RESUMO
Global distribution of salt-affected soils (SAS) has remained at about 1 billion hectares in the literature over the years despite changes in climate, sea levels, and land use patterns which influence the distribution. Lack of periodic update of input soil data, data gaps, and inconsistency are part of the reasons for constant SAS distribution in the literature. This paper proposes harmonization as a suitable alternative for managing inconsistent data and minimizing data gaps. It developed a new harmonization service for supporting country-driven global SAS information update. The service contains a global library of harmonization models for harmonizing inconsistent soil data. It also contains models for identifying gaps in SAS database and for showing global distribution where harmonization of available data is needed. The service can be used by countries to develop national SAS information and update global SAS distribution. Its data availability index is useful in identifying countries without SAS data in the global database, which is a convenient way to identify countries to mobilize when updating global SAS information. Its application in 27 countries showed that the countries have more SAS data than they currently share with the global databases and that most of their data require SAS harmonization.
RESUMO
Prostate cancer is characterized by a dependence upon androgen receptor (AR) signaling, and androgen deprivation therapy (ADT) is the accepted treatment for progressive prostate cancer. Although ADT is usually initially effective, acquired resistance termed castrate-resistant prostate cancer (CRPC) develops. PTEN and TP53 are two of the most commonly deleted or mutated genes in prostate cancer, the compound loss of which is enriched in CRPC. To interrogate the metabolic alterations associated with survival following ADT, we used an orthotopic model of Pten/Tp53 null prostate cancer. Metabolite profiles and associated regulators were compared in tumors from androgen-intact mice and in tumors surviving castration. AR inhibition led to changes in the levels of glycolysis and tricarboxylic acid (TCA) cycle pathway intermediates. As anticipated for inhibitory reciprocal feedback between AR and PI3K/AKT signaling pathways, pAKT levels were increased in androgen-deprived tumors. Elevated mitochondrial hexokinase 2 (HK2) levels and enzyme activities also were observed in androgen-deprived tumors, consistent with pAKT-dependent HK2 protein induction and mitochondrial association. Competitive inhibition of HK2-mitochondrial binding in prostate cancer cells led to decreased viability. These data argue for AKT-associated HK2-mediated metabolic reprogramming and mitochondrial association in PI3K-driven prostate cancer as one survival mechanism downstream of AR inhibition.
Assuntos
Androgênios/deficiência , Hexoquinase/metabolismo , PTEN Fosfo-Hidrolase/deficiência , Neoplasias da Próstata/metabolismo , Proteína Supressora de Tumor p53/deficiência , Androgênios/metabolismo , Animais , Metabolismo dos Carboidratos , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Humanos , Masculino , Camundongos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismoRESUMO
INTRODUCTION: The management of ballistic fractures, which are open fractures, has often been studied in wartime and has benefited from the principles of military surgery with debridement and lavage, and the use of external fixation for bone stabilization. HYPOTHESIS: In civilian practice, bone stabilization of these fractures is different and is not performed by external fixation. PATIENTS AND METHODS: Fifteen civilian ballistic fractures, Gustilo II or IIIa, two associated with nerve damage and none with vascular damage, were reviewed. After debridement and lavage, ten internal fixations and five conservative treatments were used. RESULTS: No superficial or deep surgical site infection was noted. Fourteen of the 15 fractures (93%) healed without reoperation. Eleven of the 15 patients (73%) regained normal function. DISCUSSION: Ballistic fractures have a bad reputation due to their many complications, including infections. In civilian practice, the use of internal fixation is not responsible for excessive morbidity, provided debridement and lavage are performed. Civilian ballistic fractures, when they are caused by low-velocity firearms, differ from military ballistic fractures. Although the principle of surgical debridement and lavage remains the same, bone stabilization is different and is similar to conventional open fractures.
