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1.
J Strength Cond Res ; 37(8): 1616-1622, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36728012

RESUMEN

ABSTRACT: Amonette, WE, Vazquez, J, and Coleman, AE. Cross-sectional analysis of ground reaction forces during jumps in professional baseball players. J Strength Cond Res 37(8): 1616-1622, 2023-This study described and compared force plate kinetics in major (MLB) and minor (MiLB) baseball players while performing vertical jumps (CMVJ), squat jumps (SSJ), and depth jumps (DJ). Second, comparisons were made between playing positions. Data were collected on 101 professional baseball players. Peak force, eccentric and concentric impulses, peak power, and jump height were determined from each test. Reactive strength index was computed from the DJ. Data were compared using factorial analysis of variances, alpha was set at p ≤ 0.05, and effect sizes were reported using Cohen's d . During CMVJ, MiLB players generated more force ( p = 0.04; d = 0.48), power ( p = 0.02; d = 0.42), and jumped higher ( p = 0.03; d = 0.32) than MLB players. Pitchers generated higher propulsive impulses than catchers ( p = 0.004; d = 0.93). Outfielders generated more power ( p = 0.02; d = 0.98) and jumped higher ( p = 0.049; d = 1.08) than catchers and infielders ( p = 0.025; d = 0.32). Minor league baseball players generated more force ( p = 0.002; d = 0.62), power ( p = 0.001; d = 0.84), and jumped higher ( p = 0.02; d = 0.48) than MLB players in SSJ. No differences were observed by position in SSJ. Minor league baseball players jumped higher than MLB players in the DJ ( p = 0.01; d = 0.57) and outfielders generated more power in the DJ than pitchers ( p = 0.05; d = 0.43) and catchers ( p = 0.007; d = 1.61). Reactive strength index was greater in outfielders compared with catchers ( p = 0.01; d = 1.20). These data indicate that MiLB players were generally more powerful and jumped higher than MLB players in the 3 performance tasks. The difference observed by playing level were likely related to physical preparedness at the beginning of spring training; positional differences were the result of athletic skill sets required for tactical excellence at each position.


Asunto(s)
Béisbol , Humanos , Estudios Transversales
2.
J Synchrotron Radiat ; 28(Pt 3): 688-706, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33949979

RESUMEN

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

3.
Phys Rev Lett ; 123(4): 045701, 2019 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-31491279

RESUMEN

We combined laser shock compression with in situ x-ray diffraction to probe the crystallographic state of gold (Au) on its principal shock Hugoniot. Au has long been recognized as an important calibration standard in diamond anvil cell experiments due to the stability of its face-centered cubic (fcc) structure to extremely high pressures (P >600 GPa at 300 K). This is in contrast to density functional theory and first principles calculations of the high-pressure phases of Au that predict a variety of fcc-like structures with different stacking arrangements at intermediate pressures. In this Letter, we probe high-pressure and high-temperature conditions on the shock Hugoniot and observe fcc Au at 169 GPa and the first evidence of body-centered cubic (bcc) Au at 223 GPa. Upon further compression, the bcc phase is observed in coexistence with liquid scattering as the Hugoniot crosses the Au melt curve before 322 GPa. The results suggest a triple point on the Au phase diagram that lies very close to the principal shock Hugoniot near ∼220 GPa.

4.
Phys Rev Lett ; 122(25): 255704, 2019 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-31347883

RESUMEN

Ultrafast x-ray diffraction at the LCLS x-ray free electron laser has been used to resolve the structural behavior of antimony under shock compression to 59 GPa. Antimony is seen to transform to the incommensurate, host-guest phase Sb-II at ∼11 GPa, which forms on nanosecond timescales with ordered guest-atom chains. The high-pressure bcc phase Sb-III is observed above ∼15 GPa, some 8 GPa lower than in static compression studies, and mixed Sb-III/liquid diffraction are obtained between 38 and 59 GPa. An additional phase which does not exist under static compression, Sb-I^{'}, is also observed between 8 and 12 GPa, beyond the normal stability field of Sb-I, and resembles Sb-I with a resolved Peierls distortion. The incommensurate Sb-II high-pressure phase can be recovered metastably on release to ambient pressure, where it is stable for more than 10 ns.

