[Risk factors for chronic perforating skin lesions in the area of the digits in cattle on Swiss alpine pastures]. / Risikofaktoren für chronisch perforierende Hautläsionen im Zehenbereich beim Rind auf Schweizer Alpen.

INTRODUCTION: Diseases of the digits often occur in cattle on larger cattle mountain pastures. In the late spring 2020, at the time of the ascent of 1554 cattle to 11 high altitude alpine pastures in the Lower Engadine region, lesions in the area of the digits were clinically assessed and documented. 254 cattle were of non-cantonal and 1300 of local origin (Lower Engadine; postal code CH-75XX). Skin lesions in the area of the digits, identified as digital dermatitis (DD; Mortellaro's disease), were further classified according to the DD scoring system. Nonspecific skin lesions with clinical evidence of granulation tissue formation were termed chronic penetrating skin lesions (CPSL). At the end of the alpine pasturing season, in the early fall (descent of cattle from the alpine pastures), the procedure was repeated, and biopsies were taken from randomly selected cattle with CPSL. Digital dermatitis lesions were found in 34 of 1551 cattle at ascent, but no case of CPSL was found at that time. At descent, 19 of 1529 cattle had DD lesions and 88 cattle had CPSL. The clinical appearance of the CPSL was consistent with chronic skin lesions caused by penetrating skin lacerations. Histologically, the majority of the CPSL were classified as chronic hyperplastic dermatitis with granulation tissue formation. In all CPSL biopsies examined by PCR, Fusobacterium necrophorum and Porphyromonas levii, but neither Dichelobacter nodosus nor the tested Treponema species were detected. Fluorescence in situ hybridization revealed a negative result for Treponema species in all biopsies. In the regression analysis, cattle in the age group of 365 to 730 days had an increased risk for the presence of CPSL compared to the age group of 160 to 365 days (odds ratio (OR) = 4,95; confidence interval (CI) = 1,97-12,43). Holstein cattle had an increased risk of developing CPSL compared to Brown cattle (OR = 2,92; CI = 1,46-5,86) and cattle of non-cantonal origin showed a massively higher risk compared to local cattle (OR = 10,59; CI = 5,79 - 19,37). The statistically significant associations found in the present study can be taken into account in the selection of animals for summer pasturing on high altitudes in the future in order to reduce the prevalence of CPSL and consequently reduce the antimicrobial use. Spread of DD during the alpine pasturing season within the cattle groups examined was not found.

INTRODUCTION: Des atteintes aux onglons sont souvent observées sur les grands alpages de bovins. Des altérations au niveau des onglons ont été examinées cliniquement et répertoriées chez 1554 bovins lors de leur arrivée sur 11 alpages en Basse-Engadine, en provenance d'un autre canton (n = 254) ou de la localité à laquelle l'alpage appartenait (n = 1300, numéro postal 75XX), au moment de la montée à l'alpage en 2020. Les altérations cutanées diagnostiquées comme dermatite digitale (DD; maladie de Mortellaro) ont de plus été classifiées selon les scores en usage pour la DD. Les lésions cutanées non-spécifiques présentant une formation de tissu de granulation ont été enregistrées comme lésions cutanées perforantes chroniques (LCPC). La procédure a été répétée lors de la désalpe et une biopsie a été prise de chez des animaux présentant des LCPC choisis au hasard. Les caractéristiques de la topographie de l'alpage et celles du sol, ainsi que la densité d'occupation ont été enregistrées pour chaque alpage. Des lésions de DD ont été constatées chez 34 des 1551 bovins lors de la montée à l'alpage, mais aucun cas de LCPC n'a été observé. Lors de la désalpe, 19 des 1551 bovins présentaient des lésions de DD et 88 une LCPC. L'apparence des LCPC correspondait à des lésions cutanées chroniques après une blessure perforante de la peau. À l'histologie, il s'agissait la plupart du temps d'une dermatite chronique hyperplastique avec formation de tissu de granulation. Fusobacterium necrophorum et Porphyromonas levii ont été mis en évidence dans toutes les biopsies de LCPC soumises à une analyse par PCR, mais ni Dichelobacter nodosus ni les Treponema spp. recherchées n'ont été mis en évidence. L'hybridation in-situ en fluorescence était négative pour les tréponèmes dans toutes les biopsies. Selon les résultats d'une analyse de régression, les génisses âgées de 366 à 730 jours avaient un risque augmenté (Odds Ratio (OR) = 4,95; intervalle de confiance (IC) = 1,97 ­ 12,43) de présenter une LCPC en comparaison avec le groupe d'âge de 161 à 365 jours. Les bovins de race Holstein avaient un risque augmenté de présenter une LCPC en comparaison avec ceux de race grise (OR = 2,92; IC = 1,46 ­ 5,86), et les animaux en provenance d'autres cantons présentaient un risque massivement plus élevé que le cheptel local (OR = 10,59; IC = 5,79 ­ 19,37). Aucune différence significative n'a été observée dans la topographie ou dans la densité d'occupation entre les alpages avec et sans cas de LCPC. Les associations statistiquement significatives constatées dans cette étude peuvent être prises en compte à l'avenir lors de la sélection d'animaux pour l'alpage, dans le but de réduire la prévalence de LCPC, de diminuer la quantité d'antibiotiques administrés et d'améliorer le bien-être animal. Une propagation de la DD pendant la saison d'alpage n'a pas été constatée dans les groupes de bovins inclus dans l'étude.

