LIPSS-based functional surfaces produced by multi-beam nanostructuring with 2601 beams and real-time thermal processes measurement.

A unique combination of the ultrashort high-energy pulsed laser system with exceptional beam quality and a novel Diffractive Optical Element (DOE) enables simultaneous production of 2601 spots organized in the square-shaped 1 × 1 mm matrix in less than 0.01 ms. By adjusting the laser and processing parameters each spot can contain Laser Induced Periodic Surface Structures (LIPSS, ripples), including high-spatial frequency LIPSS (HFSL) and low-spatial frequency LIPSS (LSFL). DOE placed before galvanometric scanner allows easy integration and stitching of the pattern over larger areas. In addition, the LIPSS formation was monitored for the first time using fast infrared radiometry for verification of real-time quality control possibilities. During the LIPSS fabrication, solidification plateaus were observed after each laser pulse, which enables process control by monitoring heat accumulation or plateau length using a new signal derivation approach. Analysis of solidification plateaus after each laser pulse enabled dynamic calibration of the measurement. Heat accumulation temperatures from 200 to 1000 °C were observed from measurement and compared to the theoretical model. The temperature measurements revealed interesting changes in the physics of the laser ablation process. Moreover, the highest throughput on the area of 40 × 40 mm reached 1910 cm2/min, which is the highest demonstrated throughput of LIPSS nanostructuring, to the best of our knowledge. Thus, showing great potential for the efficient production of LIPSS-based functional surfaces which can be used to improve surface mechanical, biological or optical properties.

[Early detection of occupational skin diseases in sewer workers]. / Früherkennung von berufsspezifischen Hauterkrankungen bei Kanalarbeitern.

BACKGROUND: Skin diseases affect 30-70% of the world population, and globally, skin cancer rates are continuously increasing. In this respect, prevention programs and early detection of skin diseases are of particular importance. OBJECTIVES: To screen sewer workers for skin diseases with regard to their work-related risk. METHODS: Employees of the municipal utilities in Munich (Münchner Stadtentwässerung) underwent a whole-body examination of the skin, conducted by two dermatologists. In addition, all employees completed a paper-based questionnaire on risk behavior and preventive measures. RESULTS: We examined 81 employees (79 men, 2 women, mean age 45.7 ± 9.5 years). Skin lesions in need of treatment were found in 30.9% (n = 25): the most frequent diagnosis was mycosis pedis (16.1%). In addition, one employee was diagnosed with basal cell carcinoma and two with actinic keratoses. According to the questionnaire, 43.5% of the employees had undergone a physician-led skin cancer screening in the past, whereas sun-protection practices were rarely applied. CONCLUSION: According to our findings, employee skin cancer screening seems to be beneficial for the detection of work-related skin diseases and is associated with a high participation rate. Furthermore, the study suggests that sewer workers have a high rate of mycosis pedis, possibly a work-related effect.

The role of the general practitioner in cancer care: a survey of the patients' perspective.

PURPOSE: Modern cancer care is provided in highly specialized structures as certificated centres and comprehensive cancer center, as well as specialized practices. In contrast, the position of the general practitioner (GP) is less well characterised and there is a lack of information about his importance in the care for cancer patients. The aim of our survey was to assess the role of GPs in German cancer care from patients' perspective. METHODS: In several steps we developed a standardized anonymous questionnaire in cooperation with the German Association of General Practitioners and the Federal Association of German Self-Help Groups. This questionnaire was used in a print and an online version and distributed by the self-help organizations to their members. RESULTS: Seven hundred and forty participants took part in the survey, 66.5% women and 30.1% men. 71% had visited the GP during cancer therapy and 34.5% discussed decisions concerning diagnostics and therapy with him. The most relevant reasons to visit the GP during cancer therapy were to get a blood test (63.3%), comorbidities (42.7%) and complaints and side effects (38.3%). For the latter, most often a detailed discussion ensued (57%), fooled by a prescription (37.7%). In 63.4% the GP offered support when patients had some questions or worries concerning their cancer. Yet, 17% of the patients reported that the GP did not try to help. 85.5% of the participants thought that it is important that their GP is informed about the therapy on a regular basis. For 77.0%, a simultaneous care provided by the GP is important or very important. CONCLUSION: Our survey points to the importance of the GP during cancer therapy from the patient's point of view. Patients want their GP to take an active part in the cancer therapy. Furthermore, early integration of the GP may also enhance early integration of palliative care and also help family members and caregivers. A strategy to integrate GPs is the establishment of shared care models, in which GPs are supported by specialists and get additional training in cancer care.