5.
Phys Rev Lett ; 118(2): 025501, 2017 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-28128621

RESUMEN

Using x-ray diffraction at the Linac Coherent Light Source x-ray free-electron laser, we have determined simultaneously and self-consistently the phase transitions and equation of state (EOS) of the lightest transition metal, scandium, under shock compression. On compression scandium undergoes a structural phase transition between 32 and 35 GPa to the same bcc structure seen at high temperatures at ambient pressures, and then a further transition at 46 GPa to the incommensurate host-guest polymorph found above 21 GPa in static compression at room temperature. Shock melting of the host-guest phase is observed between 53 and 72 GPa with the disappearance of Bragg scattering and the growth of a broad asymmetric diffraction peak from the high-density liquid.

6.
Physiol Plant ; 160(1): 98-110, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28074485

RESUMEN

This study addressed whether the winter annual Arabidopsis thaliana can adjust foliar phloem and xylem anatomy both differentially and in parallel. In plants acclimated to hot vs cool temperature, foliar minor vein xylem-to-phloem ratio was greater, whereas xylem and phloem responded concomitantly to growth light intensity. Across all growth conditions, xylem anatomy correlated with transpiration rate, while phloem anatomy correlated with photosynthetic capacity for two plant lines (wild-type Col-0 and tocopherol-deficient vte1 mutant) irrespective of tocopherol status. A high foliar vein density (VD) was associated with greater numbers and cross-sectional areas of both xylem and phloem cells per vein as well as higher rates of both photosynthesis and transpiration under high vs low light intensities. Under hot vs cool temperature, high foliar VD was associated with a higher xylem-to-phloem ratio and greater relative rates of transpiration to photosynthesis. Tocopherol status affected development of foliar vasculature as dependent on growth environment. The most notable impact of tocopherol deficiency was seen under hot growth temperature, where the vte1 mutant exhibited greater numbers of tracheary elements (TEs) per vein, a greater ratio of TEs to sieve elements, with smaller individual sizes of TEs, and resulting similar total areas of TEs per vein and transpiration rates compared with Col-0 wild-type. These findings illustrate the plasticity of foliar vascular anatomy acclimation to growth environment resulting from independent adjustments of the vasculature's components.


Asunto(s)
Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Luz , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/metabolismo , Tocoferoles/farmacología , Fotosíntesis/efectos de los fármacos , Temperatura
7.
BMC Public Health ; 17(1): 211, 2017 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-28212638

RESUMEN

BACKGROUND: The wide-ranging program of reforms brought about by the Health and Social Care Act (2012) in England fundamentally changed the operation of the public health system, moving responsibility for the commissioning and delivery of services from the National Health Service to locally elected councils and a new national public health agency. This paper explores the ways in which the reforms have altered public health commissioning. METHODS: We conducted multi-methods research over 33 months, incorporating national surveys of Directors of Public Health and local council elected members at two time-points, and in-depth case studies in five purposively selected geographical areas. RESULTS: Public health commissioning responsibilities have changed and become more fragmented, being split amongst a range of different organisations, most of which were newly created in 2013. There is much change in the way public health commissioning is done, in who is doing it, and in what is commissioned, since the reforms. There is wider consultation on decisions in the local council setting than in the NHS, and elected members now have a strong influence on public health prioritisation. There is more (and different) scrutiny being applied to public health contracts, and most councils have embarked on wide-ranging changes to the health improvement services they commission. Public health money is being used in different ways as councils are adapting to increasing financial constraint. CONCLUSIONS: Our findings suggest that, while some of the intended opportunities to improve population health and create a more joined-up system with clearer leadership have been achieved, fragmentation, dispersed decision-making and uncertainties regarding funding remain significant challenges. There have been profound changes in commissioning processes, with consequences for what health improvement services are ultimately commissioned. Time (and further research) will tell if any of these changes lead to improved population health outcomes and reduced health inequalities, but many of the opportunities brought about by the reforms are threatened by the continued flux in the system.


