Evidence for a Common Toolbox Based on Necrotrophy in a Fungal Lineage Spanning Necrotrophs, Biotrophs, Endophytes, Host Generalists and Specialists

The Sclerotiniaceae (Ascomycotina, Leotiomycetes) is a relatively recently evolved lineage of necrotrophic host generalists, and necrotrophic or biotrophic host specialists, some latent or symptomless. We hypothesized that they inherited a basic toolbox of genes for plant symbiosis from their common ancestor. Maintenance and evolutionary diversification of symbiosis could require selection on toolbox genes or on timing and magnitude of gene expression. The genes studied were chosen because their products have been previously investigated as pathogenicity factors in the Sclerotiniaceae. They encode proteins associated with cell wall degradation: acid protease 1 (acp1), aspartyl protease (asps), and polygalacturonases (pg1, pg3, pg5, pg6), and the oxalic acid (OA) pathway: a zinc finger transcription factor (pac1), and oxaloacetate acetylhydrolase (oah), catalyst in OA production, essential for full symptom production in Sclerotinia sclerotiorum. Site-specific likelihood analyses provided evidence for purifying selection in all 8 pathogenicity-related genes. Consistent with an evolutionary arms race model, positive selection was detected in 5 of 8 genes. Only generalists produced large, proliferating disease lesions on excised Arabidopsis thaliana leaves and oxalic acid by 72 hours in vitro. In planta expression of oah was 10–300 times greater among the necrotrophic host generalists than necrotrophic and biotrophic host specialists; pac1 was not differentially expressed. Ability to amplify 6/8 pathogenicity related genes and produce oxalic acid in all genera are consistent with the common toolbox hypothesis for this gene sample. That our data did not distinguish biotrophs from necrotrophs is consistent with 1) a common toolbox based on necrotrophy and 2) the most conservative interpretation of the 3-locus housekeeping gene phylogeny – a baseline of necrotrophy from which forms of biotrophy emerged at least twice. Early oah overexpression likely expands the host range of necrotrophic generalists in the Sclerotiniaceae, while specialists and biotrophs deploy oah, or other as-yet-unknown toolbox genes, differently

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Laparoscopy for stage IV melanoma in two organs

Metastatic melanoma remains a disease associated with poor outcomes. Traditionally, surgical intervention plays a minimal role in its treatment. However, more recent studies document that complete surgical resection of distant metastases is associated with 5-year survival rates of 15% to 30%. These rates are greater than that reported for single-agent or combination chemotherapy, biologic agents or immunotherapy. This case report outlines a unique presentation of stage IV melanoma within the gastrointestinal tract located in 2 different organs. On the basis of the patient\u27s clinical findings, laparoscopic surgery was performed for palliation of intestinal obstruction and bleeding. This approach resulted in less postoperative pain, earlier mobilization, and a faster return to daily activities. To our knowledge, this case details the only known account that uses a laparoscopic approach to palliate stage IV melanoma at 2 synchronous sites; the stomach and small bowel. The literature regarding the treatment of metastatic melanoma is also briefly reviewed. Copyright © 2010 by Lippincott Williams & Wilkins

Laparoscopic sleeve gastrectomy for linear scleroderma

Linear scleroderma is a rare type of autoimmune connective-tissue disorder and is one of five known types of localized, nonsystemic scleroderma. This type of localized scleroderma affects the skin and subcutaneous tissues and induces extensive fibrosis and atrophy of the affected limbs. The disease is, characteristically, a unilateral phenomenon and usually affects the lower extremities. Due to its underlying pathophysiology, linear scleroderma is rarely associated with morbid obesity. This article documents the case of a 45-year-old female with a 35-year history of unilateral linear scleroderma, who subsequently developed morbid obesity of her contralateral side. Due to her linear scleroderma, she was unable to exercise effectively and developed hemiobesity associated with arthritis, lower back pain, and percholesterolemia. Based on her hemiobesity and associated comorbidities, she underwent a laparoscopic sleeve gastrectomy. ostoperatively, she has lost 20kg or 75% of her excess weight, with a resolution of joint and back pain and hypercholesterolemia at 12-month follow-up. This article describes a unique application for a sleeve gastrectomy in the setting of linear scleroderma and hemiobesity. © 2010 Mary Ann Liebert, Inc

Laparoscopic resection of a retroperitoneal cystic lymphangioma in an adult

Cystic lymphangiomas are rare, benign anomalies of the lymphatic system. More than 95% of cystic lymphangiomas occur in the head, neck, and axilla with only 1% in the retroperitoneum. Most of these cases are diagnosed by the second year of life with only a handful of adult cases. Once a symptomatic cystic lesion of the abdomen or retroperitoneum is diagnosed, treatment usually consists of surgical excision. Traditionally, surgery requires a laparotomy. This paper describes a patient with a retroperitoneal cyst who underwent a successful laparoscopic resection. The etiology and management of adult retroperitoneal cysts are reviewed as well. Copyright © 2010 by Lippincott Williams & Wilkins