Conjugation of SUMO to p85 leads to a novel mechanism of PI3K regulation.

Class IA phosphatidylinositol 3-kinases (PI3Ks) are composed of p110 catalytic and p85 regulatory subunits. How regulatory subunits modulate PI3K activity remains only partially understood. Here we identified SUMO (small ubiquitin-related modifier) as a new player modulating this regulation. We demonstrate that both p85ß and p85α are conjugated to SUMO1 and SUMO2. We identified two lysine residues located at the inter-SH2 domain on p85ß, a critical region required for inhibition of p110, as being required for SUMO conjugation. A SUMOylation-defective mutant p85ß shows higher activation of the PI3K pathway, and increased cell migration and transformation. Moreover, the cancer-related KS459del mutant in p85α was less efficiently SUMOylated compared with the wild-type protein. Finally, our results show that SUMO modulates p85 tyrosine phosphorylation, a modification correlating with PI3K pathway activation. Thus, SUMO reduces the levels of tyrosine-phosphorylated-p85 while loss of SUMOylation results in increased tyrosine phosphorylation of p85. In summary, we identify SUMO as a new important player in the regulation of the PI3K pathway through modulation of p85.

[GLYCEMIC CONTROL IN DIABETES MELLITUS PATIENTS WITH CHRONIC KIDNEY DISEASE ­ HOW TO CHOOSE HYPOGLYCEMIC AGENT]?

The management of hyperglycemia in patients with chronic kidney disease (CKD) is complex, and the goals and methods regarding glycemic control are not clearly defined. Although aggressive glycemic control seems to be advantageous in early diabetic nephropathy, outcome data supporting tight glycemic control in patients with advanced CKD are lacking. Challenges in the management of such patients include monitoring difficulties and the complexity of available treatments. In this article, we review the current treatment options for patients with diabetes and CKD discussing all hypoglycemic agents that currently are available, as well as insulin, along with their indications and contraindications. The aim is to provide useful information to family physicians when deciding on individualized glycemic goals and appropriate therapy for patients with early or end stages of CKD.

[KIDNEY DISEASE IN DIABETIC PATIENTS ­ THE ROLE OF FAMILY MEDICINE PHYSICIAN].

The alarming rates of diabetes mellitus incidence and progression continue despite deployment of all current treatments. Kidney disease can be a particularly devastating complication, as it is associated with significant reductions in both length and quality of life. A variety of forms of kidney disease can be seen in people with diabetes, including diabetic nephropathy, ischemic damage related to vascular disease and hypertension, as well as other renal diseases that are unrelated to diabetes. Following an extensive PubMed search, this review provides a brief view on the screening for chronic kidney disease (CKD) in people with diabetes, how to treat them to slow down the progression of CKD and when to refer them to specialist care. This review also emphasizes the basic challenge in treating diabetic patients, which is to shift the main criterion from the disease-oriented to person-centered approach in the context of treating the patient as a whole.

[HEPATOCELLULAR CARCINOMA ­ NEWS IN DIAGNOSIS, FOLLOW UP AND TREATMENT AND ROLE OF FAMILY PHYSICIAN].

Hepatocellular carcinoma (HCC) is the most common malignancy of the liver, the sixth most common cause of cancer and the third leading cause of cancer-related deaths worldwide. Its incidence has increased dramatically throughout the world mainly driven by the increasing numbers of persons with long-standing chronic hepatitis C virus (HCV) infection who develop cirrhosis. Although 90% of HCV-associated HCC cases occur concurrently with cirrhosis, 30% to 50% of liver cancers associated with chronic HBV occur in the absence of cirrhosis. Since most people with chronic hepatitis are asymptomatic until cirrhosis or HCC is established, initial diagnosis and management of chronic hepatitis rely on primary care physicians to identify and screen high-risk individuals. Studies show that family physicians have inadequate knowledge about screening and counseling for chronic hepatitis and HCC. There is evidence of advances in surgical and nonsurgical therapies in the treatment of HCC, thus different associations have updated their recommendations following these clinical and scientific advances. The aim of this review is to make family physicians familiar with novelties in identifying high-risk patients, implementing an appropriate screening strategy, diagnosis and treatment, and to assist them in the decision-making process according to evidence based data.

