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1.
Surgeon ; 22(3): 166-173, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38521683

RESUMO

BACKGROUND: Long-course neoadjuvant chemoradiotherapy (NCRT), followed by surgery after an interval of 6-8 weeks, represents standard of care for patients with locally advanced rectal cancer (LARC). Increasing this interval may improve rates of complete pathological response (pCR) and tumour downstaging. We performed a meta-analysis comparing standard (SI, within 8 weeks) versus longer (LI, after 8 weeks) interval from NCRT to surgery. METHODS: PubMed, Embase, and Cochrane databases were searched up to 31 August 2022. Randomized controlled trials (RCTs) comparing SI with LI after NCRT for LARC were included. The primary endpoint was pCR rate. Secondary endpoints included rates of R0 resection, circumferential resection margin positivity (+CRM), TME completeness, lymph node yield (LNY), operative duration, tumour downstaging (TD), sphincter preservation, mortality, postoperative complications, surgical site infection (SSI) and anastomotic leak (AL). Random effects models were used to calculate pooled effect size estimates. RESULTS: Four RCTs encompassing 867 patients were included. There were 539 males (62.1%). LI was associated with a higher pCR rate (OR 0.61, 95%CI â€‹= â€‹0.39-0.95, p â€‹= â€‹0.03), and more TD (OR 0.60, 95%CI â€‹= â€‹0.37-0.97, p â€‹= â€‹0.04) compared to SI. However, there was no difference in rates of R0 resection (p â€‹= â€‹0.87), +CRM (p â€‹= â€‹0.66), sphincter preservation (p â€‹= â€‹0.26), incomplete TME (p â€‹= â€‹0.49), LNY (p â€‹= â€‹0.55), SSI (p â€‹= â€‹0.33), AL (p â€‹= â€‹0.20), operative duration (p â€‹= â€‹0.07), mortality (p â€‹= â€‹0.89) or any surgical complication (p â€‹= â€‹0.91). CONCLUSIONS: A LI to surgery after NCRT for LARC increases pCR and TD rates. Local recurrence or survival were not assessed due to unavailable data. We recommend deferring TME until after an interval of 8 weeks following completion of NCRT.


Assuntos
Terapia Neoadjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/mortalidade , Tempo para o Tratamento , Quimiorradioterapia
2.
J Soils Sediments ; 23(12): 4187-4207, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38037661

RESUMO

Purpose: This research aimed to determine if a severe wildfire caused changes in the source of sediment being delivered to downstream aquatic systems and evaluate the use of polycyclic aromatic hydrocarbons (PAHs) and color properties as tracers. Methods: Sediment samples were collected from 2018 to 2021 in three tributaries impacted by the 2018 Shovel Lake wildfire and from two sites on the mainstem of the Nechako River, British Columbia. Source samples were collected from burned and unburned soils as well as from channel banks and road-deposited sediment. Samples were analyzed for color properties and for the 16 US Environmental Protection Agency priority PAHs. After statistical tests to determine the conservatism and ability to discriminate between sources by the tracers, the MixSIAR unmixing model was used, and its outputs were tested using virtual mixtures. Result: In the tributaries, burned topsoil was an important contributor to sediment (up to 50%). The mainstem Nechako River was not influenced as significantly by the fires as the greatest contributor was banks (up to 89%). The color properties provided more realistic results than those based on PAHs. Conclusion: In smaller watersheds, the wildfire had a noticeable impact on sediment sources, though the impacts of the fire seemed to be diluted in the distal mainstem Nechako River. Color tracers behaved conservatively and discriminated between contrasting sources. Due to their low cost and reliability, they should be considered more widely. While PAHs did not work in this study, there are reasons to believe they could be a useful tracer, but more needs to be understood about their behavior and degradation over time. Supplementary Information: The online version contains supplementary material available at 10.1007/s11368-023-03565-0.

