Non-Invasive Gene Expression Testing to Rule Out Melanoma.

The Pigmented Lesion Assay (PLA) is a gene expression test that helps rule out melanoma and has the potential to reduce the need for surgical biopsies of atypical pigmented skin lesions. Utilizing a new technological platform for the non-invasive profiling of skin, the assay analyzes samples collected from adhesive patches for expression of two key genes (PRAME and LINC00518) known to be overexpressed in melanoma. The test result is binary (positive/negative) based on the detection of one or both genes. PLA positive cases are generally biopsied to establish the histopathologic diagosis, while PLA negative cases are considered for ongoing monitoring. The combination of visual inspection with histopathology, the current gold standard for melanoma diagnosis, has a relatively low negative predictive value (NPV) of approximately 83%, meaning that 17% of melanomas will be interpreted as benign lesions. In contrast, the PLA has a very high NPV (>99%). Further, with its high specificity (69-91%), use of the PLA can reduce the number of false positive samples subjected to histopathology review. By adding the PLA to the current care pathway, the number of surgical biopsies needed to find a melanoma (number needed to biopsy) is markedly reduced from 20-25 biopsies for dermatologists and 39 biopsies for physician assistants, to an average of 2.7. To date, unnecessary surgical procedures of benign lesions have been reduced by 88% based on a sample of more than 20,000 analyzed cases. This has resulted in fewer missed melanomas and significant cost savings to health care systems.

[Warning about risk of invasive infections in splenectomized patients. Experiences from University Hospital Brno, Czech Republic, in 2011]. / Upozornení na nebezpecí invazivních infekcí u splenektomovaných pacientu. Zkusenosti z FN Brno 2011.

Syndrome of fulminant sepsis in splenectomized (overwhelming postsplenectomy infection - OPSI) is feared and often fatal infectious complication in patients after splenectomy. The risk of syndrome of fulminant sepsis in splenectomized in these persons persists lifelong and doesn't diminish during the time. Etiologically, encapsulated bacterias like Streptococcus pneumoniae, Haemophilus influenzae group b and Neisseria meningitidis are involved. As the mortality of syndrome of fulminant sepsis in splenectomized is very high, it is indispensable to educate and vaccinate persons in risk. The authors present case reports of three splenectomized patients who were hospitalized for invasive pneumococcal infection in the University Hospital Brno, Czech Republic, in 2011.

[Febrile pancytopenia and hepatosplenomegaly as leading symptoms of visceral leishmaniasis]. / Febrilní pancytopenie a hepatosplenomegalie jako hlavní symptomy viscerální leishmaniózy.

The authors present a case report of a patient with febrile pancytopenia, hepatosplenomegaly and weight loss as main symptoms of visceral leishmaniasis. Standard treatment regimen with amphothericin B led to relapse of the disease after several weeks. The definitive cure of the disease was achieved with cytostatic miltefosin (Impavido©), which is not registered in the Czech Republic. The aim of this article is to point out this imported protozoan infection and its basic clinical and laboratory features.

Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120(ctn).

Cadherin cell-cell adhesion proteins play an important role in modulating the behavior of tumor cells. E-cadherin serves as a suppressor of tumor cell invasion, and when tumor cells turn on the expression of a non-epithelial cadherin, they often express less E-cadherin, enhancing the tumorigenic phenotype of the cells. Here, we show that when A431 cells are forced to express R-cadherin, they dramatically downregulate the expression of endogenous E- and P-cadherin. In addition, we show that this downregulation is owing to increased turnover of the endogenous cadherins via clathrin-dependent endocytosis. p120(ctn) binds to the juxtamembrane domain of classical cadherins and has been proposed to regulate cadherin adhesive activity. One way p120(ctn) may accomplish this is to serve as a rheostat to regulate the levels of cadherin. Here, we show that the degradation of E-cadherin in response to expression of R-cadherin is owing to competition for p120(ctn).

Ayurveda's role in preventing disease.

