South American Programme: Brazil.

1355-

Antifungals In Eye Infections: Drugs And Routes Of Administration

Treatment of fungal eye infections represents a challenge to the ophthalmology practice. For an adequate therapeutic response, besides correct drug choice, it is necessary an effectively administration. This script gathers information about the major antifungal drugs used in eye infections, their concentrations and main administration routes.722132141Leber, T.H., Keratomycosis aspergillina als ursache von hypopyonkeratites (1879) Graefes Ach Clin Exp Ophthalmol, 25, pp. 285-301Alfonso, E.C.G.A., Miller, D., Fungal keratitis (2011) Cornea: fundamentals, diagnosis and management, , In: Krachmer JH, Mannis MJ, Holland EJ, editors.3rd ed. 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ACP J Club. 2003;139(1):15. N Engl J Med. 2003;348(13):1287-8author reply 1287-8Shirley, S.F., Little, J.R., Immunopotentiating effects of amphotericin B (1979) I.Enhanced contact sensitivity in mice. J Immunol., 123 (6), pp. 2878-2882Shirley, S.F., Little, J.R., Immunopotentiating effects of amphotericin B (1979) II Enhanced in vitro proliferative responses of murine lymphocytes. J Immunol., 123 (6), pp. 2883-2889Green, W.R., Bennett, J.E., Goos, R.D., Ocular penetration of amphotericin B: a report of laboratory studies and a case report of postsurgical cephalosporium endophthalmitis (1965) Arch Ophthalmol, 73, pp. 769-775Goldblum, D., Frueh, B.E., Zimmerli, S., Böhnke, M., Treatment of postkeratitis fusarium endophthalmitis with amphotericin B lipid complex (2000) Cornea, 19 (6), pp. 853-856O'Day, D.M., Head, W.S., Robinson, R.D., Stern, W.H., Freeman, J.M., Intraocular penetration of systemically administered antifungal agents (1985) Curr Eye Res, 4 (2), pp. 131-134. , Erratum in: Curr Eye Res 1986;5(7):547Qu, L., Li, L., Xie, H., Corneal and aqueous humor concentrations of amphotericin B using three different routes of administration in a rabbit model (2010) Ophthalmic Res, 43 (3), pp. 153-158Pleyer, U., Grammer, J., Pleyer, J.H., Kosmidis, P., Friess, D., Schmidt, K.H., Thiel, H.J., Studies with local administration of liposome incorporated amphotericin (1995) Amphotericin B-bioavailability in the cornea Ophthalmologe, 92 (4), pp. 469-475. , GermanO'Day, D.M., Head, W.S., Robinson, R.D., Clanton, J.A., Corneal penetration of topical amphotericin B and natamycin (1986) Curr Eye Res, 5 (11), pp. 877-882O'Day, D.M., Ray, W.A., Head, W.S., Robinson, R.D., Influence of the corneal epithelium on the efficacy of topical antifungal agents (1984) Invest Ophthalmol Vis Sci, 25 (7), pp. 855-859Hirose, H., Terasaki, H., Awaya, S., Yasuma, T., Treatment of fungal corneal ulcers with amphotericin B ointment (1997) Am J Ophthalmol, 124 (6), pp. 836-838Wood, T.O., Williford, W., Treatmen of keratomycosis with amphotericin B 015% (1976) Am J Ophthalmol., 81 (6), pp. 847-849O'Day, D.M., Selection of appropriate antifungal therapy (1987) Cornea, 6 (4), pp. 238-245. , ReviewO'Day, D.M., Ray, W.A., Robinson, R.D., Head, W.S., Williams, T.E., Differences in response in vivo to amphotericin B among Candida albicans strains (1991) Invest Ophthalmol Vis Sci, 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(1989) Aust N Z J Ophthalmol, 17 (3), pp. 295-297Fitzsimons, R., Peters, A.L., Miconazole and ketoconazole as a satisfactory first-line treatment for keratomycosis (1986) Am J Ophthalmol, 101 (5), pp. 605-608Gupta, S.K., Efficacy of miconazole in experimental keratomycosis (1986) Aust N Z J Ophthalmol, 14 (4), pp. 373-376Foster, C.S., Miconazole therapy for keratomycosis (1981) Am J Ophthalmol, 91 (5), pp. 622-629Ishibashi, Y., Kaufman, H.E., The effects of subconjunctival miconazole in the treatment of experimental Candida keratitis in rabbits (1985) Arch Ophthalmol, 103 (10), pp. 1570-1573Thomas, P.A., Current perspectives on ophthalmic mycoses (2003) Clin Microbiol Rev, 16 (4), pp. 730-797Uchida, K., Abe, S., Yamaguchi, H., The postantifungal effect (PAFE) of itraconazole, in comparison with those of miconazole and fluconazole, on Candida Species (2006) Microbiol Immunol, 50 (9), pp. 679-685Heel, R.C., Brogden, R.N., Speight, T.M., Avery, G.S., Econazole: a review of its antifungal 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Khan, R., Sharma, S., Chatterjee, P.K., Clinical and experimental mycotic corneal ulcer caused by Aspergillus fumigatus and the effect of oral ketoconazole in the treatment (1989) Mycopathologia, 106 (3), pp. 133-141Marangon, F.B., Miller, D., Giaconi, J.A., Alfonso, E.C., In vitro investigation of voriconazole susceptibility for keratitis and endophthalmitis fungal pathogens (2004) Am J Ophthalmol, 137 (5), pp. 820-825Rajasekaran, J., Thomas, P.A., Kalavathy, C.M., Joseph, P.C., Abraham, D.J., Itraconazole therapy for fungal keratitis (1987) Indian J Ophthalmol, 35 (5-6), pp. 157-160Abad, J.C., Foster, C.S., Fungal keratitis (1996) Int Ophthalmol Clin, 36 (3), pp. 1- 15. , ReviewKlotz, S.A., Zahid, M., Bartholomew, W.R., Revera, P.M., Butrus, S., Candida albicans keratitis treated successfully with itraconazole (1996) Cornea, 15 (1), pp. 102-104O'Day, D.M., Foulds, G., Williams, T.E., Robinson, R.D., Allen, R.H., Head, W.S., Ocular uptake of fluconazole following oral administration (1990) Arch Ophthalmol, 108 (7), pp. 1006-1008Thakar, M., Oral fluconazole therapy for keratomycosis (1994) Acta Ophthalmol (Copenh), 72 (6), pp. 765-767Urbak, S.F., Degn, T., Fluconazole in the management of fungal ocular infections (1994) Ophthalmologica, 208 (3), pp. 147-156Mahdy, R.A., Nada, W.M., Wageh, M.M., Kader, M.A., Saleh, M.M., Alswad, M.M., Assessment safety and efficacy of a combination therapy of topical amphotericin B and subconjunctival fluconazole for the treatment of fungal keratitis (2010) Cutan Ocul Toxicol, 29 (3), pp. 193-197Yilmaz, S., Maden, A., Severe fungal keratitis treated with subconjunctival fluconazole (2005) Am J Ophthalmol, 140 (3), pp. 454-458. , Comment in Am J Ophthalmol. 