[Bone marrow fibrosis in primary myelofibrosis in relation to myelodysplasia- and age-related mutations of hematopoietic cells]. / Knochenmarkfibrose bei primärer Myelofibrose in Abhängigkeit von myelodysplasie- und altersassoziierten Mutationen der Hämatopoese.

Besides histopathological findings, there are no indicators of increased risk for fibrotic progression in myeloproliferative neoplasms (MPNs). Age-related clonal hematopoiesis (ARCH) or clonal hematopoiesis of indetermined potential (CHIP) are frequent findings in the elderly and combinations with MPN driver mutations (JAK2, MPL, and CALR) have been described. To determine the impact of ARCH/CHIP-related mutations for the development of fibrosis in primary myelofibrosis (PMF), the mutational status of cases with fibrotic progression from grade 0 to grade 2/3 (n = 77) as evidenced by follow-up bone marrow biopsies (median 6.2 years) was compared to prefibrotic PMF samples without the development of fibrosis (n = 27; median follow-up 7.3 years). Frequent ARCH/CHIP-associated mutations (TET2, ASXL1, DNMT3A) demonstrable at presentation were not connected with fibrotic progression. However, mutations that are rarely found in ARCH/CHIP (SRSF2, U2AF1, SF3B1, IDH1/2, and EZH2) were present in 24.7% of cases with later development of fibrosis and not detectable in cases staying free from fibrosis (P = 0.0028). Determination of tumor mutational burden (TMB) in a subgroup of cases (n = 32) did not show significant differences (7.68 mutations/MB vs. 6.85 mutations/MB). We conclude that mutations rarely found in ARCH/CHIP provide an independent risk factor for rapid fibrotic progression (median 2.0 years) when already manifest at first presentation.

The dangers of the bread clip - CT imaging and management: a case report.

Most ingested foreign objects pass the gastrointestinal tract without serious consequences. A particular foreign object has been described related to serious adverse events such as gastrointestinal bleeding and small bowel obstruction: a plastic bread clip. During the diagnostic phase the morphology of this item is not always recognized during ultrasonography or CT imaging. In this case report we describe the diagnosis and management of a patient with a small bowel perforation caused by ingestion of a bread clip.

α-Methylacyl-coenzyme A racemase (AMACR, p504s) is a marker to distinguish malignant melanomas from dysplastic nevi and melanocytic nevi.

Routinely processed skin biopsies are still the mainstay for the diagnosis of melanocytic skin neoplasms (MSNs) and are considered the "gold standard" for individual patient management and clinical trials. The diagnostic challenge of melanocytic lesions of the skin prompts histopathologists to consider new diagnostic tools; among these, immunohistochemistry. We aimed to find putative new immunohistochemical markers, which can supplement the histological criteria used to detect dysplasia. In this immunohistochemical study, we chose a panel of promising biomarkers which could potentially differentiate between different MSN entities. These included α-methylacyl-coenzyme A racemase (AMACR; p504s), which is involved in the degradation of branched chained fatty acid derivates. We analysed a cohort of benign nevi and malignant melanomas. The design of the study included 78 melanocytic skin neoplasms (26 malignant melanomas and 52 benign nevi) in a tissue microarray. Immunohistochemistry of cyclin-dependent kinase inhibitor 2A (p16Ink4a), methylacyl-coenzyme A racemase (AMACR), cyclin D1, and E-cadherin was performed and assessed. We have observed that the p16Ink4a, AMACR, cyclin D1, and E-cadherin showed no exclusive staining for nevi or melanomas. However, a significant overexpression of AMACR was found in malignant melanomas compared to benign nevi. AMACR overexpression was also associated with an increased p16Ink4a staining. Our results suggest AMACR as an immunohistochemical marker for distinguishing malignant melanomas and dysplastic nevi from conventional melanocytic nevi.

Locally led adaptation: Promise, pitfalls, and possibilities.

Locally led adaptation (LLA) has recently gained importance against top-down planning practices that often exclude the lived realities and priorities of local communities and create injustices at the local level. The promise of LLA is that adaptation would be defined, prioritised, designed, monitored, and evaluated by local communities themselves, enabling a shift in power to local stakeholders, resulting in more effective adaptation interventions. Critical reflections on the intersections of power and justice in LLA are, however, lacking. This article offers a nuanced understanding of the power and justice considerations required to make LLA useful for local communities and institutions, and to resolve the tensions between LLA and other development priorities. It also contributes to a further refinement of LLA methodologies and practices to better realise its promises. Ultimately, we argue that the utility of the LLA framing in promoting climate justice and empowering local actors needs to be tested empirically.

[The risks of tanning with the Barbie drug]. / De risico's van bruin worden met de barbiedrug.