SUMOylation regulates AKT1 activity.

Serine threonine kinase AKT has a central role in the cell, controlling survival, proliferation, metabolism and angiogenesis. Deregulation of its activity underlies a wide range of pathological situations, including cancer. Here we show that AKT is post-translationally modified by the small ubiquitin-like modifier (SUMO) protein. Interestingly, neither SUMO conjugation nor activation of SUMOylated AKT is regulated by the classical AKT targeting to the cell membrane or by the phosphoinositide 3-kinase pathway. We demonstrate that SUMO induces the activation of AKT, whereas, conversely, down-modulation of the SUMO machinery diminishes AKT activation and cell proliferation. Furthermore, an AKT SUMOylation mutant shows reduced activation, and decreased anti-apoptotic and pro-tumoral activities in comparison with the wild-type protein. These results identify SUMO as a novel key regulator of AKT phosphorylation and activity.

The RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-κB activity and T-cell activation.

Accurate regulation of nuclear factor-κB (NF-κB) activity is crucial to prevent a variety of disorders including immune and inflammatory diseases. Active NF-κB promotes IκBα and A20 expression, important negative regulatory molecules that control the NF-κB response. In this study, using two-hybrid screening we identify the RING-type zinc-finger protein 114 (RNF114) as an A20-interacting factor. RNF114 interacts with A20 in T cells and modulates A20 ubiquitylation. RNF114 acts as negative regulator of NF-κB-dependent transcription, not only by stabilizing the A20 protein but also IκBα. Importantly, we demonstrate that in T cells, the effect of RNF114 is linked to the modulation of T-cell activation and apoptosis but is independent of cell cycle regulation. Altogether, our data indicate that RNF114 is a new partner of A2O involved in the regulation of NF-κB activity that contributes to the control of signaling pathways modulating T cell-mediated immune response.

Effects of stress reduction on cardiovascular risk factors in type 2 diabetes patients with early kidney disease - results of a randomized controlled trial (HEIDIS).

Current guidelines for the treatment of type 2 diabetes focus on pharmacological treatment of glucose and cardio-vascular risk factors. The aim of this prospective randomized controlled intervention study was to examine the effects of a psychosocial intervention on clinical endpoints and risk factors in patients with type 2 diabetes and early diabetic kidney disease.110 patients were randomized to receive an 8-week mindfulness-based stress reduction (MBSR) training (n = 53) compared to standard care (n = 57). The study was carried out open-labelled and randomization was performed computer-generated in a 1:1 ratio. Primary outcome of the study was the change in urinary albumin excretion (albumin-creatinine-ratio, ACR); secondary outcomes were metabolic parameters, intima media thickness (IMT), psychosocial parameters and cardiovascular events.89 patients (42 in control group and 47 in intervention group) were analysed after 3 years of follow-up. After 1 year, the intervention group showed a reduction of ACR from 44 [16/80] to 39 [20/71] mg/g, while controls increased from 47 [16/120] to 59 [19/128] mg/g (p = 0.05). Parallel to the reduction of stress levels after 1 year, the intervention-group additionally showed reduced catecholamine levels (p < 0.05), improved 24 h-mean arterial (p < 0.05) and maximum systolic blood pressure (p < 0.01), as well as a reduction in IMT (p < 0.01). However, these effects were lost after 2 and 3 years of follow-up.This is the first study to show that a psychosocial intervention improves cardiovascular risk factors in high risk type 2 diabetes patients. Trial-Registration: NCT00263419 http://clinicaltrials.gov/ct2/show/NCT00263419 TRIAL REGISTRATION: clinicaltrials.gov-Identifier: NCT00263419.

Cutaneous Mycobacterium chelonae infection in Edinburgh and the Lothians, South-East Scotland, U.K.