2006;141(4):783author reply 783-4Mahdy, R.A., Nada, W.M., Wageh, M.M., Topical amphotericin B and subconjunctival injection of fluconazole combination therapy versus topical amphotericin B monotherapy in treatment of keratomycosis (2010) J Ocul Pharmacol Ther, 26 (3), pp. 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W.F., Lin, T.K., Sponsel, W.E., Graybill, J.R., Voriconazole in the treatment of fungal eye infections: a review of current literature (2008) Br J Ophthalmol, 92 (7), pp. 871-878Herbrecht, R., Denning, D.W., Patterson, T.F., Bennett, J.E., Greene, R.E., Oestmann, J.W., Kern, W.V., Pauw, P.B., Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group.Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis (2002) N Engl J Med, 347 (6), pp. 408- 15. , Comment in N Engl J Med. 2002;347(25):2080-1author reply 2080-1. N Engl J Med. 2002;347(25):2080-1author reply 2080-1. N Engl J Med. 2004;350(9):950-2Freda, R., Use of oral voriconazole as adjunctive treatment of severe cornea fungal infection: case report (2006) Arq Bras Oftalmol, 69 (3), pp. 431-434Hariprasad, S.M., Mieler, W.F., Holz, E.R., Gao, H., Kim, J.E., Chi, J., Prince, R.A., Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans (2004) Arch Ophthalmol, 122 (1), pp. 42-47Gao, H., Pennesi, M., Shah, K., Qiao, X., Hariprasad, S.M., Mieler, W.F., Safety of intravitreal voriconazole: electroretinographic and histopathologic studies (2003) Trans Am Ophthalmol Soc, 101, pp. 183-189. , discussion 189Anderson, K.L., Mitra, S., Salouti, R., Pham, T.A., Taylor, H.R., Fungal keratitis caused by Paecilomyces lilacinus associated with a retained intracorneal hair (2004) Cornea, 23 (5), pp. 516-521Bunya, V.Y., Hammersmith, K.M., Rapuano, C.J., Ayres, B.D., Cohen, E.J., Topical and oral voriconazole in the treatment of fungal keratitis (2007) Am J Ophthalmol, 143 (1), pp. 151-153Lee, S.J., Lee, J.J., Kim, S.D., Topical and oral voriconazole in the treatment of fungal keratitis (2009) Korean J Ophthalmol, 23 (1), pp. 46-48Nulens, E., Eggink, C., Rijs, A.J., Wesseling, P., Verweij, P.E., Keratitis caused by Scedosporium apiospermum successfully treated with a cornea transplant and voriconazole (2003) J Clin Microbiol, 41 (5), pp. 2261-2264Polizzi, A., Siniscalchi, C., Mastromarino, A., Saccà, S.C., Effect of voriconazole on a corneal abscess caused by fusarium (2004) Acta Ophthalmol Scand, 82 (6), pp. 762-764Al-Badriyeh, D., Neoh, C.F., Stewart, K., Kong, D.C., Clinical utility of voriconazole eye drops in ophthalmic fungal keratitis (2010) Clin Ophthalmol, 4, pp. 391-405Dupuis, A., Tournier, N., Moal, L.G., Venisse, N., Preparation and stability of voriconazole eye drop solution (2009) Antimicrob Agents Chemother, 53 (2), pp. 798-799Clode, A.B., Davis, J.L., Salmon, J., Michau, T.M., Gilger, B.C., Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses (2006) Am J Vet Res, 67 (2), pp. 296-301Prakash, G., Sharma, N., Goel, M., Titiyal, J.S., Vajpayee, R.B., Evaluation of intrastromal injection of voriconazole as a therapeutic adjunctive for the management of deep recalcitrant fungal keratitis (2008) Am J Ophthalmol, 146 (1), pp. 56-59Siatiri, H., Daneshgar, F., Siatiri, N., Khodabande, A., The effects of intrastromal voriconazole injection and topical voriconazole in the treatment of recalcitrant Fusarium keratitis (2011) Cornea, 30 (8), pp. 872-875Sharma, N., Agarwal, P., Sinha, R., Titiyal, J.S., Velpandian, T., Vajpayee, R.B., Evaluation of intrastromal voriconazole injection in recalcitrant deep fungal keratitis: case series (2011) Br J Ophthalmol, 95 (12), pp. 1735-1737Giaconi, J.A., Marangon, F.B., Miller, D., Alfonso, E.C., Voriconazole and fungal keratitis: a report of two treatment failures (2006) J Ocul Pharmacol Ther, 22 (6), pp. 437-439Diekema, D.J., Messer, S.A., Hollis, R.J., Jones, R.N., Pfaller, M.A., Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi (2003) J Clin Microbiol, 41 (8), pp. 3623-3626Johnson, L.B., Kauffman, C.A., Voriconazole: a new triazole antifungal agent (2003) Clin Infect Dis, 36 (5), pp. 630-637Espinel-Ingroff, A., Boyle, K., Sheehan, D.J., In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: review of the literature (2001) Mycopathologia, 150 (3), pp. 101-115Marco, F., Pfaller, M.A., Messer, S.A., Jones, R.N., Antifungal activity of a new triazole, voriconazole (UK-109,496), compared with three other antifungal agents tested against clinical isolates of filamentous fungi (1998) Med Mycol, 36 (6), pp. 433-436Ullmann, A.J., Cornely, O.A., Burchardt, A., Hachem, R., Kontoyiannis, D.P., Töpelt, K., Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection (2006) Antimicrob Agents Chemother, 50 (2), pp. 658-666Cuenca-Estrella, M., Gomez-Lopez, A., Mellado, E., Buitrago, M.J., Monzon, A., Rodriguez-Tudela, J.L., Head-to-head comparison of the activities of currently available antifungal agents against 3,378 Spanish clinical isolates of yeasts and filamentous fungi (2006) Antimicrob Agents Chemother, 50 (3), pp. 917-921Torres, H.A., Hachem, R.Y., Chemaly, R

