The effects of hypothetical behavioral interventions on the 13-year incidence of overweight/obesity in children and adolescents.

BACKGROUND: In view of the high burden of childhood overweight/obesity (OW/OB), it is important to identify targets for interventions that may have the greatest effects on preventing OW/OB in early life. Using methods of causal inference, we studied the effects of sustained behavioral interventions on the long-term risk of developing OW/OB based on a large European cohort. METHODS: Our sample comprised 10 877 children aged 2 to < 10 years at baseline who participated in the well-phenotyped IDEFICS/I.Family cohort. Children were followed from 2007/08 to 2020/21. Applying the parametric g-formula, the 13-year risk of developing OW/OB was estimated under various sustained hypothetical interventions on physical activity, screen time, dietary intake and sleep duration. Interventions imposing adherence to recommendations (e.g. maximum 2 h/day screen time) as well as interventions 'shifting' the behavior by a specified amount (e.g. decreasing screen time by 30 min/day) were compared to 'no intervention' (i.e. maintaining the usual or so-called natural behavior). Separately, the effectiveness of these interventions in vulnerable groups was assessed. RESULTS: The 13-year risk of developing OW/OB was 30.7% under no intervention and 25.4% when multiple interventions were imposed jointly. Meeting screen time and moderate-to-vigorous physical activity (MVPA) recommendations were found to be most effective, reducing the incidence of OW/OB by -2.2 [-4.4;-0.7] and -2.1 [-3.7;-0.8] percentage points (risk difference [95% confidence interval]), respectively. Meeting sleep recommendations (-0.6 [-1.1;-0.3]) had a similar effect as increasing sleep duration by 30 min/day (-0.6 [-0.9;-0.3]). The most effective intervention in children of parents with low/medium educational level was being member in a sports club; for children of mothers with OW/OB, meeting screen time recommendations and membership in a sports club had the largest effects. CONCLUSIONS: While the effects of single behavioral interventions sustained over 13 years were rather small, a joint intervention on multiple behaviors resulted in a relative reduction of the 13-year OW/OB risk by between 10 to 26%. Individually, meeting MVPA and screen time recommendations were most effective. Nevertheless, even under the joint intervention the absolute OW/OB risk remained at a high level of 25.4% suggesting that further strategies to better prevent OW/OB are required.

Dietary calcium intake and adiposity in children and adolescents: Cross-sectional and longitudinal results from IDEFICS/I.Family cohort.

BACKGROUND AND AIMS: Studies in children and adolescents suggest that higher dairy consumption may exert a protective effect on adiposity. However, only few studies examined the association between dietary calcium intake and body mass measures with conflicting results. We evaluated the association between total dietary calcium, calcium from dairy and non-dairy sources and anthropometric indices in a large European cohort of children and adolescents. METHODS AND RESULTS: As many as 6,696 children belonging to the IDEFICS study were eligible for the cross-sectional analysis (Boys = 51%; age 6.0 ± 1.8 years; mean ± SD). Of these, 2,744 were re-examined six years later (Boys = 49.6%; age = 11.7 ± 1.8 years) in the framework of the I.Family study. The exposures were the baseline energy-adjusted total, dairy and non-dairy calcium intakes measured by a validated 24-h dietary recall. Multivariable linear regression was used to determine the association between calcium intake and z-scores of anthropometric indices (body mass index, BMI; waist circumference, WC; sum of skinfolds, SS; fat mass index, FMI) at baseline, and their variation over the 6 years follow-up. The association of dietary calcium with the incidence of overweight/obesity was also assessed. At baseline, an inverse association between total calcium intake and all the adiposity indices was consistently observed in boys, while only SS and FMI were significant in girls. The prevalence of overweight/obesity decreased significantly (P < 0.0001) across tertiles of calcium intake, in both sexes. Over the follow-up, boys with higher baseline calcium intake value showed significantly lower increase in BMI, WC and FMI z-scores, while in girls only a lower increase in WC z-score was observed. Only in boys, the risk to become overweight/obese decreased significantly across tertiles of calcium intake. Similar results were observed by analyzing only dietary calcium from dairy, while no association was observed between non-dairy calcium and adiposity indices. CONCLUSIONS: We showed in a large cohort of European children and adolescents that dietary calcium intake may play a role in the modulation of body fat in developmental age. The association between dietary calcium and adiposity indices was driven by dairy calcium, while no effect was observed for non-dairy calcium intake. The existence of a sex-related difference in the association deserves further investigations.

