[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.

[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.

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.

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.

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.

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.

Ge(1-x) Mn(x) clusters: central structural and magnetic building blocks of nanoscale wire-like self-assembly in a magnetic semiconductor.

Controlled nanoscale self-assembly of magnetic entities in semiconductors opens novel perspectives for the tailoring of magnetic semiconductor films and nanostructures with room temperature functionality. We report that a strongly directional self-assembly in growth direction in Mn-alloyed Ge is due to a stacking of individual Ge(1-x)Mn(x) clusters. The clusters represent the relevant entities for the magnetization of the material. They are formed of a core-shell structure displaying a Mn concentration gradient. While the magnetic moments seem to be carried by the shells of the clusters, their core is magnetically inactive.

ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability.

NF-kappa B1 p105 forms a high-affinity, stoichiometric interaction with TPL-2, a MEK kinase essential for TLR4 activation of the ERK mitogen-activated protein kinase cascade in lipopolysaccharide (LPS)-stimulated macrophages. Interaction with p105 is required to maintain TPL-2 metabolic stability and also negatively regulates TPL-2 MEK kinase activity. Here, affinity purification identified A20-binding inhibitor of NF-kappa B 2 (ABIN-2) as a novel p105-associated protein. Cotransfection experiments demonstrated that ABIN-2 could interact with TPL-2 in addition to p105 but preferentially formed a ternary complex with both proteins. Consistently, in unstimulated bone marrow-derived macrophages (BMDMs), a substantial fraction of endogenous ABIN-2 was associated with both p105 and TPL-2. Although the majority of TPL-2 in these cells was complexed with ABIN-2, the pool of TPL-2 which could activate MEK after LPS stimulation was not, and LPS activation of TPL-2 was found to correlate with its release from ABIN-2. Depletion of ABIN-2 by RNA interference dramatically reduced steady-state levels of TPL-2 protein without affecting levels of TPL-2 mRNA or p105 protein. In addition, ABIN-2 increased the half-life of cotransfected TPL-2. Thus, optimal TPL-2 stability in vivo requires interaction with ABIN-2 as well as p105. Together, these data raise the possibility that ABIN-2 functions in the TLR4 signaling pathway which regulates TPL-2 activation.

NF-kappaB1 p105 negatively regulates TPL-2 MEK kinase activity.

Activation of the oncogenic potential of the MEK kinase TPL-2 (Cot) requires deletion of its C terminus. This mutation also weakens the interaction of TPL-2 with NF-kappaB1 p105 in vitro, although it is unclear whether this is important for the activation of TPL-2 oncogenicity. It is demonstrated here that TPL-2 stability in vivo relies on its high-affinity, stoichiometric association with NF-kappaB1 p105. Formation of this complex occurs as a result of two distinct interactions. The TPL-2 C terminus binds to a region encompassing residues 497 to 534 of p105, whereas the TPL-2 kinase domain interacts with the p105 death domain. Binding to the p105 death domain inhibits TPL-2 MEK kinase activity in vitro, and this inhibition is significantly augmented by concomitant interaction of the TPL-2 C terminus with p105. In cotransfected cells, both interactions are required for inhibition of TPL-2 MEK kinase activity and, consequently, the catalytic activity of a C-terminally truncated oncogenic mutant of TPL-2 is not affected by p105. Thus, in addition to its role as a precursor for p50 and cytoplasmic inhibitor of NF-kappaB, p105 is a negative regulator of TPL-2. Insensitivity of C-terminally truncated TPL-2 to this regulatory mechanism is likely to contribute to its ability to transform cells.

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.

The highly acidic C-terminal region of the yeast initiation factor subunit 2 alpha (eIF-2 alpha) contains casein kinase phosphorylation sites and is essential for maintaining normal regulation of GCN4.

Regulation of the effective activity of eukaryotic initiation factor 2 (eIF-2) in protein synthesis is known to involve phosphorylation of its alpha subunit. Two mammalian enzymes, the haem-controlled repressor (HCR) and the double-stranded RNA-activated inhibitor (dsI), phosphorylate Ser-51 of the alpha subunit, thereby inhibiting the exchange of bound nucleotides on, and thus the recycling of, eIF-2. In Saccharomyces cerevisiae, the equivalent serine seems to be phosphorylated by the GCN2 protein kinase, which is activated by amino acid starvation. However, in the present paper we show that this is not the only site of phosphorylation in yeast eIF-2 alpha. We report the preparation of recombinant yeast eIF-2 alpha from Escherichia coli and its use in in vitro phosphorylation studies. Mammalian HCR and dsI are shown to phosphorylate specifically Ser-51 of yeast eIF-2 alpha, whereas extracts from yeast cells do not. Instead, at least one of three serine residue in the acidic C-terminal region of this protein is phosphorylated by fractions of yeast possessing casein kinase activities 1 and 2. A triple Ser-->Ala mutant form of yeast eIF-2 alpha was found to be no longer phosphorylated by either of the yeast (or mammalian) casein kinase activities in vitro. Isoelectric focusing of yeast extracts confirmed that the mutated sites normally act as sites of phosphorylation in vivo. The same mutant was used to show that the three sites have no essential function under normal physiological conditions in yeast. In contrast, deletion of the 13 amino acid long C-terminal region of eIF-2 alpha, including the three phosphorylation sites, led to derepression of GCN4 in vivo. Thus removal of the short, highly acidic C-terminal region of eIF-2 alpha has the same regulatory effect on translational (re)initiation as phosphorylation of the Ser-51 residue of the wild-type protein. This result provides new insight into the role of eIF-2 alpha activity in the regulation of translational (re-) initiation.