BACKGROUND: We reviewed all cases of Mycobacterium chelonae infection seen in our department between 1 January 2008 and 31 December 2012. OBJECTIVES: To review the epidemiology, clinical features and management of cutaneous M. chelonae in South-East Scotland, and to compare prevalence data with the rest of Scotland. METHODS: The Scottish Mycobacteria Reference Laboratory database was searched for all cases of cutaneous mycobacterial infections. RESULTS: One hundred and thirty-four cases of cutaneous mycobacterial infection were recorded. Sixty-three were tuberculous; of the remaining 71, M. chelonae was the most common nontuberculous organism (27 cases). National Health Service (NHS) Lothian Health Board was the area with highest incidence in the Scotland (12 cases). Three main groups of patients in the NHS Lothian Health Board contracted M. chelonae: immunosuppressed patients (n = 6); those who had undergone tattooing (n = 4); and others (n = 2). One case is, we believe, the first report of M. chelonae cutaneous infection associated with topical corticosteroid immunosuppression. The majority of patients were treated with clarithromycin monotherapy. CONCLUSION: The most prevalent nontuberculous cutaneous mycobacterial organism in Scotland is M. chelonae. The prevalence of M. chelonae in Edinburgh and the Lothians compared with the rest of Scotland is disproportionately high, possibly owing to increased local awareness and established facilities for mycobacterial studies. Immunosuppression with prednisolone appears to be a major risk factor. The first outbreak of tattoo-related M. chelonae infection in the U.K. has been reported. Clinicians should be aware of mycobacterial cutaneous infection and ensure that diagnostic skin samples are cultured at the optimal temperatures.

Identification of the NF-κB inhibitor A20 as a key regulator for human adipogenesis.

The zinc-finger protein A20 is a key player in the negative feedback regulation of the nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) pathway in response to multiple stimuli. Tumor necrosis factor alpha (TNFα), a cytokine with pleiotropic effects on cellular proliferation and differentiation, dramatically increases A20 expression in all tissues. As TNFα inhibits adipocyte differentiation, we have determined the contribution of A20 to the adipogenic capacity of human mesenchymal stromal cells (MSCs). Here we show that A20 is constitutively expressed in MSCs, which previously has been observed only in cells that are either tumor or immune cells (T/B lymphocytes). TNFα stimulation induced a rapid degradation of A20 protein mediated exclusively by the proteasome in MSCs and not by caspases. This degradation is concomitant to the induction of its own mRNA, which suggests that a tight regulation of NF-κB signaling in MSCs is fundamental. On one hand, we demonstrate that the knockdown of A20-mediated transcript dramatically decreases the adipogenic capacity of MSCs, which correlates with the phenotype observed in the presence of TNFα. On the other hand, A20 overexpression blocks NF-κB activation and drives to increased adipogenesis, even in the presence of TNFα treatment. In conclusion, our data demonstrate that the presence of A20 allows MSCs to differentiate into adipocytes by maintaining NF-κB signaling at a basal state.

The south-east Scotland dermatology workload study: 30 years' analysis.

BACKGROUND: Dermatological activity data have been collected for the same region of south-east Scotland (population 1·24 million), approximately every 5 years, since 1981. This has allowed assessment of trends in demand from primary and secondary care, and activity within secondary care dermatology services, assisting planning of dermatological services. OBJECTIVES: To quantify dermatology outpatient workload across the same population to allow comparison with previous studies for trends in practice. METHODS: During November 2010, a standardized proforma was completed for all National Health Service and private practice dermatology outpatient consultations. Demographic data, source and reason for referral, diagnoses, investigations, treatments and disposal were recorded, and comparisons made with five previous studies. RESULTS: A total of 5470 consultations were recorded: 2882 new and 2588 review patients (new to review ratio 1 : 0·9, male to female 1 : 1·3, mean age 49 years, range 1 month to 101 years). Ninety-one per cent of referrals came from primary care and 9% from secondary care. Fifty-eight per cent of referrals were for diagnosis and 32% for hospital management. Diagnostic concordance between referrer and dermatologist ranged from 94% for acne to 14% for melanoma. Benign tumours accounted for 30% of referrals, malignant tumours 13%, dermatitis 13·3%, psoriasis 6·2% and acne/rosacea 5%. The referral rate rose to 23·2/1000 population per annum, with the increase coming mainly from primary care. CONCLUSIONS: Demand for dermatology continues to increase: new referrals have risen by 134% in 30 years, with a 36% increase in the last 5 years, despite corresponding population increases of 5·3% and 3%, respectively.

Sarcolemmal KATP channel modulators and cardiac arrhythmias.