Initial experiences with the Hemopatch® as a hemostatic agent in zero-ischemia partial nephrectomy.

PURPOSE: Nephron-sparing surgery (NSS) is the gold standard treatment for resectable renal tumors. In the last decade, laparoscopic partial nephrectomy (LPN) has evolved in technical, surgical and oncological aspects and is an accepted treatment option for local-stage renal tumors. Improvements in not only surgical techniques, but also potent hemostats have encouraged this evolution. Here, we report our initial experiences with a new hemostatic agent, Hemopatch(®) (polyethylene glycol-coated collagen patch, Baxter), in zero-ischemia LPN. METHODS: Seven patients with confirmed renal masses were enrolled and subjected to zero-ischemia LPN. In all cases, Hemopatch(®) was applied to the tumor resection site after suturing of the renal parenchyma. The following clinical data were captured for analysis: staging information, PADUA and RENAL nephrometry scores, operation time, blood loss, complications, pathology and hospitalization length. RESULTS: The median tumor size was 30.0 mm (range 9.5-72). The median PADUA and RENAL nephrometry scores were 6 (range 6-7) and 4 (range 4-6), respectively. All LPNs were performed with the zero-ischemia technique. In six of the seven patients, parenchymal suturing of the resection site was performed. No uncontrolled bleeding was observed. The median operation duration was 139 min (range 103-194), the median blood loss was 325 cc (range 50-700) and the median hospitalization length was 6 days (range 4-7). Hemopatch(®) provided sufficient hemostasis in all cases. No postoperative complications were observed. CONCLUSIONS: Although this study is limited to a small set of initial experiences with Hemopatch(®) in LPN, it proves the feasibility and reliability of this new hemostat. Following further evaluation in prospective randomized comparative studies, Hemopatch(®) might represent a promising tool in NSS.

C-reactive protein reference percentiles among pre-adolescent children in Europe based on the IDEFICS study population.

OBJECTIVES: C-reactive protein (CRP) is involved in a wide range of diseases. It is a powerful marker for inflammatory processes used for diagnostic and monitoring purposes. We aimed to establish reference values as data on the distribution of serum CRP levels in young European children are scarce. SUBJECTS: Reference values of high-sensitivity CRP concentrations were calculated for 9855 children aged 2.0-10.9 years, stratified by age and sex. The children were recruited during the population-based European IDEFICS study (Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and infantS) with 18 745 participants recruited from 2007 to 2010. RESULTS: In 44.1% of the children, CRP values were below or equal the detection limit of 0.2 mg/l. Median CRP concentrations showed a slight negative age trend in boys and girls, whereas serum CRP values were slightly higher in girls than in boys across all age groups. CONCLUSIONS: Our population-based reference values of CRP may guide paediatric practice as elevated values may require further investigation or treatment. Therefore, the presented reference values represent a basis for clinical evaluation and for future research on risk assessment of diseases associated with increased CRP levels among children.

Reference values of whole-blood fatty acids by age and sex from European children aged 3-8 years.