BACKGROUND: Melanotan II, also known as 'Barbie drugs', can be purchased over the internet and in gyms to facilitate sunless tanning. The purchased product is a alpha-melanocyte-stimulating hormone (α-MSH) analogue, which stimulates the production of eumelanin to get skin pigmentation. However, previous research showed that Melanotan supports the development of new pigmented and dysplastic naevi. CASE REPORT: We report a case of a 27 year old male, with no relevant medical history, who presented at the emergency department two hours after subcutaneous self-administration of Melanotan II. He suffered from sympathomimetic symptoms and was treated with lorazepam, supplemental potassium and intravenous fluid resuscitation. CONCLUSION: This case reports underlines self-administration of Melanotan II is not without potential side effects, although Melanotan II is easily available on the internet and in gyms.

Climate change research and the search for solutions: rethinking interdisciplinarity.

Growing political pressure to find solutions to climate change is leading to increasing calls for multiple disciplines, in particular those that are not traditionally part of climate change research, to contribute new knowledge systems that can offer deeper and broader insights to address the problem. Recognition of the complexity of climate change compels researchers to draw on interdisciplinary knowledge that marries natural sciences with social sciences and humanities. Yet most interdisciplinary approaches fail to adequately merge the framings of the disparate disciplines, resulting in reductionist messages that are largely devoid of context, and hence provide incomplete and misleading analysis for decision-making. For different knowledge systems to work better together toward climate solutions, we need to reframe the way questions are asked and research pursued, in order to inform action without slipping into reductionism. We suggest that interdisciplinarity needs to be rethought. This will require accepting a plurality of narratives, embracing multiple disciplinary perspectives, and shifting expectations of public messaging, and above all looking to integrate the appropriate disciplines that can help understand human systems in order to better mediate action.

Learning from recovery after Hurricane Mitch.

This paper reviews how Nicaragua has recovered from Hurricane Mitch of October 1998. In particular, it examines how the assumptions and claims that were made during initial recovery planning have proven relevant in light of subsequent development. One must consider the response to Hurricane Mitch from the perspective of the broader trends that have driven recovery, including household, community and government initiatives and the wider economic context. Recovery efforts have not 'transformed' Nicaragua. In fact, market upheavals and livelihood changes in rural areas have had a more profound impact on poverty profiles than recovery programmes. Social protection programmes have been piloted, but patron-client ties and relations with aid providers are still more reliable sources of support in a time of crisis. Risk reduction has become more deeply integrated into the rural development discourse than was the case before the disaster, but risk reduction initiatives continue to place undue emphasis on hazard response rather than addressing vulnerability.

Urinary tract infections in a university hospital: pathogens and antibiotic susceptibility.

BACKGROUND: A substantial group of patients visit the emergency department (ED) with complaints of urinary tract infections (UTI). Treatment advice is based on national and local public health surveillance data. It is unclear whether this advice is adequate for hospitals with selected patient populations, such as university hospitals. METHODS: We performed a retrospective study on patients visiting the ED of the Erasmus University Medical Center (Erasmus MC) in the Netherlands from January 1st, 2013 until December 31st, 2014 with a suspected complicated UTI (cUTI) and positive urinary cultures. Patient data, data concerning the ED visit and microbiological data were analysed. RESULTS: 439 patients visited the ED, of whom 429 had a cUTI. Our results were compared with NethMap data. Distribution of uropathogens was comparable with the overall distribution in the Netherlands. Antibiotic susceptibility was comparable for intravenous antibiotics, but was lower for oral antibiotics. Susceptibility for empiric antibiotic therapy (i.e., cefuroxime and gentamyicin) was 96.2%. Pathogens differed from the index culture in 56.2% 104/185) of the urinary cultures available from the previous year. Using logistic regression, we found that a shorter time between last admission to the initiated antibiotic regimen was associated with lower susceptibility of cultured uropathogens. CONCLUSION: The distribution and antibiotic susceptibility of uropathogens for intravenous antibiotics in a Dutch university hospital is comparable with overall distribution in the Netherlands. Empiric antibiotic therapy in our local guideline appears to be an adequate antibiotic regimen for cUTI and we therefore recommend treating patients accordingly. Extension of the chosen regimen based on earlier cultured pathogens is advised, and narrowing of the antibiotic regimen strongly discouraged.

A serine protease is involved in the initiation of DNA damage-induced apoptosis.

Caspases are considered to be the key effector proteases of apoptosis. Initiator caspases cleave and activate downstream executioner caspases, which are responsible for the degradation of numerous cellular substrates. We studied the role of caspases in apoptotic cell death of a human melanoma cell line. Surprisingly, the pancaspase inhibitor zVAD-fmk was unable to block cleavage of poly(ADP-ribose) polymerase (PARP) after treatment with etoposide, while it did prevent DEVDase activity. It is highly unlikely that caspase-2, which is a relatively zVAD-fmk-resistant caspase, is mediating etoposide-induced PARP cleavage, as a preferred inhibitor of this caspase could not prevent cleavage. In contrast, caspase activation and PARP degradation were blocked by pretreatment of the cells with the serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF). We therefore conclude that a serine protease regulates an alternative initiation mechanism that leads to caspase activation and PARP cleavage. More importantly, while zVAD-fmk could not rescue melanoma cells from etoposide-induced death, the combination with AEBSF resulted in substantial protection. This indicates that this novel pathway fulfills a critical role in the execution of etoposide-induced programmed cell death.