Endoscopic study of the intranasal ostium in external dacryocystorhinostomy postoperative. Influence of saline solution and 5-fluorouracil

PURPOSE: To study, through endoscopy, the postoperative structural changes of the intranasal ostium following external dacryocystorhinostomy and to evaluate the influence of saline solution and 5-fluorouracil. METHODS: Fifty patients were distributed into the following groups: Group SS-dacryocystorhinostomy and an injection of saline solution during surgery (13 patients); Group 5-FUI-dacryocystorhinostomy and an injection of 5 fluorouracil during surgery (17 patients); Group C-dacryocystorhinostomy only (11 patients); Group 5-FU3-dacryocystorhinostomy and 3 injections, 1 during surgery and 1 on the third and fifth postsurgical days (9 patients). RESULTS: Pair-wise group comparisons using the nonparametric Mann-Whitney test revealed that there was a significant reduction of the ostium area only in Group 5-FU1 vs. Group SS on the 60(th) postoperative day (P < .01); however, a comparative study among the 4 groups using the Kruskal-Wallis test showed no significant changes in the ostium area on the 60(th) postoperative day. The ostium area within groups at the 30(th) vs 60(th) postoperative day was significantly reduced for Group C (P < .05; Mann-Whitney test); no significant changes were found for the other groups. DISCUSSION: These results suggest that the use of 5-fluorouracil in external dacryocystorhinostomy does not significantly influence the final size of the surgical fistula as determined 2 months postsurgery.621414