OBJECTIVES: To establish reference values for fatty acids (FA) especially for n-3 and n-6 long-chain polyunsaturated FAs (LC PUFA) in whole-blood samples from apparently healthy 3-8-year-old European children. The whole-blood FA composition was analysed and the age- and sex-specific distribution of FA was determined. DESIGN AND SUBJECTS: Blood samples for FA analysis were taken from 2661 children of the IDEFICS (identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study cohort. Children with obesity (n=454) and other diseases that are known to alter the FA composition (n=450) were excluded leaving 1653 participants in the reference population. MEASUREMENTS: The FA composition of whole blood was analysed from blood drops by a rapid, validated gas chromatographic method. RESULTS: Pearson correlation coefficients showed an age-dependent increase of C18:2n-6 and a decrease of C18:1n-9 in a subsample of normal weight boys and girls. Other significant correlations with age were weak and only seen either in boys or in girls, whereas most of the FA did not show any age dependence. For age-dependent n-3 and n-6 PUFA as well as for other FA that are correlated with age (16:0, C18:0 and C18:1n-9) percentiles analysed with the general additive model for location scale and shape are presented. A higher median in boys than in girls was observed for C20:3n-6, C20:4n-6 and C22:4n-6. CONCLUSIONS: Given the reported associations between FA status and health-related outcome, the provision of FA reference ranges may be useful for the interpretation of the FA status of children in epidemiological and clinical studies.

ramR mutations in clinical isolates of Klebsiella pneumoniae with reduced susceptibility to tigecycline.

Five Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline (MIC, 2 microg/ml) were analyzed. A gene homologous to ramR of Salmonella enterica was identified in Klebsiella pneumoniae. Sequencing of ramR in the nonsusceptible Klebsiella strains revealed deletions, insertions, and point mutations. Transformation of mutants with wild-type ramR genes, but not with mutant ramR genes, restored susceptibility to tigecycline and repressed overexpression of ramA and acrB. Thus, this study reveals a molecular mechanism for tigecycline resistance in Klebsiella pneumoniae.

Potentially modifiable determinants of malnutrition in older adults: A systematic review.

BACKGROUND & AIMS: Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults. METHODS: A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence. RESULTS: Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition. CONCLUSION: There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly ageing population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition.

Effects of combined supplementation with B vitamins and antioxidants on plasma levels of asymmetric dimethylarginine (ADMA) in subjects with elevated risk for cardiovascular disease.

Elevated plasma asymmetric dimethylarginine (ADMA) concentrations have been suggested as a potential risk factor for cardiovascular disease (CVD). Studies indicate a linkage between hyperhomocysteinemia, oxidative stress and ADMA metabolism. We tested the hypothesis that combined supplementation of B vitamins and antioxidants reduces ADMA concentrations in subjects with at least two CVD risk factors. A total of 123 men and women (58+/-8.1 years) were randomly assigned to take either a preparation including B vitamins and antioxidants (verum) or placebo for 6 months in a double-blind design. Blood concentrations of ADMA, symmetric dimethylarginine (SDMA), L-arginine, B vitamins, total homocysteine (tHcy), alpha-tocopherol, antioxidant capacity (TEAC), and oxLDL were measured pre- and post-intervention. Treatment with verum significantly decreased tHcy (-2.14 micromol/L; P<0.001) and significantly increased TEAC values (+39.3 microM; P<0.022), but no effect on ADMA was observed. OxLDL was significantly reduced in verum (-7.3 U/L; P=0.001) and placebo (-9.2U/L; P<0.001). At baseline, significant correlations were found only between ADMA and SDMA (r=0.281; P=0.002), L-arginine/ADMA and SDMA (r=-0.294; P<0.001), L-arginine/ADMA and oxLDL (r=-0.281; P=0.016), and L-arginine/ADMA and age (r=-0.231; P=0.010). Our results indicate that combined supplementation of B vitamins and antioxidants is not an adequate strategy to reduce ADMA plasma levels in subjects with elevated CVD risk.

Cleavage of SNAP-25 ameliorates cancer pain in a mouse model of melanoma.