Cardiac atrial and ventricular arrhythmias are major causes of mortality and morbidity. Ischemic heart disease is the most common cause underlying 1) the development of ventricular fibrillation that results in sudden cardiac death and 2) atrial fibrillation that can lead to heart failure and stroke. Current pharmacological agents for the treatment of ventricular and atrial arrhythmias exhibit limited effectiveness and many of these agents can cause serious adverse effects - including the provocation of lethal ventricular arrhythmias. Sarcolemmal ATP-sensitive potassium channels (sarcK(ATP)) couple cellular metabolism to membrane excitability in a wide range of tissues. In the heart, sarcK(ATP) are activated during metabolic stress including myocardial ischemia, and both the opening of sarcK(ATP) and mitochondrial K(ATP) channels protect the ischemic myocardium via distinct mechanisms. Myocardial ischemia leads to a series of events that promote the generation of arrhythmia substrate eventually resulting in the development of life-threatening arrhythmias. In this review, the possible mechanisms of the anti- and proarrhythmic effects of sarcK(ATP) modulation as well as the influence of pharmacological K(ATP) modulators are discussed. It is concluded that in spite of the significant advances made in this field, the possible cardiovascular therapeutic utility of current sarcK(ATP) channel modulators is still hampered by the lack of chamber-specific selectivity. However, recent insights into the chamber-specific differences in the molecular composition of sarcKATP in addition to already existing cardioselective sarcK(ATP) channel modulators with sarcK(ATP) isoform selectivity holds the promise for the future development of pharmacological strategies specific for a variety of atrial and ventricular arrhythmias.

Electrically detected magnetic resonance of neutral donors interacting with a two-dimensional electron gas.

We have measured the electrically detected magnetic resonance of donor-doped silicon field-effect transistors in resonant X- (9.7 GHz) and W-band (94 GHz) microwave cavities. The two-dimensional electron gas resonance signal increases by 2 orders of magnitude from X to W band, while the donor resonance signals are enhanced by over 1 order of magnitude. Bolometric effects and spin-dependent scattering are inconsistent with the observations. We propose that polarization transfer from the donor to the two-dimensional electron gas is the main mechanism giving rise to the spin resonance signals.

Electrically detected magnetic resonance in a W-band microwave cavity.

We describe a low-temperature sample probe for the electrical detection of magnetic resonance in a resonant W-band (94 GHz) microwave cavity. The advantages of this approach are demonstrated by experiments on silicon field-effect transistors. A comparison with conventional low-frequency measurements at X-band (9.7 GHz) on the same devices reveals an up to 100-fold enhancement of the signal intensity. In addition, resonance lines that are unresolved at X-band are clearly separated in the W-band measurements. Electrically detected magnetic resonance at high magnetic fields and high microwave frequencies is therefore a very sensitive technique for studying electron spins with an enhanced spectral resolution and sensitivity.

Avian influenza A virus monitoring in wild birds in Bavaria: occurrence and heterogeneity of H5 and N1 encoding genes.

To define avian influenza virus prevalence in wild birds in Bavaria, 12,930 tracheal, cloacal swabs or tissue samples from various waterfowl species were screened between January 2006 and December 2007. In 291 (2.3%) birds, genomes of influenza A viruses were detected by reverse transcription real-time PCR (rRT-PCR) targeting the matrix protein genes. Furthermore, solitary H5 hemagglutinin or N1 neuraminidase encoding genes were identified in 35 (0.3%) apparently healthy birds; whereas highly pathogenic (HPAI) H5N1 virus genomes were only diagnosed in dead wild birds (n = 93; 0.7%) found across this federal state region. In this study, multiple import events for H5N1 viruses were confirmed during 2006 and 2007. In addition, our findings argue against an existing HPAI H5N1 reservoir in aquatic birds in Bavaria. By contrast, phylogenetic analyses of the H5 or N1 sequences of low pathogenic avian influenza (LPAI) viruses revealed a marked diversity and multiple genetic lineages. This diversity of LPAI H5 and N1 subtype components indicates the existence of LPAI HA and NA gene pools which differ from the Bavarian HPAI H5N1. Moreover, the hemagglutinin amino acid differences between LPAI H5 viruses of a western European genotypic lineage observed in wild birds suggest a continuous evolution of LPAI viruses in Bavaria.