for [C2C1Im][OcOSO3]. Oligo(ethyleneglycol)ether (PEG) functionalities in the cation lead to a surface composition close to bulk stoichiometry and thus a loss in enrichment of the chains. This effect is attributed to attractive interactions between the oxygen atoms on the cation to the hydrogen atoms on the imidazolium ring for [Et(EG)2MIm] [Tf2N] and [Me(EG)3MIm][Tf2N].

Influence of different anions on the surface composition of ionic liquids studied using ARXPS.

Angle-resolved X-ray photoelectron spectroscopy has been used to study the influence of different types of anions on the surface composition of ionic liquids (ILs). We have investigated nine ILs with the same cation, 1-octyl-3-methylimidazolium [C(8)C(1)Im](+), but very different anions. In all cases, an enrichment of the cation alkyl chains is found at the expense of the polar cation head groups and the anions in the first molecular layer. This enhancement effect decreases with increasing size of the anion, which means it is most pronounced for the smallest anions and least pronounced for the largest anions. A simple model is proposed to explain the experimental observations.

Probing individual quantum dots: noise in self-assembled systems.

In this work we explore the noise characteristics in lithographically-defined two terminal devices containing self-assembled InAs/InP quantum dots. The experimental ensemble of InAs dots show random telegraph noise (RTN) with tuneable relative amplitude-up to 150%-in well defined temperature and source-drain applied voltage ranges. Our numerical simulation indicates that the RTN signature correlates with a very low number of quantum dots acting as effective charge storage centres in the structure for a given applied voltage. The modulation in relative amplitude variation can thus be associated to the altered electrostatic potential profile around such centres and enhanced carrier scattering provided by a charged dot.