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Background: Endometriosis is a common gynecological disorder described as the presence of functional endometrial tissue outside the uterus, which can also be found in extrapelvic locations. Although patients seeking treatment for endometriosis usually present to gynecologists, there are rare cases of endometriosis encountered by plastic surgeons in routine practice, either incidentally or as a concomitant finding. Methods: We present a rare case of a 36-year-old woman with symptoms of panniculitis desiring panniculectomy. During surgery, an abdominal mass was excised and confirmed by pathological analysis to be endometriosis. A comprehensive literature review was conducted using the PubMed search engine of the National Institutes of Health to identify cases of endometriosis in plastic surgery. Following screening of the results, 14 articles were included in this analysis that fit the criteria of our search. Results: Of the 14 articles reviewed, cutaneous endometriosis was the most common subtype found in plastic surgery. None of the studies described findings of endometriosis in routine panniculectomies. Several identified endometriosis discovered during cosmetic abdominoplasties. Conclusions: Endometriosis encountered in plastic surgery is a rare but clinically important occurrence, with the cutaneous subtype representing the majority of cases. Endometriosis should always be on the differential diagnosis when an abdominal mass is found in a patient with a history of abdominal surgery. Abdominal masses found during routine aesthetic or reconstructive surgery should be submitted for tissue analysis to guide possible secondary treatments.
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The last new herbicidal modes-of-action with commercial significance were introduced to the marketplace multiple decades ago. Serious weed resistance to most herbicidal classes have since emerged with widespread use. Aryl pyrrolidinone anilides represent an entirely new mode-of-action class of herbicides that interfere with de novo pyrimidine biosynthesis in plants via inhibition of dihydroorotate dehydrogenase. The chemical lead for this new herbicide class discovery was identified from high-volume sourced greenhouse screening that required structural reassignment of the hit molecule followed by an extensive synthetic optimization effort. With excellent grass weed control and pronounced safety on rice, the selected commercial development candidate has a proposed common name of tetflupyrolimet and represents the first member of the new HRAC (Herbicide Resistance Action Committee) Group 28. This paper describes the discovery path to tetflupyrolimet with an added focus on the bioisosteric modifications pursued in optimization, including replacements of the lactam core itself.
Assuntos
Herbicidas , Herbicidas/farmacologia , Plantas Daninhas , Controle de Plantas Daninhas , Poaceae , Produtos Agrícolas , Resistência a HerbicidasRESUMO
Turbulence-enhanced mixing of upper ocean heat allows interaction between the tropical atmosphere and cold water masses that impact climate at higher latitudes thereby regulating air-sea coupling and poleward heat transport. Tropical cyclones (TCs) can drastically enhance upper ocean mixing and generate powerful near-inertial internal waves (NIWs) that propagate down into the deep ocean. Globally, downward mixing of heat during TC passage causes warming in the seasonal thermocline and pumps 0.15 to 0.6 PW of heat into the unventilated ocean. The final distribution of excess heat contributed by TCs is needed to understand subsequent consequences for climate; however, it is not well constrained by current observations. Notably, whether or not excess heat supplied by TCs penetrates deep enough to be kept in the ocean beyond the winter season is a matter of debate. Here, we show that NIWs generated by TCs drive thermocline mixing weeks after TC passage and thus greatly deepen the extent of downward heat transfer induced by TCs. Microstructure measurements of the turbulent diffusivity ([Formula: see text]) and turbulent heat flux (J[Formula: see text]) in the Western Pacific before and after the passage of three TCs indicate that mean thermocline values of [Formula: see text] and J[Formula: see text] increased by factors of 2 to 7 and 2 to 4 (95% confidence level), respectively, after TC passage. Excess mixing is shown to be associated with the vertical shear of NIWs, demonstrating that studies of TC-climate interactions ought to represent NIWs and their mixing to accurately capture TC effects on background ocean stratification and climate.
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Mesoionic pyrido[1,2-a]pyrimidinones are a unique class of heterocyclic compounds. Compounds from this class with a n-propyl group substituted at the 1 position of the mesoionic core were discovered with interesting insecticidal activity in our screen. In this overview, we showcase how a bioisosteric replacement strategy was applied during the discovery and optimization of this class of compounds. Through exploring various substituents at the 1 position, evaluating a variety of mesoionic bicyclic ring scaffolds, and examining substituents on the phenyl group at the 3 position of the mesoionic core as well as substituents on the mesoionic ring skeleton, many compounds were discovered with excellent hopper activity or potent activity against a wide range of Lepidoptera. Ultimately, dicloromezotiaz was identified for commercial development to control a broad spectrum of lepidopteran pests.