Assessment Of Visual Health Campaign Activities At Schools - Teachers' Perception

Purpose: 1) To assess the opinion of teachers involved in visual screening of school-age children and their referral to ophthalmologic examination within the "Eye-to-Eye National Campaign for Visual Disorders Prevention and Rehabilitation" (Campanha Nacional de Prevenção e Reabilitação Visual Olho no Olho); 2) To identify the teachers' perception with respect to the training received for conducting the campaign. Methods: A descriptive study has been conducted, based on data recorded from the application of a questionnaire to 1,517 elementary school teachers working in public schools in 27 Brazilian states. The following items were examined: received orientation, use of educational videos and handbooks, supplied explanations, difficulties, questions and overall campaign assessment. Results: 82.0% of the teachers stated they had received orientation and 92.0% stated they had read the "Teacher Orientation Manual", Among those who received orientation, 47.0% stated it had been supplied by school officials; 30.0%, by healthcare agents, and 23.0% by ophthalmologists. In the self-assessment of performance, 58.0% reported no difficulties; 32.0% reported questions concerning the campaign activities and the professionals who most frequently asked to provide clarification were those from the State Education Agency (38.0%), followed by the school director (20,0%), Conclusions: Most teachers considered themselves adequately trained and oriented to take part in the campaign. Teachers' training was provided by administrative officials, previously trained by ophthalmologists ("multiplying effect") and the small percentage of questions raised indicated the validity of the procedure. Concerns have been raised as to the information about the ophthalmologic examination, transportation of the children and delivery of glasses. This kind of program always presents some difficulties and requires adjustments. It should, indeed, be improved, perhaps through a closer involvement of the community and families during its development.702239245Krueguer EA. Prevenção da cegueira na infância. Planejamento. Arq Bras Oftalmol. 1969;32(1):23-5Toledo, S.A., (1938) Cooperação da escola primária no combate ao tracoma, pp. 134-138. , São Paulo: Revista Os Tribunais;Castro, R.S., Correção óptica em escolares e condição de uso dos óculos. [tese (2001), Campinas: Faculdade de Ciências Médicas da Universidade Estadual de Campinas;Kara-José, N., Ferrarini, M.L., Temporini, E.R., Avaliação do desenvolvimento do plano de oftalmologia sanitária escolar em três anos de sua aplicação no Estado de São Paulo (1977) Arq Bras Oftalmol, 40 (1), pp. 9-15Conselho Brasileiro de Oftalmologia: 60 anos de CBOlivro demonstrativogestão 1999-2001. São Paulo:CBO2001Alves, M.R., Kara-José, N., Manual de Orientação ao professor (1998) Campanha Nacional de Reabilitação Visual "Olho no Olho", , São Paulo: Impresa Oficial;Oliveira, R.C.S., José, N.K., Arieta, C.E.L., Manual da boa visão do escolar: Solucionando dúvidas sobre o olho e a visão (2001) São PauloBrasília: Conselho Regional de Oftalmologia, , Ministério da Educação;Brasileiro de Oftalmologia, C., Ofício - CBO da Campanha "Olho no Olho (2001) Quadro analítico dos resultados finais e parciais 2001, , São Paulo: CBO;José, N.K., organizador, (1996) Prevenção da cegueira por catarata, pp. 55-80. , Campinas: Unicamp;Kara-Jos, C., Gonçalves, E.R., Carvalho, R.S., organizadores, (2006) Olho no olho: Campanha nacional de prevenção à cegueira e reabilitação visual do escolar, , Rio de Janeiro: Cultura Médica;Temporini, E.R., Kara-José, N., Rigolizzo, H.B., Envolvimento de pessoal da comunidade em projeto de detecção de ambliopia em pré-escolares (1983) Arq Bras Oftalmol, 46 (3), pp. 85-89Alves, M.R., Temporini, E.R., Kara-José, N., Atendimento oftalmológico de escolares do sistema público de ensino no município de São Paulo: Aspectos médico-sociais (2000) Arq Bras Oftalmol, 63 (5), pp. 359-363Russ, H.H.A., Temporini, E.R., Kara-José, N., Impacto da Campanha Olho no Olho em escolas de ensino fundamental: Percepção do pessoal de ensino (2004) Arq Bras Oftalmol, 67 (2), pp. 311-321Temporini, E.R., Kara-José, N., Taiar, A., Ferrarini, M.L., Validade da aferição da. acuidade visual realizada pelo professor em escolares de 1a a 4a séries de primeiro grau de uma escola pública do município de São Paulo, Brasil (1977) Rev Saúde Pública, 11, pp. 229-237Brasileiro de Oftalmologia, C., (1998) Ofício CBO: "Orientações Gerais aos Coordenadores Estaduais, Municipais e demais participantes da Campanha", , São Paulo: CBO;Temporini, E.R., Percepção de professores do sistema de ensino do Estado de São Paulo sobre seu preparo em saúde do escolar (1988) Rev Saúde Pública, 22 (5), pp. 411-421Cavalcante, S.M., José, N.K., Temporini, E.R., Percepção de pais de escolares da 1a série do ensino fundamental a respeito da campanha Olho no Olho 2000, na cidade de Maceió-Alagoas (2004) Arq Bras Oftalmol, 67 (1), pp. 87-91Abud, A.B., Ottaiano, J.A.A., Aspectos socioeconômicos que influenciam no comparecimento ao exame oftalmológico de escolares com alterações visuais (2004) Arq Bras Oftalmol, 67 (5), pp. 773-77