BACKGROUND: Cancer pain is associated with increased pain sensitivity to noxious (hyperalgesia) and normally innocuous (allodynia) stimuli due to activation of nociceptors by tumour-derived mediators or tumour infiltration of nerves. The pain sensitization is accompanied by modifications in gene expression, but specifically regulated genes are largely unknown. The 25 kDa synaptosomal-associated protein (SNAP-25) is involved in chemical neurotransmission at the synaptic cleft. Its inhibition by Botulinum neurotoxin A (BoNT/A) has been associated with antinociceptive effects in migraine, inflammatory and neuropathic pain. However, its potential to reduce tumour-associated pain remains to be clarified. METHODS: We applied a melanoma model of tumour pain in C57BL/6 mice and investigated SNAP-25 expression and regulation by qRT-PCR, Western Blot and immunofluorescence as well as tumour-associated mechanical allodynia with and without BoNT/A treatment. RESULTS: We found increased SNAP-25 expression in the dorsal root ganglia and the sciatic nerve. Intraplantar injection of BoNT/A induced the cleavage of SNAP-25 in these tissues and was associated with decreased mechanical allodynia after therapeutic treatment at early and late stages of tumour pain while the tumour size was not affected. CONCLUSIONS: Our data indicate that SNAP-25 plays a role in tumour pain but has no influence on the initiation and progression of skin cancer. Its cleavage inhibits the development of allodynia in the mouse melanoma model and might be useful as new therapeutic approach for the treatment of cancer pain. WHAT DOES THIS STUDY ADD?: SNAP-25 is differentially regulated during melanoma-induced tumour pain. Its cleavage by BoNT/A might be a suitable therapeutic option for tumour pain patients since tumour-associated pain can be strongly and significantly reduced after preventive and therapeutic BoNT/A treatment, respectively.

Blood fatty acid composition in relation to allergy in children aged 2-9 years: results from the European IDEFICS study.

BACKGROUND/OBJECTIVES: Blood polyunsaturated fatty acids (PUFA) are involved in allergy development, but the etiological role of n-6 and n-3 PUFA is still controversial. A European multicenter study of children (IDEFICS) provided the opportunity to explore the cross-sectional association between fatty acids (FA) and allergy. SUBJECTS/METHODS: Blood FA levels were measured in 2600 children aged 2-9 years and were recorded as the percentage of weight of all FA detected. Logistic regression of allergy status on FA components was adjusted for age, sex, country, body mass index, family history of allergic disease, breast-feeding, and number of siblings. The results were given as odds ratios (OR) for current vs no allergy ever and an increase in FA by 1 s.d. RESULTS: Overall, higher proportions of n-6 PUFA were associated with higher odds of allergy (OR=1.21 (1.05, 1.40)). Monounsaturated FA (MUFA) were associated with reduced risk for allergy (OR=0.75 (0.65, 0.87)), whereas saturated FA did not differ by allergy status. The strongest associations were observed in children <4 years old, with ORs of allergy given as 1.62 (1.15, 2.29) for n-3 PUFA and 0.63 (0.42, 0.95) for MUFA. With regard to individual FA, these associations were independently observed for docosapentaenoic acid (22:5 n-3) and oleic acid (18:1 n-9). CONCLUSIONS: Both PUFA subtypes were positively associated with allergy in an age-dependent manner, whereas MUFA was associated with less allergy. The observation of high proportions of n-3 PUFA in allergic children younger than 4 years might help to understand the nature of early onset of atopic disease.

Selenium and antioxidant vitamin status of elderly German women.