[Complications of the 180 Watt XPS™ GreenLight laser-results of 1283 procedures]. / Komplikationen der 180-W-XPS™-GreenLight-Laserung ­ Ergebnisse bei 1283 Prozeduren.

BACKGROUND: The aim of this study was to classify and analyze postoperative complications under a new inspection method. This study assessed all patients who presented to the urologic ward within the first 3 months after their surgery. METHODS: A total of 170 patients suffered from complications due to the surgery; 29 patients experienced complications that were not directly correlated with the surgery. Age, American Society of Anesthesiologists (ASA) score, the emitted laser energy of the 180 Watt XPS™ GreenLight laser measured in joules, and the complications which led to the renewed hospitalization such as hematuria, urinary retention, and infection were analyzed and compared in the two groups of patients. RESULTS: Most complications that occurred were urinary retention and hematuria (50.6% and 49.4% of all patients, respectively). Of the patients with hematuria, 86.75% were under anticoagulant therapy medication. CONCLUSION: Compared with the reference approval study (Goliath trial) that included 135 multicentric patients (14.07% of patients presented with a complication classified as Clavien-Dindo II), the rate of complications was similar. This outcome is surprising because the patients treated with the GreenLight laser in the present study were classified as geriatric patients not only according to their age but also in their ASA score which is an indication of multiple other pathologies and administered medications. To achieve long-term postoperative success for these patients, the interface between the ambulatory and the hospital care should be optimized.

Old known and possible new biomarkers of ANCA-associated vasculitis.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises a group of multisystem disorders involving severe, systemic, small-vessel vasculitis with short- and long term serious and life-threating complications. Despite the simplification of treatment, fundamental aspects concerning assessment of its efficacy and its adaptation to encountered complications or to the relapsing/remitting/subclinical disease course remain still unknown. The pathogenesis of AAV is complex and unique, and despite the progress achieved in the last years, much has not to be learnt. Foremost, there is still no accurate marker enabling us to monitoring disease and guide therapy. Therefore, the disease management relays often on clinical judgment and follows a" trial and error approach". In the recent years, an increasing number of new molecules s have been explored and used for this purpose including genomics, B- and T-cell subpopulations, complement system factors, cytokines, metabolomics, biospectroscopy and components of our microbiome. The aim of this review is to discuss both the role of known historical and clinically established biomarkers of AAV, as well as to highlight potential new ones, which could be used for timely diagnosis and monitoring of this devastating disease, with the goal to improve the effectiveness and ameliorate the complications of its demanding therapy.

