Screening forCronobacterSpecies in Powdered and Reconstituted Infant Formulas and from Equipment Used in Formula Preparation in Maternity Hospitals

Background/Aims: Cronobacter spp. have been identified as being of considerable risk to neonates. The occurrence of organism in infant formulas is therefore of considerable interest. Methods: The occurrence of Cronobacter spp. in infant feeds (formulas and fortified cow’s milk) was determined using most probable number (MPN) analysis, and from formula preparation utensils. Ninety nine samples were analyzed, of which 42 were unopened cans of powdered infant formula (PIF), 25 reconstituted infant formulas in feeding bottles, 27 utensils used from the preparation of infant formula, and 5 samples of fortified cow’s milk. Presumptive Cronobacter spp. isolates were identified using the 7 allele multilocus sequence typing (MLST) scheme. Results: C. sakazakii, C. malonaticus and C. muytjensii were recovered from PIF. Although the incidence of Cronobacter in PIF was 29% (12/42), the level was low with an average of 0.54 MPN/100g. According to MLST profiling, C. sakazakii was the most frequently isolated Cronobacter species, and C. sakazakii ST4 (associated with neonatal meningitis) was recovered from 2/42 PIF samples at 0.51 and 0.92 MPN/100g. Conclusions: Cronobacter spp. can be isolated from PIF and therefore strict hygienic practices during PIF preparation are important to minimize neonate exposure and reduce the risk of severe infections

Cellular Agriculture and Intellectual Property Law

This is the author accepted manuscript. The final version is available from ElsevierIntellectual Property (IP) rights have been inextricably intertwined with the emergence of transformative technologies as means to reward intellectual creation since the beginning of human ingenuity. Cell-cultivation technology to produce food for human consumption is no exception. From trade secrets to patents and trademarks, the production of food for human consumption using cell-cultivation technology confronts innovators, manufacturers, regulators and consumers with an array of challenges. What we understand as IP, and how we engage with it, will shape the contours of academic discourse, public policy debates and entrepreneurial success. Equally, encountering IP law at a multiplicity of levels, cellular agriculture as an emerging field of enquiry appears to challenge Lockean approaches to IP as a legal monopoly, questioning their limits to promote social progress. This chapter explores IP rights in cellular agriculture to elucidate the extent to which they are deployed to generate optimal public welfare. The central tenet of the proposition in this chapter, that ‘open science’ may be a critical element in a flourishing innovation ecosystem, reflects on the significance of calibrating IP rights to display societal benefits, and on the potential to construe cell-cultivation technology as a ‘technology of abundance’. Here, the argument is not that IP rights necessarily have to be operationalised as scarce resources to enable innovation. Rather, this long-held presumption of exhaustion is explored through a public interest lens, contending that IP law has the ability to invigorate multiple tonalities in new, sustainable global economic governance mechanisms, while being mindful of, and in fact amplify, a variety of seemingly unrelated elements uniting to address complex social challenges. It also offers reflections on reconciling diverging jurisdictional approaches to regulating IP that takes account of emerging legal risks in a post-scarcity economy

Impact of benign prostatic hyperplasia pharmacological treatment on transrectal prostate biopsy adverse effects