OBJECTIVE: Low antioxidant intake and status have been shown to be associated with an elevated risk for various diseases. Data on the status of antioxidant vitamins, selenium and coenzyme Q10 of younger female seniors are scarce. The aim of this study was to assess the status of these antioxidants, as well as influencing factors such as dietary intake, anthropometric data and educational level in female seniors (60-70 years) in Germany. DESIGN: Dietary intake of alpha-tocopherol, beta-carotene and ascorbic acid was determined by a 3-day diet record. Serum concentrations of alpha-tocopherol, beta-carotene, ascorbic acid, selenium and coenzyme Q10 were measured. Anthropometric measures, socioeconomic and educational status were assessed. SETTING: In total, 178 elderly women without severe diseases in the region of Hannover, Germany, were included in the study. The mean (+/- s.d.) age and BMI of the women was 63.2 (2.73) years and 25.6 (3.77) kg/m2, respectively. The study participants were generally better educated than the overall German female population. RESULTS: Dietary intake of the ascorbic acid and alpha-tocopherol was below RDA in six and 75% of the women, respectively. In comparison to estimated desirable serum concentrations of alpha-tocopherol, ascorbic acid, beta-carotene and selenium, lower concentrations were found in 23, 1, 6, and 39% of the women, respectively. Ascorbic acid (r = 0.205, P = 0.009) and beta-carotene (r = 0.173, P = 0.025) intake were significantly associated with serum concentrations. Beta-carotene concentrations were influenced by the type of diet, BMI, and school education (R2 = 0.128, P < 0.001). Serum selenium was positively associated with alcohol intake (r = 0.229, P = 0.003). Neither employment nor vocational training was predictive for the serum concentrations of antioxidant vitamins, selenium or coenzyme Q10. CONCLUSIONS: Poor status of selenium and alpha-tocopherol is highly prevalent even among younger, well-educated female seniors, whereas ascorbic acid and beta-carotene status seems sufficient in most women.

Monitoring the development of intertidal habitats on former agricultural land after the managed realignment of coastal defences at Tollesbury, Essex, UK.

The managed realignment of coastal defences and subsequent creation of intertidal habitats is one of several 'soft' engineering options that could reduce the costs of maintaining embankments and at the same time deliver environmental benefits. The managed realignment at Tollesbury was one of the first in the UK, undertaken as an experimental test case to improve understanding of the practical techniques and processes involved. Independent studies were undertaken on the development of soils, benthic invertebrates and vegetation within the site in addition to methods of enhancing the process of natural colonisation of saltmarsh plants. Bathymetric and vegetation monitoring were undertaken on the adjacent estuary to determine any breach effect that may be attributed to the realignment. This paper summarises the results from the vegetation, sedimentation and invertebrate monitoring and discusses the implications for other managed realignment schemes in the UK.

[Complications after dermal fillers and their treatment]. / Komplikationen nach Faltenunterspritzung und ihre Behandlung.

All dermal fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of these risks and be prepared to accept them. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., the implantation of a long-lasting filler substance was too superficial). Such adverse events can be treated with intradermal 5-fluorouracil and steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunological phenomena such as late-onset allergy and non-allergic foreign body granulomas. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions should remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granulomas in the subcutaneous fat.

Secondary structure, stability and tetramerisation of recombinant K(V)1.1 potassium channel cytoplasmic N-terminal fragment.

The recombinant N-terminal fragment (amino acids 14-162) of a tetrameric voltage-gated potassium channel (K(V)1.1) has been studied using spectroscopic techniques. Evidence is presented that it forms a tetramer in aqueous solution, whereas when solubilised in 1% Triton X-100 it remains monomeric. The secondary structure content of both monomeric and tetrameric K(V)1.1 N-terminal fragment has been estimated from FTIR and CD spectroscopy to be 20-25% alpha-helix, 20-25% beta-sheet, 20% turns and 30-40% random coil. Solubilisation of the protein in detergent is shown by hydrogen-deuterium exchange analysis to alter tertiary structure rather than secondary structure and this may be the determining factor in tetramerisation ability. Using molecular modelling we propose a supersecondary structure consisting of two structural domains.