Very-high-frequency oscillations in the main peak of a magnetar giant flare.

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.

Health related quality of life associated with extreme obesity in adolescents - results from the baseline evaluation of the YES-study.

BACKGROUND: Obesity can significantly reduce health-related quality of life (HRQoL) and may lead to numerous health problems even in youths. This study aimed to investigate whether HRQoL varies among youths with obesity depending on grade of obesity and other factors. METHODS: For the Youths with Extreme obesity Study (YES) (2012-2014), a prospective multicenter cohort study, a baseline sample of 431 obese and extremely obese adolescents and young adults (age 14 to 24 years, BMI ≥30 kg/m2) was recruited at four German university medical centers and one job center. Obesity grade groups (OGG) were defined according to BMI (OGG I: 30-34.9 kg/m2, OGG II: 35-39.9 kg/m2, OGG III (extreme obesity): ≥40 kg/m2). HRQoL was measured with the Euroqol-5D-3 L (EQ-5D-3 L), DISABKIDS chronic generic (DCGM-31) and the KINDLR obesity module. Differences between OGGs were assessed with logistic and linear regression models, adjusting for age, sex, and study center in the base model. In a second regression analysis, we included other characteristics to identify possible determinants of HRQoL. RESULTS: Three hundred fifty-two adolescents (mean age: 16.6 (±2.4), mean BMI: 39.1 (±7.5) kg/ m2) with available HRQoL data were analysed. HRQoL of youths in all OGGs was markedly lower than reference values of non-obese adolescents. Adjusting for age and sex, HRQoL of youths in OGG III significantly impaired compared to OGG I. Youths in OGG III were 2.15 times more likely to report problems with mobility in the EQ-5D-3 L than youths in OGG I. A mean difference of 9.7 and 6.6 points between OGG III and I were found for DCGM-31 and KINDL respectively and 5.1 points between OGG II and I for DCGM-31. Including further variables into the regression models, showed that HRQoL measured by DCGM-31 was significantly different between OGGs. Otherwise, female sex and having more than 4 h of daily screen time were also associated with lower HRQoL measured by DCGM-31 and KINDL. CONCLUSION: HRQoL of adolescents with obesity is reduced, but HRQoL of adolescents with extreme obesity is particularly affected. Larger and longitudinal studies are necessary to understand the relation of extreme obesity and HRQoL, and the impact of other lifestyle or socioeconomic factors. TRIAL REGISTRATION: Clinicaltrials.gov NCT01625325; German Clinical Trials Register (DRKS) DRKS00004172.

Safety of apnea testing for the diagnosis of brain death: a comprehensive study on neuromonitoring data and blood gas analysis.

BACKGROUND AND PURPOSE: Here, we studied the safety of apnea testing (AT) for the determination of brain death with regard to intracranial pressure (ICP), cerebral perfusion and arterial blood gas parameters. We hypothesized that ICP only increases when cerebral perfusion pressure (CPP) remains positive during AT. METHODS: A total of 34 patients who fulfilled brain death criteria were identified by chart review (2009-2017). We analysed ICP, CPP and mean arterial pressure (MAP) prior to AT, during AT and after AT, as well as arterial pH, paCO2 , paO2 and arterial O2 saturation at the start and end of AT. RESULTS: Intracranial pressure was 87.9 ± 17.7 mmHg (mean ± SD) prior to AT, 89.9 ± 17.2 mmHg during AT and 86.4 ± 15.2 mmHg after AT (P = 0.9). CPP was -6.9 ± 12.8 mmHg prior to AT, -7.1 ± 13.7 mmHg during AT and -8.6 ± 13.0 mmHg after AT (P = 0.98), respectively. MAP was 82.9 ± 14.6 mmHg prior to AT, 84.7 ± 13.9 mmHg during AT and 79.7 ± 9.6 mmHg after AT (P = 0.57), respectively. A total of 10 patients had positive CPP (8.6 ± 4.3 mmHg), but ICP did not increase during AT. Arterial pH decreased from 7.43 ± 0.06 to 7.22 ± 0.06 (P < 0.05), paCO2 increased from 38.6 ± 4.2 to 69.6 ± 8.0 mmHg (P < 0.05), paO2 decreased from 416.3 ± 113.4 to 289.2 ± 146.5 mmHg (P < 0.05), and O2 saturation was stable at 99.8 ± 0.4% and 98.2 ± 3.2% (P = 0.39). CONCLUSIONS: Apnea testing had no detrimental effect on ICP, CPP, MAP or oxygenation, regardless of the presence of an initially positive CPP. The lack of further ICP elevations is presumably explained by critical closing pressures above individual CPP levels during AT.