3.
J Environ Qual ; 47(6): 1327-1338, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30512068

RESUMO

Dynamic soil chemical interactions with conservation agricultural practices and soil biota are largely unknown. Therefore, this study aims to quantify long-term (12-yr) impacts of cover crops, poultry litter, crop rotations, no-tillage, and their interactions on dynamic soil properties and to determine their relationships with nutrient cycling, crop yield, and soil biodiversity (soil microbial and earthworm communities). Main effects were 13 different cropping sequences of soybean [ (L.) Merr.], corn ( L.), and cotton ( L.) at the Research and Education Center at Milan, TN, and eight sequences of corn and soybean at the Middle Tennessee Research and Education Center, Spring Hill, TN. Sequences were repeated in 4-yr phases from 2002 to 2014. Split-block cover crop treatments consisted of winter wheat ( L.), hairy vetch ( Roth), poultry litter, and a fallow control. Soil C and nutrient fluxes were calculated at surface (0-5 cm) and subsurface (5-15 cm) layers during Years 0, 2, 4, 8, and 12. After 12 yr, weighted means (0-15 cm) of soil pH, P, K, Ca, Mg, total N, and C were greater under poultry litter-amended soils compared with cover crops ( < 0.05). In addition, continuous corn sequences resulted in greater soil K, N, and C concentrations than soybean-soybean-corn-corn rotations ( < 0.05). Poultry litter treatments were positively correlated with greater soil fertility levels, as well as higher crop yield and soil biodiversity. These results underscore linkages between manure additions and cropping sequences, within the nutrient cycling, soil health, and crop production continuum.


Assuntos
Agricultura/métodos , Fertilizantes , Solo/química , Animais , Aves Domésticas
4.
J Labelled Comp Radiopharm ; 59(4): 175-86, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26991121

RESUMO

The 24th annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK on Friday 6th November 2015. The meeting was attended by 77 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral presentations, short 'flash' presentations in association with particular posters and poster presentations. The scientific areas covered included isotopic synthesis, regulatory issues, applications of labelled compounds in imaging, isotopic separation and novel chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium was divided into a morning session chaired by Dr Rebekka Hueting (University of Oxford, UK) and afternoon sessions chaired by Dr Sofia Pascu (University of Bath, UK) and by Dr Alan Dowling (Syngenta, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK).

5.
Ir Med J ; 108(1): 21-2, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25702350

RESUMO

Single stage en bloc abdominoperineal resection and sacrectomy, with a myocutaneous flap closure is a relatively uncommon procedure. Our case study of a 77 year old man with a locally invasive rectal adenocarcinoma highlights the complex intraoperative management of such a patient.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Retais , Sacro , Neoplasias da Coluna Vertebral , Idoso , Colectomia , Humanos , Masculino , Osteotomia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Sacro/patologia , Sacro/cirurgia , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Retalhos Cirúrgicos
6.
Ir Med J ; 108(3): 78-81, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25876299

RESUMO

As part of the National Clinical Programme on healthcare-associated infection prevention, a Royal College of Surgeons in Ireland (RCSI) and Royal College of Physicians of Ireland (RCPI) working group developed a quality improvement tool for prevention of surgical site infection (SS). We aimed to validate the effectiveness of an educational campaign, which utilises this quality improvement tool to prevent SSI in a tertiary hospital. Prior to the SSI educational campaign, surgical patients were prospectively audited and details of antibiotic administration recorded. Prophylactic antibiotic administration recommendations were delivered via poster and educational presentations. Post-intervention, the audit was repeated. 50 patients were audited pre-intervention, 45 post-intervention. Post-intervention, prophylaxis within 60 minutes prior to incision increased from 54% to 68% (p = 0.266). Appropriate postoperative prescribing improved from 71% to 92% (p = 0.075). A multifaceted educational program may be effective in changing SSI prevention practices.


