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BackgroundSelecting a training program is one of the most challenging choices an applicant to the Match has to make.DiscussionTo make an informed decision, applicants should do a comprehensive research and carefully plan their upcoming steps. Factors that might influence the applicants' decision include geography, program reputation, specific areas of academic focus, subspecialty interests, university-versus community-based training, length of training and interest in combined programs. Such information can be gathered from published material, websites, and personal advice (from faculty, residents and advisors). This process is time-consuming and stressful.ConclusionTherefore, in this article we elaborate on the above to facilitate this process for applicants.

Optic nerve head astrocytes are the specialized glia cells that provide structural and trophic support to the optic nerve head. In response to cellular injury, optic nerve head astrocytes undergo reactive astrocytosis, the process of cellular activation associated with cytoskeletal remodeling, increases in the rate of proliferation and motility, and the generation of Reactive Oxygen Species. Antioxidant intervention has previously been proposed as a therapeutic approach for glaucomatous optic neuropathy, however, little is known regarding the response of optic nerve head astrocytes to antioxidants under physiological versus pathological conditions. The goal of this study was to determine the effects of three different antioxidants, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (Mn-TM-2-PyP), resveratrol and xanthohumol in primary optic nerve head astrocytes. Effects on the expression of the master regulator nuclear factor erythroid 2-related factor 2 (Nrf2), the antioxidant enzyme, manganese-dependent superoxide dismutase 2 (SOD2), and the pro-oxidant enzyme, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), were determined by quantitative immunoblotting. Furthermore, efficacy in preventing chemically and reactive astrocytosis-induced increases in cellular oxidative stress was quantified using cell viability assays. The results were compared to the effects of the prototypic antioxidant, Trolox. Antioxidants elicited highly differential changes in the expression levels of Nrf2, SOD2, and NOX4. Notably, Mn-TM-2-PyP increased SOD2 expression eight-fold, while resveratrol increased Nrf2 expression three-fold. In contrast, xanthohumol exerted no statistically significant changes in expression levels. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) uptake and lactate dehydrogenase (LDH) release assays were performed to assess cell viability after chemically and reactive astrocytosis-induced oxidative stress. Mn-TM-2-PyP exerted the most potent glioprotection by fully preventing the loss of cell viability, whereas resveratrol and xanthohumol partially restored cell viability. Our data provide the first evidence for a well-developed antioxidant defense system in optic nerve head astrocytes, which can be pharmacologically targeted by different classes of antioxidants.

Adrenal insufficiency is divided into three types based on the etiology of its development. In primary adrenal insufficiency, pathology resides in end-organ failure at the level of the adrenal cortex, while in secondary and tertiary adrenal insufficiency, impairment rests in the pituitary gland and hypothalamus, respectively. Regardless of etiology, adrenal insufficiency results in a hypocortisolemic condition. While the relationship between neuropsychiatric symptoms, especially psychosis, and hypercortisolemia has been extensively documented, the development of hypocortisolemia-induced psychosis is less common. We present a case of secondary adrenal insufficiency caused by a pituitary tumor. During the course of evaluation and treatment, the patient developed a psychotic episode. We will briefly review the condition of adrenal insufficiency and propose how hypocortisolemia can result in psychosis. [ABSTRACT FROM AUTHOR]

Portal and/or mesenteric thrombosis is a rare occurrence, and often an underlying hypercoagulable slate can be found. We describe a case in which a mesenteric infarction due to mesenteric venous thrombosis occurred as the first manifestation of an inherited type I deficiency of protein S, whereas signs of portal thrombosis emerged later. [ABSTRACT FROM AUTHOR]

: Acute coronary syndrome represents one of the most common causes of admittance to emergency rooms in Western countries. Despite being in the majority of cases the mirror of coronary atherosclerosis, more rare causes could be hidden beyond this presentation, whose identification is often crucial for patients' outcome. We hereby present the case of a 44-year-old woman, with a history of relapsing-remitting multiple sclerosis in treatment with natalizumab, who was admitted to our division for an acute coronary syndrome. At arrival, anaemia and severe thrombocytopenia were observed; thus, no antiplatelet agent was administered. Within a few hours, aphasia occurred. Clinical presentation and the identification of schistocytes at blood smear led to the suspicion of thrombotic thrombocytopenic purpura, which was then confirmed by laboratory analysis. Immediate high-dose steroids and plasma exchange allowed discharging of the patient within a few days without neurological or cardiac sequelae.

Background: Although serum beta-2 microglobulin (B2M) represents a key variable for symptomatic multiple myeloma (MM) prognostication, its role in predicting the risk of progression of asymptomatic MM to symptomatic disease has not been explored., Methods: This study was bases on a consecutive series of 148 patients with asymptomatic MM and explored the cumulative probability of progression to symptomatic MM as the primary endpoint., Results: In univariate analysis, a serum B2M level >2.5 mg/L was associated with an increased probability of disease progression (5-year risk, 64.5%; P < .001) along with serum monoclonal component (sMC) (P < .001), urinary monoclonal component (uMC) (P < .001), and bone marrow plasma cells (BMPCs) (P < .001). In multivariate analysis, serum B2M was selected as an independent predictor of progression (hazard ratio, 3.30; P = .002). Serum B2M was combined with sMC, uMC, and BMPC to create a risk-stratification model based on 4 groups with different risk of progression: very low (5-year risk, 0%), low-intermediate (5-year risk, 19.6%), high-intermediate (5-year risk, 60.7%), and high (5-year risk, 80.7%). The model that included serum B2M along with sMC, uMC, and BMPC was able to predict disease progression better than the model that was based on sMC, uMC, and BMPC without serum B2M (C statistics, 0.760 vs 0.726)., Conclusions: The current results indicated that 1) serum B2M is an independent predictor of asymptomatic MM progression, and 2) serum B2M adds prognostic information when combined with the most widely used prognosticators of asymptomatic MM progression., ((c) 2010 American Cancer Society.)