Asunto(s)
Reforma de la Atención de Salud/organización & administración , Administración de los Servicios de Salud , Medicina Estatal/organización & administración , Contratos , Inglaterra , Humanos , Liderazgo
8.
Plant Cell Environ ; 39(7): 1549-58, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26832121

RESUMEN

The plasticity of leaf form and function in European lines of Arabidopsis thaliana was evaluated in ecotypes from Sweden and Italy grown under contrasting (cool versus hot) temperature regimes. Although both ecotypes exhibited acclimatory adjustments, the Swedish ecotype exhibited more pronounced responses to the two contrasting temperature regimes in several characterized features. These responses included thicker leaves with higher capacities for photosynthesis, likely facilitated by a greater number of phloem cells per minor vein for the active loading and export of sugars, when grown under cool temperature as opposed to leaves with a higher vein density and a greater number of tracheary elements per minor vein, likely facilitating higher rates of transpirational water loss (and thus evaporative cooling), when grown under hot temperature with high water availability. In addition, only the Swedish ecotype exhibited reduced rosette growth and greater levels of foliar tocopherols under the hot growth temperature. These responses, and the greater responsiveness of the Swedish ecotype compared with the Italian ecotype, are discussed in the context of redox signalling networks and transcription factors, and the greater range of environmental conditions experienced by the Swedish versus the Italian ecotype during the growing season in their native habitats.


Asunto(s)
Arabidopsis/anatomía & histología , Hojas de la Planta/anatomía & histología , Temperatura , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Italia , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Transpiración de Plantas , Haz Vascular de Plantas/crecimiento & desarrollo , Suecia , Tocoferoles/metabolismo
9.
Br J Dermatol ; 174(1): 165-8, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26595446

RESUMEN

BACKGROUND: The current recommended treatment for lentigo maligna (LM) is surgical resection, which can cause significant scarring. The reported recurrence rate after Mohs micrographic surgery is 0-6·25%. There is little published data on long-term outcome after imiquimod therapy. Several reports record progression to LM melanoma during treatment. Clinical assessment of clearance is difficult. Histological confirmation is preferred but risks sampling error and missing areas of invasion. Confocal microscopy can be used to assess entire lesions. OBJECTIVES: To assess the 5-year recurrence rate of LM after imiquimod treatment. METHODS: Forty patients with LM were treated with imiquimod between 2002 and 2007. Their previous treatments included cryotherapy, incomplete surgical excision and radiotherapy. All applied imiquimod three times per week for 6 weeks; 25 (62·5%) experienced inflammation. The other 15 (37·5%) then applied imiquimod five times per week for a further 4 weeks; all experienced inflammation. All patients were subsequently examined and biopsied. Clinical clearance did not always correlate with histological clearance. Eleven patients (27·5%) had residual LM on histology and underwent surgical excision. At the time of this study, three patients had died (deaths were unrelated to LM). Eighteen of the 27 patients (66·7%) who were clear on biopsy after imiquimod attended for the study and were assessed using confocal microscopy (Vivascope 1500 and 3000). RESULTS: The recurrence rate of LM in patients who were clear on histology after imiquimod treatment who attended for this follow-up study was 0% (n = 18). CONCLUSIONS: Imiquimod is an effective long-term treatment for LM. Its use avoids potentially disfiguring surgical resection.


Asunto(s)
Aminoquinolinas/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Faciales/tratamiento farmacológico , Peca Melanótica de Hutchinson/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Imiquimod , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología
10.
J Public Health (Oxf) ; 38(3): e201-e208, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26487701

RESUMEN

BACKGROUND: Following the Health and Social Care Act in England, public health teams were formally transferred from the NHS to local authorities in April 2013. METHODS: Online survey of Directors of Public Health (DsPH) in local authorities in England (n = 152) to investigate their experience within local government 1 year on. Tests of association were used to explore relationships between the perceived integration and influence of public health, and changes in how the public health budget was being spent. RESULTS: The organization of and managerial arrangements for public health within councils varied. Most DsPH felt that good relationships had been established within the council, and the move had made them more able to influence priorities for health improvement, even though most felt their influence was limited. Changes in commissioning using the public health budget were already widespread and included the de-commissioning of services. CONCLUSIONS: There was a widespread feeling amongst DsPH that they had greater influence since the reforms, and that this went across the local authority and beyond. Public health's influence was most apparent when the transfer of staff to local government had gone well, when collaborative working relationships had developed, and when local partnership groups were seen as being effective.