Effects and Implications of Wearing a Face Mask on Cardiopulmonary Performance During Exercise

The coronavirus disease 2019 (COVID-19) pandemic has prompted the use of a face mask (FM) to minimize the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. The use of an FM being an accepted precautionary measure to reduce viral transmission, there is a need for examining the physiological effects of wearing an FM, specifically during exercise. PURPOSE: To assess the impact of wearing a surgical FM on cardiopulmonary parameters and exercise performance. METHODS: Nine males and 9 females (age = 21.6 ± 2.5 yrs; BMI = 24.4 ± 3.1 kg/m2) participated in 2 laboratory visits where they completed a graded maximal exercise test using a modified Bruce Protocol. Participants were randomized to which laboratory visit they would complete first, with face mask (WFM) or without face mask (WOFM), which were performed at least 48 hours apart. Expired gases, blood pressure, heart rate, blood O2 saturation including perfusion index, and the Borg Rating of Perceived Exertion (RPE) were measured and compared between the WFM and WOFM trials at 6 different intensities (rest, 40%, 55%, 70%, 80%, and 100% VO2max), using a two-way repeated measures ANOVA. RESULTS: There was a significant difference in VO2 (p = 0.001 and n2 = 0.73) between the WFM (38.5 ± 6.8 mL/kg/min) and WOFM (44.3 ± 7.4 mL/kg/min) trials only at the 100% VO2max intensity, where significantly lower values were also found during the WFM trial for respiratory rate (40.0 ± 6.8 vs 47.8 ± 8.9 bpm, p = 0.001, n2 = 0.62), respiratory exchange ratio (1.07 ± 0.08 vs 1.14 ± 0.64, p = 0.001, n2 = 0.52), and the partial pressure of expired oxygen (125.7 ± 3.5 vs 129.4 ± 3.1 mmHg, p = 0.0001, n2 = 0.54). In contrast, the partial pressure of expired carbon dioxide (32.8 ± 3.1 vs 30.8 ± 3.3 mmHg, p = 0.01, n2 = 0.33) was significantly higher during the WFM trial only at 100% VO2max intensity. No other parameters significantly differed at any of the intensities. CONCLUSION: Oxygen consumption was lower with face masks only as participants advanced from 80% to maximal effort. Notably, participants had a slower respiratory rate and exhaled a higher concentration of carbon dioxide with face masks. This result suggests that expired carbon dioxide accumulated under the face masks and participants subsequently rebreathed this expired carbon dioxide. There is no evidence that suggests exercise below 80% of VO2max while wearing face masks will cause any concerning changes in cardiopulmonary parameters. However, it is recommended that future studies examine how different types of face masks may affect cardiopulmonary function during exercise in a variety of subject populations

Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion

Offspring of obese mothers suffer higher risks of type 2 diabetes due to increased adiposity and decreased β cell function. To date, the sex-differences in offspring islet insulin secretion during early life has not been evaluated extensively, particularly prior to weaning at postnatal day 21 (P21). To determine the role of maternal obesity on offspring islet insulin secretion, C57BL/6J female dams were fed chow or western diet from 4 weeks prior to mating to induce maternal obesity. First, offspring of chow-fed and obese dams were evaluated on postnatal day 21 (P21) prior to weaning for body composition, glucose and insulin tolerance, and islet phasic insulin-secretion. Compared to same-sex controls, both male and female P21 offspring born to obese dams (MatOb) had higher body adiposity and exhibited sex-specific differences in glucose tolerance and insulin secretion. The male MatOb offspring developed the highest extent of glucose intolerance and lowest glucose-induced insulin secretion. In contrast, P21 female offspring of obese dams had unimpaired insulin secretion. Using SAX-HPLC, we found that male MatOb had a decrease in pancreatic heparan sulfate glycosaminoglycan, which is a macromolecule critical for islet health. Notably, 8-weeks-old offspring of obese dams continued to exhibit a similar pattern of sex-differences in glucose intolerance and decreased islet insulin secretion. Overall, our study suggests that maternal obesity induces sex-specific changes to pancreatic HSG in offspring and a lasting effect on offspring insulin secretion, leading to the sex-differences in glucose intolerance