Assuntos
Antibioticoprofilaxia , Período Perioperatório , Desenvolvimento de Pessoal/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/normas , Prática Clínica Baseada em Evidências , Humanos , Irlanda , Modelos Educacionais , Período Perioperatório/educação , Período Perioperatório/métodos , Melhoria de Qualidade
7.
J Environ Qual ; 52(1): 88-99, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36314063

RESUMO

Information on how forage species influence sediment and nutrient transport in runoff is required for limiting non-point source pollution from broiler litter applications. In this study, we examined the effects of five forage species (eastern gamagrass [Tripsacum dactyloides (L.) L.], Kernza [Thinopyrum intermedium (Host) Barkworth & D.R. Dewey], silphium [Silphium integrifolium Michx.], switchgrass [Panicum virgatum L.], and winter wheat [Triticum aestivum L.]) on runoff nutrient losses from broiler litter-amended (5.6 Mg ha-1 ) and non-amended plots (control) following four simulated rainfall (5 cm h-1 ) events that were applied to these plots in late spring and early fall of 2019 and 2021. Runoff collected for 30 min was analyzed for total suspended solids (TSS) and nutrients (total organic carbon [TOC], soluble reactive phosphorus [SRP], total dissolved phosphorus [TDP], total phosphorus [TP], total nitrogen [TN], ammonium-nitrogen [NH4 -N], and nitrate-nitrogen [NO3 -N]). Total sediment and nutrient losses increased 5- to 19-fold following litter application for all species, which reduced to background levels during fall rainfall events. Across the four simulated rainfall events, switchgrass resulted in lower cumulative losses of TSS, TOC, SRP, TDP, TP, and NO3 -N than gamagrass and wheat but did not differ from Kernza and silphium for litter-amended treatments. The performance of newly introduced perennial crops (Kernza and silphium) was similar or better than that of gamagrass in terms of cumulative runoff sediment and nutrient losses. Results show high potential for Kernza, silphium, and switchgrass to improve water quality when used in forage-vegetative filter strip systems.


Assuntos
Galinhas , Panicum , Animais , Esterco , Nitrogênio/análise , Nutrientes , Triticum , Fósforo , Chuva , Proteínas de Ligação a DNA , Movimentos da Água
8.
Sci Total Environ ; 856(Pt 1): 158927, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36152844

RESUMO

Failures of mine tailings storage facilities (TSF) can have profound and long-lasting effects on the downstream receiving environment. Virtually all spills to date have been into river systems without large lakes that may buffer downstream impacts. In August 2014, the failure of the Mount Polley copper (Cu)-gold mine TSF in British Columbia, Canada, released ~25 × 106 m3 of water and solids; globally, this is the second largest TSF spill in history. Over 18 × 106 m3 was delivered to Quesnel Lake, which is ~9 km from the TSF and is the third deepest lake in North America, and a crucial habitat for Pacific salmon and trout populations. We determined the sediment-associated Cu concentrations and fluxes in Quesnel River, downstream of the lake, from August 2014 to February 2021 based on the analysis of >400 samples of sediment, mainly collected using a continuous-flow centrifuge. During each winter since the spill, Cu concentrations in the fluvial sediment in the upper reaches of the river (~35 km from the TSF) were elevated relative to regional background concentrations and samples collected before the spill. Maximum Cu concentrations were ~410 mg kg-1 which exceeds Canadian sediment quality guidelines for the protection of aquatic organisms (197 mg kg-1). Monitoring of Quesnel Lake since the spill shows that these annual pulses in the winter are due to resuspension of unconsolidated tailings and sediments at the bottom of Quesnel Lake, during autumnal lake turnover, which become mixed throughout the water column and subsequently flow into Quesnel River. Results show that while large lakes may buffer downstream aquatic systems from contaminated sediment, they may prolong the environmental impact. These findings are crucial in understanding how lake processes may modify the effects of TSF spills on downstream aquatic systems.


