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1.
Biol Sport ; 41(1): 235-244, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38188110

RESUMO

This study aimed to explore the interaction between growth rate on specific injury incidence and burden on pre-, circa- and post-peak height velocity (PHV) periods. Injury and stature data collected during the 2000-2020 seasons in an elite football academy were retrospectively analysed. Only players with height measurements from childhood until the attainment of adult height were included in the study (N = 84). Growth data were smoothed using a cubic spline to calculate daily growth rate and height. Growth rate was categorised into three groups: fast (> 7.2 cm/year), moderate (3.5-7.2 cm/year) and slow (< 3.5 cm/year). Percentage of observed adult height was used to classify players as pre-PHV (< 88%), circa-PHV (88-95%) or post-PHV (> 95%). Overall and specific injury incidence and burden and rate ratios for comparisons between growth rate groups were calculated on pre-, circa- and post-PHV periods, separately. Overall injury incidence and burden were greater in pre-PHV players with quicker growth rates compared to players growing moderately and slowly. All in all, players with more rapid growth-rates were at higher risk for growth-related injuries in all pre-, circa- and post-PHV periods. Post-PHV, the incidence and burden of joint/ligament injuries were 2.4 and 2.6-times greater in players growing slowly compared to players growing moderately. Practitioners should monitor growth rate and maturity status and consider their interaction to facilitate the design of targeted injury risk reduction strategies.

2.
Ann Bot ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37968940

RESUMO

BACKGROUND AND AIM: Plant disjunctions have fascinated biogeographers and ecologists for a long time. We use tribe Bocageeae (Annonaceae), a predominantly Neotropical plant group distributed across several present-day Neotropical biomes and with an African-American disjunction, to investigate long-distance dispersal mediated by frugivorous animals at both intercontinental and intracontinental scales. METHODS: We reconstructed a species-level phylogeny of tribe Bocageeae with a dataset composed of 116 nuclear markers. We sampled 70% of Bocageeae species, covering its geographic range and representing all eight genera. We estimated divergence times using BEAST, inferred ancestral range distributions and reconstructed ancestral states for fruit traits related to long-distance dispersal in a Bayesian framework. KEY RESULTS: The ancestral Bocageeae date to the Early Eocene and were inferred to occur in Africa and proto-Amazonia. Its ancestral fruits were large and dehiscent. The first lineage split gave rise to an exclusively Neotropical clade during the Middle Eocene, in proto-Amazonia. Range exchange between the Amazon and the Atlantic Forest occurred at least once during the Miocene, and from Amazonia to Central America and Mexico, during the Early Miocene. Transitions in different sets of fruit morphologies were inferred to be related to dispersal events across South American regions/biomes. CONCLUSIONS: In Bocageeae mammals may have been responsible for long-distance dispersal through the Boreotropics. In the Neotropics, proto-Amazonia is proposed to be the source for dispersal to other tropical American biomes. Long-distance dispersal may have happened via a wide range of dispersal guilds, depending on frugivore radiations, diversity, and abundance at particular time periods and places. Hence, inter- and intracontinental dispersal may not rely on a single dispersal syndrome or guild, but more on the availability of frugivorous lineages for seed dispersal.

3.
J Sports Sci ; 40(10): 1127-1136, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35285754

RESUMO

Adolescence is a period of increased injury risk in youth footballers; however, no studies have considered the influence of growth-related factors and exposure time upon injury risk. Forty-nine elite male youth footballers were prospectively monitored for growth, lower-limb growth, maturation, training volume and injury for one season. Generalised linear mixed-effects models were used to model growth rate, lower-limb growth rate, maturation, and smoothed week-to-week changes in exposure on time-loss injury risk. The relationship between growth rate and injury incidence was linear (P = 0.031) and injury burden was non-linear (P = 0.019). The relationship between lower-limb growth rate and injury incidence was linear and positive (P = 0.098). A non-linear relationship was observed between lower-limb growth rate and injury burden (P = 0.001). A non-linear relationship between Percentage of Predicted Adult Stature and both injury incidence and injury burden were found, with peak risk occurring at 92% and 95% , respectively. There was a positive linear relationship between week-to-week changeand injury incidence (P = 0.001), and a non-linear relationship between week-to-week change and injury burden (P = 0.01). Practitioners should monitor the timing and rate of the growth spurt and exposure time to identify players at greater injury risk.