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Inseticidas , Lepidópteros , Animais , Inseticidas/farmacologia , PirimidinonasRESUMO
A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program that led to the identification of dicloromezotiaz as a potent insecticide to control a broad range of lepidoptera. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.
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Lepidópteros/efeitos dos fármacos , Pirimidinonas/química , Pirimidinonas/farmacologia , Receptores Nicotínicos/metabolismo , Animais , Inseticidas/química , Inseticidas/farmacologia , Ligação Proteica/efeitos dos fármacos , Receptores Nicotínicos/química , Relação Estrutura-AtividadeRESUMO
CONTEXT: - Acute pulmonary injury may occur as a result of myriad direct or indirect pulmonary insults, often resulting in hypoxemic respiratory failure and clinical acute respiratory distress syndrome. Histologically, most patients will exhibit diffuse alveolar damage on biopsy, but other histologic patterns may be encountered, such as acute eosinophilic pneumonia, acute fibrinous and organizing pneumonia, and diffuse alveolar hemorrhage with capillaritis. OBJECTIVE: - To review the diagnostic features of various histologic patterns associated with a clinical picture of acute lung injury, and to discuss key features in the differential diagnosis. DATA SOURCES: - The review is drawn from pertinent peer-reviewed literature and the personal experience of the authors. CONCLUSIONS: - Acute pulmonary injury is a significant cause of morbidity and mortality. In addition to diffuse alveolar damage, pathologists should be aware of alternate histologic patterns of lung disease that may present with a similar clinical presentation because this may impact treatment decisions and disease outcome.
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Lesão Pulmonar Aguda/diagnóstico , Lesão Pulmonar Aguda/patologia , HumanosRESUMO
BACKGROUND: As the world population grows towards 9 billion by 2050, it is projected that food production will need to increase by 60%. A critical part of this growth includes the safe and effective use of insecticides to reduce the estimated 20-49% loss of global crop yields owing to pests. The development of new insecticides will help to sustain this protection and overcome insecticide resistance. RESULTS: A novel class of mesoionic compounds has been discovered, with exceptional insecticidal activity on a range of Hemiptera and Lepidoptera. These compounds bind to the orthosteric site of the nicotinic acetylcholine receptor and result in a highly potent inhibitory action at the receptor with minimal agonism. The synthesis, biological activity, optimization and mode of action will be discussed. CONCLUSION: Triflumezopyrim insect control will provide a powerful tool for control of hopper species in rice throughout Asia. Dicloromezotiaz can provide a useful control tool for lepidopteran pests, with an underexploited mode of action among these pests. © 2016 Society of Chemical Industry.
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Hemípteros/efeitos dos fármacos , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Periplaneta/efeitos dos fármacos , Animais , Afídeos/efeitos dos fármacos , Afídeos/crescimento & desenvolvimento , Hemípteros/crescimento & desenvolvimento , Proteínas de Insetos/metabolismo , Inseticidas/síntese química , Mariposas/crescimento & desenvolvimento , Antagonistas Nicotínicos/metabolismo , Periplaneta/crescimento & desenvolvimentoRESUMO
A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program which led to the discovery of triflumezopyrim as a highly potent insecticide controlling various hopper species. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.
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Descoberta de Drogas , Inseticidas/farmacologia , Ortópteros/efeitos dos fármacos , Piridinas/farmacologia , Pirimidinonas/farmacologia , Animais , Relação Dose-Resposta a Droga , Inseticidas/química , Estrutura Molecular , Piridinas/química , Pirimidinonas/química , Especificidade da Espécie , Relação Estrutura-AtividadeRESUMO
A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species, particularly hemiptera and lepidoptera. Mode-of-action studies showed that they act on nicotinic acetylcholine receptors (nAChRs) primarily as inhibitors. Here we report the discovery, evolution, and preparation of this class of chemistry. Our efforts in structure-activity relationship elucidation and biological activity evaluation are also presented.
