Validation of the ACSID-11 for consistent screening of specific Internet-use disorders based on ICD-11 criteria for gaming disorder: A multitrait-multimethod approach.

INTRODUCTION: With the inclusion of gaming disorder in the ICD-11, diagnostic criteria were introduced for this relatively new disorder. These criteria may be applied to other potential specific Internet-use disorders. The 11-item Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) was developed for consistent screening of gaming disorder, online buying-shopping disorder, online pornography-use disorder, social networks-use disorder, and online gambling disorder. This study tested the construct validity of the ACSID-11, including convergent and divergent measures. METHODS: The ACSID-11 measures five behavioral addictions with the same set of items by following the principles of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The ACSID-11 was administered to a convenience sample of active Internet users (N = 1597) together with validated and established measures of each specific Internet-use disorder along with screeners for mental health. Included are the Ten-Item Internet Gaming Disorder Test (IGDT-10), the Bergen Shopping Addiction Scale (BSAS), the Problematic Pornography Consumption Scale (PPCS), the Bergen Social Media Addiction Scale (BSMAS) and the Berlin Inventory of Gambling behavior - Screening (BIG-S). The ACSID-11 was compared convergently and divergently through a multitrait-multimethod approach along with contingency tables with the other Internet-use disorder screeners. RESULTS: The multitrait-multimethod results shows that each behavior assessed with the ACSID-11 has moderate to strong correlations (r's from 0.462 to 0.609) with the scores of the corresponding established measures and, furthermore, positive correlations (r's from 0.122 to 0.434) with measures of psychological distress and further shows that the ACSID-11 can be used for a comprehensive assessment of different behaviors. The contingency tables reveal large divergences between the ACSID-11 and other screening instruments concerning the classification of problematic specific Internet use based on the given cut-off values. CONCLUSION: The current work provides additional validation for the ACSID-11. Accordingly, this tool can be considered as reliable and valid for the simultaneous assessment of different Internet-use disorders: gaming disorder, online buying-shopping disorder, online pornography use disorder, social networks use disorder, and online gambling disorder. With a subsequent clinical validation of the scale and the proposed cut-off score, the ACSID-11 will be a thoroughly validated useful screening tool for clinical practice.

Lockdown, a selective small-molecule inhibitor of the integrin phosphatase PPM1F, blocks cancer cell invasion.

Phosphatase PPM1F is a regulator of cell adhesion by fine-tuning integrin activity and actin cytoskeleton structures. Elevated expression of this enzyme in human tumors is associated with high invasiveness, enhanced metastasis, and poor prognosis. Thus, PPM1F is a target for pharmacological intervention, yet inhibitors of this enzyme are lacking. Here, we use high-throughput screening to identify Lockdown, a reversible and non-competitive PPM1F inhibitor. Lockdown is selective for PPM1F, because this compound does not inhibit other protein phosphatases in vitro and does not induce additional phenotypes in PPM1F knockout cells. Importantly, Lockdown-treated glioblastoma cells fully re-capitulate the phenotype of PPM1F-deficient cells as assessed by increased phosphorylation of PPM1F substrates and corruption of integrin-dependent cellular processes. Ester modification yields LockdownPro with increased membrane permeability and prodrug-like properties. LockdownPro suppresses tissue invasion by PPM1F-overexpressing human cancer cells, validating PPM1F as a therapeutic target and providing an access point to control tumor cell dissemination.

Severe polymicrobial and fungal periprosthetic osteomyelitis persisting after hip disarticulations treated with caspofungin in risk patients: a case series.