No evidence of bovine papillomavirus type 1 or 2 infection in healthy equids.

BACKGROUND: There is a large body of evidence supporting bovine papillomavirus types 1 and 2 (BPV1; BPV2) as aetiological agents of equine sarcoids. However, there is conflicting data regarding BPV1/2 infection in sarcoid-free equids. OBJECTIVES: Data obtained between 2007 and 2017 by BPV1/2 screening of sarcoids and nonsarcoid tumours vs. samples from healthy equids are presented to help clarify this issue. STUDY DESIGN: Cross-sectional study. METHODS: Tumour material obtained from horses, donkeys and mules with confirmed sarcoids (n = 130), suspected sarcoids (n = 120), or nonsarcoid lesions (n = 70), skin biopsies from 102 tumour-free horses and dandruff/hair roots from 35 tumour-free donkeys and mules were screened for BPV1/2 infection. Sample DNA was extracted and validated by equine ß-actin PCR. BPV1/2 screening was performed by BPV1/2 E5-specific PCR allowing for the detection of less than 10 viral DNA molecules. Twenty-six amplicons were bidirectionally sequenced and compared to known E5 variants using BLAST program. RESULTS: BPV1/2 E5 PCR scored positive for 130/130 diagnosed sarcoids, 63/120 suspected sarcoids and 13/70 nonsarcoid lesions, whereas 137/137 DNA aliquots derived from tumour-free equids tested negative. On predicted E5 protein level, six different BPV1 E5 variants were identified. MAIN LIMITATIONS: The diagnosis of equine sarcoid was not confirmed in 120 lesions. CONCLUSIONS: Lack of BPV1/2 E5 DNA in tumour-free equids and the prevalence of sarcoid disease in young adult individuals suggest that the time span between initial infection and sarcoid development is short. This contrasts with the long phase of virus latency characterising infection of humans by carcinogenic papillomaviruses. Presence of BPV1/2 DNA in several cases of poor wound healing/hypergranulation and dermatitis points to these skin disorders being possibly co-induced by BPV1/2. PCR screening of tumour tissue/scrapings for BPV1/2 DNA represents a reliable tool for the rapid validation of a clinical diagnosis of equine sarcoid.

[Hemodynamic target variables in the intensive care unit]. / Hämodynamische Zielvariablen auf der Intensivstation.

Despite broad availability, extended hemodynamic monitoring is used in practice only in the minority of critical care patients. Pathophysiological reasoning suggests that systemic perfusion pressure (and thereby arterial as well as central venous pressure), cardiac stroke volume, and the systemic oxygen balance are key variables in maintaining adequate organ perfusion. In line with these assumptions, several studies support that a goal-directed optimization of these hemodynamic variables leads to a reduction in morbidity and mortality. The appropriate monitoring modality should be selected following echocardiographic evaluation of biventricular function. Ideally, high-risk patients with limited right ventricular function should be monitored with a pulmonary artery catheter. In patients with preserved right ventricular function, transpulmonary thermodilution with special consideration of extravascular lung water seems to be sufficient to guide hemodynamic therapy.

Peptide-based multi-agonists: a new paradigm in metabolic pharmacology.