Assuntos
Lagos , Poluentes Químicos da Água , Colúmbia Britânica , Cobre/análise , Monitoramento Ambiental , Sedimentos Geológicos/análise , Água/análise , Poluentes Químicos da Água/análise
9.
Pediatr Blood Cancer ; 59(4): 685-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22180290

RESUMO

BACKGROUND: Sickle cell disease (SCD) is characterized by frequent disease-related events that require acute care. It is unknown to what extent patients utilize multiple hospitals for acute care. We examined the continuity pattern of acute care visits to the hospital or emergency department. We hypothesized that among patients with multiple SCD related acute care visits, children experience more concentrated hospital care than adults and privately insured patients experience more concentrated hospital care than publicly insured patients. PROCEDURE: We conducted a retrospective cohort study using data from the 2005 and 2006 Healthcare Cost and Utilization Project State Inpatient Databases and State Emergency Department Databases. Subjects included patients with SCD ≥ 1 year of age. The primary outcome was proportion of patients with multiple acute care visits to a single hospital. RESULTS: A total of 13,533 patients made ≥ 2 acute SCD-related visits. Of the 5,030 children, 77.3% went to the same hospital for all visits. In contrast, of the 8,503 adults, only 51.3% visited the same hospital. Adolescents were more likely than adults to go to one hospital [adjusted relative risk (ARR) 1.40, confidence interval (CI) 1.35-1.45]. Those with public insurance and the uninsured had a decreased probability of using one hospital (ARR 0.96, CI 0.94-0.99, and ARR 0.83, CI 0.79-0.88, respectively). CONCLUSIONS: Adults and patients with public insurance or no insurance are more likely to use multiple hospitals for acute care. By receiving acute care at multiple hospitals, patients with SCD experience dispersed and fragmented care potentially leading to decreased care quality.


Assuntos
Anemia Falciforme/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Doença Aguda , Adolescente , Adulto , Fatores Etários , Anemia Falciforme/complicações , Criança , Pré-Escolar , Continuidade da Assistência ao Paciente , Feminino , Humanos , Lactente , Masculino , Medicaid , Pessoas sem Cobertura de Seguro de Saúde , Estados Unidos , Adulto Jovem
10.
Sci Total Environ ; 824: 153725, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35150668

RESUMO

Watershed and pasture health is a transdisciplinary concern and crucial to promoting sustainable practices. The aim of this study is to identify effective systems-level conservation pasture management practices in a longitudinal study following 14 years of consistent management by i) teasing apart complex relationships between multivariate water and soil quality using principal component analysis (PCA); and ii) identifying interactions among variables that contribute most to watershed health within catchments using partial least squares-path modeling (PLS-PM) based on five treatments: hayed (H), continuously grazed (CG), rotationally grazed (R), rotationally grazed with an unfertilized buffer strip (RB), and rotationally grazed with an unfertilized fenced riparian buffer (RBR). Over 14 years, H and RBR systems had greater watershed health based on runoff water quality parameters. Therefore, management systems that keep forage heights >10-cm, have less frequent vegetative removal, and riparian filter strips promote watershed health. Of the over 20 runoff variables measured over 14 study years, only electrical conductivity and annual total suspended solid loads constructed a significant water quality PLS-PM model. Water quality was positively influenced by pasture management and precipitation, with long-term pasture management driving runoff parameters and water quality. Overall, animal grazing days was not only related to grazing intensity, but to animal manure inputs and soil compaction, and adversely related to watershed health. Study results denote that best management strategies such as rotational grazing and riparian buffer strips prevent pasture system degradation and maintain carrying capacity while reducing anthropogenic pressure on soil and water systems.


Assuntos
Esterco , Solo , Animais , Conservação dos Recursos Naturais , Estudos Longitudinais , Qualidade da Água
11.
Sci Rep ; 9(1): 2705, 2019 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-30804448

RESUMO

The West Basin of Quesnel Lake (British Columbia, Canada) suffered a catastrophic disturbance event in August 2014 when mine tailings and scoured natural material were deposited into the lake's West Basin due to an impoundment failure at the adjacent Mount Polley copper-gold mine. The deposit covered a significant portion of the West Basin floor with a thick layer of material. Since lake sediments host bacterial communities that play key roles in the geochemical cycling in lacustrine environments, it is important to understand which groups inhabit the newly deposited material and what this implies for the ecological function of the West Basin. Here we report a study conducted two years post-spill, comparing the bacterial communities from sediments of both disturbed and undisturbed sites. Our results show that sediments from disturbed sites differed in physical and chemical properties than those in undisturbed sites (e.g. higher pH, particle size and Cu concentration). Furthermore, bacterial communities from the disturbed sites appeared to be legacy communities from the tailings impoundment, with metabolic potential revolving mainly around the cycling of S and metals, whereas the ones from the undisturbed sites were associated with the cycling of N.