A model for presenting accelerometer paradata in large studies : ISCOLE

Background: We present a model for reporting accelerometer paradata (process-related data produced from survey administration) collected in the International Study of Childhood Obesity Lifestyle and the Environment (ISCOLE), a multi-national investigation of >7000 children (averaging 10.5 years of age) sampled from 12 different developed and developing countries and five continents. Methods: ISCOLE employed a 24-hr waist worn 7-day protocol using the ActiGraph GT3X+. Checklists, flow charts, and systematic data queries documented accelerometer paradata from enrollment to data collection and treatment. Paradata included counts of consented and eligible participants, accelerometers distributed for initial and additional monitoring (site specific decisions in the face of initial monitoring failure), inadequate data (e.g., lost/malfunction, insufficient wear time), and averages for waking wear time, valid days of data, participants with valid data (>= 4 valid days of data, including 1 weekend day), and minutes with implausibly high values (>= 20,000 activity counts/min). Results: Of 7806 consented participants, 7372 were deemed eligible to participate, 7314 accelerometers were distributed for initial monitoring and another 106 for additional monitoring. 414 accelerometer data files were inadequate (primarily due to insufficient wear time). Only 29 accelerometers were lost during the implementation of ISCOLE worldwide. The final locked data file consisted of 6553 participant files (90.0% relative to number of participants who completed monitoring) with valid waking wear time, averaging 6.5 valid days and 888.4 minutes/day (14.8 hours). We documented 4762 minutes with implausibly high activity count values from 695 unique participants (9.4% of eligible participants and Conclusions: Detailed accelerometer paradata is useful for standardizing communication, facilitating study management, improving the representative qualities of surveys, tracking study endpoint attainment, comparing studies, and ultimately anticipating and controlling costs.Peer reviewe

Environment and shipping drive environmental DNA beta-diversity among commercial ports

The spread of nonindigenous species by shipping is a large and growing global problem that harms coastal ecosystems and economies and may blur coastal biogeographical patterns. This study coupled eukaryotic environmental DNA (eDNA) metabarcoding with dissimilarity regression to test the hypothesis that ship-borne species spread homogenizes port communities. We first collected and metabarcoded water samples from ports in Europe, Asia, Australia and the Americas. We then calculated community dissimilarities between port pairs and tested for effects of environmental dissimilarity, biogeographical region and four alternative measures of ship-borne species transport risk. We predicted that higher shipping between ports would decrease community dissimilarity, that the effect of shipping would be small compared to that of environment dissimilarity and shared biogeography, and that more complex shipping risk metrics (which account for ballast water and stepping-stone spread) would perform better. Consistent with our hypotheses, community dissimilarities increased significantly with environmental dissimilarity and, to a lesser extent, decreased with ship-borne species transport risks, particularly if the ports had similar environments and stepping-stone risks were considered. Unexpectedly, we found no clear effect of shared biogeography, and that risk metrics incorporating estimates of ballast discharge did not offer more explanatory power than simpler traffic-based risks. Overall, we found that shipping homogenizes eukaryotic communities between ports in predictable ways, which could inform improvements in invasive species policy and management. We demonstrated the usefulness of eDNA metabarcoding and dissimilarity regression for disentangling the drivers of large-scale biodiversity patterns. We conclude by outlining logistical considerations and recommendations for future studies using this approach.Fil: Andrés, Jose. Cornell University. Department Of Ecology And Evolutionary Biology;Fil: Czechowski, Paul. Cornell University. Department Of Ecology And Evolutionary Biology; . University of Otago; Nueva Zelanda. Helmholtz Institute for Metabolic, Obesity and Vascular Research; AlemaniaFil: Grey, Erin. University of Maine; Estados Unidos. Governors State University; Estados UnidosFil: Saebi, Mandana. University of Notre Dame; Estados UnidosFil: Andres, Kara. Cornell University. Department Of Ecology And Evolutionary Biology;Fil: Brown, Christopher. California State University Maritime Academy; Estados UnidosFil: Chawla, Nitesh. University of Notre Dame; Estados UnidosFil: Corbett, James J.. University of Delaware; Estados UnidosFil: Brys, Rein. Research Institute for Nature and Forest; BélgicaFil: Cassey, Phillip. University of Adelaide; AustraliaFil: Correa, Nancy. Ministerio de Defensa. Armada Argentina. Instituto Universitario Naval de la Ara. Escuela de Ciencias del Mar; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; ArgentinaFil: Deveney, Marty R.. South Australian Research And Development Institute; AustraliaFil: Egan, Scott P.. Rice University; Estados UnidosFil: Fisher, Joshua P.. United States Fish and Wildlife Service; Estados UnidosFil: vanden Hooff, Rian. Oregon Department of Environmental Quality; Estados UnidosFil: Knapp, Charles R.. Daniel P. Haerther Center for Conservation and Research; Estados UnidosFil: Leong, Sandric Chee Yew. National University of Singapore; SingapurFil: Neilson, Brian J.. State of Hawaii Division of Aquatic Resources; Estados UnidosFil: Paolucci, Esteban Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Pfrender, Michael E.. University of Notre Dame; Estados UnidosFil: Pochardt, Meredith R.. M. Rose Consulting; Estados UnidosFil: Prowse, Thomas A. A.. University of Adelaide; AustraliaFil: Rumrill, Steven S.. Oregon Department of Fish and Wildlife; Estados UnidosFil: Scianni, Chris. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Instituto para el Estudio de la Biodiversidad de Invertebrados; Argentina. Marine Invasive Species Program; Estados UnidosFil: Sylvester, Francisco. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Instituto para el Estudio de la Biodiversidad de Invertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: Tamburri, Mario N.. University of Maryland; Estados UnidosFil: Therriault, Thomas W.. Pacific Biological Station; CanadáFil: Yeo, Darren C. J.. National University of Singapore; SingapurFil: Lodge, David M.. Cornell University. Department Of Ecology And Evolutionary Biology