Obesity and its comorbidities, such as type 2 diabetes, are pressing worldwide health concerns. Available anti-obesity treatments include weight loss pharmacotherapies and bariatric surgery. Whilst surgical interventions typically result in significant and sustained weight loss, available pharmacotherapies are far less effective, typically decreasing body weight by no more than 5-10%. An emerging class of multi-agonist drugs may eventually bridge this gap. This new class of specially tailored drugs hybridizes the amino acid sequences of key metabolic hormones into one single entity with enhanced potency and sustained action. Successful examples of this strategy include multi-agonist drugs targeting the receptors for glucagon-like peptide-1 (GLP-1), glucagon and the glucose-dependent insulinotropic polypeptide (GIP). Due to the simultaneous activity at several metabolically relevant receptors, these multi-agonists offer improved body weight loss and glucose tolerance relative to their constituent monotherapies. Further advancing this concept, chimeras were generated that covalently link nuclear acting hormones such as oestrogen, thyroid hormone (T3 ) or dexamethasone to peptide hormones such as GLP-1 or glucagon. The benefit of this strategy is to restrict the nuclear hormone action exclusively to cells expressing the peptide hormone receptor, thereby maximizing combinatorial metabolic efficacy of both drug constituents in the target cells whilst preventing the nuclear hormone cargo from entering and acting on cells devoid of the peptide hormone receptor, in which the nuclear hormone might have unwanted effects. Many of these multi-agonists are in preclinical and clinical development and may represent new and effective tools in the fight against obesity and its comorbidities.

Are peptide conjugates the golden therapy against obesity?

Obesity is a worldwide pandemic, which can be fatal for the most extremely affected individuals. Lifestyle interventions such as diet and exercise are largely ineffective and current anti-obesity medications offer little in the way of significant or sustained weight loss. Bariatric surgery is effective, but largely restricted to only a small subset of extremely obese patients. While the hormonal factors mediating sustained weight loss and remission of diabetes by bariatric surgery remain elusive, a new class of polypharmacological drugs shows potential to shrink the gap in efficacy between a surgery and pharmacology. In essence, this new class of drugs combines the beneficial effects of several independent hormones into a single entity, thereby combining their metabolic efficacy to improve systems metabolism. Such unimolecular drugs include single molecules with agonism at the receptors for glucagon, glucagon-like peptide 1 and the glucose-dependent insulinotropic polypeptide. In preclinical studies, these specially tailored multiagonists outperform both their mono-agonist components and current best in class anti-obesity medications. While clinical trials and vigorous safety analyses are ongoing, these drugs are poised to have a transformative effect in anti-obesity therapy and might hopefully lead the way to a new era in weight-loss pharmacology.

Molecular allergen profiling in horses by microarray reveals Fag e 2 from buckwheat as a frequent sensitizer.

BACKGROUND: Companion animals are also affected by IgE-mediated allergies, but the eliciting molecules are largely unknown. We aimed at refining an allergen microarray to explore sensitization in horses and compare it to the human IgE reactivity profiles. METHODS: Custom-designed allergen microarray was produced on the basis of the ImmunoCAP ISAC technology containing 131 allergens. Sera from 51 horses derived from Europe or Japan were tested for specific IgE reactivity. The included horse patients were diagnosed for eczema due to insect bite hypersensitivity, chronic coughing, recurrent airway obstruction and urticaria or were clinically asymptomatic. RESULTS: Horses showed individual IgE-binding patterns irrespective of their health status, indicating sensitization. In contrast to European and Japanese human sensitization patterns, frequently recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass, likely due to specific respiratory exposure around paddocks and near the ground. The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S-albumin Fag e 2 from buckwheat, which recently gained importance not only in human but also in horse diet. CONCLUSION: In line with the One Health concept, covering human health, animal health and environmental health, allergen microarrays provide novel information on the allergen sensitization patterns of the companion animals around us, which may form a basis for allergen-specific preventive and therapeutic concepts.

Circulating levels of miR-122 and nonalcoholic fatty liver disease in pre-pubertal obese children.