Assuntos
Traumatismos em Atletas , Futebol , Adolescente , Adulto , Humanos , Masculino , Traumatismos em Atletas/epidemiologia , Estatura , Incidência , Extremidade Inferior/lesões , Futebol/lesões
4.
Environ Geochem Health ; 44(8): 2615-2628, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34365569

RESUMO

Information on PAH distribution in the water level fluctuation zone (WLFZ) of Three Gorges Reservoir is limited. In this study, we investigated PAH distribution and sources and assessed PAH risks, over one annual water level fluctuation cycle (June 2017-June 2018) at four elevations spanning the WLFZ (145 m, 155 m, 165 m and 175 m) at seven locations in the water level fluctuation zone along Xiangxi River. The mean total PAH concentration in June 2018 (953 ng g-1) was significantly higher than in June 2017 (494 ng g-1), and the horizontal and vertical distributions of PAHs changed significantly. The changes in distribution patterns provided evidence for the cause of increased PAH levels, which were attributed to construction of the Xiangxi River Bridge. Thus, this study of PAH dynamics in the WLFZ soils of Xiangxi Bay also provided valuable information on the impact of bridge construction on WLFZ soils. The change in PAH levels among stations implicated sediment disturbance resulting from bridge construction as the major contributor to the increased PAH levels. Source characterization, based on the ratios of certain PAHs, indicates that PAHs are mainly from the combustion of petroleum fuels, biomass and coal. These ratios indicated that the proportion of PAHs from fuel combustion increased from 2017 to 2018, implicating the heavy equipment used during bridge construction as another source of the increased PAH levels. The incremental lifetime cancer risk (ILCR) model was used to assess the health risk of the PAHs and the range among all age groups (10-5-10-4) indicates a potential health risk. The mean effects range-median quotient (M-ERM-Q) was used to assess the ecological risk of PAHs and the range (0.1-0.5) indicates low to medium risk. The increase in PAH levels from 2017 to 2018 increased the risk to public health and the environment. The results of this investigation provide a reference for ecological restoration of the WLFZ and support development of effective policies for environmental and public health. Further, the results provide information on the impact of bridge construction on WLFZ soils and identify research needed to more fully understand PAH dynamics in WLFZ soils.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Baías , China , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Medição de Risco , Solo , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
5.
Fish Physiol Biochem ; 45(5): 1771-1777, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31209689

RESUMO

Fish physiology and behavior are affected by exposure to light of varying colors, but little is known about the effects on swimming performance and metabolism. The purpose of this study was to measure the effects of light color on the swimming performance of bighead carp (Aristichthys nobilis), a planktivorous fish species widely used in aquaculture. Stepped velocity testing was conducted in a modified Brett-type swim tunnel respirometer to determine critical swimming speed (Ucrit), oxygen consumption (MO2), and excess post-exercise oxygen consumption (EPOC) for juvenile bighead carp under red, yellow, blue, and green lights at 25 °C. Ucrit was significantly lower for fish swimming under yellow and green lights compared with red and blue light. Cost of transport (COT), a measure of swimming efficiency, also varied with color. The results, obtained under controlled conditions, add to our knowledge on the effects of artificial color light on fish physiology and behavior and inform decisions on the use of artificial color light in aquaculture and fishway design.