BACKGROUND: Periprosthetic fungal infections are considered rare and opportunistic infections. Treatment is difficult, and established standards do not yet exist. The choice of the appropriate antifungal drug might affect the patient outcome. CASES: All the three cases presented showed polybacterial recurrent infection of the revision hip arthroplasty. All patients were of younger age, had multiple revisions of the endoprosthesis, each had a large partial femoral replacement greater than 40% of the femoral length, gentamycin-loaded cement, and a long anchoring distance of the used intramedullary stem. Due to the severe life-threatening infection with deep osteomyelitis, an amputation had to be performed. However, despite surgical intervention, the fungal dominated infection persisted. Finally, only the use of caspofungin allowed permanent infection control. CONCLUSION: The polybacterial infection is driven by the symbiosis between fungi and bacteria. Therefore, eradication of the fungus is required to achieve elimination of the bacteria. Antimycotics of the echinocandin-class, such as caspofungin, may be considered as initial treatment.

A Randomized Study of Food Pictures-Influenced Decision-Making Under Ambiguity in Individuals With Morbid Obesity.

BACKGROUND AND AIMS: In addition to craving responses to salient food cues, the anticipation of short-term rewarding consumption of palatable food may overrun the anticipation of long-term negative consequences of obesity. The present investigation addressed the potential interplay of food cravings and decision-making abilities in individuals with obesity. METHOD: Study 1 included 107 bariatric surgery candidates with class 2/3 obesity (OB-group) and study 2 included 54 individuals with normal weight/pre-obesity (nonOB-group). In both studies, standardized questionnaires concerning food cravings, food addiction, and psychopathology were administered. A cue-reactivity paradigm was used to measure craving responses toward semi-individualized images of highly palatable, processed food/fruit (appetitive food cues) compared to images of raw vegetables (non-appetitive food cues). Decision-making was measured with a modified computerized version of the Iowa Gambling Task (IGT) with food pictures. Both groups were divided into two subgroups that were randomized to different IGT conditions. In one IGT condition the advantageous IGT card decks were covered by pictures of palatable, processed food or fruit and the disadvantageous decks by images of raw vegetables (= congruent condition), and in the other IGT condition vice versa. RESULTS: Participants in the OB-group admitted on average higher craving responses toward palatable, processed food or fruit cues compared to pictures of raw vegetables. This was not the case in the nonOB-group. Contrary to our hypothesis, decision-making performance in both groups was worse when pictures of palatable, processed food or fruit were associated with advantageous IGT card decks compared to performance when those pictures were linked to the disadvantageous decks. The interference effect of food pictures processing on advantageous decision-making has been observed particularly in those individuals of the OB-group who exhibited high craving responses toward palatable, processed food cues or high levels of food addiction. DISCUSSION: The results indicate that food pictures processing interferes with decision-making, regardless of weight status. Opposed to the hypothesis, stronger tendencies to avoid than to approach pictures presenting processed, tasty food were observed. Further research should examine how cognitive avoidance tendencies toward processed, high energy food and approach tendencies toward healthy food can be transferred to real life situations.

The Cards and Lottery Task: Validation of a New Paradigm Assessing Decision Making Under Risk in Individuals With Severe Obesity.

BACKGROUND: A growing body of research demonstrated impaired executive functions in individuals with severe obesity, including increased sensitivity to reward and impulsive decision making under risk conditions. For the assessment of decision making in patients with severe obesity, studies widely used the Iowa Gambling Task (IGT) or the Delay Discounting Task (DDT), which cover short-term or long-term consequences of decisions only. A further development originating from the field of addiction research is the Cards and Lottery Task (CLT), in which each decision made has conflicting immediate and long-term consequences at the same time. The present study aimed to validate the CLT in individuals with severe obesity. METHODS: Patients with severe obesity (N = 78, 67% women, 42.9 ± 10.4 years old, body mass index of 48.1 ± 8.3 kg/m2) were included. Convergent validity was evaluated using the computerized Delay Discounting Task and well-established self-report questionnaires assessing different aspects of impulsivity. For discriminant validity, CLT performance was compared between symptom groups characterized by high versus low impulsivity. The task's clinical validity was evaluated based on associations with general and eating disorder psychopathology, and body mass index. Test-retest reliability was determined by administering the CLT in n = 31 participants without weight-loss treatment one year later. The task's sensitivity to change due to weight loss was evaluated by retesting n = 32 patients one year after receiving obesity surgery. RESULTS: The number of advantageous decisions in the CLT was significantly positively associated with delay discounting and effortful control, and significantly negatively correlated with behavioral impulsivity. CLT performance differed significantly between individuals with and without symptoms of attention-deficit/hyperactivity disorder and between samples with severe obesity and healthy controls. Clinically, CLT performance was significantly associated with general, but not eating disorder psychopathology. The CLT showed moderate test-retest reliability after one year in weight-stable individuals and was sensitive to change in those undergoing obesity surgery. CONCLUSIONS: This study identified the CLT to be a highly promising, new complex measure of short- and long-term decision making with good reliability and validity in individuals with severe obesity. Future studies should assess its association with the IGT and predictive value for real-life health behavior.