OBJECTIVES: The liver-specific miR-122 was proposed as biomarker for NAFLD in adults. Here, we investigated the relationship between miR-122 levels, parameters of liver metabolism and NAFLD in pre-pubertal obese children. METHODS: Parameters of liver metabolism (ALT, AST and GGT) of three European cohorts were included (German cohort [n = 71; age: 11.53 ± 1.29 years; BMI z-score: 2.96 ± 0.64], Italian cohort [n = 45; age: 9.60 ± 2.11 years; BMI z-score: 3.57 ± 1.16], Slovenian cohort [n = 31; age: 7.53 ± 1.47 years; BMI z-score: 3.66 ± 0.88]). MiR-122 levels and CK18 concentrations were measured in fasting blood samples. In the German and Italian cohort, the diagnosis of NAFLD and grading of NAFLD was assessed by ultrasound. RESULTS: NAFLD was diagnosed in n = 50 patients of the German cohort (29.6%) and in n = 29 patients (72.5%) of the Italian cohort. In all three cohorts, miR-122 was positively correlated with ALT and AST as well as with CK18 concentrations. MiR-122 levels were higher in children with NAFLD compared with healthy controls. CONCLUSIONS: MiR-122 levels in pre-pubertal obese children could be a potential biomarker for paediatric NAFLD.

Equine papillomavirus type 2: An equine equivalent to human papillomavirus 16?

In horses, squamous cell carcinomas (SCC) commonly affect the external genitals. There is growing evidence that equine papillomavirus type 2 (EcPV2) infection promotes disease development. To assess the possible association of EcPV2 with equine SCCs of the head (HSCC), 15 HSCC DNA samples were screened by E6/E7, E2, and LCR PCR and amplicons were analysed for sequence variations. The physical form of EcPV2 in HSCC, genital lesions, and smegma from horses with SCC was then addressed using EcPV2 immunocapture PCR (IC/PCR) for detection of virion, and E6 vs. E2 qPCR to investigate possible integration events. Four of 15 HSCC tested positive for EcPV2 DNA and harboured known or novel genetic variants of E6, E7, E2 and the LCR. Eighteen of 35 sample extracts including 3/4 smegma samples scored positive by IC/PCR, suggesting that about 51% of tested extracts harboured virions. E6/E2 qPCR from tumour DNA revealed E2/E6 copies/cell ranging between <1 (E2; E6) and 797 (E2) or 1434 (E6). IC/PCR-positive smegma samples contained higher E2 and E6 copy numbers, ranging between 1490 and 4.95×105 (E2) or 2227 and 8.54×105 (E6) copies/cell. Together with IC/PCR results, this finding suggests that smegma can serve as a rich EcPV2 reservoir. HSCCs harboured significantly lower viral DNA amounts (<1-25 copies/cell) than most genital tumour and smegma DNA isolates. The majority of samples contained more E6 than E2 DNA, with E6:E2 ratios ranging between 0.88 and 4.12. Although not statistically significant (P>0.05), this finding suggests that EcPV2 can integrate into the equine host cell genome.

Aqueous extract from Orthosiphon stamineus leaves prevents bladder and kidney infection in mice.