Background. Benign prostatic hyperplasia (BPH) pharmacological treatment may promote a decrease in prostate vascularization and bladder neck relaxation with theoretical improvement in prostate biopsy morbidity, though never explored in the literature. Methods. Among 242 consecutive unselected patients who underwent prostate biopsy, after excluding those with history of prostate biopsy/surgery or using medications not for BPH, we studied 190 patients. On the 15th day after procedure patients were questioned about symptoms lasting over a week and classified according to pharmacological BPH treatment. Results. Thirty-three patients (17%) were using alpha-blocker exclusively, five (3%) 5-alpha-reductase inhibitor exclusively, twelve (6%) patients used both medications, and 140 (74%) patients used none. There was no difference in regard to age among groups (P = 0.5). Postbiopsy adverse effects occurred as follows: hematuria 96 (50%), hematospermia 53 (28%), hematochezia 22 (12%), urethrorrhagia 19 (10%), fever 5 (3%), and pain 20 (10%). There was a significant negative correlation between postbiopsy hematuria and BPH pharmacological treatment with stronger correlation for combined use of 5-alpha-reductase inhibitor and alpha-blocker over 6 months (P = 0.0027). Conclusion. BPH pharmacological treatment, mainly combined for at least 6 months seems to protect against prostate biopsy adverse effects. Future studies are necessary to confirm our novel results. © 2014 Marina Zamuner et al.Benign prostatic hyperplasia (BPH) pharmacological treatment may promote a decrease in prostate vascularization and bladder neck relaxation with theoretical improvement in prostate biopsy morbidity, though never explored in the literature. Methods. Amongsem informaçãosem informação(2013) Overview: Prostate Cancer. How Many Men Get Prostate Cancer?, , http://www.cancer.org/acs/groups/cid/documents/webcontent/003072-pdf.pdfRabbani, F., Stroumbakis, N., Kava, B.R., Cookson, M.S., Fair, W.R., Incidence and clinical significance of false-negative sextant prostate biopsies (1998) Urologe - Ausgabe A, 37 (6), p. 660Thompson, I.M., Pauler, D.K., Goodman, P.J., Tangen, C.M., Lucia, M.S., Parnes, H.L., Minasian, L.M., Coltman Jr., C.A., Prevalence of prostate cancer among men with a prostate-specific antigen level ≤4.0 ng per milliliter (2004) New England Journal of Medicine, 350 (22), pp. 2239-2246+2321. , DOI 10.1056/NEJMoa031918Ahrens, M.J., Bertin, P.A., Vonesh, E.F., Meade, T.J., Catalona, W.J., Georganopoulou, D., PSA enzymatic activity: A new biomarker for assessing prostate cancer aggressiveness (2013) Prostate, 73 (16), pp. 1731-1737. , 10.1002/pros.22714Rifkin, M.D., Alexander, A.A., Pisarchick, J., Matteucci, T., Palpable masses in the prostate: Superior accuracy of US-guided biopsy compared with accuracy of digitally guided biopsy (1991) Radiology, 179 (1), pp. 41-42. , 2-s2.0-0025969342Loeb, S., Vellekoop, A., Ahmed, H.U., Catto, J., Emberton, M., Nam, R., Rosario, D.J., Lotan, Y., Systematic review of complications of prostate biopsy (2013) European Urology, 64 (6), pp. 876-892. , 10.1016/j.eururo.2013.05.049Shen, P.-F., Zhu, Y.-C., Wei, W.-R., Li, Y.-Z., Yang, J., Li, Y.-T., Li, D.-M., Zeng, H., The results of transperineal versus transrectal prostate biopsy: A systematic review and meta-analysis (2012) Asian Journal of Andrology, 14 (2), pp. 310-315. , 2-s2.0-84858059084 10.1038/aja.2011.130Kravchick, S., Cytron, S., Mamonov, A., Peled, R., Linov, L., Effect of short-term dutasteride therapy on prostate vascularity in patients with benign prostatic hyperplasia: A pilot study (2009) Urology, 73 (6), pp. 1274-1278. , 2-s2.0-67349198057 10.1016/j.urology.2008.08.461Liao, C.-H., Guh, J.-H., Chueh, S.-C., Yu, H.-J., Anti-angiogenic effects and mechanism of prazosin (2011) Prostate, 71 (9), pp. 976-984. , 2-s2.0-79955575350 10.1002/pros.21313Keledjian, K., Borkowski, A., Kim, G., Isaacs, J.T., Jacobs, S.C., Kyprianou, N., Reduction of human prostate tumor vascularity by the α1- adrenoceptor antagonist terazosin (2001) Prostate, 48 (2), pp. 71-78. , DOI 10.1002/pros.1083Angulo, J., Cuevas, P., Fernández, A., La Fuente, J.M., Allona, A., Moncada, I., De Tejada, I.S., Tadalafil enhances the inhibitory effects of tamsulosin on neurogenic contractions of human prostate and bladder neck (2012) The Journal of Sexual Medicine, 9 (9), pp. 2293-2306. , 10.1111/j.1743-6109.2012.02821.xReis, L.O., Zani, E.L., Alonso, J.C., Simões, F.A., Rejowski, R.F., Ferreira, U., Does the criterion for prostate biopsy indication impact its accuracy? A prospective population-based outpatient clinical setting study (2011) Actas Urologicas Espanolas, 35 (1), pp. 10-14. , 2-s2.0-79151485525 10.1016/j.acuro.2010.06.011Junqueira, V.C.N., Zogbi, O., Cologna, A., Dos Reis, R.B., Tucci, Jr.S., Reis, L.O., Westphalen, A.C., Muglia, V.F., Is a visible (hypoechoic) lesion at biopsy an independent predictor of prostate cancer outcome? (2012) Ultrasound in Medicine and Biology, 38 (10), pp. 1689-1694. , 10.1016/j.ultrasmedbio.2012.06.006Reis, L.O., Reinato, J.A.S., Silva, D.C., Matheus, W.E., Denardi, F., Ferreira, U., The impact of core biopsy fragmentation in prostate cancer (2010) International Urology and Nephrology, 42 (4), pp. 965-969. , 2-s2.0-78751646334 10.1007/s11255-010-9720-0Anastasiadis, A., Zapała, L., Cordeiro, E., Antoniewicz, A., Dimitriadis, G., De Reijke, T., Complications of prostate biopsy (2013) Expert Review of Anticancer Therapy, 13 (7), pp. 829-837. , 10.1586/14737140.2013.811056Campeggi, A., Ouzaid, I., Xylinas, E., Lesprit, P., Hoznek, A., Vordos, D., Abbou, C.C., De La Taille, A., Acute bacterial prostatitis after transrectal ultrasound-guided prostate biopsy: Epidemiological, bacteria and treatment patterns from a 4-year prospective study (2013) International Journal of Urology, 21 (2), pp. 152-155. , 10.1111/iju.12207Pinkhasov, G.I., Lin, Y.-K., Palmerola, R., Smith, P., Mahon, F., Kaag, M.G., Dagen, J.E., Raman, J.D., Complications following prostate needle biopsy requiring hospital admission or emergency department visits - Experience from 1000 consecutive cases (2012) BJU International, 110, pp. 369-374. , 2-s2.0-84856569661 10.1111/j.1464-410X.2011.10926.xPeyromaure, M., Ravery, V., Messas, A., Toublanc, M., Boccon-Gibod, L., Boccon-Gibod, L., Pain and morbidity of an extensive prostate 10-biopsy protocol: A prospective study in 289 patients (2002) Journal of Urology, 167 (1), pp. 218-221Ozdal, O.L., Ozden, C., Benli, K., Gokkaya, S., Bulut, S., Memis, A., Effect of short-term finasteride therapy on peroperative bleeding in patients who were candidates for transurethral resection of the prostate (TUR-P): A randomized controlled study (2005) Prostate Cancer and Prostatic Diseases, 8 (3), pp. 215-218. , DOI 10.1038/sj.pcan.4500818, PII 4500818Pastore, A.L., Mariani, S., Barrese, F., Palleschi, G., Valentini, A.M., Pacini, L., Petrozza, V., Cappa, M., Transurethral resection of prostate and the role of pharmacological treatment with dutasteride in decreasing surgical blood loss (2013) Journal of Endourology, 27 (1), pp. 68-70. , 10.1089/end.2012.0231Hahn, R.G., Fagerström, T., Tammela, T.L.J., Van Vierssen Trip, O., Beisland, H.O., Duggan, A., Morrill, B., Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride (2007) BJU International, 99 (3), pp. 587-594. , 2-s2.0-33846934500 10.1111/j.1464-410X.2006.06619.xArratia-Maqueo, J.A., Garza-Cortés, R., Gómez-Guerra, L.S., Cortés-Gonzlez, J.R., Effect of one month treatment with dutasteride on transurethral resection of the prostate (2010) Actas Urologicas Espanolas, 34 (10), pp. 866-869. , 2-s2.0-78049478337 10.1016/j.acuro.2010.06.00