Observation of substrate diffusion and ligand binding in enzyme crystals using high-repetition-rate mix-and-inject serial crystallography

18 pags, 11 figs, 5 tabsHere, we illustrate what happens inside the catalytic cleft of an enzyme when substrate or ligand binds on single-millisecond timescales. The initial phase of the enzymatic cycle is observed with near-atomic resolution using the most advanced X-ray source currently available: the European XFEL (EuXFEL). The high repetition rate of the EuXFEL combined with our mix-and-inject technology enables the initial phase of ceftriaxone binding to the Mycobacterium tuberculosis β-lactamase to be followed using time-resolved crystallography in real time. It is shown how a diffusion coefficient in enzyme crystals can be derived directly from the X-ray data, enabling the determination of ligand and enzyme-ligand concentrations at any position in the crystal volume as a function of time. In addition, the structure of the irreversible inhibitor sulbactam bound to the enzyme at a 66 ms time delay after mixing is described. This demonstrates that the EuXFEL can be used as an important tool for biomedically relevant research.This work was supported by the National Science Foundation Science and Technology Center 'BioXFEL' through award STC-1231306, and in part by the US Department of Energy, Office of Science, Basic Energy Sciences under contract DESC0002164 (AO, algorithm design and development) and by the National Science Foundation under contract Nos. 1551489 (AO, underlying analytical models) and DBI-2029533 (AO, functional conformations). This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. 1450681 to JLO. The work was also supported by funds from the National Institutes of Health grant R01 GM117342-0404. Funding and support are also acknowledged from the National Institutes of Health grant R01 GM095583, from the Biodesign Center for Applied Structural Discovery at ASU, from National Science Foundation award No. 1565180 and the US Department of Energy through Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. KAZ was supported by the Cornell Molecular Biophysics Training Program (NIH T32-GM008267). This work was also supported by the Cluster of Excellence 'CUI: Advanced Imaging of Matter' of the Deutsche Forschungsgemeinschaft (DFG), EXC 2056, project ID 390715994. CFEL is supported by the Gottfried Wilhelm Leibniz Program of the DFG, the 'X-probe' project funded by the European Union 2020 Research and Innovation Program under Marie Sklodowska-Curie grant agreement 637295, the European Research Council, 'Frontiers in Attosecond X-ray Science: Imaging and Spectroscopy (AXSIS)', ERC-2013-SyG 609920, and the Human Frontiers Science Program grant RGP0010 2017. This work is also supported by the AXSIS project funded by the European Research Council under the European Union Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement No. 609920.Peer reviewe