Analysis of poor outcomes after laparoscopic adjustable gastric banding

Background: Recent studies document excess weight loss (EWL) of more than 50% with the laparoscopic adjustable gastric band (LGB). This study reviews the LGB experience at an urban academic center in terms of complications, reoperative rates, and comorbidities. Methods: In this study, 144 consecutive patients undergoing LGB were prospectively reviewed. Data were collected including weight, body mass index (BMI), excess weight loss (EWL), comorbidities, and complications. Demographics were analyzed using a t-test. Linear regression was used to analyze the relationship of BMI, race, and age to EWL at 12 months. Results: The study participants were 130 women with a mean age of 43 ± 11 years, a mean weight of 127.1 kg ± 20.5 kg, and a mean BMI of 45.6 ± 6.1. The mean follow-up period was 16 months. The mean EWL was 20% ± 14% at 6 months (n = 118), 26% ± 16% at 12 months (n = 106), 30% ± 20% at 18 months (n = 68), and 34% ± 23% at 24 months (n = 43). Patients with a BMI higher than 50 kg/m2 had a lower EWL at 12 months than patients with a BMI lower than 50 kg/m2 (P = 0.00005). The mean EWL at 12 months was significantly less for African Americans than for Caucasians (P = 0.0046; 95% confidence interval [CI] 3-15%). Patients older than 50 years had a lower EWL, but the difference was not statistically significant (P = 0.07). Complete and partial resolution of comorbidities occurred for 10% and 4% of the patients, respectively. Removal of the band with revision to a sleeve gastrectomy for inadequate EWL was required for 14 patients (11.5%). Complications occurred for 8% of the patients (n = 15) including port flipping, stoma obstruction, tube disconnection, port infections, dysphagia, and band slippage. Overall, 16.7% of the patients (n = 24) required reoperation. Conclusion: After LGB, a majority of the patients failed to achieve a 50% EWL, and 16.7% required reoperation. Laparoscopic adjustable gastric banding may not be the optimal bariatric procedure for patients older than 50 years, patients with a BMI higher than 50 kg/m2, or African Americans. © 2010 Springer Science+Business Media, LLC

Impact of cane use on bone marrow lesion volume in people with medial knee osteoarthritis (CUBA trial)

Background. No effective cure exists for knee osteoarthritis (OA). Low-burden self-management strategies that can slow disease progression are needed. Bone marrow lesions (BMLs) are a source of knee pain and accelerate cartilage loss. Importantly, they may be responsive to biomechanical off-loading treatments. Objective. The study objective is to investigate whether, in people with medial tibi-ofemoral OA, daily cane use for 12 weeks reduces the volume of medial tibiofemoral BMLs and improves pain, physical function, and health-related quality of life. Design. This study will be an assessor-masked, 2-arm, parallel-group, multisite randomized controlled trial. Setting. The community will serve as the setting for this study. Participants. The study participants will be people who are 50 years old or older and have medial tibiofemoral OA and at least 1 medial tibiofemoral BML. Intervention. The participants will be allocated to either the cane group (using a cane daily whenever walking for 12 weeks) or the control group (not using any gait aid for 12 weeks). Measurements. Outcomes will be measured at baseline and 13 weeks. The primary outcome will be total medial tibiofemoral BML volume measured from magnetic resonance imaging. Secondary outcomes will include BML volume of the medial tibia and/or femur, knee pain overall and on walking, physical function, participant-perceived global change, and health-related quality of life. Additional measures will include physical activity, cointerventions, adverse events, participation, participant demographics, cane training process measures and feasibility, barriers to and facilitators of cane use, and loss to follow-up. Limitations. People who are morbidly obese will not be included because of difficulties with magnetic resonance imaging. Conclusions. The findings of this study will help to determine whether cane use can alter disease progression in people with medial tibiofemoral OA and/or influence clinical symptoms. This study may directly influence clinical guidelines for the management of knee OA

Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation - Potential implications for cyclooxygenase-2 inhibition

Recent increased adverse cardiovascular events observed with selective cyclooxygenase-2 inhibition led to the withdrawal of rofecoxib ( Vioxx) and valdecoxib ( Bextra), but the mechanisms underlying these atherothrombotic events remain unclear. Prostacyclin is the major end product of cyclooxygenase-2 in vascular endothelium. Using a naturally occurring mutation in the prostacyclin receptor, we report for the first time that a deficiency in prostacyclin signaling through its G protein-coupled receptor contributes to atherothrombosis in human patients. We report that a prostacyclin receptor variant ( R212C) is defective in adenylyl cyclase activation in both patient blood and in an in vitro COS-1 overexpression system. This promotes increased platelet aggregation, a hallmark of atherothrombosis. Our analysis of patients in 3 separate white cohorts reveals that this dysfunctional receptor is not likely an initiating factor in cardiovascular disease but that it accelerates the course of disease in those patients with the greatest risk factors. R212C was associated with cardiovascular disease only in the high cardiovascular risk cohort ( n = 980), with no association in the low-risk cohort ( n = 2293). In those at highest cardiovascular risk, both disease severity and adverse cardiovascular events were significantly increased with R212C when compared with age- and risk factor-matched normal allele patients. We conclude that for haploinsufficient mutants, such as the R212C, the enhanced atherothrombotic phenotype is likely dependent on the presence of existing atherosclerosis or injury ( high risk factors), analogous to what has been observed in the cyclooxygenase-2 inhibition studies or prostacyclin receptor knockout mice studies. Combining both biochemical and clinical approaches, we conclude that diminished prostacyclin receptor signaling may contribute, in part, to the underlying adverse cardiovascular outcomes observed with cyclooxygenase-2 inhibition