Assuntos
Carpas/fisiologia , Luz , Consumo de Oxigênio/fisiologia , Natação/fisiologia , Animais , Comportamento Animal , Metabolismo Energético
6.
Ecotoxicol Environ Saf ; 154: 137-144, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29459163

RESUMO

A pot-culture experiment was conducted to assess the effects of selenium (Se) (0.5 mg kg-1) on Trifolium repens exposed to various levels of diesel (0, 15, 20, 25 g kg-1) for 30 days and 60 days. Exposure to diesel for 60 day led to concentration-dependent decreases in root morphogenesis, chlorophyll content and CAT activity, and to dose-dependent increases in MDA content and SOD activity. The residual diesel concentration in soil increased and the removal efficiency decreased with soil diesel concentration. The chlorophyll content and residual diesel concentration after were slightly higher at 30 days than at 60days. Application of Se to soil increased Trifolium repens tolerance to diesel and significantly increased the phytoremediation effect at 60 days, with a removal rate of 36 ±â€¯8%, compared to 28 ±â€¯7% in the control. These results contribute to the ongoing effort to develop an effective phytoremediation system for soils highly contaminated by diesel.


Assuntos
Gasolina/análise , Selênio/farmacologia , Poluentes do Solo/análise , Solo/química , Trifolium/crescimento & desenvolvimento , Biodegradação Ambiental , Biomassa , Relação Dose-Resposta a Droga , Gasolina/toxicidade , Selênio/análise , Microbiologia do Solo , Poluentes do Solo/toxicidade , Trifolium/efeitos dos fármacos , Trifolium/metabolismo
7.
Blood ; 126(25): 2686-94, 2015 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-26472751

RESUMO

Idelalisib is a first-in-class oral inhibitor of PI3Kδ that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naïve older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375 mg/m(2) weekly ×8 and idelalisib 150 mg twice daily continuously for 48 weeks. Patients completing 48 weeks without progression could continue to receive idelalisib on an extension study. The median time on treatment was 22.4 months (range, 0.8-45.8+). The overall response rate (ORR) was 97%, including 19% complete responses. The ORR was 100% in patients with del(17p)/TP53 mutations and 97% in those with unmutated IGHV. Progression-free survival was 83% at 36 months. The most frequent (>30%) adverse events (any grade) were diarrhea (including colitis) (64%), rash (58%), pyrexia (42%), nausea (38%), chills (36%), cough (33%), and fatigue (31%). Elevated alanine transaminase/aspartate transaminase was seen in 67% of patients (23% grade ≥3). The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naïve older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL. This study is registered at ClinicalTrials.gov as #NCT01203930.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Purinas/administração & dosagem , Purinas/efeitos adversos , Quinazolinonas/administração & dosagem , Quinazolinonas/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Resultado do Tratamento
8.
Blood ; 123(22): 3406-13, 2014 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-24615776

RESUMO

Idelalisib (GS-1101, CAL-101), an oral inhibitor of phosphatidylinositol 3-kinase-δ, was evaluated in a phase I study in 64 patients with relapsed indolent non-Hodgkin lymphoma (iNHL). Patients had a median (range) age of 64 (32-91) years, 34 (53%) had bulky disease (≥1 lymph nodes ≥5 cm), and 37 (58%) had refractory disease. Patients had received a median (range) of 4 (1-10) prior therapies. Eight dose regimens of idelalisib were evaluated; idelalisib was taken once or twice daily continuously at doses ranging from 50 to 350 mg. After 48 weeks, patients still benefitting (n = 19; 30%) enrolled into an extension study. Adverse events (AEs) occurring in 20% or more patients (total%/grade ≥3%) included diarrhea (36/8), fatigue (36/3), nausea (25/3), rash (25/3), pyrexia (20/3), and chills (20/0). Laboratory abnormalities included neutropenia (44/23), anemia (31/5), thrombocytopenia (25/11), and serum transaminase elevations (48/25). Twelve (19%) patients discontinued therapy due to AEs. Idelalisib induced disease regression in 46/54 (85%) of evaluable patients achieving an overall response rate of 30/64 (47%), with 1 patient having a complete response (1.6%). Median duration of response was 18.4 months, median progression-free survival was 7.6 months. Idelalisib is well tolerated and active in heavily pretreated, relapsed/refractory patients with iNHL. These trials were registered at clinicaltrials.gov as NCT00710528 and NCT01090414.