XAF1 as a modifier of p53 function and cancer susceptibility

Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers.Fil: Pinto, Emilia M.. St. Jude Children's Research Hospital; Estados UnidosFil: Figueiredo, Bonald C.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Chen, Wenan. St. Jude Children's Research Hospital; Estados UnidosFil: Galvao, Henrique C.R.. Hospital de Câncer de Barretos; BrasilFil: Formiga, Maria Nirvana. A.c.camargo Cancer Center; BrasilFil: Fragoso, Maria Candida B.V.. Universidade de Sao Paulo; BrasilFil: Ashton Prolla, Patricia. Universidade Federal do Rio Grande do Sul; BrasilFil: Ribeiro, Enilze M.S.F.. Universidade Federal do Paraná; BrasilFil: Felix, Gabriela. Universidade Federal da Bahia; BrasilFil: Costa, Tatiana E.B.. Hospital Infantil Joana de Gusmao; BrasilFil: Savage, Sharon A.. National Cancer Institute; Estados UnidosFil: Yeager, Meredith. National Cancer Institute; Estados UnidosFil: Palmero, Edenir I.. Hospital de Câncer de Barretos; BrasilFil: Volc, Sahlua. Hospital de Câncer de Barretos; BrasilFil: Salvador, Hector. Hospital Sant Joan de Deu Barcelona; EspañaFil: Fuster Soler, Jose Luis. Hospital Clínico Universitario Virgen de la Arrixaca; EspañaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. St. Jude Children's Research Hospital; Estados UnidosFil: Vaur, Dominique. Comprehensive Cancer Center François Baclesse; FranciaFil: Odone Filho, Vicente. Universidade de Sao Paulo; BrasilFil: Brugières, Laurence. Institut de Cancerologie Gustave Roussy; FranciaFil: Else, Tobias. University of Michigan; Estados UnidosFil: Stoffel, Elena M.. University of Michigan; Estados UnidosFil: Maxwell, Kara N.. University of Pennsylvania; Estados UnidosFil: Achatz, Maria Isabel. Hospital Sirio-libanês; BrasilFil: Kowalski, Luis. A.c.camargo Cancer Center; BrasilFil: De Andrade, Kelvin C.. National Cancer Institute; Estados UnidosFil: Pappo, Alberto. St. Jude Children's Research Hospital; Estados UnidosFil: Letouze, Eric. Centre de Recherche Des Cordeliers; FranciaFil: Latronico, Ana Claudia. Universidade de Sao Paulo; BrasilFil: Mendonca, Berenice B.. Universidade de Sao Paulo; BrasilFil: Almeida, Madson Q.. Universidade de Sao Paulo; BrasilFil: Brondani, Vania B.. Universidade de Sao Paulo; BrasilFil: Bittar, Camila M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Emerson W.S.. Hospital Do Câncer de Cascavel; BrasilFil: Mathias, Carolina. Universidade Federal do Paraná; BrasilFil: Ramos, Cintia R.N.. Hospital de Câncer de Barretos; BrasilFil: Machado, Moara. National Cancer Institute; Estados UnidosFil: Zhou, Weiyin. National Cancer Institute; Estados UnidosFil: Jones, Kristine. National Cancer Institute; Estados UnidosFil: Vogt, Aurelie. National Cancer Institute; Estados UnidosFil: Klincha, Payal P.. National Cancer Institute; Estados UnidosFil: Santiago, Karina M.. A.c.camargo Cancer Center; BrasilFil: Komechen, Heloisa. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Paraizo, Mariana M.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Parise, Ivy Z.S.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Hamilton, Kayla V.. St. Jude Children's Research Hospital; Estados UnidosFil: Wang, Jinling. St. Jude Children's Research Hospital; Estados UnidosFil: Rampersaud, Evadnie. St. Jude Children's Research Hospital; Estados UnidosFil: Clay, Michael R.. St. Jude Children's Research Hospital; Estados UnidosFil: Murphy, Andrew J.. St. Jude Children's Research Hospital; Estados UnidosFil: Lalli, Enzo. Institut de Pharmacologie Moléculaire et Cellulaire; FranciaFil: Nichols, Kim E.. St. Jude Children's Research Hospital; Estados UnidosFil: Ribeiro, Raul C.. St. Jude Children's Research Hospital; Estados UnidosFil: Rodriguez-Galindo, Carlos. St. Jude Children's Research Hospital; Estados UnidosFil: Korbonits, Marta. Queen Mary University of London; Reino UnidoFil: Zhang, Jinghui. St. Jude Children's Research Hospital; Estados UnidosFil: Thomas, Mark G.. Colegio Universitario de Londres; Reino UnidoFil: Connelly, Jon P.. St. Jude Children's Research Hospital; Estados UnidosFil: Pruett-Miller, Shondra. St. Jude Children's Research Hospital; Estados UnidosFil: Diekmann, Yoan. Colegio Universitario de Londres; Reino UnidoFil: Neale, Geoffrey. St. Jude Children's Research Hospital; Estados UnidosFil: Wu, Gang. St. Jude Children's Research Hospital; Estados UnidosFil: Zambetti, Gerard P.. St. Jude Children's Research Hospital; Estados Unido