Asunto(s)
Administración en Salud Pública , Presupuestos/organización & administración , Humanos , Gobierno Local , Innovación Organizacional , Administración en Salud Pública/economía , Administración en Salud Pública/legislación & jurisprudencia , Administración en Salud Pública/métodos , Administración en Salud Pública/estadística & datos numéricos , Medicina Estatal/legislación & jurisprudencia , Medicina Estatal/organización & administración , Medicina Estatal/estadística & datos numéricos , Encuestas y Cuestionarios , Reino Unido
11.
J Exp Bot ; 66(2): 541-8, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25403918

RESUMEN

Plant-mediated RNA interference (RNAi) has been successfully used as a tool to study gene function in aphids. The persistence and transgenerational effects of plant-mediated RNAi in the green peach aphid (GPA) Myzus persicae were investigated, with a focus on three genes with different functions in the aphid. Rack1 is a key component of various cellular processes inside aphids, while candidate effector genes MpC002 and MpPIntO2 (Mp2) modulate aphid-plant interactions. The gene sequences and functions did not affect RNAi-mediated down-regulation and persistence levels in the aphids. Maximal reduction of gene expression was ~70% and this was achieved at between 4 d and 8 d of exposure of the aphids to double-stranded RNA (dsRNA)-producing transgenic Arabidopsis thaliana. Moreover, gene expression levels returned to wild-type levels within ~6 d after removal of the aphids from the transgenic plants, indicating that a continuous supply of dsRNA is required to maintain the RNAi effect. Target genes were also down-regulated in nymphs born from mothers exposed to dsRNA-producing transgenic plants, and the RNAi effect lasted twice as long (12-14 d) in these nymphs. Investigations of the impact of RNAi over three generations of aphids revealed that aphids reared on dsMpC002 transgenic plants experienced a 60% decline in aphid reproduction levels compared with a 40% decline of aphids reared on dsRack1 and dsMpPIntO2 plants. In a field setting, a reduction of the aphid reproduction by 40-60% would dramatically decrease aphid population growth, contributing to a substantial reduction in agricultural losses.


Asunto(s)
Áfidos/genética , Arabidopsis/fisiología , Patrón de Herencia/genética , Interferencia de ARN , Animales , Áfidos/crecimiento & desarrollo , Arabidopsis/genética , Regulación hacia Abajo/genética , Genes de Insecto , Plantas Modificadas Genéticamente
12.
J Strength Cond Res ; 29(7): 1759-65, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25353082

RESUMEN

The purpose of this article was to compare times to first base in Major League Baseball games to determine whether running velocity decreases to the foul line and first base among players with differing years of playing experience. From 1998 to 2012, 1,185 sprint times to first base were analyzed: 469 outfielders, 601 infielders, and 115 catchers. The players were divided into differing experience categories depending on their years of service in Major League Baseball: 1-5, 6-10, 11-15, and 16-20+ years. Velocity at the foul line and first base was compared and interval accelerations were reported. Comparisons were completed by playing position, and within left- and right-handed batters. Left-handed outfielders exhibited reduced velocities at 6-10 (p = 0.04), 11-15 (p = 0.004), and 16-20 years (p < 0.001) compared with 1-5 years; there were no statistical differences in velocity at the foul line. Right-handed outfielders exhibited significantly reduced velocities at first base in 6-10 (p = 0.002) and 11-15 years (p = 0.001); they also had a reduced velocities at the foul line in 6-10 (p = 0.004) and 11-15 years (p = 0.009). Right-handed infielders had reduced velocities at first base in 11-15 years (p < 0.001). No other differences were observed within infielders at first base or the foul line. There were no differences within the compared variables for catchers. Decreases in running velocity to first base with experience are seen in outfielders but are less prominent in infielders and catchers. Although physical capabilities for sprinting may decline with age, it is possible that through repetition more experienced players perfect the skill-related component of running to first base, thus preserving speed.