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Inseticidas/química , Inseticidas/toxicidade , Antagonistas Nicotínicos/química , Antagonistas Nicotínicos/toxicidade , Pirimidinonas/química , Pirimidinonas/toxicidade , Animais , Hemípteros/efeitos dos fármacos , Hemípteros/fisiologia , Proteínas de Insetos/metabolismo , Lepidópteros/efeitos dos fármacos , Lepidópteros/fisiologia , Receptores Nicotínicos/metabolismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVES: The goal of this study is to assess the ability of the T2Candida platform (T2 Biosystems, Lexington, MA) to accurately identify Candida species from pediatric blood specimens with low volumes. METHODS: Whole blood from 15 children with candidemia was collected immediately following blood culture draw. The amount of blood required by the system was reduced by pipetting whole blood directly onto the T2Candida cartridge. Specimens were subsequently run on the T2Dx Instrument (T2 Biosystems). RESULTS: The T2Candida panel provided the appropriate result for each specimen compared with blood culture-based species identification and correctly identified 15 positive and nine negative results in 3 to 5 hours. While the time to species identification for blood culture was not reported, the T2Candida results include species data. CONCLUSIONS: T2Candida can be used to efficiently diagnose or rule out candidemia using low-volume blood specimens from pediatric patients. This could result in improved time to appropriate antifungal therapy or reduction in unnecessary empirical antifungal therapy.
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Candidemia/diagnóstico , Candidemia/microbiologia , DNA Fúngico/análise , Técnicas Microbiológicas , Hemocultura/métodos , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase/métodosRESUMO
N-Substituted amino-2(5H)-oxazolones A are a novel class of insecticides acting as nicotinic acetylcholine receptor (nAChR) agonists and show potent activity against hemipteran insect species. Here we report the discovery and preparation of this class of chemistry. Our efforts in SAR elucidation, biological activity evaluation, as well as mode-of-action studies are also presented.
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Insetos/efeitos dos fármacos , Inseticidas/química , Oxazolona/química , Aminação , Animais , Insetos/fisiologia , Inseticidas/toxicidade , Oxazolona/toxicidade , Receptores Nicotínicos/metabolismoRESUMO
Anthranilic diamides are an exceptionally active class of insect control chemistry that selectively activates insect ryanodine receptors causing mortality from uncontrolled release of calcium ion stores in muscle cells. Work in this area led to the successful commercialization of chlorantraniliprole for control of Lepidoptera and other insect pests at very low application rates. In search of lower logP analogs with improved plant systemic properties, exploration of cyano-substituted anthranilic diamides culminated in the discovery of a second product candidate, cyantraniliprole, having excellent activity against a wide range of pests from multiple insect orders. Here we report on the chemistry, biology and structure-activity trends for a series of cyanoanthranilic diamides from which cyantraniliprole was selected for commercial development.
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Canais de Cálcio/química , Inseticidas/química , Pirazóis/química , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , ortoaminobenzoatos/química , Animais , Afídeos , Inseticidas/síntese química , Lepidópteros , Estrutura Molecular , Pirazóis/síntese química , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Relação Estrutura-Atividade , ortoaminobenzoatos/síntese químicaRESUMO
INTRODUCTION: Acellular dermal matrices (ADMs) have become increasingly popular for use in plastic surgery. There has been an increase in the number of products that have paralleled their usage in various clinical settings and specifically breast surgery. METHODS: A direct comparison of the most common ADMs used in breast surgery was performed including physical characteristics, level of sterility, maximum load sustained (N), stiffness (N/mm), and tensile strength (N/cm). A comprehensive review of the literature was also performed, detailing known results and complications. RESULTS: The direct comparison of most common ADMs is detailed along with a review of 26 series of breast reconstruction manuscripts involving the usage of ADMs. Specifically, Strattice and Permacol had the highest values of maximum loads sustained, stiffness, and tensile strength. CONCLUSIONS: ADMs have a role in breast surgery that continues to be defined. Future long-term follow-up remains crucial to the identification of the optimal biologic mesh.