BACKGROUND: Extracts from the leaves of Orthosiphon stamineus are used in phytotherapy for treatment of uncomplicated urinary tract infections. PURPOSES: Evaluation of an aqueous extract against infection with uropathogenic Escherichia coli in vivo; investigation of underlying microbiological mechanisms. STUDY DESIGN: In vivo studies in mice and in vitro investigations on cytotoxicity, antiadhesive potential, influence on bacterial gene expression and quorum sensing. METHODS: Extract OWE was prepared by hot water extraction. For in vivo studies BALB/c mice were used in an UPEC infection model. The effect of OWE on bacterial load in bladder/kidney tissue was monitored in pre- and posttreatment. Cytotoxicity of OWE against different UPEC strains, T24 bladder/A498 kidney cells, gene expression analysis, monitoring of phenotypic motility and quorum sensing was investigated by standard methods of microbiology. RESULTS: OWE was quantified (UHPLC) according to the content of rosmarinic acid, cichoric acid, caffeic acid. Three- and 5-day treatment of animals with OWE (750mg/kg) after transurethral infection with UPEC CFT073 reduced the bacterial load in bladder and kidney, similar to norfloxacin. Four- and 7-day pretreatment of mice prior to the infection with UPEC NU14 reduced bacterial bladder colonization. In vitro investigations indicated that OWE (≤2mg/ml) has no cytotoxic or proliferation-inhibiting activity against different UPEC strains as well as against T24 bladder and A498 kidney cells. OWE exerts a dose dependent antiadhesive activity against UPEC strains NU14 and UTI89. OWE reduced gene expression of fimH, but evoked increase of the expression of motility/fitness gene fliC. Increase of bacterial motility on gene level was confirmed by a changed bacterial phenotype by an increased bacterial motility in soft agar assay. OWE inhibited in a concentration-dependent manner bacterial quorum sensing. CONCLUSION: OWE is assessed as a strong antiadhesive plant extract for which the traditional use in phytotherapy for UTI might be justified.

New approach shows no association between maternal milk fatty acid composition and childhood wheeze or asthma.

BACKGROUND: Previous observational studies have implied breastmilk fatty acid composition may play a role in the development of atopic eczema or atopic sensitization in breastfed infants and toddlers. However, studies investigating associations with wheeze and asthma in later childhood are scarce and did not account for inherent correlation of compositional data. Our aim was to explore the association of maternal milk fatty acid composition with childhood wheezing phenotypes and asthma up to age 13 years using a new statistical approach. METHODS: Breastmilk was collected 6 weeks and 6 months postdelivery in the Ulm Birth Cohort Study (n=720 and n=454, respectively). Concentrations of 28 fatty acids were measured by high-resolution capillary gas-liquid chromatography. To control for constant-sum constraint, concentration data were transformed using the centered log ratio method. Compositional biplots and correlation matrices were used to group centered log ratio transformed fatty acids. Adjusted risk ratios with parent-reported wheezing phenotypes and doctor-diagnosed asthma were computed using a modified Poisson regression. RESULTS: We observed no straightforward evidence of associations between overall breastmilk fatty acid composition and specific wheeze phenotypes or doctor-diagnosed asthma. CONCLUSION: Using appropriate statistical methodology, we report null associations. These findings may partly be attributable to several cohort-specific factors associated with breastfeeding and breastmilk collection. Further studies could improve on ours by analyzing samples of breastmilk and formula and by including all children for whom these are exclusively or together the major source of fatty acids in the first months of life.

Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort.

OBJECTIVE: We aimed to determine the prevalence of melanocortin-4 receptor (MC4R) variants in a large German cohort of children with obesity in a pediatric outpatient clinic and to ascertain whether there is a specific phenotype associated with loss-of-function variants as previously reported. STUDY DESIGN: Eight hundred and ninety-nine patients from our pediatric obesity clinic were screened for MC4R variants by DNA sequencing after PCR amplification. Retrospective statistical analysis of anthropometric and metabolic characteristics was performed, comparing patients with and without MC4R variants across the entire cohort (n=586) as well as in case-control analysis using patients with common sequence MC4R individually matched for age, sex and body mass index standard deviation score (SDS) (n=11 case-control pairs). RESULTS: We identified heterozygous variants within the coding region of the MC4R gene in n=22 (2.45%) patients. Fourteen (1.56%) had a variant that impaired receptor function. One new frameshift (p.F152Sfs), an yet unpublished nonsense mutation (p.Q156X) and one nonsynonymous variation (p.V65E) described in the Mouse Genome Database were detected. Across the whole cohort, at all ages, mean height SDS in subjects with impaired receptor function was higher than in patients with common sequence MC4R. In matched individuals, this trend persisted (8 of the 11 pairs) within the case-control setting. No differences were found regarding metabolic characteristics. CONCLUSIONS: The observed prevalence of mutations causing impaired receptor function in this large cohort is comparable to other pediatric cohorts. MC4R deficiency tends to lead to a taller stature, confirming previous clinical reports. The association of MC4R mutations with a distinct phenotype concerning metabolic characteristics remains questionable.