Tumor lysis syndrome, which develops after effective therapy of malignant conditions and leads to hyperuricemia, hyperkaliemia, hyperphosphatemia, hypocalcemia and elevated lactate dehydrogenase, is uncommon in solid tumors. In breast carcinoma it can be associated with tamoxifen flare, i.e. a transient increase in symptoms, mainly bone pain, observed shortly after the start of tamoxifen therapy. We report the case of a patient with advanced breast carcinoma involving the pleural space, unresponsive to combined chemotherapy, who experienced rapid worsening after the initiation of letrozole. Her symptoms included shock, bilateral pleural effusion, cardiac tamponade and oliguria. Laboratory parameters disclosed elevated transaminase, lactate dehydrogenase, uric acid and D-dimer blood levels. The patient was in critical condition for nearly 2 weeks. She improved progressively and has remained well and in complete remission for 20 months. This clinical picture suggests increased damage to the pleura (and probably the pericardium) and rapid leakage of tumor products, following the start of endocrine therapy. Letrozole is a non-steroidal aromatase inhibitor which is used in advanced breast cancer, resistant to first-line endocrine/chemotherapeutic treatment. Our review of the literature did not disclose any other descriptions of flare and tumor lysis syndrome after aromatase inhibitor therapy. Moreover, this case was characterized by atypical and complex clinical features. The aim of this presentation is to point out the practical significance, in neoplastic patients, of the differential diagnosis between symptoms due to tumor progression and those associated with anomalous reactions to therapy.

The centralization of body fat, particularly in abdominal or visceral depots, is associated with qualitative and quantitative lipid abnormalities. Examples of these qualitative alterations include changes in low density lipoprotein composition, namely an increased number of small or dense low density lipoprotein particles, which seem to be prone to increased lipid oxidation. Oxidative modification of low density lipoproteins is involved in atherosclerotic development of the arterial wall. Alterations of lipid composition often arise in a context of insulin resistance with hyperinsulinism. Genetic features, such as apolipoprotein E polymorphism, also play a significant role in lipoprotein metabolism. The principle treatment of obesity and associated dyslipidemia is to reduce energy intake through diet. Moderate exercise is effective, especially in patients with insulin resistance. Drug therapy is considered primarily for patients who refuse to make behavioral changes.

Objective: The role of the hepatitis C virus (HCV) in the etiology of type II mixed cryoglobulinemia (MC) has been well established, but the pathogenetical relationships among the virus, the immune system, the natural history of MC, and lymphoproliferation in the bone marrow and liver need to be further elucidated., Methods: Eighty-two patients with HCV positive type II MC and 20 subjects with chronic hepatitis C without MC were studied: bone marrow and liver specimens were examined by routine histology and immunohistochemistry, particularly focusing on parameters related to disease behaviour, such as the expression of the bcl-2 oncogene product and the proliferation-associated Ki67 antigen., Results: In most MC patients there were lymphoid infiltrates within the bone marrow showing a monomorphic cytology, frequent immunoglobulin light chain monotypic restriction, expression of the anti-apoptotic bcl-2 oncogene product, and a low proliferative capacity (Ki-67 < 3%). On the other hand, in all non-cryoglobulinemic patients a bone marrow picture of reactive lymphoplasmacytosis was found. In both MC and chronic hepatitis patients, the liver biopsy showed portal infiltrates consisting of T-cells, associated with a significant B-cell component; the latter was particularly abundant in MC, where it was frequently arranged in pseudo-follicles. The B-cell component expressed the bcl-2 oncogene product and CD5 antigen, thus suggesting that the immune system is actively involved in the production of liver damage both in MC and non-cryoglobulinemic patients. It is worth noting that in MC patients (but not in the non-cryoglobulinemic patients) these CD5+/bcl-2+ B-cells frequently also exhibited a monotypic restriction bearing an IgM kappa., Conclusion: Our findings in these liver and bone marrow studies further support the role of a lymphoproliferative disorder in the pathology of type II MC: the B cells involved accumulate due to the inhibition of apoptosis, and their low proliferative index justifies the indolent course of the disease. HCV probably interacts with these B-cells, facilitating their clonal expansion.

Objective: In order to investigate HCV associated thrombocytopenia, 6 patients suffering from this disease, in the absence of splenomegaly and other common causes of peripheral platelet destruction, underwent laboratory and scintigraphic tests., Results: Thrombokinetic studies revealed a significant, nearly linear, delayed splenic accumulation with normal or low-normal values for the average platelet life span, low-normal recovery, and depressed platelet production. Megakariopoiesis was normal or slightly increased. HCV infection of the megakariocytes was found in two patients. Autoantibodies and liver disease were also investigated., Conclusions: A role of immunological mechanisms in HCV associated thrombocytopenia appears to be ruled out. The authors conclude that tests for HCV infection should be included in the evaluation of thrombocytopenia in adults and a possible direct involvement of HCV cannot be excluded.

Parenchymal neoplastic invasion of the kidneys is a common postmortem finding in patients who have died from advanced non Hodgkin's lymphomas (NHL). However, it rarely causes major clinical consequences, such as impairment of glomerular and tubular function, acute or rapidly progressive renal failure. Renal involvement is even less frequent as a first manifestation of NHL, the so-called "primary" renal lymphoma. A review of the main clinical, diagnostic and pathological aspects of three cases observed in our division is presented here.