Assuntos
Fraturas Cominutivas/cirurgia , Fraturas Expostas/cirurgia , Ferimentos por Arma de Fogo/cirurgia , Adulto , Antibioticoprofilaxia , Desbridamento , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Fraturas Expostas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Militares , Radiografia , Irrigação Terapêutica , Fraturas da Ulna/cirurgia , Ferimentos por Arma de Fogo/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVES: The goal of our work was to evaluate the results of the Isis(®) trapeziometacarpal prosthesis. METHODS: Our retrospective study included 26 patients, 30 prosthesis. The mean follow-up was 30 months. Preoperatively, the pain was 8.1 out of 10, the QuickDASH was 68.5 and the average Kapandji score was 7.8. The Dell's stage was 2.3. The prosthesis used was hybrid: the trapezial cup was cemented in 90% of cases, and the metacarpal stem was cementless. RESULTS: Eighty-seven percent of patients were satisfied or very satisfied. At last follow-up, the pain was 3.4 out of 10, the QuickDASH was 37.8, and the average Kapandji score 9.1. The range of motion in flexion-extension and abduction-adduction were respectively 30.5° and 31.7±11°. The strength of the key-pinch, pulp-pinch and grasp averaged 75% of the contralateral side. On radiologic review, the rate of radiolucent lines was 20%, and the loosening or non-osteointegration rate 10%. No dislocation was noted. One surgical revision was necessary for symptomatic metacarpal non-osteointegration. The survival rate of the prosthesis was 93% at 42 months. DISCUSSION: Clinical results are good. However, the rate of abnormal radiographic images (30%) at 30 months follow-up must incite caution. Although these prosthetic loosenings seem to be less symptomatic, a longer follow-up is necessary to assess the sustainability of clinical results and the future of these periprosthetic radiolucent lines. This led us to change our practice to using noncemented prostheses from now on.
Assuntos
Artroplastia de Substituição/métodos , Articulações Carpometacarpais/cirurgia , Prótese Articular , Osteoartrite/cirurgia , Polegar/cirurgia , Trapézio/cirurgia , Articulações Carpometacarpais/patologia , Feminino , Seguimentos , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/patologia , Medição da Dor , Desenho de Prótese , Amplitude de Movimento Articular , Reoperação , Estudos Retrospectivos , Polegar/patologia , Trapézio/patologia , Resultado do TratamentoRESUMO
Epithelial-mesenchymal transition (EMT) is a developmental program of signaling pathways that determine commitment to epithelial and mesenchymal phenotypes. In the prostate, EMT processes have been implicated in benign prostatic hyperplasia and prostate cancer progression. In a model of Pten- and TP53-null prostate adenocarcinoma that progresses via transforming growth factor ß-induced EMT, mesenchymal transformation is characterized by plasticity, leading to various mesenchymal lineages and the production of bone. Here we show that SLUG is a major regulator of mesenchymal differentiation. As microRNAs (miRs) are pleiotropic regulators of differentiation and tumorigenesis, we evaluated miR expression associated with tumorigenesis and EMT. Mir-1 and miR-200 were reduced with progression of prostate adenocarcinoma, and we identify Slug as one of the phylogenetically conserved targets of these miRs. We demonstrate that SLUG is a direct repressor of miR-1 and miR-200 transcription. Thus, SLUG and miR-1/miR-200 act in a self-reinforcing regulatory loop, leading to amplification of EMT. Depletion of Slug inhibited EMT during tumorigenesis, whereas forced expression of miR-1 or miR-200 inhibited both EMT and tumorigenesis in human and mouse model systems. Various miR targets were analyzed, and our findings suggest that miR-1 has roles in regulating EMT and mesenchymal differentiation through Slug and functions in tumor-suppressive programs by regulating additional targets.
Assuntos
Adenocarcinoma/patologia , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Neoplasias da Próstata/patologia , Fatores de Transcrição/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/fisiopatologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Retroalimentação Fisiológica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/patologia , Camundongos , PTEN Fosfo-Hidrolase/deficiência , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/fisiopatologia , Fatores de Transcrição da Família Snail , Fator de Crescimento Transformador beta/farmacologia , Proteína Supressora de Tumor p53/deficiênciaRESUMO
The perception of inspiratory resistive (R) loads was studied in nonasthmatic children and in children with a history of life-threatening asthma. It was hypothesized that the children with life-threatening asthma would have a reduced sensitivity to added mechanical loads as measured by magnitude estimation of resistive loads (ME). The subjects were screened from the experimenter and seated in a sound-isolated room in a lounge chair facing an oscilloscope, and they respired through a nonbreathing valve with the inspiratory port connected to the loading manifold. The oscilloscope displayed the inspiratory V, and each subject was required to inspire to the same peak V for each breath. The subject's inspiratory background R was measured by the interrupter method. Five magnitudes of R loads and no-load were presented randomly 10 times each for a single inspiration after the illumination of a light cue. The subjects were initially given a training trial breathing to the V target. The loads were presented in two trials. The load was estimated using the modified Borg scale. The slope of the log-log relationship between R load magnitude and the ME is a measure of the sensitivity of the subject to R loads. The slope for children with life-threatening asthma was significantly less than that for asthmatic and nonasthmatic children. There were no significant differences in the slope related to race, sex or age in the nonasthmatic children or in the asthmatic children. The reduced sensitivity to increased R loads suggests that these children are at risk of a life-threatening asthmatic attack in part because of an underestimation or delay in the perception of the increased mechanical load that occurs during an asthmatic attack.