Principles of skin care in the elderly.

With aging, skin undergoes progressive structural and functional degeneration that leaves it prone to a wide variety of bothersome and even serious conditions and diseases. As skin conditions and diseases may affect all ages from cradle to grave, a disproportionate burden will clearly fall on the elderly and may significantly impact on quality of life (QoL). With a reduced ability of the skin to regenerate, the elderly are at an increased risk of skin breakdowns from even the simplest insults. It is therefore vital that skin care in the late adulthood is seen as a priority among both clinicians and caregivers. The scientific literature on diagnosing and assessing age-related skin conditions and diseases is vast; however, when it comes to preventive care and treatment, the scientific data available is less profound, and the recommendations are often based on personal experience, opinions or at best on consensus documents rather than on scientific data retrieved from controlled clinical trials. In addition to the absence of the scientific data, the imprecise terminology to describe the topical products, as well as the lack of understanding the essence of the vehicle, contributes to vague and often unhelpfully product recommendations. This paper aims to elucidate some basic principles of skincare, the choice of skincare products and their regulatory status. The paper discusses adherence to topical therapies, percutaneous absorption in the elderly, and skin surface pH and skin care. Lastly, it also discusses skin care principles in selected age related skin conditions and diseases.

Phytochemical characterization and in vitro wound healing activity of leaf extracts from Combretum mucronatum Schum. & Thonn.: Oligomeric procyanidins as strong inductors of cellular differentiation.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from Combretum mucronatum Schum. & Thonn. are traditionally used for wound healing in Western Africa. Aqueous and hydroalcoholic extracts of the dried leaves recently have been shown to stimulate viability of human keratinocytes and dermal fibroblasts. AIM OF THE STUDY: Phytochemical characterization of the herbal material, development of a validated HPLC methodology for quality control, and pinpointing the underlying pharmacological mechanism under in vitro conditions to understand the impact of C. mucronatum extracts on human skin cells. MATERIALS AND METHODS: Extracts obtained from the leaves from C. mucronatum by using solvents with different polarities (petrol ether, dichloromethane, ethanol-water 50%, water) were investigated concerning phytochemical composition by GC-MS, LC-MS and in part after fractionation and isolation of purified compounds. For quality control of the herbal material an ICH-2 validated UHPLC method was developed for quantification of the lead compounds epicatechin, procyanidin B2, vitexin and isovitexin. In vitro studies were performed using HaCaT keratinocyte cell line, primary keratinocytes and primary skin fibroblasts with determination of viability (MTT assay), cell proliferation (BrdU incorporation ELISA), cell toxicity (LDH release) and keratinocyte differentiation, using involucrin and keratin K10 as differentiation marker (confocal laser scanning microscopy, Western blot). RESULTS: A detailed phytochemical composition analysis of the extracts from the leaves from C. mucronatum was performed (compounds 1-34) and epicatechin, procyanidin B2, vitexin and isovitexin are assessed to be the lead compounds of the polar extract. Quantitative UHPLC investigations indicated mature leaves to have higher polyphenol content in comparison to young leaves. The drying process of the plant material was shown to have great influence on the content of the lead compounds. The aqueous extract (0.1-100µg/mL) did not change cell viability of dermal fibroblasts and keratinocytes but inhibited cellular proliferation rates significantly at 100µg/mL. The extract stimulated cellular differentiation of primary keratinocytes significantly at 1 and 10µg/mL. Procyanidin B2 at 1 and 10µM was shown to be responsible for the induction of this cellular differentiation, while epicatechin, and procyanidins B5, C1 and D1 were inactive. CONCLUSION: The in vitro effects of the aqueous extract on the skin cells rationalized the remedial effect in wound healing and possibly accounts for the reason why this plant may be widely used for this purpose. On the basis of this study extracts from the leaves of C. mucronatum therefore have potential for the use in wound healing.