Changes in visual attention towards food cues after obesity surgery: An eye-tracking study.

Research documented the effectiveness of obesity surgery (OS) for long-term weight loss and improvements in medical and psychosocial sequelae, and general cognitive functioning. However, there is only preliminary evidence for changes in attentional processing of food cues after OS. This study longitudinally investigated visual attention towards food cues from pre- to 1-year post-surgery. Using eye tracking (ET) and a Visual Search Task (VST), attentional processing of food versus non-food cues was assessed in n = 32 patients with OS and n = 31 matched controls without weight-loss treatment at baseline and 1-year follow-up. Associations with experimentally assessed impulsivity and eating disorder psychopathology and the predictive value of changes in visual attention towards food cues for weight loss and eating behaviors were determined. During ET, both groups showed significant gaze duration biases to non-food cues without differences and changes over time. No attentional biases over group and time were found by the VST. Correlations between attentional data and clinical variables were sparse and not robust over time. Changes in visual attention did not predict weight loss and eating disorder psychopathology after OS. The present study provides support for a top-down regulation of visual attention to non-food cues in individuals with severe obesity. No changes in attentional processing of food cues were detected 1-year post-surgery. Further studies are needed with comparable methodology and longer follow-ups to clarify the role of biased visual attention towards food cues for long-term weight outcomes and eating behaviors after OS.

Downgrading of type 2 diabetes mellitus (T2DM) after obesity surgery: duration and severity matter.

BACKGROUND: There is overwhelming evidence for the antidiabetic effect of obesity surgery, but few reports involve objective longitudinal measurements of severity of type-2 diabetes mellitus (T2DM). This study applies a grading scheme and analyses the prognostic impact of routine clinical factors. MATERIAL AND METHODS: This retrospective study includes 77 obese diabetic patients with a preoperative BMI of 48.9 ± 7.8 kg/m(2) who underwent gastric banding (n = 4), Roux-en-Y gastric bypass (n = 57), or sleeve gastrectomy (n = 16) between 2007 and 2013. A 6-point scoring system graded the level of antidiabetic therapy. Downgrading was calculated from the difference between pre- and postoperative grades. RESULTS: Downgrading reached its maximum at 3 months well before maximal weight loss: one grade in 6 (8 %) patients, two grades in 36 (47 %) patients, and three or more grades in 20 (26 %) patients. Age, gender, and preoperative weight had no impact on downgrading. There were no significant differences between gastric banding (median 1; 0-2), gastric bypass (median 2; 0-5), and sleeve gastrectomy (median 2; 0-4). Preoperative duration of T2DM and its severity grade were independent prognostic factors in multivariate analysis. The rate of patients who could discontinue insulin was more than 80 % when the duration of preexisting T2DM was less than 5 years as compared to 62 % when the duration was more than 5 years. CONCLUSION: The severity of T2DM downgrades in most patients within the initial period of postoperative weight loss. Downgrading increases with shorter duration and lower severity grade of pre-existing T2DM.

Torticollis under cyclobenzaprine.