Comparative Study Of Planned And Unplanned Excisions For The Treatment Of Soft Tissue Sarcoma Of The Extremities.

Unplanned excision of soft tissue sarcomas is common because benign soft tissue lesions are very frequent. This study evaluated the impact of unplanned resections on overall survival, local recurrence and distant metastasis in patients with soft tissue sarcomas of the extremities. In total, 52 patients who were diagnosed with soft tissue sarcomas between May 2001 and March 2011 were analyzed in a retrospective study. Of these patients, 29 (55.8%) had not undergone previous treatment and the remaining 23 (44.2%) patients had undergone prior resection of the tumor without oncological planning. All subsequent surgical procedures were performed at the same cancer referral center. The follow-up ranged from 6 to 122 months, with a mean of 39.89 months. Age, lesion size and depth, histological grade, surgical margins, overall survival, local and distant recurrence and adjuvant therapies were compared. Residual disease was observed in 91.3% of the re-resected specimens in the unplanned excision group, which exhibited greater numbers of superficial lesions, low histological grades and contaminated surgical margins compared with the re-resected specimens in the planned excision group. No differences were observed in local recurrence and 5-year overall survival between the groups, but distant metastases were significantly associated with planned excision after adjustment for the variables. There was no difference between patients undergoing unplanned excision and planned excision regarding local recurrence and overall survival. The planned excision group had a higher risk of distant metastasis, whereas there was a high rate of residual cancer in the unplanned excision group.69579-8