Assuntos
Antineoplásicos/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Purinas/uso terapêutico , Quinazolinonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Purinas/administração & dosagem , Purinas/efeitos adversos , Purinas/farmacocinética , Quinazolinonas/administração & dosagem , Quinazolinonas/efeitos adversos , Quinazolinonas/farmacocinética , Terapia de Salvação , Resultado do Tratamento
9.
MMWR Morb Mortal Wkly Rep ; 65(23): 602-5, 2016 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-27309884

RESUMO

Although both men and women have reproductive health care needs, family planning providers traditionally focus services toward women (1,2). Challenges in providing family planning services to men, including preconception health, infertility, contraceptive, and sexually transmitted disease (STD) care (3,4), include their infrequent use of preventive health services, a perceived lack of need for these services (1,5), and the lack of provider guidance regarding men's reproductive health care needs (4). Since 1970, the National Title X Family Planning Program has provided cost-effective and confidential family planning and related preventive health services with priority for services to low-income women and men. To examine men's use of services at Title X service sites, CDC and the U.S. Department of Health and Human Services' Office of Population Affairs (OPA) analyzed data from the 2003-2014 Family Planning Annual Reports (FPAR), annual data that are required of all Title X-funded agencies. During 2003-2014, 3.8 million males visited Title X service sites in the United States and the percentage of family planning users who were male nearly doubled from 4.5% (221,425 males) in 2003 to 8.8% (362,531 males) in 2014. In 2014, the percentage of family planning users who were male varied widely by state, ranging from ≤1% in Mississippi, Tennessee, and Alabama to 27.2% in the District of Columbia (DC). Title X service sites are increasingly providing services for males. Health care settings might want to adopt the framework employed by Title X clinics to better provide family planning and related preventative services to men (3).


Assuntos
Serviços de Planejamento Familiar/estatística & dados numéricos , Adolescente , Adulto , Humanos , Masculino , Estados Unidos , Adulto Jovem
10.
Plants (Basel) ; 13(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38256742

RESUMO

During botanical expeditions focused on the study of Annonaceae in Thailand, specimens resembling Friesodielsia glauca were collected from the lower part of peninsular Thailand but were believed to differ from that species in vegetative, flower, and fruit characters. A morphological investigation of the new specimens and species complex was conducted. Specimens (including types of F. glauca and similar species collected from Thailand and adjacent regions) were examined in the following herbaria: A, BK, BM, BKF, E, K, KEP, KKU, L, PSU, QBG, SING, and US. As a consequence, the new species Friesodielsia parvimitra, endemic to peninsular Thailand, is described and illustrated. The conservation status of the new species was provisionally assessed as Critically Endangered (CR, B2ab(iii)) following the IUCN's guidelines. In addition, F. argentea, previously regarded F. glauca, is reinstated here as a distinct species based on several morphological differences and is reported as a new record from Thailand. Photographs, line drawings, and a revised key to F. glauca and similar species are presented.

11.
Phys Rev Lett ; 111(11): 113002, 2013 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-24074082

RESUMO

We present a method for determining the phase and contrast of a single shot of an atom interferometer. The application of a phase shear across the atom ensemble yields a spatially varying fringe pattern at each output port, which can be imaged directly. This method is broadly relevant to atom-interferometric precision measurement, as we demonstrate in a 10 m 87Rb atomic fountain by implementing an atom-interferometric gyrocompass with 10 mdeg precision.