The muscle-relaxing 5-HT(2) receptor antagonist cyclobenzaprine is structurally closely related to amitriptyline. It is widely used to treat patients presenting with back pain and fibromyalgia. Very rarely cyclobenzaprine toxicity can result in extrapyramidal symptoms, but occurrence of torticollis has not been reported so far. We report on a patient presenting with torticollis and myoclonic movements after treatment with cyclobenzaprine, who was successfully treated with intravenous biperiden. This case might be additional evidence for the necessity of appropriate dosage in case of liver impairment. Secondly there are possibly consequences as regards the therapy of motor side effects.

Differentiation of angiogenic burden in human cancer xenografts using a perfusion-type optical contrast agent (SIDAG).

INTRODUCTION: Use of fluorescence imaging in oncology is evolving rapidly, and nontargeted fluorochromes are currently being investigated for clinical application. Here, we investigated whether the degree of tumour angiogenesis can be assessed in vivo by planar and tomographic methods using the perfusion-type cyanine dye SIDAG (1,1'-bis- [4-sulfobutyl]indotricarbocyanine-5,5'-dicarboxylic acid diglucamide monosodium). METHOD: Mice were xenografted with moderately (MCF7, DU4475) or highly vascularized (HT1080, MDA-MB435) tumours and scanned up to 24 hours after intravenous SIDAG injection using fluorescence reflectance imaging. Contrast-to-noise ratio was calculated for all tumours, and fluorochrome accumulation was quantified using fluorescence-mediated tomography. The vascular volume fraction of the xenografts, serving as a surrogate marker for angiogenesis, was measured using magnetic resonance imaging, and blood vessel profile (BVP) density and vascular endothelial growth factor expression were determined. RESULTS: SIDAG accumulation correlated well with angiogenic burden, with maximum contrast to noise ratio for MDA-MB435 (P < 0.0001), followed by HT1080, MCF7 and DU4475 tumours. Fluorescence-mediated tomography revealed 4.6-fold higher fluorochrome concentrations in MDA-MB435 than in DU4475 tumours (229 +/- 90 nmol/l versus 49 +/- 22 nmol/l; P < 0.05). The vascular volume fraction was 4.5-fold (3.58 +/- 0.9% versus 0.8 +/- 0.53%; P < 0.01), blood vessel profile density 5-fold (399 +/- 36 BVPs/mm2 versus 78 +/- 16 BVPs/mm2) and vascular endothelial growth factor expression 4-fold higher for MDA-MB435 than for DU4475 tumours. CONCLUSION: Our data suggest that perfusion-type cyanine dyes allow assessment of angiogenesis in vivo using planar or tomographic imaging technology. They may thus facilitate characterization of solid tumours.

Special conditions allow binding of the siderophore salmochelin to siderocalin (NGAL-lipocalin).

Siderocalin is part of the innate immune system and is secreted by epithelial cells in the early stages of inflammation. This protein binds catecholate siderophores such as enterobactin with high affinity. As a consequence, the iron supply and growth of the siderophore-producing bacteria is disturbed. Recombinant siderocalin isolated from strains of Escherichia coli K-12 contained bound enterobactin. Very low amounts of siderocalin were isolated from another K-12 strain unable to produce enterobactin, which indicated that enterobactin might stabilize the recombinant protein. Siderocalin isolated from E. coli strain Nissle 1917, which produces the glucosylated enterobactin salmochelin, contained a mixture of bound salmochelin (55%) and enterobactin (45%). The growth of an enterobactin-producing E. coli K-12 strain but not of the same strain carrying a plasmid encoding iroBCDEN and therefore able to produce salmochelin was suppressed when siderocalin was added to the medium, which indicated that salmochelin is bound by siderocalin before siderocalin folds into its final conformation in the cell, and that binding of salmochelin to matured siderocalin is not possible. Salmochelin is mainly produced by pathogenic enterobacteria. Glucosylation of enterobactin may be a mechanism by which these bacteria evade trapping of the enterobactin by siderocalin.

A fetal sheep liver extract containing immunostimulatory substances including LPS acts as leukocyte activator in cells of LPS responder and non responder mice.