Modern medical science is currently in the throes of a revolution which is likely to have a dramatic impact on both the theory of medicine and the way it is practised. The mechanistic model which served biomedicine well for many years is gradually collapsing, thanks to the efforts of dedicated researchers who have looked beyond that model's flaws. Thus we now know that networks of chemical communication exist between the nervous and immune systems, and that prayer at a distance can positively affect the conditions of those who are seriously ill, even when the prayer and the patient are not known to one another. Another participant in this exciting climate of change and ferment is Ayurveda, India's ancient medical system. While Ayurveda has already contributed much to modern medicine (reserpine, gugulipid, plastic surgery), its real contributions are yet to be made. While some of these are likely to come in matters of materia medica and technique, most will likely be derived from Ayurveda's way of seeing the world, its "darshana." This paper outlines a few of the ways in which Ayurveda's "vision" is likely to facilitate medicine's ability to teach people not just how to avoid disease but how to proactively develop and maintain a healthy "state."

A large HPGe detector for the non-destructive radioassay of an ultra-low-background counting facility.

We present the use of a low background counting facility, equipped with a p-type 80% relative efficiency HPGe detector, protected by active and passive shielding, and large enough to count a 10 in photo-multiplier tube (PMT). A GEANT4 Monte-Carlo of this detector was developed and tuned to 3% accuracy. We report the U, Th, and K content in three different types of PMTs used in current neutrino experiments, with accuracies of ~10ppb for U and Th and of ~15ppm for K.

Search for proton decay via p-->e+pi0 and p-->micro+pi0 in a large water Cherenkov detector.

We have searched for proton decays via p-->e;{+}pi;{0} and p-->micro;{+}pi;{0} using data from a 91.7 kt.yr exposure of Super-Kamiokande-I and a 49.2 kt.yr exposure of Super-Kamiokande-II. No candidate events were observed with expected backgrounds induced by atmospheric neutrinos of 0.3 events for each decay mode. From these results, we set lower limits on the partial lifetime of 8.2 x 10;{33} and 6.6 x 10;{33} years at 90% confidence level for p-->e;{+}pi;{0} and p-->micro;{+}pi;{0} modes, respectively.

Oral formulations of budesonide: a novel treatment for inflammatory bowel disease.

Budesonide is a promising drug for a variety of documented applications and has potential in gastroenterology. Its unique local mechanism of delivery and efficient first-pass metabolism, resulting in fewer systemic adverse effects than with conventional glucocorticoids, makes this a desirable drug for clinical practice. This drug has shown promise in treating a wide spectrum of inflammatory diseases from inflammatory bowel disease and other colitides to autoimmune liver diseases. Future research should focus on ways to increase delivery methods to promote long-term usage for maintenance therapy for the disease entities listed above, as well as for other potential nongastrointestinal conditions.

Treatment of cyclic vomiting syndrome.

Cyclic vomiting syndrome (CVS) is a relatively rare but highly incapacitating disorder. It is seen both in children and adults, although classically it has been perceived as a pediatric gastrointestinal disorder. Recent studies have demonstrated that this disorder indeed can be seen in adults and is highly disabling. Although classically associated with migraine headaches in the pediatric form, this relationship is less well established in adults. This has major implications for management in that traditionally, one of the major avenues for treatment of pediatric CVS has been antimigraine drugs. An additional factor that obscures a review of CVS treatment is the fact that because of its relative rarity, no randomized controlled trials (RCTs) have been performed. In the absence of RCTs, it is difficult to make definitive recommendations regarding treatment. The literature to date consists of case reports and open-ended case series. However, despite these limitations, it is the goal of this article to present in a comprehensive manner the options available for the treatment of CVS. Recognizing the limitations in the literature, it is clear that a number of treatment strategies that can often prove effective for the treatment of these complicated and often-challenging patients are available. Treatment is divided between acute intervention, when a patient is actively and severely vomiting, and prophylactic treatment for patients in their "interictal" phase, the goal of which is reducing frequency and intensity of subsequent episodes. Finally, we are beginning to identify possible mechanisms of the cause of CVS. Once these are better understood, this will provide the basis for further improvement in treatment.