12.
Phys Rev Lett ; 111(8): 083001, 2013 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-24010433

RESUMO

We show that light-pulse atom interferometry with atomic point sources and spatially resolved detection enables multiaxis (two rotation, one acceleration) precision inertial sensing at long interrogation times. Using this method, we demonstrate a light-pulse atom interferometer for 87Rb with 1.4 cm peak wave packet separation and a duration of 2T=2.3 s. The inferred acceleration sensitivity of each shot is 6.7×10(-12)g, which improves on previous limits by more than 2 orders of magnitude. We also measure Earth's rotation rate with a precision of 200 nrad/s.

13.
Sci Total Environ ; 905: 166924, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37704145

RESUMO

Plastic surfaces are colonized by microorganisms and biofilms are formed in the natural aquatic environment. As the biofilm develops, it changes the density and buoyancy of the plastic-biofilm complex, results in plastic sinking, and increases the heavy metals accumulated by biofilm's mobility and availability in aquatic ecosystems. In this experiment, biofilms were cultured on five colors of polyvinyl chloride (PVC; transparent, green, blue, red, black) in an aquatic environment to investigate the effects of plastic color on biofilm formation and development (Phase 1) and to study the effects of being sunk below the photic zone on biofilm (Phase 2). The PVC color significantly affected the biofilm formation rate but had no impact on the final biofilm biomass. After sinking the biofilm-PVC below the photic zone in Phase 2, the layer of diatoms on the biofilm surface began to disintegrate, and the biomass and Chlorophyll-a (Chla) content of the biofilm decreased, except on the red PVC. Below the photic zone, the microbial community of the biofilm changed from primarily autotrophic microbes to mostly heterotrophic microbes. Microbial diversity increased and extracellular polymeric substances (EPS) content decreased. The primary factor leading to microbial diversity and community structure changes was water depth rather than PVC color. The changes induced in the biofilm led to an increase in the concentration of all heavy metals in the biofilm, related to the increase in microbial diversity. This study provides new insights into the biofilm formation process and the effects on a biofilm when it sinks below the photic zone.


Assuntos
Metais Pesados , Cloreto de Polivinila , Ecossistema , Biofilmes , Matriz Extracelular de Substâncias Poliméricas
14.
Environ Sci Pollut Res Int ; 30(43): 97591-97600, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37596476

RESUMO

Root systems are sensitive to voltage and tend to improve the degradation of organic pollutants by promoting the root exudates and increasing microbial enzyme activity in the rhizosphere under the effect of electrokinetic. In this study, electrokinetic-assisted phytoremediation (EKPR) was applied for the remediation of soil containing phenanthrene (PHE) and pyrene (PYR). Direct current (DC) voltage (1 V cm-1) was applied across the soils for 30 days following 3 treatment schedules (0 h, 4 h, and 12 h per day), referred to as treatments EK0, EK4, and EK12. Electrokinetic assistance improved phytoremediation. Compared to EK0, the removal of PHE and PYR increased by 51.79% and 45.07% for EK4 and by 43.18% and 38.75% for EK12. The applied voltage promoted root growth, stimulated the root exudate release, and increased accumulation of PHE and PYR by plants, and the effect was most pronounced in treatment EK4. Catalase and urease activities in rhizosphere soil also increased, by respective increments of 44.51% and 40.86% for EK4 and by 28.53% and 21.24% for EK12. In this study, we demonstrated that a low voltage applied for an appropriate duration (4 h per day) improves removal of PAHs by stimulating root growth, promoting the root exudate release and enhancing enzyme activity in the microbiome of rhizosphere soil.


