A Pilot Study Investigating the Utilization of Crest Pads for Treatment of Toe Callus and Ulceration (Presentation)

Patients with lesser-toe deformities are at increased risk of developing calluses and ulcers on the distal ends of the affected digits because of the increased pressures applied to these areas. The number of diabetic patients in the United States continues to increase, along with associated comorbidities such as peripheral vascular disease and peripheral neuropathy. These conditions predispose patients to developing foot ulcerations, especially if foot deformities are present. Crest pads are a simple-to-make, inexpensive option to treat calluses and ulcerations on the distal ends of digits; however, there is no research available that support their use. Crest pads consist of rolled gauze covered in moleskin, with a large opening that fits over several toes and lies on the dorsal aspect of the foot, with the padded portion resting under the toes. Over several days of use, the pad molds to the plantar aspect of the toes, offloading pressure from the distal end of the affected digit(s). The sample was obtained through a retrospective chart review of patients identified as having had at least one nail care visit and at least one follow-up visit at a vascular surgery practice between August 2011 and December 2014. Potential subjects with toe deformities who presented with callus or ulcer on the distal end of a digit were considered for inclusion, if they received a crest pad as part of their treatment plan. The scholarly project was a preintervention or postintervention design with subjects acting as their own controls. McNemar\u27s test was used to analyze the results which were statistically significant (P \u3c .0001 at first callus follow-up and P = .0002 at second callus follow-up) for callus, hemorrhagic callus, and/or ulcer improvement following the crest pad intervention. The results of this scholarly project support the use of crest pads in patients with lesser-toe deformities to treat distal toe calluses and/or ulcerations

Global shortage of technical agars: back to basics (resource management)

Bacteriological and technical agars are in short supply with potential consequences for research, public health, and clinical labs around the world. To diagnose bottlenecks and sustainability problems that may be putting the industry at risk, we analyzed the available time series for the global landings of Gelidium, the most important raw materials for the industry. Data on the harvest of Gelidium spp. have been reported since1912, when Japan was the only producer. After World War II the diversification of harvested species and producing countries resulted in a strong increase in global landings. Maximum harvest yields of almost 60,000 t year(-1) in the 1960s were sustained until the 1980s, after which landings decreased continuously to the present. In the 2010s, a reduction in the global production to about 25,000 t year(-1) was observed, which was lower than the yields of the 1950s. Landings by important producers such as Japan, Korea, Spain, and Portugal have collapsed. This is the ultimate cause of the present shortage of bacteriological and technical agars. However, an important factor at play is the concentration of the global landings of Gelidium in Morocco, as its relative contribution increased from 23% in the 1960s to the present 82%. Two specific bottlenecks were identified: restrictive export quotas of unprocessed Gelidium in favor of the national agar industry and resource management regulations that were apparently not enforced resulting in over-harvesting and resource decline. The global industry may well be dependent on resource management basics. Simple harvest statistics must be gathered such as the harvest effort and the variation of harvest yields along the harvest season. We discuss how this information is fundamental to manage the resource. The available harvest statistics are generally poor and limited and vary significantly among different sources of data. Probable confusions between dry and wet weight reporting and poor discrimination of the species harvested need to be resolved

Changes in visual function after intraocular pressure reduction using antiglaucoma medications

Purpose To evaluate the change in visual function after starting glaucoma treatment and correlate this to a decrease in intraocular pressure (IOP) in primary open-angle glaucoma patients.Methods A prospective, randomized clinical trial was carried out involving 54 glaucoma patients (54 eyes). After inclusion, patients randomly received timolol maleate 0.5%, brimonidine tartrate 0.2%, or travoprost 0.004% in one randomly selected eye. Patients underwent Goldmann applanation tonometry, visual acuity test, standard automated perimetry (SAP), visual quality perception test (visual analogue scale), and contrast sensitivity (CS) test, in a random order before and after the 4-week glaucoma treatment.Results There were statistically significant changes in IOP (mean change [standard deviation], 7.8 [3.6] mmHg, P 0.001), SAP mean deviation index (0.84 [2.45] dB, P = 0.02), visual quality perception (0.56 [1.93], P = 0.045), and CS at frequencies of 12 cycles/degree (0.10 [0.37], P = 0.03) and 18 cycles/degree (0.18 [0.42], P = 0.02) after the 4-week treatment when compared with baseline. No statistically significant differences were found between the treatment groups in visual function changes after treatment (P > 0.40). No significant correlations between IOP reduction and changes in visual function were found (P > 0.30).Conclusions Visual quality perception, visual field mean deviation index, and CS at higher frequencies improve after starting glaucoma therapy. However, no correlation was found between IOP reduction and changes in visual function, and no differences were found in visual function when the three medications studied were compared. Eye (2009) 23, 1081-1085; doi:10.1038/eye.2008.226; published online 1 August 2008Universidade Federal de São Paulo, Glaucoma Serv, Dept Ophthalmol, BR-01404001 São Paulo, BrazilUniversidade Federal de São Paulo, Glaucoma Serv, Dept Ophthalmol, BR-01404001 São Paulo, BrazilWeb of Scienc

Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification

Stromal-derived intratumoural heterogeneity (ITH) has been shown to undermine molecular stratification of patients into appropriate prognostic/predictive subgroups. Here, using several clinically relevant colorectal cancer (CRC) gene expression signatures, we assessed the susceptibility of these signatures to the confounding effects of ITH using gene expression microarray data obtained from multiple tumour regions of a cohort of 24 patients, including central tumour, the tumour invasive front and lymph node metastasis. Sample clustering alongside correlative assessment revealed variation in the ability of each signature to cluster samples according to patient-of-origin rather than region-of-origin within the multi-region dataset. Signatures focused on cancer-cell intrinsic gene expression were found to produce more clinically useful, patient-centred classifiers, as exemplified by the CRC intrinsic signature (CRIS), which robustly clustered samples by patient-of-origin rather than region-of-origin. These findings highlight the potential of cancer-cell intrinsic signatures to reliably stratify CRC patients by minimising the confounding effects of stromal-derived ITH

The EYA Tyrosine Phosphatase Activity Is Pro-Angiogenic and Is Inhibited by Benzbromarone

Eyes Absents (EYA) are multifunctional proteins best known for their role in organogenesis. There is accumulating evidence that overexpression of EYAs in breast and ovarian cancers, and in malignant peripheral nerve sheath tumors, correlates with tumor growth and increased metastasis. The EYA protein is both a transcriptional activator and a tyrosine phosphatase, and the tyrosine phosphatase activity promotes single cell motility of mammary epithelial cells. Since EYAs are expressed in vascular endothelial cells and cell motility is a critical feature of angiogenesis we investigated the role of EYAs in this process. Using RNA interference techniques we show that EYA3 depletion in human umbilical vein endothelial cells inhibits transwell migration as well as Matrigel-induced tube formation. To specifically query the role of the EYA tyrosine phosphatase activity we employed a chemical biology approach. Through an experimental screen the uricosuric agents Benzbromarone and Benzarone were found to be potent EYA inhibitors, and Benzarone in particular exhibited selectivity towards EYA versus a representative classical protein tyrosine phosphatase, PTP1B. These compounds inhibit the motility of mammary epithelial cells over-expressing EYA2 as well as the motility of endothelial cells. Furthermore, they attenuate tubulogenesis in matrigel and sprouting angiogenesis in the ex vivo aortic ring assay in a dose-dependent fashion. The anti-angiogenic effect of the inhibitors was also demonstrated in vivo, as treatment of zebrafish embryos led to significant and dose-dependent defects in the developing vasculature. Taken together our results demonstrate that the EYA tyrosine phosphatase activity is pro-angiogenic and that Benzbromarone and Benzarone are attractive candidates for repurposing as drugs for the treatment of cancer metastasis, tumor angiogenesis, and vasculopathies

Hepatobiliary and pancreatic tuberculosis: A two decade experience

<p>Abstract</p> <p>Background</p> <p>Isolated hepatobiliary or pancreatic tuberculosis (TB) is rare and preoperative diagnosis is difficult. We reviewed our experience over a period two decades with this rare site of abdominal tuberculosis.</p> <p>Methods</p> <p>The records of 18 patients with proven histological diagnosis of hepatobiliary and pancreatic tuberculosis were reviewed retrospectively. The demographic features, sign and symptoms, imaging, cytology/histopathology, procedures performed, outcome and follow up data were obtained from the departmental records. The diagnosis of tuberculosis was based on granuloma with caseation necrosis on histopathology or presence of acid fast bacilli.</p> <p>Results</p> <p>Of 18 patients (11 men), 11 had hepatobiliary TB while 7 had pancreatic TB. Two-thirds of the patients were < 40 years (mean: 42 yrs; range 19–70 yrs). The duration of the symptoms varied between 2 weeks to 104 weeks (mean: 20 weeks). The most common symptom was pain in the abdomen (n = 13), followed by jaundice (n = 10), fever, anorexia and weight loss (n = 9). Five patients (28%) had associated extra-abdominal TB which helped in preoperative diagnosis in 3 patients. Imaging demonstrated extrahepatic bile duct obstruction in the patients with jaundice and in addition picked up liver, gallbladder and pancreatic masses with or without lymphadenopathy (peripancreatic/periportal). Preoperative diagnosis was made in 4 patients and the other 14 were diagnosed after surgery. Two patients developed significant postoperative complications (pancreaticojejunostomy leak <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> intraabdominal abscess <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>) and 3 developed ATT induced hepatotoxicity. No patient died. The median follow up period was 12 months (9 – 96 months).</p> <p>Conclusion</p> <p>Tuberculosis should be considered as a differential diagnosis, particularly in young patients, with atypical signs and symptoms coming from areas where tuberculosis is endemic and preoperative tissue and/or cytological diagnosis should be attempted before labeling them as hepatobiliary and pancreatic malignancy.</p

A Novel Acyl-CoA Beta-Transaminase Characterized from a Metagenome

BACKGROUND: Bacteria are key components in all ecosystems. However, our knowledge of bacterial metabolism is based solely on the study of cultivated organisms which represent just a tiny fraction of microbial diversity. To access new enzymatic reactions and new or alternative pathways, we investigated bacterial metabolism through analyses of uncultivated bacterial consortia. METHODOLOGY/PRINCIPAL FINDINGS: We applied the gene context approach to assembled sequences of the metagenome of the anaerobic digester of a municipal wastewater treatment plant, and identified a new gene which may participate in an alternative pathway of lysine fermentation. CONCLUSIONS: We characterized a novel, unique aminotransferase that acts exclusively on Coenzyme A (CoA) esters, and proposed a variant route for lysine fermentation. Results suggest that most of the lysine fermenting organisms use this new pathway in the digester. Its presence in organisms representative of two distinct bacterial divisions indicate that it may also be present in other organisms