Asunto(s)
Aceleración , Béisbol/fisiología , Carrera/fisiología , Adolescente , Adulto , Estudios Transversales , Mano , Humanos , Masculino , Estudios Retrospectivos , Factores de Tiempo , Adulto Joven
13.
Psychiatr Q ; 86(3): 419-33, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25601029

RESUMEN

There is a pressing need to develop community interventions that will address stigma against mental illness in rural India. This cross-sectional study will compare social representations of depression in villages where educational programs have targeted mental illness and stigma versus control villages. Participants from the villages exposed to the educational interventions (n = 146) will be compared with a sample from six control villages (n = 187) in the same geographic region, using a structured questionnaire. The impact of the intervention as a predictor for questionnaire score will be assessed along with socio-demographic variables. The intervention villages showed higher levels of literacy regarding depression and lower levels of stigma, after adjusting for all other socio-demographic variables. While some demographic factors associated with the knowledge and attitudes towards depression are not modifiable, our research provides evidence in favor of the positive influence a community grassroots intervention can have on mental health literacy in rural settings.


Asunto(s)
Depresión/psicología , Conocimientos, Actitudes y Práctica en Salud , Población Rural , Estigma Social , Adolescente , Adulto , Anciano , Femenino , Educación en Salud , Humanos , India , Masculino , Persona de Mediana Edad , Características de la Residencia , Adulto Joven
14.
J Vet Cardiol ; 51: 124-137, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38128418

RESUMEN

INTRODUCTION/OBJECTIVES: Manual compression has been standard of care for maintaining hemostasis after percutaneous endovascular intervention, but can be time-consuming and associated with vascular complications. Alternative closure methods include the figure-of-eight suture (Z-stitch) and vascular closure device (VCD) techniques. We hypothesized that compared to manual compression, Z-stitch and VCD would significantly reduce time-to-hemostasis after transvenous access, and the proportion of dogs with vascular patency would not differ significantly among treatments. ANIMALS: Forty-six client-owned dogs undergoing percutaneous transvenous interventional procedures. MATERIALS AND METHODS: Dogs with vessel diameter <5 mm were randomized to undergo manual compression or Z-stitch, while those with vessel diameter ≥5 mm were randomized to undergo manual compression, Z-stitch, or VCD. Time-to-hemostasis, bleeding scores, presence of vascular patency one day and two to three months post-procedure, and complications were recorded. Data are presented as median (95% confidence interval). RESULTS: In all 46 dogs, the right external jugular vein was used. Time-to-hemostasis was significantly shorter in the Z-stitch (2.1 [1.8-2.9] minutes) compared to VCD (8.6 [6.1-11.8] minutes; P<0.001) and manual compression (10.0 [10.0-20.0] minutes; P<0.001) groups. Time-to-hemostasis was significantly shorter in the VCD vs. manual compression (P=0.027) group. Bleeding scores were significantly greater at 5 and 10 min (P<0.001 and 0.013, respectively) in manual compression, compared to Z-stitch group. There was no difference in the proportion of dogs with vascular patency between groups (P=0.59). CONCLUSIONS: Z-stitch and VCD are effective venous hemostasis methods after percutaneous transvenous intervention, with Z-stitch providing the most rapid time-to-hemostasis. Both Z-stitch and VCD techniques have low complication rates and effectively maintain vascular patency.


Asunto(s)
Enfermedades de los Perros , Técnicas Hemostáticas , Hemorragia Posoperatoria , Dispositivos de Cierre Vascular , Procedimientos Quirúrgicos Vasculares , Animales , Perros , Enfermedades de los Perros/cirugía , Arteria Femoral/cirugía , Técnicas Hemostáticas/efectos adversos , Técnicas Hemostáticas/veterinaria , Resultado del Tratamiento , Dispositivos de Cierre Vascular/veterinaria , Dispositivos de Cierre Vascular/efectos adversos , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/instrumentación , Procedimientos Quirúrgicos Vasculares/métodos , Hemorragia Posoperatoria/prevención & control , Hemorragia Posoperatoria/veterinaria
15.
J Vet Cardiol ; 51: 86-96, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38118234

RESUMEN

INTRODUCTION/OBJECTIVES: The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. ANIMALS: Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max). RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 µg/mL (0.45-1.17 µg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 µg/mL (1.91-2.48 µg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose. CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.