Purified fractions from a fetal sheep liver extract (FSLE) were investigated, in a murine model, for induction of leukocyte stimulating activities. The fractions FSLE-1 and FSLE-2 induced splenocyte proliferation in vitro in C57Bl/10ScSn (LPS responder) mice comparable to LPS, and in C57Bl/10ScCr (LPS non responder) mice. They also stimulated the release of nitrogen radicals in bone marrow-derived macrophages (BMDM) from several mouse inbred strains including both C57Bl/10ScSn and C57Bl/10ScCr mice. Stimulation of NO production could be blocked by L-NMMA, an inhibitor of iNOS, and enhanced by the simultaneous addition of IFN-gamma. Moreover, stimulation of macrophages by FSLE-1 and FSLE-2 induced a cytostatic effect of the activated macrophages for Abelson 8-1 tumor cells. The stimulatory activity of the purified fractions is partially due to trace amounts of LPS derived from the fetal liver extract which was enriched during purification. Our results may help to explain the beneficial effect of the extract in patients which has been observed clinically.

Combination of enoxaparin and fibroblast growth factor-1 increases myocardial blood flow and capillary density after myocardial infarction in rabbits.

OBJECTIVE: The effect of enoxaparin and fibroblast growth factor-1 (FGF-1) on post-infarction capillary density and regional myocardial blood flow (RMBF) was examined. METHODS: New Zealand White rabbits received an intramyocardial injection of either physiological saline, FGF-1 + enoxaparin, FGF-1 or enoxaparin directly after ligation of the left anterior descending artery. RMBF and capillary density were investigated using fluorescent microspheres and histological examination. RESULTS: One week after infarction a significant difference in the number of capillaries could be demonstrated within the FGF-1 + enoxaparin group (p < 0.001 versus the control group), the FGF-1 group (p < 0.01) and the enoxaparin group (p < 0.05). Treatment with FGF-1 + enoxaparin resulted in a significantly increased number of capillaries compared to treatment with FGF-1 (p < 0.05) and enoxaparin (p < 0.05) alone. Additionally, all groups treated with FGF-1 and/or enoxaparin showed a significant increase of microvessel density in the treated ischemic border zone compared to the non-treated ischemic border zone (p < 0.001 for FGF-1 + enoxaparin, p < 0.01 for FGF-1, p < 0.05 for enoxaparin). RMBF was significantly increased within the FGF-1 + enoxaparin group compared to the control group (p < 0.05). Moreover, perfusion rates within the FGF-1 + enoxaparin-treated area did not significantly differ from the pre-infarction values. CONCLUSION: Treatment with either enoxaparin or FGF-1 or FGF-1 + enoxaparin resulted in increased microvessel growth. However, only the combination of enoxaparin with FGF-1 promotes capillary growth and RMBF. Thus, we conclude that enoxaparin enhances the angiogenic potential of intramyocardially injected FGF-1 in the acutely infarcted rabbit heart.

Triacyl-lipopentapeptide adjuvants: TLR2-dependent activation of macrophages and modulation of receptor-mediated cell activation by altering acyl-moieties.

Synthetic lipopeptides derived from bacterial lipoprotein are efficient immunoadjuvants. In vitro they activate antigen presenting cells (APCs) to induce the translocation of nuclear factor kappa B (NF-kappaB) and the activation of further transcription factors. This results in the expression of genes encoding cytokines such as IL-1, IL-6, TNF-alpha and in the release of reactive oxygen/nitrogen intermediates. The molecular structure of microbial products determines TLR specificity and thus their activatory potential and immunoadjuvanticity. In the present study, we investigated the lipopeptide-induced activation of leukocytes at different cellular levels by applying derivatives of a synthetic lipopentapeptide-fatty acid library. Our results show that TLR2 plays a key role for the activation of bone marrow-derived macrophages (BMDMs) by lipopentapeptide derivatives and that the fatty acid composition of the lipopeptides determines their activation potential and TLR specificity.