Assuntos
Bactérias/isolamento & purificação , Sedimentos Geológicos/microbiologia , Monitoramento Ambiental/métodos , Hábitos , Lagos
12.
J Environ Qual ; 48(4): 880-888, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31589680

RESUMO

A vegetated filter strip (VFS) is a measure commonly implemented in agricultural landscapes for the purpose of improving water quality. However, much of the evidence to support their effectiveness comes from warm regions dominated by rainfall driven runoff. This study assessed the performance of VFS plots and compared them with annual crop strips to reduce phosphorus (P) levels in runoff in the cold climate of the Canadian Prairies. Analysis of water samples from 22 events during the study indicated no significant difference in the inflow and outflow concentrations of total dissolved P (TDP) or total P (TP) for either the VFS or the annual crop strips. Although the VFS plots had little effect on TDP or TP during the spring, they performed better during the growing season, reducing mean TP concentrations in five out of seven, or 71%, of these events. The VFS plots did not perform as well during the fall events, with the overall mean TP concentration in runoff increasing after flowing through the filters during this time period.


Assuntos
Agricultura , Fósforo , Canadá , Estações do Ano , Movimentos da Água , Qualidade da Água
13.
J Environ Qual ; 48(2): 297-304, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30951134

RESUMO

Nitrogen runoff from pastures fertilized with animal manure, such as poultry litter, can result in accelerated eutrophication. The objective of this study was to evaluate the long-term effects of grazing management and buffer strips on N runoff from pastures fertilized with poultry litter. A 12-yr study was conducted on 15 small watersheds in Booneville, AR, using five management practices: continuous grazing, haying, rotational grazing, rotational grazing with an unfertilized buffer strip, and rotational grazing with a fenced unfertilized riparian buffer. Poultry litter was applied annually at a rate of 5.6 Mg ha. Concentrations and loads of total N, NO-N, NH-N, organic N, and total organic C in runoff varied intra- and interannually and coincided with precipitation trends. Overall, the greatest component of total N in runoff was organic N. Rotational grazing resulted in the highest concentrations and loads of all forms of N in runoff compared with other treatments, including the continuously grazed paddocks, which were grazed almost twice as much. Total organic C concentrations and loads in runoff were also higher from rotationally grazed watersheds than other treatments. Rotational grazing is considered a best management practice that typically reduces soil erosion; hence, the mechanism by which it caused higher N and C runoff is unclear. Nitrogen runoff losses from rotationally grazed pastures were reduced by 44% with unfertilized buffer strips, by 54% with fenced unfertilized riparian buffers, and by 52% by converting pastures to hayfields.


Assuntos
Criação de Animais Domésticos/métodos , Nitrogênio/análise , Poluentes da Água/análise , Poluição da Água/prevenção & controle , Agricultura , Animais , Monitoramento Ambiental , Fertilizantes , Esterco , Aves Domésticas
14.
JIMD Rep ; 41: 81-89, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29671225

RESUMO

The early progressive form of the X-linked disorder, Hunter syndrome or mucopolysaccharidosis type II (MPS II) (OMIM #309900), is characterized by cognitive decline, and pulmonary and cardiac complications that often cause death before 20 years of age. Deficiency of the lysosomal enzyme, iduronate-2-sulfatase (EC 3.1.6.13) results in deposition of the glycosaminoglycans, dermatan, and heparan sulfate in various tissues. In recent years, enzyme replacement therapy (ERT) has become the mainstay of treatment, but is expensive and ineffective in arresting cognitive decline. Hematopoietic stem cell transplantation (HSCT) also provides enzyme replacement, and may be effective in stabilizing neurocognitive function if initiated early, though data are limited. We present a case series of four patients who demonstrated neurocognitive stabilization with early HSCT. HSCT is a potentially underutilized treatment strategy for select groups of MPS II patients.