Assuntos
Ophiopogon , Hidrocarbonetos Policíclicos Aromáticos , Biodegradação Ambiental , Solo
15.
PhytoKeys ; 207: 1-532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36760862

RESUMO

Annonaceae is a major pantropical family with 113 genera and about 2550 species. Cameroon is one of the most biodiverse countries in Africa but its flora remains incompletely known. In this volume of the Flora of Cameroon, we describe 166 native taxa representing 163 species in 28 native genera within the family Annonaceae. A total of 22 species (about 13%) are endemic to the country. We provide keys to all native genera, species, and infraspecific taxa. For each species a detailed morphological description and a map of its distribution in Cameroon are provided. Distribution maps and diversity analyses are based on a taxonomically verified database of 2073 collections. Across Africa, Cameroon is a center of diversity for Annonaceae harboring one of the highest numbers of species and genera. For example, Cameroon harbors the highest number of African species for the only pantropical genus of Annonaceae, Xylopia. Annonaceae are found across all 10 administrative regions of Cameroon but diversity is concentrated within the tropical rain forest areas situated in the south and South-West. The areas around Bipindi and Mount Cameroon show the highest levels of diversity, but this is correlated with collection effort. Line drawings and/or photographs accompany most species. One species new to science Uvariopsisetugeana Dagallier & Couvreur sp. nov. is described. We also undertake a number of nomenclatural changes such as lectotypifications, six new synonymies and two new combinations (Uvariaanisotricha (Le Thomas) Couvreur, comb. nov.; Uvariodendronfuscumvar.giganteum (Engl.) Dagallier & Couvreur, comb. nov.).


RésuméLes Annonacées sont une grande famille pantropicale avec 113 genres et 2550 espèces. Le Cameroun est l'un des pays les plus riches en biodiversité d'Afrique mais sa flore reste incomplètement connue. Dans ce volume de la Flore du Cameroun, nous décrivons 166 taxons représentant 163 espèces dans 28 genres au sein de la famille des Annonaceae. Au total, 22 espèces (environ 13%) sont endémiques du pays. Nous fournissons une clé de tous les genres et espèces et des infra-espèces au sein des genres. Pour chaque espèce une description morphologique détaillée et une carte de sa répartition au Cameroun sont fournies. Les cartes de distribution et les analyses de diversité sont basées sur une base de données taxonomiquement vérifiée de 2073 collections. À travers l'Afrique, le Cameroun est un centre de diversité pour les Annonacées abritant l'un des plus grands nombres d'espèces et de genres. Par exemple, le Cameroun abrite le plus grand nombre d'espèces africaines pour le seul genre pantropical d'Annonaceae, Xylopia. Les Annonaceae sont présentent dans les 10 régions du Cameroun, mais la plus grande diversité est concentrée dans les régions abritant la forêt tropicale humide située au sud et au sud-ouest. Les zones autour de Bipindi et du Mont Cameroun présentent les niveaux de diversité les plus élevés, mais cela est corrélé à l'effort de collecte. Des dessins et/ou des photographies accompagnent la plupart des espèces. Une espèce nouvelle pour la science Uvariopsisetugeana Dagalier & Couvreur sp. nov. est décrite. Nous entreprenons également un certain nombre de changements nomenclaturaux tels que des lectotypifications, six nouvelles synonymies et deux nouvelles combinaisons (Uvariaanisotricha (Le Thomas) Couvreur, comb. nov.; Uvariodendronfuscumvar.giganteum (Engl.) Dagalier & Couvreur, comb. nov.).