[Implications of TCGA Network Data on 2nd Generation Immunotherapy Concepts Based on PD-L1 and PD-1 Target Structures]. / Implikationen der TCGA Netzwerkdaten für Zweit-Generations-Immuntherapiekonzepte auf Basis der PD-L1 und PD-1 Zielstrukturen.

The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al. report that increased protein expression of PD-L1 (CD274/ B7-H1) in tumour cells and tumour-infiltrating immune cells (TILs; lymphocytes and histiocytes) is associated with unfavourable clinical pathological parameters as well as poor survival. In small pilot groups of mRCC patients it was found that increased PD-L1 protein expression in tumours and TILs may be correlated with the objective response to anti-PD-1 treatment. Sometimes, however, a very wide variety of response rates was observed, which raises the question if this can be explained by individual expression levels of PD-L1 (CD 274) or PD-1 (PDCD1).Recently published data from the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) Network now provide a genome-wide data base that allows us to review or validate the molecular results obtained in clear cell renal cell carcinomas (ccRCC) to date.In this study, we analysed the TCGA KIRC mRNA expression data for PD-L1 and PD-1 for a possible association with clinical pathological parameters and the survival of 417 ccRCC patients.The mRNA expression of PD-L1 in primary nephrectomy specimens revealed no significant association with unfavourable clinical parameters. Interestingly, though, a positive correlation with patient survival was found (HR=0,59, p=0,006).These results, which partly contradict the concept applied to date, point out the necessity to ascertain the characteristics of PD-L1 and PD-1 expression at mRNA and protein level in an appropriately sized patient population and evaluate the clinical significance.

[Partial Nephrectomy in cT1 Renal Tumours: Conventional Laparoscopic Partial Nephrectomy Compared with LESS Partial Nephrectomy in SITUS Technique]. / Nierenteilresektion bei cT1 Nierentumoren: Vergleich der konventionellen laparoskopischen Nierenteilresektion mit der LESS Nierenteilresektion in SITUS-Technik.

BACKGROUND: Partial nephrectomy is the treatment of choice for clinical stage 1 renal tumours. Open partial nephrectomy is the standard operative technique. The use of minimally-invasive strategies such as laparoscopic, robot-assisted partial nephrectomy or laparoendoscopic single site (LESS) partial nephrectomy has increased in recent years. PATIENTS/MATERIAL AND METHODS: In this retrospective study, patients undergoing laparoscopic partial nephrectomy between December 2008 and November 2013 were evaluated. All patients presented with renal lesions suspicious for malignancy. Operations were performed as conventional laparoscopic transperitoneal partial nephrectomies (cLPN) or LESS partial nephrectomies (LESS-PN) in SITUS technique (single incision transumbilical surgery). The aim of the study was to compare perioperative outcome parameters such as duration of surgery, time of ischaemia, complications, need for transfusion, conversion rates, changes in renal function and duration of hospital stay in both groups. RESULTS: A total of 85 laparoscopic partial nephrectomies were performed in this study (72 cLPN and 13 LESS-PN). The average tumour size was 2.68±1.47 cm (cLPN) vs. 2.46±1.11 cm (LESS-PN). The mean duration of surgery was 175.17±50.026 min (cLPN) and 185.77±35.991 min (LESS-PN). 45 (62.5%) operations (cLPN) vs. 10 (76.9%) (LESS-PN) were performed in zero-ischaemia technique. There were no significant differences in perioperative outcome parameters between both groups. Postoperative complication rates (Clavien-Dindo≥3) were 11.1% (cLPN) vs. 7.7% (LESS-PN). CONCLUSIONS: LESS partial nephrectomy in SITUS technique is an attractive alternative to conventional laparoscopic and open partial nephrectomy.

Effect of corticosteroids on the phrenic nerve-diaphragm of preparation treated with hemicholinium. A possible model of myasthenia gravis.