15.
Cell Transplant ; 27(8): 1210-1221, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30016879

RESUMO

Intramuscular administration of mesenchymal stromal cells (MSCs) represents a therapeutic option for diabetic critical limb ischemia. Autologous or allogeneic approaches may be used but disease-induced cell dysfunction may limit therapeutic efficacy in the former. Our aim was to compare the efficacy of allogeneic and autologous MSC transplantation in a model of hindlimb ischemia in diabetes mellitus and to determine whether allogeneic transplantation would result in the activation of an immune response. MSCs were isolated from C57BL/6 (B6) and diabetic obese C57BKSdb/db mice. Phosphate-buffered saline (control group), and MSCs (1 × 106) from B6 (allogeneic group) or C57BKSdb/db (syngeneic group) were administered intramuscularly into the ischemic thigh of C57BKSdb/db mice following the induction of hindlimb ischemia. MSCs derived from both mouse strains secrete several angiogenic factors, suggesting that the potential therapeutic effect is due to paracrine signaling. Administration of allogeneic MSCs significantly improved blood perfusion as compared with the control group on week 2 and 3, post-operatively. In comparison with the control group, syngeneic MSCs significantly improved blood perfusion at week 2 only. There was no statistical difference in blood perfusion between allogeneic and syngeneic MSC groups at any stages. There was no statistical difference in ambulatory and necrosis score among the three groups. Amputation of toes was only observed in the control group (one out of seven animals). Alloantibody was detected in three out of the eight mice that received allogeneic MSCs but was not observed in the other groups. In summary, we demonstrated comparable efficacy after transplantation of autologous and allogeneic MSCs in a diabetic animal model despite generation of an immune response.


Assuntos
Complicações do Diabetes/complicações , Membro Posterior/irrigação sanguínea , Isquemia/complicações , Isquemia/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Neovascularização Fisiológica , Animais , Células Cultivadas , Complicações do Diabetes/sangue , Complicações do Diabetes/imunologia , Modelos Animais de Doenças , Membro Posterior/imunologia , Isquemia/sangue , Isquemia/imunologia , Isoanticorpos/sangue , Isoanticorpos/imunologia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Camundongos Endogâmicos C57BL , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos
16.
Oncogene ; 25(2): 207-17, 2006 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-16170355

RESUMO

Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFbeta and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFbeta/BMP pathway, which interacts with the Pten signaling pathway.


Assuntos
Alopecia/genética , Carcinoma de Células Escamosas/genética , Diferenciação Celular , Folículo Piloso/anormalidades , Transdução de Sinais , Neoplasias Cutâneas/genética , Proteína Smad4/fisiologia , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Carcinoma de Células Escamosas/patologia , Núcleo Celular/metabolismo , Proliferação de Células , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Ativação Enzimática , Epiderme/patologia , Feminino , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Hiperplasia/etiologia , Hibridização In Situ , Integrases , Queratinócitos/citologia , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/embriologia , Pele/crescimento & desenvolvimento , Neoplasias Cutâneas/patologia , Proteína Smad4/genética , Fator de Crescimento Transformador beta/metabolismo
17.
Environ Pollut ; 147(1): 131-7, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17029684

RESUMO

Nutrient losses to surface waters following fertilization contribute to eutrophication. This study was conducted to compare the impacts of fertilization with inorganic fertilizer, swine (Sus scrofa domesticus) manure or poultry (Gallus domesticus) litter on runoff water quality, and how the duration between application and the first runoff event affects resulting water quality. Fertilizers were applied at 35 kg P ha-1, and the duration between application and the first runoff event varied between 1 and 29 days. Swine manure was the greatest risk to water quality 1 day after fertilization due to elevated phosphorus (8.4 mg P L-1) and ammonium (10.3 mg NH4-N L-1) concentrations; however, this risk decreased rapidly. Phosphorus concentrations were 2.6 mg L-1 29 days after fertilization with inorganic fertilizer. This research demonstrates that manures might be more environmentally sustainable than inorganic fertilizers, provided runoff events do not occur soon after application.