16.
NEJM Evid ; 1(1): EVIDoa2100001, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-38319241

RESUMO

BACKGROUND: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein present on many cancers. Zilovertamab vedotin (ZV) is an antibody­drug conjugate comprising a monoclonal antibody recognizing extracellular ROR1, a cleavable linker, and the anti-microtubule cytotoxin monomethyl auristatin E. METHODS: In this phase 1, first-in-human, dose-escalation study, we accrued patients with previously treated lymphoid cancers to receive ZV every 3 weeks until the occurrence of cancer progression or unacceptable toxicity had occurred. RESULTS: We enrolled 32 patients with tumor histologies of mantle cell lymphoma (MCL) (n=15), chronic lymphocytic leukemia (n=7), diffuse large B-cell lymphoma (DLBCL) (n=5), follicular lymphoma (n=3), Richter transformation lymphoma (n=1), or marginal zone lymphoma (n=1). Patients had received a median of four previous drug and/or cellular therapies. Starting dose levels were 0.5 (n=1), 1.0 (n=3), 1.5 (n=3), 2.25 (n=11), and 2.5 (n=14) mg per kg of body weight (mg/kg). Pharmacokinetic and pharmacodynamic data documented systemic ZV exposure and exposure-dependent ZV targeting of ROR1 on circulating tumor cells. As expected with an monomethyl auristatin E-containing antibody­drug conjugate, adverse events (AEs) included acute neutropenia and cumulative neuropathy resulting in a recommended ZV dosing regimen of 2.5 mg/kg every 3 weeks. No clinically concerning AEs occurred to suggest ROR1-mediated toxicities or nonspecific ZV binding to normal tissues. ZV induced objective tumor responses in 7 of 15 patients with MCL (47%; 4 partial and 3 complete) and in 3 of 5 patients with DLBCL (60%; 1 partial and 2 complete); objective tumor responses were not observed among patients with other tumor types. CONCLUSIONS: In heavily pretreated patients, ZV demonstrated no unexpected toxicities and showed evidence of antitumor activity, providing clinical proof of concept for selective targeting of ROR1 as a potential new approach to cancer therapy. (ClinicalTrials.gov number, NCT03833180.)


Assuntos
Linfoma de Célula do Manto , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Humanos , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Linfoma de Célula do Manto/tratamento farmacológico , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico
17.
J Vasc Interv Radiol ; 22(4): 529-32, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21354817

RESUMO

The authors report a novel application of cement augmentation for treatment of a symptomatic sternal fracture. Sternal fractures often cause debilitating pain and can affect ventilation. Given the success of vertebroplasty in patients in treating back pain, the authors used a similar technique in a 56-year-old woman with chronic obstructive pulmonary disease and an acute comminuted sternal fracture refractory to conservative management. The authors used computed tomography guidance and cement augmentation for the fracture. The patient subsequently reported good pain relief and improved breathing. Sternoplasty may be a viable alternative for patients with sternal fractures and refractory pain.


Assuntos
Cimentos Ósseos , Fraturas Cominutivas/terapia , Procedimentos Ortopédicos , Dor/prevenção & controle , Polimetil Metacrilato/administração & dosagem , Radiografia Intervencionista/métodos , Esterno/lesões , Tomografia Computadorizada por Raios X , Feminino , Fraturas Cominutivas/complicações , Fraturas Cominutivas/diagnóstico por imagem , Humanos , Injeções , Pulmão/fisiopatologia , Pessoa de Meia-Idade , Dor/diagnóstico por imagem , Dor/etiologia , Medição da Dor , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Esterno/diagnóstico por imagem , Resultado do Tratamento
18.
Lab Invest ; 89(5): 513-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19274046

RESUMO

Tenofovir disoproxil fumarate (TDF) is an analog of adenosine monophosphate that inhibits HIV reverse transcriptase in HIV/AIDS. Despite its therapeutic success, renal tubular side effects are reported. The mechanisms and targets of tenofovir toxicity were determined using '2 x 2' factorial protocols, and HIV transgenic (TG) and wild-type (WT) littermate mice with or without TDF (5 weeks). A parallel study used didanosine (ddI) instead of TDF. At termination, heart, kidney, and liver samples were retrieved. Mitochondrial DNA (mtDNA) abundance, and histo- and ultrastructural pathology were analyzed. Laser-capture microdissection (LCM) was used to isolate renal proximal tubules for molecular analyses. Tenofovir increased mtDNA abundance in TG whole kidneys, but not in their hearts or livers. In contrast, ddI decreased mtDNA abundance in the livers of WTs and TGs, but had no effect on their hearts or kidneys. Histological analyses of kidneys showed no disruption of glomeruli or proximal tubules with TDF or ddI treatments. Ultrastructural changes in renal proximal tubules from TDF-treated TGs included an increased number and irregular shape of mitochondria with sparse fragmented cristae. LCM-captured renal proximal tubules from TGs showed decreased mtDNA abundance with tenofovir. The results indicate that tenofovir targets mitochondrial toxicity on the renal proximal tubule in an AIDS model.