Desmoid Tumor In Patients With Familial Adenomatous Polyposis.

Desmoid tumors constitute one of the most important extraintestinal manifestations of familial adenomatous polyposis. The development of desmoids is responsible for increasing morbidity and mortality rates in cases of familial adenomatous polyposis. To evaluate the occurrence of desmoid tumors in familial adenomatous polyposis cases following prophylactic colectomy and to present patient outcome. Between 1984 and 2008, 68 patients underwent colectomy for familial adenomatous polyposis at the School of Medical Sciences Teaching Hospital, University of Campinas, SP, Brazil. Desmoid tumors were found in nine (13.2%) of these patients, who were studied retrospectively by consulting their medical charts with respect to clinical and surgical data. Of nine patients, seven (77.8%) were submitted to laparotomy for tumor resection. Median age at the time of surgery was 33.9 years (range 22-51 years). Desmoid tumors were found in the abdominal wall in 3/9 cases (33.3%) and in an intra-abdominal site in the remaining six cases (66.7%). Median time elapsed between ileal pouch-anal anastomosis and diagnosis of desmoid tumor was 37.5 months (range 14-60 months), while the median time between colectomy with ileorectal anastomosis and diagnosis was 63.7 months (range 25-116 months). In 6/9 (66.7%) patients with desmoid tumors, the disease was either under control or there was no evidence of tumor recurrence at a follow-up visit made a mean of 63.1 months later (range 12-240 months). Desmoid tumors were found in 13.2% of cases of familial adenomatous polyposis following colectomy; therefore, familial adenomatous polyposis patients should be followed-up and surveillance should include abdominal examination to detect signs and symptoms. Treatment options include surgery and clinical management with antiestrogens, antiinflammatory drugs or chemotherapy.47373-

Targeted imaging of integrins in cancer tissues using photocleavable Ru(ii) polypyridine complexes as mass-tags

Targeted epitope-based mass spectrometry imaging (MSI) utilizes laser cleavable mass-tags bound to targeting moieties for detecting proteins in tissue sections. Our work constitutes the first proof-of-concept of a novel laser desorption ionization (LDI)-MSI strategy using photocleavable Ru(ii) polypyridine complexes as mass-tags for imaging of integrins avß3 in human cancer tissues

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

Demonstrating the reliability of in vivo metabolomics based chemical grouping:towards best practice

While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidance is required. The MetAbolomics ring Trial for CHemical groupING (MATCHING), comprising six industrial, government and academic ring-trial partners, evaluated inter-laboratory reproducibility and worked towards best-practice. An independent team selected eight substances (WY-14643, 4-chloro-3-nitroaniline, 17α-methyl-testosterone, trenbolone, aniline, dichlorprop-p, 2-chloroaniline, fenofibrate); ring-trial partners were blinded to their identities and modes-of-action. Plasma samples were derived from 28-day rat tests (two doses per substance), aliquoted, and distributed to partners. Each partner applied their preferred liquid chromatography–mass spectrometry (LC–MS) metabolomics workflows to acquire, process, quality assess, statistically analyze and report their grouping results to the European Chemicals Agency, to ensure the blinding conditions of the ring trial. Five of six partners, whose metabolomics datasets passed quality control, correctly identified the grouping of eight test substances into three categories, for both male and female rats. Strikingly, this was achieved even though a range of metabolomics approaches were used. Through assessing intrastudy quality-control samples, the sixth partner observed high technical variation and was unable to group the substances. By comparing workflows, we conclude that some heterogeneity in metabolomics methods is not detrimental to consistent grouping, and that assessing data quality prior to grouping is essential. We recommend development of international guidance for quality-control acceptance criteria. This study demonstrates the reliability of metabolomics for chemical grouping and works towards best-practice