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Derme Acelular , Mamoplastia/métodos , Fenômenos Biomecânicos , Colágeno , Feminino , Humanos , Mastectomia , Reoperação , Resistência à Tração , Suporte de CargaRESUMO
BACKGROUND: With the increasing popularity of skin-sparing mastectomy techniques, implant-based breast reconstruction and use of perioperative radiation therapy, there is a growing need to scrutinize the effects they have on breast reconstruction. This study examined the effect of radiation on implant-based breast reconstruction in patients who had skin-sparing or conventional mastectomies in terms of complication, reoperation, and capsular contracture rates. PATIENTS AND METHODS: A retrospective review of 227 implant-based breast reconstructions in 132 mastectomy patients by a single surgeon was undertaken. All cases occurred over a four-year period (2006-2009) at a single institution. Complication, re-operation, and capsular contracture rates were tabulated against immediate and delayed reconstruction, skin-sparing and conventional mastectomy implant-based reconstruction, and irradiated and non-irradiated groups. Chi-square test was performed for statistical analysis. RESULTS: The overall complication and reoperation rates of 15% and 10% in these 227 reconstructions compare favorably to reviewed series. Delayed reconstruction, skin-sparing mastectomy and irradiation were all associated with a significantly increased rate of re-operation, but not to an increase in complication or capsular contracture rates. CONCLUSION: The results of this study were more favourable than those of similar studies reported in the current literature, suggesting an increased role for implant-based reconstruction in the setting of adjuvant radiotherapy for patients that undergo skin-sparing mastectomy.
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Implantes de Mama , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia/métodos , Terapia Combinada/efeitos adversos , Feminino , Humanos , Mamoplastia/efeitos adversos , Mastectomia/efeitos adversos , Radioterapia/efeitos adversos , Radioterapia/métodos , Estudos Retrospectivos , Fatores de TempoRESUMO
Desmoid tumors constitute 0.02% to 0.03% of all tumors. Consequently, few case reports exist for breast desmoids, even fewer identifying bilateral disease. We present a case report of a patient with bilateral breast desmoids and shoulder desmoid without evidence of FAP or Gardner syndrome. This case report explores the clinical, radiographic, pathologic, and treatment elements for desmoid tumors as well as a review of the literature.
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Neoplasias da Mama/diagnóstico , Fibromatose Agressiva/diagnóstico , Síndrome de Gardner , Adulto , Neoplasias da Mama/etiologia , Feminino , Fibromatose Agressiva/etiologia , HumanosRESUMO
Rahima Banu, the world's last endemic case of severe smallpox, Variola Major, developed rash on October 16, 1975 on Bhola Island, Bangladesh. Achieving eradication in a country destroyed by war challenged the achievement of smallpox eradication. Between January 1, 1972 and December 31, 1975, 225,000 smallpox cases and 45,000 smallpox deaths occurred. Adapting the global smallpox eradication strategies of surveillance, the detection of smallpox cases, and containment, the interruption of smallpox transmission, utilized progress toward three objectives to monitor performance: (1) surveillance - the percent of smallpox infected villages detected within 14 days of the first case of rash, (2) knowledge of the reward - public knowledge of the current amount of the reward for reporting smallpox, and (3) containment - the percent of infected villages interrupting smallpox transmission within 14 days of detection. Failures to achieve these objectives led to the identification and implementation of improved strategies that eventually achieved eradication. Essential to this success was a tripartite partnership of the citizens of Bangladesh, the Bangladesh Ministry of Health, its field staff, and staff and resources mobilized by the World Health Organization.
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Erradicação de Doenças/história , Erradicação de Doenças/métodos , Varíola/epidemiologia , Varíola/prevenção & controle , Bangladesh/epidemiologia , História do Século XX , Humanos , Varíola/mortalidadeRESUMO
Atpenins and harzianopyridone represent a unique class of penta-substituted pyridine-based natural products that are potent inhibitors of complex II (succinate-ubiquinone oxidoreductase) in the mitochondrial respiratory chain. These compounds block electron transfer in oxidative phosphorylation by inhibiting oxidation of succinate to fumarate and the coupled reduction of ubiquinone to ubiquinol. From our investigations of complex II inhibitors as potential agricultural fungicides, we report here on the synthesis and complex II inhibition for a series of synthetic atpenin analogs against both mammalian and fungal forms of the enzyme. Synthetic atpenin 2e provided optimum mammalian and fungal inhibition with slightly higher potency than natural occurring atpenin A5.