Asunto(s)
Sotalol , Gatos , Animales , Estudios Cruzados , Infusiones Intravenosas/veterinaria , Cromatografía Líquida de Alta Presión/veterinaria , Disponibilidad Biológica , Administración Oral , Semivida
16.
Nat Genet ; 14(3): 312-5, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8896561

RESUMEN

Murine models of human carcinogenesis are exceedingly valuable tools to understand genetic mechanisms of neoplastic growth. The identification of recurrent chromosomal rearrangements by cytogenetic techniques serves as an initial screening test for tumour specific aberrations. In murine models of human carcinogenesis, however, karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size. Fluorescence in situ hybridization (FISH) with mouse chromosome specific painting probes can complement conventional banding analysis. Although sensitive and specific, FISH analyses are restricted to the visualization of only a few mouse chromosomes at a time. Here we apply a novel imaging technique that we developed recently for the visualization of human chromosomes to the simultaneous discernment of all mouse chromosomes. The approach is based on spectral imaging to measure chromosome-specific spectra after FISH with differentially labelled mouse chromosome painting probes. Utilizing a combination of Fourier spectroscopy, CCD-imaging and conventional optical microscopy, spectral imaging allows simultaneous measurement of the fluorescence emission spectrum at all sample points. A spectrum-based classification algorithm has been adapted to karyotype mouse chromosomes. We have applied spectral karyotyping (SKY) to chemically induced plasmocytomas, mammary gland tumours from transgenic mice overexpressing the c-myc oncogene and thymomas from mice deficient for the ataxia telangiectasia (Atm) gene. Results from these analyses demonstrate the potential of SKY to identify complex chromosomal aberrations in mouse models of human carcinogenesis.


Asunto(s)
Aberraciones Cromosómicas , Cromosomas , Cariotipificación/métodos , Proteínas Serina-Treonina Quinasas , Animales , Proteínas de la Ataxia Telangiectasia Mutada , Proteínas de Ciclo Celular , Proteínas de Unión al ADN , Modelos Animales de Enfermedad , Genes myc , Humanos , Hibridación Fluorescente in Situ/métodos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Ratones Transgénicos , Neoplasias/genética , Plasmacitoma/genética , Proteínas/genética , Proteínas Supresoras de Tumor
17.
Clin Exp Immunol ; 170(2): 212-21, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23039892

RESUMEN

Dendritic cells (DC) in HIV-1-infected individuals are decreased and their dysfunction has been implicated in HIV-1 immunopathogenesis. The mechanism of their dysfunction remains unclear, thus we analysed the expression of membrane molecules associated with immune regulation and DC activation in myeloid (mDC) and plasmacytoid DC (pDC) in therapy-naive and highly active anti-retroviral therapy (HAART)-treated HIV-1(+) patients. DC from healthy controls, untreated HIV-1(+) and HAART-treated patients were assessed by flow cytometry for expression of: anergy and apoptosis inducing molecules [programmed death (PD)-1 and its ligands PD-L1 and PD-L2], inhibitory and regulatory T cell-inducing molecules [immunoglobulin-like transcript (ILT)-3 and ILT-4], interferon (IFN)-α inhibitory receptor (ILT-7) and co-stimulatory molecules (CD80, CD83, and CD86). pDC from untreated HIV-1(+) patients expressed significantly lower levels of ILT-7 compared to healthy controls, while HAART-treated patients showed normal expression. pDC were also found to express moderately higher levels of PD-L1 and ILT-3 and lower levels of PD-L2 receptors in untreated patients compared to controls and HAART-treated patients. No significant changes were observed in mDC. There were no associations between the percentages and levels of expression of these molecules by pDC and viral load or CD4 T cell count. In conclusion, pDC but not mDC from HIV-1(+) patients with active viraemia display higher levels of apoptosis and T regulatory-inducing molecules and may be predisposed to chronically produce IFN-α through down-regulation of ILT-7. HAART restored normal expression levels of these receptors.


Asunto(s)
Células Dendríticas/inmunología , Infecciones por VIH/inmunología , Células Mieloides/inmunología , Adulto , Antígenos CD/inmunología , Antígenos CD/metabolismo , Terapia Antirretroviral Altamente Activa/métodos , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Estudios de Cohortes , Células Dendríticas/metabolismo , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Infecciones por VIH/patología , VIH-1/inmunología , Humanos , Inmunofenotipificación , Masculino , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Células Mieloides/metabolismo , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Receptores de Superficie Celular/inmunología , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/inmunología , Receptores Inmunológicos/metabolismo , Viremia/inmunología , Viremia/metabolismo , Adulto Joven
18.
Ann Surg Oncol ; 19(12): 3896-3905, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22549288