Ribosomal affinity and translational initiation in Escherichia coli. In vitro investigations using translational initiation regions of differing efficiencies from the atp operon.

The atp operon of Escherichia coli comprises nine genes that are differentially expressed. The control of the atp genes' expression rates has been shown to be exercised primarily at the level of translational initiation, but how is this achieved in molecular terms? In order to study the interactions of 30 S ribosomal subunits with specifically the translational initiation regions (TIRs) of atpB, atpE and atpG, restriction fragments bearing these TIRs were excised from the atp operon and cloned into an SP6 promoter transcription vector. mRNA transcripts were made in vitro and used in primer extension inhibition studies and equilibrium mRNA-30 S ribosomal subunit binding measurements. The binding of 30 S ribosomal subunits blocked primer extension 14 to 15 bases downstream from the respective translational start codons. The affinities of binding of 30 S ribosomal subunits showed the relationship atpE greater than atpB greater than atpG. This was also the order of the efficiency of translation promoted by the respective TIRs, both in vivo and on the in vitro synthesized mRNA fragments. Thus, the affinity of 30 S ribosomal subunits is at least to some extent correlated with the rate of translational initiation.

Role of Abscisic Acid in Drought-Induced Freezing Tolerance, Cold Acclimation, and Accumulation of LT178 and RAB18 Proteins in Arabidopsis thaliana.

To study the role of abscisic acid (ABA) in development of freezing tolerance of Arabidopsis thaliana, we exposed wild-type plants, the ABA-insensitive mutant abi1, and the ABA-deficient mutant aba-1 to low temperature (LT), exogenous ABA, and drought. Exposure of A. thaliana to drought stress resulted in a similar increase in freezing tolerance as achieved by ABA treatment or the initial stages of acclimation, suggesting overlapping responses to these environmental cues. ABA appears to be involved in both LT- and drought-induced freezing tolerance, since both ABA mutants were impaired in their responses to these stimuli. To correlate enhanced freezing tolerance with the presence of stress-specific proteins, we characterized the accumulation of RAB18 and LTI78 in two ecotypes, Landsberg erecta and Coimbra, and in the ABA mutants during stress response. LT- and drought-induced accumulation of RAB18 coincided with the increase in freezing tolerance and was blocked in the cold-acclimation-deficient ABA mutants. In contrast, LT178 accumulated in all genotypes in response to LT and drought and was always present when the plants were freezing tolerant. This suggests that development of freezing tolerance in A. thaliana requires ABA-controlled processes in addition to ABA-independent factors.

Alterations in Water Status, Endogenous Abscisic Acid Content, and Expression of rab18 Gene during the Development of Freezing Tolerance in Arabidopsis thaliana.

Treatments as diverse as exposure to low temperature (LT), exogenous abscisic acid (ABA), or drought resulted in a 4 to 5[deg]C increase in freezing tolerance of the annual herbaceous plant Arabidopsis thaliana. To correlate the increase in freezing tolerance with the physiological changes that occur in response to these treatments, we studied the alterations in water status, endogenous ABA levels, and accumulation of rab18 (V. Lang and E.T. Palva [1992] Plant Mol Biol 20: 951-962) mRNA. Exposure to LT and exogenous ABA caused only a minor decline in total water potential ([psi]w), in contrast to a dramatic decrease in [psi]w during drought stress. Similarly, the endogenous ABA levels were only slightly and transiently increased in LT-treated plants in contrast to a massive increase in ABA levels in drought-stressed plants. The expression of the ABA-responsive rab18 gene was low during the LT treatment but could be induced to high levels by exogenous ABA and drought stress. Taken together, these results suggest that the moderate increases in freezing tolerance of A. thaliana might be achieved by different mechanisms. However, ABA-deficient and ABA-insensitive mutants of A. thaliana have impaired freezing tolerance, suggesting that ABA is, at least indirectly, required for the development of full freezing tolerance.