A marked protective action of the corticosteroids prednisolone, hydrocortisone, and dexamethasone has been shown on a hypothetical model of myasthenia gravis, using the rat phrenic nerve-diaphragm preparation treated with hemicholinium-3. Dexamethasone is much more effective than prednisolone, and hydrocortisone is the least effective. Prednisolone has no effect on a neuromuscular block caused by choline, decamethonium, physostigmine, d-tubocurarine, and a high or low calcium ion concentration. The possible implications of the present study for myasthenic disease are discussed. It is tentatively concluded that the site of action of corticosteroids in myasthenia gravis is located presynaptically.

Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson's disease.

Pallidotomy is now widely performed for the treatment of advanced Parkinson's disease (PD). Preliminary reports of the effect of globus pallidus pars interna deep brain stimulation (GPi DBS) have also been promising. We have analyzed a cohort of 22 consecutive patients enrolled in a multicenter study. Surgery was bilateral in 17 and unilateral in five patients. At 6-month follow-up, the bilaterally GPi-implanted patients demonstrated a marked improvement when examined after drug withdrawal ("off") and under optimal medication ("on") using the Unified Parkinson's Disease Rating Scale (UPDRS). The benefit induced by the stimulation in the "off" medication condition in the total motor score was 31% and in the activities of daily living (ADL) scores was 39%. During the "on" medication period, the reduction in the total "on" dyskinesias score was 66% and in the ADL score was 32%. A similar pattern of improvement was seen in the group of patients with unilateral GPi stimulation, although a second cohort of 12 patients not included in the multicenter study showed greater improvements in "on" motor functioning. Although the effect of DBS is predominantly reversible, electrode insertion alone resulted in measurable clinical effects in the absence of stimulation. Thus, at 6-month follow-up, the benefit observed without stimulation was up to 44% in the "on" dyskinesias score and 29% in timed tapping scores undertaken in the "off" medication state. Complications among 34 patients from all centers included perioperative infection (n=3), hardware fracture (n=2), and premature battery failure (n=3). These results show a positive antiparkinsonian effect of pallidal DBS. No specific complications were observed with bilateral procedures.

Application of hydrogenase in biotechnological conversions.

Evidence will be presented in this review article that the application of hydrogenase has large biotechnological possibilities. Our investigations show: Fast reaction of hydrogenase at an electrode surface to reduce H+; Photochemical production of H2 by hydrogenase by photosensitized Ru-complexes dissolved in reversed micellar membranes and vectorial H+ transport through the membrane to the water phase; The production of fine chemicals in reversed micelles by a system containing specific enzymes, hydrogenase and H2. The rules to obtain maximal conversion rates with this system will be presented.

In vitro binding of estrogens by dietary fiber and the in vivo apparent digestibility tested in pigs.

Within the framework of experiments related to the association between dietary fiber and breast cancer an in vitro test system was used to study the binding of estrogens to various fibers (e.g. cholestyramin, lignin and cellulose) and fiber sources (e.g. wheat bran, cereals, seeds and legumes). Furthermore, the in vivo apparent digestibility of the different fiber sources was tested using a mobile nylon bag technique in intestine-cannulated pigs. Estradiol-17 beta (E2) bound more strongly to the various fibers than did estrone (E1), estriol or estrone-3-glucuronide. At increasing pH (greater than 7) binding of both E1 and E2 to wheat bran decreased significantly. Cholestyramine and lignin bound almost all estrogens present in the medium. Linseed (91%), oats (83%), barley chaff (88%) and wheat bran (82%) are other excellent binders of E2. Corn, rye and white wheat flour showed lower binding capacity with a relatively low affinity. Cereals with the highest percentage of lignin in the fiber (greater than 3%) were also the fiber sources with the lowest apparent digestibility. Estrogens bound with the highest affinity (relative to bovine serum albumin) to these fiber sources. Together with wheat bran and lignin, oats, linseed and soybean seem to be products with good perspectives for in vivo evaluation of the lowering effect of dietary fiber on estrogen exposure of estrogen-sensitive tissues.