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Complexo II de Transporte de Elétrons/antagonistas & inibidores , Inibidores Enzimáticos/química , Fungos/enzimologia , Mitocôndrias/enzimologia , Piridinas/química , Piridonas/química , Animais , Bovinos , Complexo II de Transporte de Elétrons/metabolismo , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Fosforilação Oxidativa , Piridinas/síntese química , Piridinas/farmacologia , Piridonas/síntese química , Piridonas/farmacologiaRESUMO
Incisional hernia is a potential complication of all abdominal incisions and still remains a significant problem financially and medically. Presently, there is a lack of general consensus among surgeons in regard to the optimal treatment. The midline incision is the most common used abdominal incision and it carries a high incidence of incisional hernia (up to 15%). The paramedian incision was known to lead to a small incidence of incisional hernias. This discussion is meant to bring the paramedian incision back to the picture as a hope to decrease the incidence of incisional hernia.
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Parede Abdominal/cirurgia , Hérnia Abdominal , Laparotomia/efeitos adversos , Complicações Pós-Operatórias , Hérnia Abdominal/epidemiologia , Hérnia Abdominal/etiologia , Hérnia Abdominal/prevenção & controle , Humanos , Incidência , Laparotomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND: The effect of "pre-hypertension" (pre-HTN) itself, and in combination with other cardiovascular disease (CVD) risk factors in relation to mortality has not been assessed in Asian populations. METHODS: From three cross-sectional studies conducted in Singapore (baseline 1982-1995), 5830 persons were grouped into normotensive (NT), pre-HTN or hypertensive (HTN). Follow-up (median 12.0 yrs, IQR 12-19 yrs) was done by linkage to the National Death Register. Outcomes included all-cause and CVD (ischaemic heart disease (ICD-9 410-414) and cerebrovascular accidents (ICD-9 430-438)). Cox's proportional hazards model was used to obtain adjusted hazard ratios (HRs) for risk of mortality. RESULTS: After adjustment, pre-HTN was not associated with a statistically significant increased risk of all-cause or CVD mortality. However, an increased risk for all-cause and CVD mortality, in the presence of diabetes (adjusted HR 1.8; 95%CI 1.0-2.9 and 4.4; 95%CI 1.9-10.4), smoking (adjusted HR 2.2; 95%CI 1.3-3.5 and 4.9; 95%CI 1.8-13.3), and especially, pre-existing CVD (adjusted HR 3.1; 95%CI 1.5-6.4 and 9.3; 95%CI 3.3-25.9) was found. CONCLUSIONS: Pre-HTN was not an independent risk factor for mortality. However an increased risk of mortality for pre-HTN in the presence of other CVD risk factors was observed. This finding supports current recommendations to screen for these risk factors in the pre-HTN Asian population.
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Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Hipertensão/complicações , Hipertensão/mortalidade , Adulto , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Singapura/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: This study assesses the effect of the metabolic syndrome on all-cause and cardiovascular disease (CVD) mortality in healthy Chinese, Malays and Asian Indians in Singapore. The utility of the metabolic syndrome is also compared with the Framingham risk score for prediction of mortality. METHODS: Healthy participants (n = 5699) were grouped by the presence or absence of the metabolic syndrome, and followed up (mean 14.1 years) by data linkage with the National Death Register. Risk of mortality was obtained by Cox's proportional hazards model with adjusted hazard ratios (HRs). Area under receiver operating characteristic (ROC) curves were used to compare the metabolic syndrome and Framingham risk score for prediction of mortality. RESULTS: During a follow-up of 80,236 person-years, there were 382 deaths, of which 128 were due to CVD. Individuals with the metabolic syndrome had an increased risk of mortality for 'all-causes' (males: HR 1.4, 95% confidence intervals (95%CI) 1.1-1.8; and females: HR 1.8, 95%CI 1.3-2.6). There was also an increased risk of mortality due to CVD (males: HR 3.0, 95%CI 1.9-4.8; and females: HR 2.1, 95%CI 1.1-4.0). The area under ROC for Framingham risk score was higher for both all-cause and CVD mortality than metabolic syndrome. CONCLUSIONS: Although an increased risk of 'all-cause' and CVD mortality due to the metabolic syndrome was found, the Framingham risk function still performed better than the metabolic syndrome in an Asian population. However, the metabolic syndrome should not be disregarded as it is a clinically useful entity for identifying individuals for management of its component CVD risk factors.