The critical sensor: a new type of evanescent wave immunosensor.

A new planar waveguide immunosensor has been developed in which adsorption at a surface, changing the refractive index contrast, is measured. In this "critical" sensor the change in the effective refractive index contrast is transducted to a shift of the critical reflection angle. The sensor's theoretically. In addition, an experimental sensitivity evaluation on the basis of several immunosensing experiments is presented. The obtained lower detection limit is 2 x 10(-2) nm in adlayer growth, equivalent to 12 pg/mm2 of analyte coverage. This sensitivity is comparable to the performance of the surface plasmon resonance sensors or the grating coupler sensors. However, the "critical" sensor has some advantages. These are mainly the ease of fabrication and adjustment prior to a measurement, and the fact that for an experiment no metal layer has to be used.

Mastocytosis and diffuse large B-cell lymphoma, an unlikely combination.

Systemic mastocytosis may be accompanied by a second haematological malignancy, usually of myeloid origin. However, a number of case reports describe systemic mastocytosis coexisting with a second haematological malignancy of lymphoid origin. Here, we report a case of a 74-year-old man with systemic mastocytosis who developed a diffuse large B-cell lymphoma. A short overview of the literature concerning mastocytosis accompanied by a second haematological malignancy is presented.

Optical-trapping micromanipulation using 780-nm diode lasers.

We have designed and implemented an optical-trapping configuration that uses near-infrared laser diodes. The highly divergent output beam of the diode laser was collimated by using only one aspheric compact disc lens. The resulting output beams are astigmatic and elliptic and have a flat, non-Gaussian intensity profile. Calculations and measurements were performed to investigate the influence of this profile on the trapping forces. The results show that use of a laser diode, collimated with a compact disc lens, provides a near-infrared light source that can be used for optical trapping. The light source is compact and relatively cheap and can be easily incorporated into an existing microscope.

Beliefs and behaviour of general practitioners regarding promotion of physical activity.

To assess current practice, perceived desirable practice and barriers related to the promotion of physical activity in general practice, a questionnaire was developed and distributed to all 1228 general practitioners in Perth. From these, 789 valid returns were received (71 per cent response). The mean age of the respondents was 45 years, 69 per cent were male, 52 per cent had postgraduate qualifications and 73 per cent were in full-time practice. General practitioners most frequently asked patients about their current level of physical activity and discussed physical activity programs when seeing patients with symptoms of conditions that could benefit from exercise, rather than asking all patients, new patients or patients previously seen. Walking specifically for fitness was the activity most likely to be recommended. General practitioners felt more able to offer general advice than specific advice on physical activity. Lack of time was reported most frequently as a barrier to the promotion of physical activity (47 per cent), followed by insufficient educational materials (29 per cent), and preference of patients for drug treatment (27 per cent). There were significant differences between self-reports of current practice and perceived desirable practice in the promotion of physical activity by general practitioners. Future strategies should aim to increase the frequency of advice to patients with specific health conditions.

How can and do Australian doctors promote physical activity?

BACKGROUND: Physical inactivity is recognized as an important public health issue. Yet little is known about doctors' knowledge, attitude, skills, and resources specifically relating to the promotion of physical activity. Our survey assessed the current practice, perceived desirable practice, confidence, and barriers related to the promotion of physical activity in family practice. METHODS: A questionnaire was developed and distributed to all 1,228 family practitioners in Perth, Western Australia. RESULTS: We received a 71% response (n = 789). Family practitioners are most likely to recommend walking to sedentary adults to improve fitness and they are aware of the major barriers to patients participating in physical activity. Doctors are less confident at providing specific advice on exercise and may require further skills, knowledge, and experience. Although they promote exercise to patients through verbal advice in the consultation, few use written materials or referral systems. CONCLUSIONS: There are significant differences between self-reports of current practice and perceived desirable practice in the promotion of physical activity by doctors. Future strategies need to address the self-efficacy of family physicians and involve resources of proven effectiveness. The potential of referral systems for supporting efforts to increase physical activity by Australians should be explored.

The waveguide Mach-Zender interferometer as atrazine sensor.

Immunoanalytical techniques used in combination with a highly sensitive Mach-Zender waveguide sensor give a device that is capable of fast on-line monitoring of immunoreactions. The on-line monitoring is especially attractive when the sensor can be used as an environmental probe. It is demonstrated that low concentrations of atrazine can be measured with a sensitivity around the EC limit of 100 ng/L. These measurements are performed with an inhibition technique. In combination with "a dynamic slope method" one complete measurement is done within 10 min. Sensor measurements show the same sensitivity and errors as parallel ELISAs.