Assuntos
Agricultura , Difosfatos/efeitos adversos , Fertilizantes/efeitos adversos , Esterco , Poluição da Água/análise , Animais , Galinhas , Monitoramento Ambiental/métodos , Eutrofização , Nitrogênio/análise , Fósforo/análise , Compostos de Amônio Quaternário/análise , Chuva , Suínos , Fatores de Tempo , Ureia/análise , Movimentos da Água , Poluentes Químicos da Água/análise
18.
Endocr Connect ; 6(8): 614-624, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28899898

RESUMO

INTRODUCTION: MicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA-mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort. METHODS: The study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22. RESULTS: The total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98-1.46), P = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18-2.14), P = 0.002). CONCLUSION: The rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.

19.
Poult Sci ; 85(2): 167-72, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16523609

RESUMO

Twenty-eight flocks were grown on litter in a tunnel-ventilated, curtain-sided commercial broiler house prior to this summer flock. Grid measurements were made using a photo-acoustic multigas analyzer to assess the spatial variability of litter gases (NH3, N2O, CO2, and CH4) on d 1 and 21. The pooled results for the brood and non-brood areas of the house were 1) NH3 flux was greatest in the brood area at d 1, averaging 497 mg/(m2 x h), and had a mean of 370 mg/(m2 x h) in the vacant end of the house; 2) at d 21, the non-brood area had the greater average NH3 flux, 310 mg/(m2 x h), and flux in the brood area was 136 mg/(m2 x h); 3) N2O and CH4 fluxes were <60 mg/(m2 x h); and 4) on d 1, brood CO2 flux was 6,190 mg/(m2 x h) compared with 5,490 mg/ (m2 x h) at the opposite end of the house. On d 21, these values increased to 6,540 and 9,684 mg/(m2 x h) for the brood and non-brood areas. Ammonia flux seemed most affected by litter temperature. Carbon dioxide and CH4 increased from placement to mid growout, corresponding to increased moisture, especially near the fans. Contour plots were developed using geostatistical software to visually assess the spatial disparity among the measurements. This research provides a unique view of gas flux variation within the house. Collinear factors such as house management, bird size and age, and amount of deposition are significant factors for litter gas flux and should be considered in comprehensive models for emission estimates.


Assuntos
Amônia/análise , Dióxido de Carbono/análise , Galinhas , Abrigo para Animais , Metano/análise , Óxido Nitroso/análise , Poluentes Atmosféricos/análise , Animais , Gases/análise , Concentração de Íons de Hidrogênio , Esterco/análise , Temperatura , Volatilização , Água/análise
20.
Sci Total Environ ; 565: 8-27, 2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-27155260

RESUMO

Determining soil redistribution and sediment budgets in watersheds is often challenging. One of the methods for making such determinations employs soil and sediment fingerprinting techniques, using sediment properties such as geochemistry, fallout radionuclides, and mineral magnetism. These methods greatly improve the estimation of erosion and deposition within a watershed, but are limited when determining land use-based soil and sediment movement. Recently, compound-specific stable isotopes (CSSIs), which employ fatty acids naturally occurring in the vegetative cover of soils, offer the possibility of refining fingerprinting techniques based on land use, complementing other methods that are currently in use. The CSSI method has been met with some success; however, challenges still remain with respect to scale and resolution due to a potentially large degree of biological, environmental and analytical uncertainty. By better understanding the source of tracers used in CSSI work and the inherent biochemical variability in those tracers, improvement in sample design and tracer selection is possible. Furthermore, an understanding of environmental and analytical factors affecting the CSSI signal will lead to refinement of the approach and the ability to generate more robust data. This review focuses on sources of biological, environmental and analytical variability in applying CSSI to soil and sediment fingerprinting, and presents recommendations based on past work and current research in this area for improving the CSSI technique. A recommendation, based on current information available in the literature, is to use very-long chain saturated fatty acids and to avoid the use of the ubiquitous saturated fatty acids, C16 and C18.


Assuntos
Biomarcadores/química , Monitoramento Ambiental/métodos , Ácidos Graxos/química , Sedimentos Geológicos/química , Radioisótopos/química , Rios/química , Solo/química
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