Assuntos
Nefropatia Associada a AIDS/induzido quimicamente , Adenina/análogos & derivados , Fármacos Anti-HIV/efeitos adversos , Túbulos Renais Proximais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Organofosfonatos/efeitos adversos , Nefropatia Associada a AIDS/patologia , Adenina/efeitos adversos , Animais , DNA Mitocondrial/metabolismo , Didanosina/efeitos adversos , Feminino , HIV-1 , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microdissecção , Mitocôndrias/ultraestrutura , Tenofovir , Urotélio/ultraestrutura
19.
Radiology ; 251(3): 892-900, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19474379

RESUMO

PURPOSE: To identify objective imaging characteristics that are predictors of clinical deterioration after embolization of large intracranial tumors. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by the institutional review board, and informed consent was waived. The records of twelve patients with large intracranial tumors who underwent embolization were analyzed for imaging characteristics that would portend acute neurologic deterioration following embolization. The degree of midbrain compression was calculated by using the cisternal angle (the angle formed at the intersection of a line drawn along the midsagittal plane and a line drawn along the anterior aspect of the cerebral peduncle). Angiograms were evaluated for the degree of pre- and postembolization tumor blush. Neurologic status before and after embolization was evaluated. The Wilcoxon signed rank test was used to compare the cisternal angles ipsilateral and contralateral to the tumor. The cisternal angle was measured in 100 control subjects with no mass lesions to evaluate its normal distribution. RESULTS: Of the 12 patients, three experienced acute clinical deterioration after embolization. A feature common to these patients was substantial preprocedure midbrain compression, as indicated by a cisternal angle of less than 25 degrees , which was significantly less than the mean angle in the control group. Another consistent risk factor was a strong initial tumor blush pattern and a major blush reduction following embolization. CONCLUSION: Cisternal angle is an objective measure of midbrain compression. The presence of a cisternal angle less than 25 degrees (indicating severe midbrain compression), strong tumor blush, and major postprocedure blush reduction are predictors of clinical deterioration after embolization.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Cisterna Magna/patologia , Embolização Terapêutica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico por imagem , Angiografia Cerebral , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas
20.
Aviat Space Environ Med ; 80(6): 541-5; discussion 546, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19522364

RESUMO

INTRODUCTION: Simulator sickness (SS) is a common problem during flight training and can affect both instructor pilots (IP) and student pilots (SP). This study was conducted in response to complaints about a high incidence of SS associated with use of new simulators for rotary-wing aircraft. METHODS: The problem was evaluated using the Simulator Sickness Questionnaire (SSQ) to collect data on 73 IP and 129 SP who used the new simulators. Based on analysis of these data, operator comments, and a search of the literature, we recommended limiting simulator flights to 2 h, removing unusual or unnatural maneuvers, turning off the sidescreens to reduce the field-of-view, avoiding use of improperly calibrated simulators until repaired, and stressing proper rest and health discipline among the pilots. The success of these measures was evaluated 1 yr later by collecting SSQ data on 25 IP and 50 SP. RESULTS: There was a main effect of time, in that after the recommendations were implemented, there was a significant reduction in nausea, oculomotor, and total SSQ scores from the pre-study to the post-study. There was also a main effect of experience, as IP reported significantly greater SS than SP for the same scores. DISCUSSION: Implementation of the recommendations reduced SS in the new simulators at the cost of limiting session duration and shutting down some simulator features. Although the optimal solution to the SS problem lies in addressing SS during a simulator's design stage, these recommendations can be used as interim solutions to reduce SS.


Assuntos
Aeronaves , Enjoo devido ao Movimento , Medicina Aeroespacial , Humanos , Inquéritos e Questionários , Análise e Desempenho de Tarefas
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