RESUMEN

BACKGROUND: Isolated limb infusion with melphalan (ILI-M) corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximate 29 % complete response (CR) rate. Sorafenib, a multi-kinase inhibitor, has been shown to augment tumor response to chemotherapy in preclinical studies. METHODS: A multi-institutional, dose-escalation, phase I study was performed to evaluate the safety and antitumor activity of sorafenib in combination with ILI-M. Patients with AJCC stage IIIB/IIIC/IV melanoma were treated with sorafenib starting at 400 mg daily for 7 days before and 7 days after ILI-M corrected for IBW. Toxicity, drug pharmacokinetics, and tumor protein expression changes were measured and correlated with clinical response at 3 months. RESULTS: A total of 20 patients were enrolled at two institutions. The maximum tolerated dose (MTD) of sorafenib in combination with ILI-M was 400 mg. Four dose-limiting toxicities occurred, including soft tissue ulcerations and compartment syndrome. There were three CRs (15 %) and four partial responses (20 %). Of patients with the Braf mutation, 83 % (n = 6) progressed compared with only 33 % without (n = 12). Short-term sorafenib treatment did alter protein expression as measured with reverse phase protein array (RPPA) analysis, but did not inhibit protein expression in the MAP kinase pathway. Sorafenib did not alter melphalan pharmacokinetics. CONCLUSION: This trial defined the MTD of systemically administered sorafenib in combination with ILI-M. Although some responses were seen, the addition of sorafenib to ILI-M did not appear to augment the effects of melphalan but did increase regional toxicity.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Extremidades/patología , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dosis Máxima Tolerada , Melanoma/patología , Melfalán/administración & dosificación , Estadificación de Neoplasias , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Pronóstico , Análisis por Matrices de Proteínas , Neoplasias Cutáneas/patología , Sorafenib , Distribución Tisular
19.
Clin Exp Dermatol ; 37(3): 219-26, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22277060

RESUMEN

Whole-body ultraviolet (UV)A1 (340-400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.


Asunto(s)
Enfermedades de la Piel/radioterapia , Terapia Ultravioleta/métodos , Accesibilidad a los Servicios de Salud , Humanos , Terapia Ultravioleta/efectos adversos , Reino Unido
20.
J Strength Cond Res ; 26(6): 1455-60, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22450255

RESUMEN

The purposes of this research were to (a) quantify interval sprint times between Home-Plate and the Foul-Line and the Foul-Line and First-Base, (b) determine if differences exist in interval velocities and acceleration between left- and right-handed batters or between-position groupings, and (c) to quantify determinants of time to First-Base in Major-League Baseball players during actual games. A total of 1,896 sprint times to the Foul-Line (13.7 m) and First-Base (27.4 m) were recorded in 302 baseball players by a single coach, positioned in the dugout with a hand-held stopwatch. Interval velocities and accelerations were computed between Home-Plate and the Foul-Line and the Foul-Line and First-Base; average velocity and acceleration were also determined over the entire 27.4 m. Velocity and acceleration for left-handed batters were greater than for right-handed batters from Home-Plate to the Foul-Line and from Home-Plate to First-Base; however, there were no differences in velocity or acceleration from the Foul-Line to First-Base. Interval velocity was significantly greater for outfielders and infielders compared with that for catchers from Home-Plate to the Foul-Line and from the Home-Plate to First-Base. Outfielders were faster than catchers from the Foul-Line to First-Base; no other between-group differences were evident. Accelerations from Home-Plate to the Foul-Line and from Home-Plate to First-Base were greater for outfielders compared with infielders and catchers. Infielders accelerated at greater rates than did catchers between these intervals. There were no between-position differences in acceleration from the Foul-Line to First-Base. These data indicate that time to First-Base is most affected by acceleration from Home-Plate to the Foul-Line. Coaches should implement strategies that encourage players to sprint maximally over the first 13.7 m to maximize chances of successfully reaching First-Base.


Asunto(s)
Aceleración , Rendimiento Atlético/fisiología , Béisbol/fisiología , Carrera/fisiología , Estudios de Cohortes , Lateralidad Funcional , Humanos , Masculino , Estudios Retrospectivos
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